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SBRT: A New Front-Runner in Treating Localized Renal Cell Carcinoma?
For patients with primary localized renal cell carcinoma (RCC), especially those who aren’t good candidates for surgery, noninvasive or minimally invasive ablative treatments have emerged as important options. These ablative treatments include radiofrequency ablation (RFA), microwave ablation, cryoablation, and the relative new-comer stereotactic body radiotherapy (SBRT).
But how do these approaches stack up against each other?
A recent meta-analysis published in Lancet Oncology found that SBRT appears to be equally safe and potentially more effective than other ablative treatment options for localized RCC.
“Our findings suggest that SBRT might offer a particularly advantageous option for treating larger renal cell carcinoma tumors, yielding the highest local control rates among ablative options with comparatively low rates of severe complications,” Srinivas Raman, MD, Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada, and colleagues wrote.
Outside experts who spoke with Medscape Medical News said SBRT should likely play a larger role in the management of early-stage RCC.
“Given its noninvasive nature, favorable toxicity profile, and comparable renal outcomes, SBRT warrants broader adoption,” said Shankar Siva, PhD, MBBS, a radiation oncologist at the Peter MacCallum Cancer Centre and professor at the University of Melbourne, both in Melbourne, Australia.
This new analysis is “helpful as it provides reassurance and further strong quality data to present in multidisciplinary renal rounds and tumor boards to consider the use of SBRT as an alternative to other ablative technique,” said Joelle Helou, MD, MSc, radiation oncologist, Verspeeten Family Cancer Centre, and assistant professor, Department of Oncology, Western University, both in London, Ontario, Canada.
Filling a Knowledge Gap
RCC is the most common malignancy of the kidney, accounting for > 90% of all renal malignancies. Worldwide, the incidence of RCC has continued to rise, with a 2% annual rate of increase over the past two decades.
The conventional treatment of choice is radical or partial nephrectomy; however, not all patients are ideally suited for surgery, especially those who are older or have compromised kidney function or comorbid conditions.
Ablative therapies have been integrated into clinical guidelines as evidence-based interventions to treat primary RCC. These therapies include RFA and microwave ablation — two minimally invasive thermal ablation techniques that use heat to destroy the tumor tissue — and cryoablation, which uses extreme cold to destroy the tumor tissue.
Studies have generally found similar outcomes with RFA and microwave ablation, with the choice of treatment often guided by what’s available and operator expertise. The US and European guidelines recommend these treatments, particularly for smaller tumors (< 4 cm), citing their effectiveness and minimal invasiveness.
SBRT is a relatively new noninvasive option that delivers highly focused radiation doses to the tumor across multiple sessions and may be particularly suited to larger tumors (≥ 4 cm).
National Comprehensive Cancer Network guidelines state that SBRT may be considered for nonoptimal surgical candidates with stage I, II, or III kidney cancer.
However, comparative data on these four techniques has been limited until now.
What Did the Meta-Analysis Find?
Raman and colleagues performed a systematic review and meta-analysis pooled data from 133 studies involving 8910 patients (mean age, 68 years) with localized RCC treated with one of the four ablative therapies.
Overall, across the four ablative approaches, local control rates were very similar at 1 year, ranging from 95% for cryoablation to 99% for SBRT, and at 2 years, ranging from 94% for cryoablation to 97% for SBRT. At 5 years, however, there was a slightly greater separation in outcomes favoring SBRT (95%) and RFA (92%) compared with cryoablation (90%) and microwave ablation (86%).
Although all four techniques demonstrated similar local control for small tumors measuring < 4 cm, the approaches began to diverge for larger tumors measuring ≥ 4 cm at 1, 2, and 5 years. At 5 years, for instance, SBRT had the highest local control rate (93%), outperforming RFA (79%), microwave ablation (82%), and cryoablation (85%).
Looking at survival outcomes, cancer-specific survival was 100% at 1 year across all treatments. At 5 years, small differences in cancer-specific survival were observed. For smaller tumors, cancer-specific survival ranged from 100% for both SBRT and RFA to 97% for microwave ablation and 98% for cryoablation. For larger tumors, the cancer-specific survival rate was 100% for microwave ablation, 95% for SBRT, and 94% for cryoablation.
These small differences in cancer-specific survival likely reflect differences in patient and tumor characteristics across the treatment groups, the study authors said.
Notably, patients treated with SBRT were older than those treated with microwave ablation and RFA, while also having the largest tumors, which have consistently been shown to be associated with worse local control, greater propensity for regional and distant metastases, worse survival outcomes, and increased treatment-related toxicity, the authors explained.
There were no significant differences in the rate of grade 1-2 adverse events between the ablative methods, although grade 3-4 adverse events occurred in a significantly higher proportion of patients treated with cryoablation (3%) than in those who received RFA and SBRT (2%) or microwave ablation (1%). Baseline or change in renal function, as measured by estimated glomerular filtration rate, did not differ between the ablative techniques.
Overall, the findings reinforce that, although typically offered to older patients with worse baseline renal function and much larger tumors, “SBRT maintained high effectiveness at 1, 2, and 5 years compared to thermal ablation,” Siva told Medscape Medical News.
SBRT in Clinical Practice?
Despite the mounting evidence in favor of SBRT for primary localized RCC unsuitable for surgery, “there is still some reluctance from urologists, mainly, to refer patients for consideration of SBRT,” Helou told Medscape Medical News.
This hesitance is reflected in the meta-analysis, he noted, with SBRT being the least performed ablative therapy (612 patients). Cryoablation was the most common technique used in 3726 patients, followed by RFA (2503 patients) and microwave ablation (2069 patients).
The “compelling efficacy and safety data suggest SBRT should play a larger role in managing early-stage RCC in nonsurgical candidates, particularly for larger tumors where it offers excellent long-term local control,” said Siva, who led the phase 2 FASTTRACK II study evaluating SBRT in patients with inoperable or high-risk primary RCC.
Despite patients having larger than average tumors (4.6 cm) compared with those in many other trials, Siva and colleagues reported a 100% local control rate following SBRT and no patient deaths from cancer during the study period.
The FASTTRACK II study marked “an inflection point for SBRT, and [the approach] is now slowly getting traction,” Chad Tang, MD, radiation oncologist, MD Anderson Cancer Center, Houston, told Medscape Medical News.
Overall, Raman and colleagues said decisions about ablative therapy should be “precisely tailored to the individual patient’s clinical condition and treatment objectives.” Treatment selection should, for instance, depend on tumor size, location, patient comorbidities, availability of a technique, institutional and physician expertise, and patient preference.
Looking ahead, randomized controlled trials across larger patient populations are needed to further elucidate the long-term cancer and survival outcomes associated with these ablative treatments. Research comparing ablative methods with surgery and surveillance as well as exploring other relevant clinical outcomes, such as cost-effectiveness and quality of life, should be performed as well.
“Prospective randomized trials remain essential to further refine the position of SBRT in clinical practice in patients who are surgical candidates,” Siva told Medscape Medical News.
This research had no commercial funding. Raman reported receiving personal fees from AstraZeneca, Sanofi, Knight Pharmaceuticals, Verity Pharma, and Tersera, and grants from Knight Therapeutics, AstraZeneca, and Varian. Siva reported financial relationships with AstraZeneca and Telix Pharmaceuticals. Helou and Tang had no relevant disclosures.
For patients with primary localized renal cell carcinoma (RCC), especially those who aren’t good candidates for surgery, noninvasive or minimally invasive ablative treatments have emerged as important options. These ablative treatments include radiofrequency ablation (RFA), microwave ablation, cryoablation, and the relative new-comer stereotactic body radiotherapy (SBRT).
But how do these approaches stack up against each other?
A recent meta-analysis published in Lancet Oncology found that SBRT appears to be equally safe and potentially more effective than other ablative treatment options for localized RCC.
“Our findings suggest that SBRT might offer a particularly advantageous option for treating larger renal cell carcinoma tumors, yielding the highest local control rates among ablative options with comparatively low rates of severe complications,” Srinivas Raman, MD, Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada, and colleagues wrote.
Outside experts who spoke with Medscape Medical News said SBRT should likely play a larger role in the management of early-stage RCC.
“Given its noninvasive nature, favorable toxicity profile, and comparable renal outcomes, SBRT warrants broader adoption,” said Shankar Siva, PhD, MBBS, a radiation oncologist at the Peter MacCallum Cancer Centre and professor at the University of Melbourne, both in Melbourne, Australia.
This new analysis is “helpful as it provides reassurance and further strong quality data to present in multidisciplinary renal rounds and tumor boards to consider the use of SBRT as an alternative to other ablative technique,” said Joelle Helou, MD, MSc, radiation oncologist, Verspeeten Family Cancer Centre, and assistant professor, Department of Oncology, Western University, both in London, Ontario, Canada.
Filling a Knowledge Gap
RCC is the most common malignancy of the kidney, accounting for > 90% of all renal malignancies. Worldwide, the incidence of RCC has continued to rise, with a 2% annual rate of increase over the past two decades.
The conventional treatment of choice is radical or partial nephrectomy; however, not all patients are ideally suited for surgery, especially those who are older or have compromised kidney function or comorbid conditions.
Ablative therapies have been integrated into clinical guidelines as evidence-based interventions to treat primary RCC. These therapies include RFA and microwave ablation — two minimally invasive thermal ablation techniques that use heat to destroy the tumor tissue — and cryoablation, which uses extreme cold to destroy the tumor tissue.
Studies have generally found similar outcomes with RFA and microwave ablation, with the choice of treatment often guided by what’s available and operator expertise. The US and European guidelines recommend these treatments, particularly for smaller tumors (< 4 cm), citing their effectiveness and minimal invasiveness.
SBRT is a relatively new noninvasive option that delivers highly focused radiation doses to the tumor across multiple sessions and may be particularly suited to larger tumors (≥ 4 cm).
National Comprehensive Cancer Network guidelines state that SBRT may be considered for nonoptimal surgical candidates with stage I, II, or III kidney cancer.
However, comparative data on these four techniques has been limited until now.
What Did the Meta-Analysis Find?
Raman and colleagues performed a systematic review and meta-analysis pooled data from 133 studies involving 8910 patients (mean age, 68 years) with localized RCC treated with one of the four ablative therapies.
Overall, across the four ablative approaches, local control rates were very similar at 1 year, ranging from 95% for cryoablation to 99% for SBRT, and at 2 years, ranging from 94% for cryoablation to 97% for SBRT. At 5 years, however, there was a slightly greater separation in outcomes favoring SBRT (95%) and RFA (92%) compared with cryoablation (90%) and microwave ablation (86%).
Although all four techniques demonstrated similar local control for small tumors measuring < 4 cm, the approaches began to diverge for larger tumors measuring ≥ 4 cm at 1, 2, and 5 years. At 5 years, for instance, SBRT had the highest local control rate (93%), outperforming RFA (79%), microwave ablation (82%), and cryoablation (85%).
Looking at survival outcomes, cancer-specific survival was 100% at 1 year across all treatments. At 5 years, small differences in cancer-specific survival were observed. For smaller tumors, cancer-specific survival ranged from 100% for both SBRT and RFA to 97% for microwave ablation and 98% for cryoablation. For larger tumors, the cancer-specific survival rate was 100% for microwave ablation, 95% for SBRT, and 94% for cryoablation.
These small differences in cancer-specific survival likely reflect differences in patient and tumor characteristics across the treatment groups, the study authors said.
Notably, patients treated with SBRT were older than those treated with microwave ablation and RFA, while also having the largest tumors, which have consistently been shown to be associated with worse local control, greater propensity for regional and distant metastases, worse survival outcomes, and increased treatment-related toxicity, the authors explained.
There were no significant differences in the rate of grade 1-2 adverse events between the ablative methods, although grade 3-4 adverse events occurred in a significantly higher proportion of patients treated with cryoablation (3%) than in those who received RFA and SBRT (2%) or microwave ablation (1%). Baseline or change in renal function, as measured by estimated glomerular filtration rate, did not differ between the ablative techniques.
Overall, the findings reinforce that, although typically offered to older patients with worse baseline renal function and much larger tumors, “SBRT maintained high effectiveness at 1, 2, and 5 years compared to thermal ablation,” Siva told Medscape Medical News.
SBRT in Clinical Practice?
Despite the mounting evidence in favor of SBRT for primary localized RCC unsuitable for surgery, “there is still some reluctance from urologists, mainly, to refer patients for consideration of SBRT,” Helou told Medscape Medical News.
This hesitance is reflected in the meta-analysis, he noted, with SBRT being the least performed ablative therapy (612 patients). Cryoablation was the most common technique used in 3726 patients, followed by RFA (2503 patients) and microwave ablation (2069 patients).
The “compelling efficacy and safety data suggest SBRT should play a larger role in managing early-stage RCC in nonsurgical candidates, particularly for larger tumors where it offers excellent long-term local control,” said Siva, who led the phase 2 FASTTRACK II study evaluating SBRT in patients with inoperable or high-risk primary RCC.
Despite patients having larger than average tumors (4.6 cm) compared with those in many other trials, Siva and colleagues reported a 100% local control rate following SBRT and no patient deaths from cancer during the study period.
The FASTTRACK II study marked “an inflection point for SBRT, and [the approach] is now slowly getting traction,” Chad Tang, MD, radiation oncologist, MD Anderson Cancer Center, Houston, told Medscape Medical News.
Overall, Raman and colleagues said decisions about ablative therapy should be “precisely tailored to the individual patient’s clinical condition and treatment objectives.” Treatment selection should, for instance, depend on tumor size, location, patient comorbidities, availability of a technique, institutional and physician expertise, and patient preference.
Looking ahead, randomized controlled trials across larger patient populations are needed to further elucidate the long-term cancer and survival outcomes associated with these ablative treatments. Research comparing ablative methods with surgery and surveillance as well as exploring other relevant clinical outcomes, such as cost-effectiveness and quality of life, should be performed as well.
“Prospective randomized trials remain essential to further refine the position of SBRT in clinical practice in patients who are surgical candidates,” Siva told Medscape Medical News.
This research had no commercial funding. Raman reported receiving personal fees from AstraZeneca, Sanofi, Knight Pharmaceuticals, Verity Pharma, and Tersera, and grants from Knight Therapeutics, AstraZeneca, and Varian. Siva reported financial relationships with AstraZeneca and Telix Pharmaceuticals. Helou and Tang had no relevant disclosures.
For patients with primary localized renal cell carcinoma (RCC), especially those who aren’t good candidates for surgery, noninvasive or minimally invasive ablative treatments have emerged as important options. These ablative treatments include radiofrequency ablation (RFA), microwave ablation, cryoablation, and the relative new-comer stereotactic body radiotherapy (SBRT).
But how do these approaches stack up against each other?
A recent meta-analysis published in Lancet Oncology found that SBRT appears to be equally safe and potentially more effective than other ablative treatment options for localized RCC.
“Our findings suggest that SBRT might offer a particularly advantageous option for treating larger renal cell carcinoma tumors, yielding the highest local control rates among ablative options with comparatively low rates of severe complications,” Srinivas Raman, MD, Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada, and colleagues wrote.
Outside experts who spoke with Medscape Medical News said SBRT should likely play a larger role in the management of early-stage RCC.
“Given its noninvasive nature, favorable toxicity profile, and comparable renal outcomes, SBRT warrants broader adoption,” said Shankar Siva, PhD, MBBS, a radiation oncologist at the Peter MacCallum Cancer Centre and professor at the University of Melbourne, both in Melbourne, Australia.
This new analysis is “helpful as it provides reassurance and further strong quality data to present in multidisciplinary renal rounds and tumor boards to consider the use of SBRT as an alternative to other ablative technique,” said Joelle Helou, MD, MSc, radiation oncologist, Verspeeten Family Cancer Centre, and assistant professor, Department of Oncology, Western University, both in London, Ontario, Canada.
Filling a Knowledge Gap
RCC is the most common malignancy of the kidney, accounting for > 90% of all renal malignancies. Worldwide, the incidence of RCC has continued to rise, with a 2% annual rate of increase over the past two decades.
The conventional treatment of choice is radical or partial nephrectomy; however, not all patients are ideally suited for surgery, especially those who are older or have compromised kidney function or comorbid conditions.
Ablative therapies have been integrated into clinical guidelines as evidence-based interventions to treat primary RCC. These therapies include RFA and microwave ablation — two minimally invasive thermal ablation techniques that use heat to destroy the tumor tissue — and cryoablation, which uses extreme cold to destroy the tumor tissue.
Studies have generally found similar outcomes with RFA and microwave ablation, with the choice of treatment often guided by what’s available and operator expertise. The US and European guidelines recommend these treatments, particularly for smaller tumors (< 4 cm), citing their effectiveness and minimal invasiveness.
SBRT is a relatively new noninvasive option that delivers highly focused radiation doses to the tumor across multiple sessions and may be particularly suited to larger tumors (≥ 4 cm).
National Comprehensive Cancer Network guidelines state that SBRT may be considered for nonoptimal surgical candidates with stage I, II, or III kidney cancer.
However, comparative data on these four techniques has been limited until now.
What Did the Meta-Analysis Find?
Raman and colleagues performed a systematic review and meta-analysis pooled data from 133 studies involving 8910 patients (mean age, 68 years) with localized RCC treated with one of the four ablative therapies.
Overall, across the four ablative approaches, local control rates were very similar at 1 year, ranging from 95% for cryoablation to 99% for SBRT, and at 2 years, ranging from 94% for cryoablation to 97% for SBRT. At 5 years, however, there was a slightly greater separation in outcomes favoring SBRT (95%) and RFA (92%) compared with cryoablation (90%) and microwave ablation (86%).
Although all four techniques demonstrated similar local control for small tumors measuring < 4 cm, the approaches began to diverge for larger tumors measuring ≥ 4 cm at 1, 2, and 5 years. At 5 years, for instance, SBRT had the highest local control rate (93%), outperforming RFA (79%), microwave ablation (82%), and cryoablation (85%).
Looking at survival outcomes, cancer-specific survival was 100% at 1 year across all treatments. At 5 years, small differences in cancer-specific survival were observed. For smaller tumors, cancer-specific survival ranged from 100% for both SBRT and RFA to 97% for microwave ablation and 98% for cryoablation. For larger tumors, the cancer-specific survival rate was 100% for microwave ablation, 95% for SBRT, and 94% for cryoablation.
These small differences in cancer-specific survival likely reflect differences in patient and tumor characteristics across the treatment groups, the study authors said.
Notably, patients treated with SBRT were older than those treated with microwave ablation and RFA, while also having the largest tumors, which have consistently been shown to be associated with worse local control, greater propensity for regional and distant metastases, worse survival outcomes, and increased treatment-related toxicity, the authors explained.
There were no significant differences in the rate of grade 1-2 adverse events between the ablative methods, although grade 3-4 adverse events occurred in a significantly higher proportion of patients treated with cryoablation (3%) than in those who received RFA and SBRT (2%) or microwave ablation (1%). Baseline or change in renal function, as measured by estimated glomerular filtration rate, did not differ between the ablative techniques.
Overall, the findings reinforce that, although typically offered to older patients with worse baseline renal function and much larger tumors, “SBRT maintained high effectiveness at 1, 2, and 5 years compared to thermal ablation,” Siva told Medscape Medical News.
SBRT in Clinical Practice?
Despite the mounting evidence in favor of SBRT for primary localized RCC unsuitable for surgery, “there is still some reluctance from urologists, mainly, to refer patients for consideration of SBRT,” Helou told Medscape Medical News.
This hesitance is reflected in the meta-analysis, he noted, with SBRT being the least performed ablative therapy (612 patients). Cryoablation was the most common technique used in 3726 patients, followed by RFA (2503 patients) and microwave ablation (2069 patients).
The “compelling efficacy and safety data suggest SBRT should play a larger role in managing early-stage RCC in nonsurgical candidates, particularly for larger tumors where it offers excellent long-term local control,” said Siva, who led the phase 2 FASTTRACK II study evaluating SBRT in patients with inoperable or high-risk primary RCC.
Despite patients having larger than average tumors (4.6 cm) compared with those in many other trials, Siva and colleagues reported a 100% local control rate following SBRT and no patient deaths from cancer during the study period.
The FASTTRACK II study marked “an inflection point for SBRT, and [the approach] is now slowly getting traction,” Chad Tang, MD, radiation oncologist, MD Anderson Cancer Center, Houston, told Medscape Medical News.
Overall, Raman and colleagues said decisions about ablative therapy should be “precisely tailored to the individual patient’s clinical condition and treatment objectives.” Treatment selection should, for instance, depend on tumor size, location, patient comorbidities, availability of a technique, institutional and physician expertise, and patient preference.
Looking ahead, randomized controlled trials across larger patient populations are needed to further elucidate the long-term cancer and survival outcomes associated with these ablative treatments. Research comparing ablative methods with surgery and surveillance as well as exploring other relevant clinical outcomes, such as cost-effectiveness and quality of life, should be performed as well.
“Prospective randomized trials remain essential to further refine the position of SBRT in clinical practice in patients who are surgical candidates,” Siva told Medscape Medical News.
This research had no commercial funding. Raman reported receiving personal fees from AstraZeneca, Sanofi, Knight Pharmaceuticals, Verity Pharma, and Tersera, and grants from Knight Therapeutics, AstraZeneca, and Varian. Siva reported financial relationships with AstraZeneca and Telix Pharmaceuticals. Helou and Tang had no relevant disclosures.
Two Cystic Duct Stents Appear Better Than One
according to a retrospective multicenter study.
These findings suggest that endoscopists should prioritize dual stent placement when feasible, and consider adding a second stent in patients who previously received a single stent, James D. Haddad, MD, of the University of Texas Southwestern, Dallas, and colleagues reported.
The American Gastroenterological Association (AGA) has recognized the role of endoscopic drainage in managing acute cholecystitis in high-risk patients, but specific guidance on optimal technique and follow-up remains unclear, the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.
“Despite accumulating data and increased interest in this technique, clear guidance on the ideal strategy for ETGBD is lacking,” Dr. Haddad and colleagues wrote. “For example, the optimal size, number, and follow-up of cystic duct stents for patients undergoing ETGBD has not been well established.”
To address this knowledge gap, the investigators analyzed data from 75 patients at five academic medical centers who had undergone ETGBD between June 2013 and October 2022. Patients were divided into two groups based on whether they received one or two cystic duct stents.
The primary outcome was clinical success, defined as symptom resolution without requiring another drainage procedure. Secondary outcomes included technical success (defined as successful stent placement), along with rates of adverse events and unplanned reinterventions.
Out of the 75 patients, 59 received a single stent, while 16 received dual stents. The median follow-up time was 407 days overall, with a longer follow-up in the single-stent group (433 days), compared with the double-stent group (118 days).
Clinical success was reported in 81.3% of cases, which technical success was achieved in 88.2% of cases.
Patients who received two stents had significantly lower rates of unplanned reintervention, compared with those who received a single stent (0% vs 25.4%; P = .02). The median time to unplanned reintervention in the single-stent group was 210 days.
Use of a 7 French stent was strongly associated with placement of two stents (odd ratio [OR], 15.5; P = .01). Similarly, patients with a prior percutaneous cholecystostomy tube were significantly more likely to have two stents placed (OR, 10.8; P = .001).
Adverse event rates were uncommon and not statistically different between groups, with an overall rate of 6.7%. Post-endoscopic retrograde cholangiopancreatography pancreatitis was the most common adverse event, occurring in two patients in the single-stent group and one patient in the double-stent group. There were no reported cases of cystic duct or gallbladder perforation.
“In conclusion,” the investigators wrote, “ETGBD with dual transpapillary gallbladder stenting is associated with a lower rate of unplanned reinterventions, compared with that with single stenting, and has a low rate of adverse events. Endoscopists performing ETGBD should consider planned exchange of solitary transpapillary gallbladder stents or interval ERCP for reattempted placement of a second stent if placement of two stents is not possible at the index ERCP.”
The investigators disclosed relationships with Boston Scientific, Motus GI, and ConMed.
according to a retrospective multicenter study.
These findings suggest that endoscopists should prioritize dual stent placement when feasible, and consider adding a second stent in patients who previously received a single stent, James D. Haddad, MD, of the University of Texas Southwestern, Dallas, and colleagues reported.
The American Gastroenterological Association (AGA) has recognized the role of endoscopic drainage in managing acute cholecystitis in high-risk patients, but specific guidance on optimal technique and follow-up remains unclear, the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.
“Despite accumulating data and increased interest in this technique, clear guidance on the ideal strategy for ETGBD is lacking,” Dr. Haddad and colleagues wrote. “For example, the optimal size, number, and follow-up of cystic duct stents for patients undergoing ETGBD has not been well established.”
To address this knowledge gap, the investigators analyzed data from 75 patients at five academic medical centers who had undergone ETGBD between June 2013 and October 2022. Patients were divided into two groups based on whether they received one or two cystic duct stents.
The primary outcome was clinical success, defined as symptom resolution without requiring another drainage procedure. Secondary outcomes included technical success (defined as successful stent placement), along with rates of adverse events and unplanned reinterventions.
Out of the 75 patients, 59 received a single stent, while 16 received dual stents. The median follow-up time was 407 days overall, with a longer follow-up in the single-stent group (433 days), compared with the double-stent group (118 days).
Clinical success was reported in 81.3% of cases, which technical success was achieved in 88.2% of cases.
Patients who received two stents had significantly lower rates of unplanned reintervention, compared with those who received a single stent (0% vs 25.4%; P = .02). The median time to unplanned reintervention in the single-stent group was 210 days.
Use of a 7 French stent was strongly associated with placement of two stents (odd ratio [OR], 15.5; P = .01). Similarly, patients with a prior percutaneous cholecystostomy tube were significantly more likely to have two stents placed (OR, 10.8; P = .001).
Adverse event rates were uncommon and not statistically different between groups, with an overall rate of 6.7%. Post-endoscopic retrograde cholangiopancreatography pancreatitis was the most common adverse event, occurring in two patients in the single-stent group and one patient in the double-stent group. There were no reported cases of cystic duct or gallbladder perforation.
“In conclusion,” the investigators wrote, “ETGBD with dual transpapillary gallbladder stenting is associated with a lower rate of unplanned reinterventions, compared with that with single stenting, and has a low rate of adverse events. Endoscopists performing ETGBD should consider planned exchange of solitary transpapillary gallbladder stents or interval ERCP for reattempted placement of a second stent if placement of two stents is not possible at the index ERCP.”
The investigators disclosed relationships with Boston Scientific, Motus GI, and ConMed.
according to a retrospective multicenter study.
These findings suggest that endoscopists should prioritize dual stent placement when feasible, and consider adding a second stent in patients who previously received a single stent, James D. Haddad, MD, of the University of Texas Southwestern, Dallas, and colleagues reported.
The American Gastroenterological Association (AGA) has recognized the role of endoscopic drainage in managing acute cholecystitis in high-risk patients, but specific guidance on optimal technique and follow-up remains unclear, the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.
“Despite accumulating data and increased interest in this technique, clear guidance on the ideal strategy for ETGBD is lacking,” Dr. Haddad and colleagues wrote. “For example, the optimal size, number, and follow-up of cystic duct stents for patients undergoing ETGBD has not been well established.”
To address this knowledge gap, the investigators analyzed data from 75 patients at five academic medical centers who had undergone ETGBD between June 2013 and October 2022. Patients were divided into two groups based on whether they received one or two cystic duct stents.
The primary outcome was clinical success, defined as symptom resolution without requiring another drainage procedure. Secondary outcomes included technical success (defined as successful stent placement), along with rates of adverse events and unplanned reinterventions.
Out of the 75 patients, 59 received a single stent, while 16 received dual stents. The median follow-up time was 407 days overall, with a longer follow-up in the single-stent group (433 days), compared with the double-stent group (118 days).
Clinical success was reported in 81.3% of cases, which technical success was achieved in 88.2% of cases.
Patients who received two stents had significantly lower rates of unplanned reintervention, compared with those who received a single stent (0% vs 25.4%; P = .02). The median time to unplanned reintervention in the single-stent group was 210 days.
Use of a 7 French stent was strongly associated with placement of two stents (odd ratio [OR], 15.5; P = .01). Similarly, patients with a prior percutaneous cholecystostomy tube were significantly more likely to have two stents placed (OR, 10.8; P = .001).
Adverse event rates were uncommon and not statistically different between groups, with an overall rate of 6.7%. Post-endoscopic retrograde cholangiopancreatography pancreatitis was the most common adverse event, occurring in two patients in the single-stent group and one patient in the double-stent group. There were no reported cases of cystic duct or gallbladder perforation.
“In conclusion,” the investigators wrote, “ETGBD with dual transpapillary gallbladder stenting is associated with a lower rate of unplanned reinterventions, compared with that with single stenting, and has a low rate of adverse events. Endoscopists performing ETGBD should consider planned exchange of solitary transpapillary gallbladder stents or interval ERCP for reattempted placement of a second stent if placement of two stents is not possible at the index ERCP.”
The investigators disclosed relationships with Boston Scientific, Motus GI, and ConMed.
FROM TECHNIQUES AND INNOVATIONS IN GASTROINTESTINAL ENDOSCOPY
PSA Screening in VA Patients After Age 70 Years
TOPLINE: Most men receiving care through the Veterans Health Administration (VHA) continue prostate-specific antigen (PSA) screening after aged 70 years despite low absolute risk for prostate cancer-specific mortality (PCSM), even among Black men in the healthiest quintile.
METHODOLOGY:
Researchers conducted a cohort study of 921,609 men aged 70 years receiving VHA care between 2008 and 2020, who had normal screening PSA values (< 4 ng/mL) between ages 65-69 years.
- Analysis included electronic health record data from VHA Corporate Data Warehouse, linked Medicare claims data, and VHA community care data.
- Investigators examined the value of PSA levels, race and ethnicity, and competing mortality in risk stratification for PCSM and mPCa using regression modeling.
TAKEAWAY:
The 10-year cumulative incidence of PCSM was 0.26% overall, with 95% of men having a 10-year risk < 0.73%, and higher baseline PSA levels associated with increased risk (0.79% for 3.00-3.99 ng/mL vs 0.10% for 0.20-0.99 ng/mL).
- Race and ethnicity showed modest association with PCSM risk: Black patients had a 0.79% risk of mPCa vs 0.38% for White patients. The risk of PCSM was 0.36% for Black patients vs 0.25% for White patients.
- Most patients (87%) continued PSA screening after age 70 years, with little variation by competing mortality risk or race and ethnicity.
- Low PSA (0.20-0.99 ng/mL) identified very low-risk populations with < 1% 10-year risk for prostate biopsy, clinically significant prostate cancer diagnosis, and treatment.
IN PRACTICE: "Our data suggest that a simple assessment of personal risk based on PSA values before age 70 years captures a large proportion of relevant prognostic information with respect to mPCa and PCSM risk ... Low PSA (0.20-0.99 ng/mL) was associated with very low PCSM and mPCa risk, even among the healthiest Black men," wrote the authors of the study.
SOURCE: The study was led by Alex K. Bryant,MD, MAS and the Veterans Affairs Center for Clinical Management Research in Ann Arbor. It was published online on February 14 in JAMA Network Open.
LIMITATIONS: According to the authors, any potential PCSM or mPCa reduction from continued PSA screening > age 70 years remains unproven due to lack of randomized trial data. The study relied on death certificates to define PCSM, which may have introduced misclassification error. Family history of prostate cancer was not included due to unreliable electronic medical record data availability. Additionally, veterans have higher comorbidity burdens than the general population and unique military-related environmental exposures, potentially limiting result generalizability.
DISCLOSURES: The study was supported by grants U01CA253915, PSOCA097186, R35CA274442, and R50CA221836 from the National Cancer Institute. Matthew J. Schipper, MD, reported receiving consulting fees from Innovative Analytics. Phoebe A. Tsao, MD, disclosed receiving grants from the Prostate Cancer Foundation outside the submitted work. Kristian D. Stensland, MD, reported receiving a grant from the National Institutes of Health during the conduct of the study.
TOPLINE: Most men receiving care through the Veterans Health Administration (VHA) continue prostate-specific antigen (PSA) screening after aged 70 years despite low absolute risk for prostate cancer-specific mortality (PCSM), even among Black men in the healthiest quintile.
METHODOLOGY:
Researchers conducted a cohort study of 921,609 men aged 70 years receiving VHA care between 2008 and 2020, who had normal screening PSA values (< 4 ng/mL) between ages 65-69 years.
- Analysis included electronic health record data from VHA Corporate Data Warehouse, linked Medicare claims data, and VHA community care data.
- Investigators examined the value of PSA levels, race and ethnicity, and competing mortality in risk stratification for PCSM and mPCa using regression modeling.
TAKEAWAY:
The 10-year cumulative incidence of PCSM was 0.26% overall, with 95% of men having a 10-year risk < 0.73%, and higher baseline PSA levels associated with increased risk (0.79% for 3.00-3.99 ng/mL vs 0.10% for 0.20-0.99 ng/mL).
- Race and ethnicity showed modest association with PCSM risk: Black patients had a 0.79% risk of mPCa vs 0.38% for White patients. The risk of PCSM was 0.36% for Black patients vs 0.25% for White patients.
- Most patients (87%) continued PSA screening after age 70 years, with little variation by competing mortality risk or race and ethnicity.
- Low PSA (0.20-0.99 ng/mL) identified very low-risk populations with < 1% 10-year risk for prostate biopsy, clinically significant prostate cancer diagnosis, and treatment.
IN PRACTICE: "Our data suggest that a simple assessment of personal risk based on PSA values before age 70 years captures a large proportion of relevant prognostic information with respect to mPCa and PCSM risk ... Low PSA (0.20-0.99 ng/mL) was associated with very low PCSM and mPCa risk, even among the healthiest Black men," wrote the authors of the study.
SOURCE: The study was led by Alex K. Bryant,MD, MAS and the Veterans Affairs Center for Clinical Management Research in Ann Arbor. It was published online on February 14 in JAMA Network Open.
LIMITATIONS: According to the authors, any potential PCSM or mPCa reduction from continued PSA screening > age 70 years remains unproven due to lack of randomized trial data. The study relied on death certificates to define PCSM, which may have introduced misclassification error. Family history of prostate cancer was not included due to unreliable electronic medical record data availability. Additionally, veterans have higher comorbidity burdens than the general population and unique military-related environmental exposures, potentially limiting result generalizability.
DISCLOSURES: The study was supported by grants U01CA253915, PSOCA097186, R35CA274442, and R50CA221836 from the National Cancer Institute. Matthew J. Schipper, MD, reported receiving consulting fees from Innovative Analytics. Phoebe A. Tsao, MD, disclosed receiving grants from the Prostate Cancer Foundation outside the submitted work. Kristian D. Stensland, MD, reported receiving a grant from the National Institutes of Health during the conduct of the study.
TOPLINE: Most men receiving care through the Veterans Health Administration (VHA) continue prostate-specific antigen (PSA) screening after aged 70 years despite low absolute risk for prostate cancer-specific mortality (PCSM), even among Black men in the healthiest quintile.
METHODOLOGY:
Researchers conducted a cohort study of 921,609 men aged 70 years receiving VHA care between 2008 and 2020, who had normal screening PSA values (< 4 ng/mL) between ages 65-69 years.
- Analysis included electronic health record data from VHA Corporate Data Warehouse, linked Medicare claims data, and VHA community care data.
- Investigators examined the value of PSA levels, race and ethnicity, and competing mortality in risk stratification for PCSM and mPCa using regression modeling.
TAKEAWAY:
The 10-year cumulative incidence of PCSM was 0.26% overall, with 95% of men having a 10-year risk < 0.73%, and higher baseline PSA levels associated with increased risk (0.79% for 3.00-3.99 ng/mL vs 0.10% for 0.20-0.99 ng/mL).
- Race and ethnicity showed modest association with PCSM risk: Black patients had a 0.79% risk of mPCa vs 0.38% for White patients. The risk of PCSM was 0.36% for Black patients vs 0.25% for White patients.
- Most patients (87%) continued PSA screening after age 70 years, with little variation by competing mortality risk or race and ethnicity.
- Low PSA (0.20-0.99 ng/mL) identified very low-risk populations with < 1% 10-year risk for prostate biopsy, clinically significant prostate cancer diagnosis, and treatment.
IN PRACTICE: "Our data suggest that a simple assessment of personal risk based on PSA values before age 70 years captures a large proportion of relevant prognostic information with respect to mPCa and PCSM risk ... Low PSA (0.20-0.99 ng/mL) was associated with very low PCSM and mPCa risk, even among the healthiest Black men," wrote the authors of the study.
SOURCE: The study was led by Alex K. Bryant,MD, MAS and the Veterans Affairs Center for Clinical Management Research in Ann Arbor. It was published online on February 14 in JAMA Network Open.
LIMITATIONS: According to the authors, any potential PCSM or mPCa reduction from continued PSA screening > age 70 years remains unproven due to lack of randomized trial data. The study relied on death certificates to define PCSM, which may have introduced misclassification error. Family history of prostate cancer was not included due to unreliable electronic medical record data availability. Additionally, veterans have higher comorbidity burdens than the general population and unique military-related environmental exposures, potentially limiting result generalizability.
DISCLOSURES: The study was supported by grants U01CA253915, PSOCA097186, R35CA274442, and R50CA221836 from the National Cancer Institute. Matthew J. Schipper, MD, reported receiving consulting fees from Innovative Analytics. Phoebe A. Tsao, MD, disclosed receiving grants from the Prostate Cancer Foundation outside the submitted work. Kristian D. Stensland, MD, reported receiving a grant from the National Institutes of Health during the conduct of the study.
Circulating Proteins Predict Crohn’s Disease Years in Advance
The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported.
“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.
Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted.
Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.
First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature.
In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87.
While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.
Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.
“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”
These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.
Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs.
The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation.
In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.
Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.
“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.
This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.
Nowadays, preclinical biomarker discovery for inflammatory bowel diseases (IBD) is one of the key areas of study, aiming to identify the earliest stages of disease development and to find opportunities for early intervention. The study by Grännö and colleagues taps into this area and provides a significant advancement in the early detection of Crohn’s disease (CD) with a validated 29-plasma protein biomarker signature.
With an AUC of up to 0.87 in preclinical CD cases and even 0.82 as early as 16 years before diagnosis, these findings strongly support the notion that CD has a prolonged preclinical phase that is detectable up to many years before diagnosis. Importantly, their identified protein signatures also shed light on distinct pathophysiological mechanisms between CD and ulcerative colitis (UC), with CD characterized by early disruptions in gut barrier integrity and macrophage function, while UC was more marked by upregulated inflammatory markers.
For clinical practitioners, these findings have a strong transformative potential. Following further validation in larger cohorts and allowing clinical accessibility, preclinical biomarker screening could become a routine tool for risk stratification in at-risk individuals, such as those with a strong family history or genetic predisposition. This could enable implementation of early interventions, including dietary modifications and potentially prophylactic therapies, to delay or even prevent disease onset. Given that similar approaches have proven effective in type 1 diabetes, applying this strategy to IBD could significantly alter disease progression and patient outcomes.
Challenges remain before implementation in clinical practice could be realized. Standardized thresholds for risk assessment, cost-effectiveness analyses, and potential therapeutic strategies tailored to biomarker-positive individuals require further exploration. However, this study provides important data needed for a paradigm shift in IBD management — one that moves from reactive treatment to proactive prevention.
Arno R. Bourgonje, MD, PhD, is a postdoctoral fellow at the Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and at the University Medical Center Groningen in Groningen, the Netherlands. He is involved in the European INTERCEPT consortium, which is focused on prediction and prevention of IBD. He reported no conflicts of interest.
Nowadays, preclinical biomarker discovery for inflammatory bowel diseases (IBD) is one of the key areas of study, aiming to identify the earliest stages of disease development and to find opportunities for early intervention. The study by Grännö and colleagues taps into this area and provides a significant advancement in the early detection of Crohn’s disease (CD) with a validated 29-plasma protein biomarker signature.
With an AUC of up to 0.87 in preclinical CD cases and even 0.82 as early as 16 years before diagnosis, these findings strongly support the notion that CD has a prolonged preclinical phase that is detectable up to many years before diagnosis. Importantly, their identified protein signatures also shed light on distinct pathophysiological mechanisms between CD and ulcerative colitis (UC), with CD characterized by early disruptions in gut barrier integrity and macrophage function, while UC was more marked by upregulated inflammatory markers.
For clinical practitioners, these findings have a strong transformative potential. Following further validation in larger cohorts and allowing clinical accessibility, preclinical biomarker screening could become a routine tool for risk stratification in at-risk individuals, such as those with a strong family history or genetic predisposition. This could enable implementation of early interventions, including dietary modifications and potentially prophylactic therapies, to delay or even prevent disease onset. Given that similar approaches have proven effective in type 1 diabetes, applying this strategy to IBD could significantly alter disease progression and patient outcomes.
Challenges remain before implementation in clinical practice could be realized. Standardized thresholds for risk assessment, cost-effectiveness analyses, and potential therapeutic strategies tailored to biomarker-positive individuals require further exploration. However, this study provides important data needed for a paradigm shift in IBD management — one that moves from reactive treatment to proactive prevention.
Arno R. Bourgonje, MD, PhD, is a postdoctoral fellow at the Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and at the University Medical Center Groningen in Groningen, the Netherlands. He is involved in the European INTERCEPT consortium, which is focused on prediction and prevention of IBD. He reported no conflicts of interest.
Nowadays, preclinical biomarker discovery for inflammatory bowel diseases (IBD) is one of the key areas of study, aiming to identify the earliest stages of disease development and to find opportunities for early intervention. The study by Grännö and colleagues taps into this area and provides a significant advancement in the early detection of Crohn’s disease (CD) with a validated 29-plasma protein biomarker signature.
With an AUC of up to 0.87 in preclinical CD cases and even 0.82 as early as 16 years before diagnosis, these findings strongly support the notion that CD has a prolonged preclinical phase that is detectable up to many years before diagnosis. Importantly, their identified protein signatures also shed light on distinct pathophysiological mechanisms between CD and ulcerative colitis (UC), with CD characterized by early disruptions in gut barrier integrity and macrophage function, while UC was more marked by upregulated inflammatory markers.
For clinical practitioners, these findings have a strong transformative potential. Following further validation in larger cohorts and allowing clinical accessibility, preclinical biomarker screening could become a routine tool for risk stratification in at-risk individuals, such as those with a strong family history or genetic predisposition. This could enable implementation of early interventions, including dietary modifications and potentially prophylactic therapies, to delay or even prevent disease onset. Given that similar approaches have proven effective in type 1 diabetes, applying this strategy to IBD could significantly alter disease progression and patient outcomes.
Challenges remain before implementation in clinical practice could be realized. Standardized thresholds for risk assessment, cost-effectiveness analyses, and potential therapeutic strategies tailored to biomarker-positive individuals require further exploration. However, this study provides important data needed for a paradigm shift in IBD management — one that moves from reactive treatment to proactive prevention.
Arno R. Bourgonje, MD, PhD, is a postdoctoral fellow at the Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and at the University Medical Center Groningen in Groningen, the Netherlands. He is involved in the European INTERCEPT consortium, which is focused on prediction and prevention of IBD. He reported no conflicts of interest.
The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported.
“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.
Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted.
Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.
First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature.
In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87.
While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.
Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.
“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”
These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.
Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs.
The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation.
In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.
Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.
“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.
This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.
The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported.
“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.
Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted.
Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.
First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature.
In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87.
While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.
Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.
“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”
These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.
Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs.
The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation.
In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.
Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.
“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.
This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.
FROM GASTROENTEROLOGY
No Racial Disparities in CVD Outcomes For VA Patients with Prostate Cancer Receiving ADT
TOPLINE: Veterans treated in the Veterans Health Administration (VHA) who had preexisting cardiometabolic disease and received androgen deprivation therapy (ADT) with radiation therapy developed major adverse cardiovascular events (MACE) at 4 times the rate compared to those without cardiometabolic disease. Black and White veterans showed similar cardiovascular outcomes regardless of treatment type.
METHODOLOGY:
Researchers conducted a retrospective cohort study examining 39,580 veterans in the VHA system diagnosed with prostate cancer between 2000 and 2015, following them for a median of 9.6 years to assess time to MACE diagnosis.
- Analysis utilized a 1:1 propensity score matching process to compare outcomes between treatment types (ADT with radiation therapy vs radiation therapy alone) and racial groups (Black vs White men).
- Participants had a mean age of 65.9 years at diagnosis; 68% identified as White and 32% as Black, and 83% had stage 2 disease classified with 43.1% intermediate risk. Most lived in nonrural zip codes
- Primary outcome measure was time to MACE, defined as a composite of cardiovascular death, myocardial infarction, or ischemic stroke, with patients censored at non-cardiovascular death or study end.
TAKEAWAY:
Compared to those without CMD, the hazard ratio (HR) for MACE for men with preexisting CMD who received ADT was 4.2. Those receiving radiation alone had an HR of 2.5.
- Patients diagnosed between 2010 and 2015 showed significantly lower MACE rates compared to those diagnosed in 2000 to 2005: HR, 0.23; 95% CI, 0.08-0.71 for White patients; and HR, 0.23; 95% CI, 0.07-0.77 for Black patients.
- Multiple comorbidities were associated with doubled MACE risk (HR, 2.22; 95% CI, 1.08-4.59) compared to those without comorbidities.
- No significant differences in MACE rates were observed between Black and White veterans, regardless of treatment type.
IN PRACTICE: “Within the VHA, men treated with ADT + radiation therapy for prostate cancer do not appear to be at greater risk for MACE than those receiving radiation therapy alone. Black men have similar risk of MACE as White men, whether receiving radiation therapy alone or in combination with ADT," the authors wrote.
SOURCE: The study was led by Alexander R. Lucas, Virginia Commonwealth University School of Public Health in Richmond. It was published online on February 6 in Cardio-Oncology.
LIMITATIONS: According to the authors, the retrospective nature of the data may have limited their ability to detect MACE events occurring outside the VHA. Additionally, the study was limited to men who initiated ADT prior to radiation therapy, excluding those who had surgery or radiation before ADT. The researchers also note that the analysis did not compare outcomes between different types of ADT treatments, such as GnRH agonists vs antagonists, which may have different cardiovascular risk profiles.
DISCLOSURES: Alexander R. Lucas’s work was partly funded by grants 1KO1HL161419 and NRG FP00019789. Ashit K. Paul disclosed receiving honorarium for serving on scientific consultancy panels of SANOFI-Genzyme, Bayer, and Tempus & Cardinal Health. Additional disclosures are noted but not specified in the article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication
TOPLINE: Veterans treated in the Veterans Health Administration (VHA) who had preexisting cardiometabolic disease and received androgen deprivation therapy (ADT) with radiation therapy developed major adverse cardiovascular events (MACE) at 4 times the rate compared to those without cardiometabolic disease. Black and White veterans showed similar cardiovascular outcomes regardless of treatment type.
METHODOLOGY:
Researchers conducted a retrospective cohort study examining 39,580 veterans in the VHA system diagnosed with prostate cancer between 2000 and 2015, following them for a median of 9.6 years to assess time to MACE diagnosis.
- Analysis utilized a 1:1 propensity score matching process to compare outcomes between treatment types (ADT with radiation therapy vs radiation therapy alone) and racial groups (Black vs White men).
- Participants had a mean age of 65.9 years at diagnosis; 68% identified as White and 32% as Black, and 83% had stage 2 disease classified with 43.1% intermediate risk. Most lived in nonrural zip codes
- Primary outcome measure was time to MACE, defined as a composite of cardiovascular death, myocardial infarction, or ischemic stroke, with patients censored at non-cardiovascular death or study end.
TAKEAWAY:
Compared to those without CMD, the hazard ratio (HR) for MACE for men with preexisting CMD who received ADT was 4.2. Those receiving radiation alone had an HR of 2.5.
- Patients diagnosed between 2010 and 2015 showed significantly lower MACE rates compared to those diagnosed in 2000 to 2005: HR, 0.23; 95% CI, 0.08-0.71 for White patients; and HR, 0.23; 95% CI, 0.07-0.77 for Black patients.
- Multiple comorbidities were associated with doubled MACE risk (HR, 2.22; 95% CI, 1.08-4.59) compared to those without comorbidities.
- No significant differences in MACE rates were observed between Black and White veterans, regardless of treatment type.
IN PRACTICE: “Within the VHA, men treated with ADT + radiation therapy for prostate cancer do not appear to be at greater risk for MACE than those receiving radiation therapy alone. Black men have similar risk of MACE as White men, whether receiving radiation therapy alone or in combination with ADT," the authors wrote.
SOURCE: The study was led by Alexander R. Lucas, Virginia Commonwealth University School of Public Health in Richmond. It was published online on February 6 in Cardio-Oncology.
LIMITATIONS: According to the authors, the retrospective nature of the data may have limited their ability to detect MACE events occurring outside the VHA. Additionally, the study was limited to men who initiated ADT prior to radiation therapy, excluding those who had surgery or radiation before ADT. The researchers also note that the analysis did not compare outcomes between different types of ADT treatments, such as GnRH agonists vs antagonists, which may have different cardiovascular risk profiles.
DISCLOSURES: Alexander R. Lucas’s work was partly funded by grants 1KO1HL161419 and NRG FP00019789. Ashit K. Paul disclosed receiving honorarium for serving on scientific consultancy panels of SANOFI-Genzyme, Bayer, and Tempus & Cardinal Health. Additional disclosures are noted but not specified in the article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication
TOPLINE: Veterans treated in the Veterans Health Administration (VHA) who had preexisting cardiometabolic disease and received androgen deprivation therapy (ADT) with radiation therapy developed major adverse cardiovascular events (MACE) at 4 times the rate compared to those without cardiometabolic disease. Black and White veterans showed similar cardiovascular outcomes regardless of treatment type.
METHODOLOGY:
Researchers conducted a retrospective cohort study examining 39,580 veterans in the VHA system diagnosed with prostate cancer between 2000 and 2015, following them for a median of 9.6 years to assess time to MACE diagnosis.
- Analysis utilized a 1:1 propensity score matching process to compare outcomes between treatment types (ADT with radiation therapy vs radiation therapy alone) and racial groups (Black vs White men).
- Participants had a mean age of 65.9 years at diagnosis; 68% identified as White and 32% as Black, and 83% had stage 2 disease classified with 43.1% intermediate risk. Most lived in nonrural zip codes
- Primary outcome measure was time to MACE, defined as a composite of cardiovascular death, myocardial infarction, or ischemic stroke, with patients censored at non-cardiovascular death or study end.
TAKEAWAY:
Compared to those without CMD, the hazard ratio (HR) for MACE for men with preexisting CMD who received ADT was 4.2. Those receiving radiation alone had an HR of 2.5.
- Patients diagnosed between 2010 and 2015 showed significantly lower MACE rates compared to those diagnosed in 2000 to 2005: HR, 0.23; 95% CI, 0.08-0.71 for White patients; and HR, 0.23; 95% CI, 0.07-0.77 for Black patients.
- Multiple comorbidities were associated with doubled MACE risk (HR, 2.22; 95% CI, 1.08-4.59) compared to those without comorbidities.
- No significant differences in MACE rates were observed between Black and White veterans, regardless of treatment type.
IN PRACTICE: “Within the VHA, men treated with ADT + radiation therapy for prostate cancer do not appear to be at greater risk for MACE than those receiving radiation therapy alone. Black men have similar risk of MACE as White men, whether receiving radiation therapy alone or in combination with ADT," the authors wrote.
SOURCE: The study was led by Alexander R. Lucas, Virginia Commonwealth University School of Public Health in Richmond. It was published online on February 6 in Cardio-Oncology.
LIMITATIONS: According to the authors, the retrospective nature of the data may have limited their ability to detect MACE events occurring outside the VHA. Additionally, the study was limited to men who initiated ADT prior to radiation therapy, excluding those who had surgery or radiation before ADT. The researchers also note that the analysis did not compare outcomes between different types of ADT treatments, such as GnRH agonists vs antagonists, which may have different cardiovascular risk profiles.
DISCLOSURES: Alexander R. Lucas’s work was partly funded by grants 1KO1HL161419 and NRG FP00019789. Ashit K. Paul disclosed receiving honorarium for serving on scientific consultancy panels of SANOFI-Genzyme, Bayer, and Tempus & Cardinal Health. Additional disclosures are noted but not specified in the article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication
Where Are All the Nurses? Data Show That Some States Have a Far Higher Number of Nurses Per Capita Than Others
During their 12-hour shifts, registered nurses (RNs) in Arizona and Arkansas perform many of the same tasks as RNs in Wisconsin and Wyoming: Assessing patients, monitoring vital signs, administering medications, and charting records to provide the best patient care. The work might be similar, but there are vast differences in the number of RNs in each state.
In states like Idaho, Utah, and Nevada, which have the lowest number of nurses per capita, there are as few as 7 nurses per 1000 residents, compared with South Dakota and the District of Columbia, which have double the number of nurses than underserved states — giving them the highest number of nurses per capita.
Even states with the largest number of nurses per capita are not immune to the nursing shortage. The National Bureau of Labor Statistics estimates that there will be 195,400 job openings for RNs from 2021 to 2031.
So, what makes it easier for some states to recruit and retain RNs than others?
States With the Highest Number of Nurses Per Capita
South Dakota
RNs per 1000 residents: 15.79
Average wage: $67,030 or $32.23 per hour
Average rent in Sioux Falls: $1192 per month
The Midwestern state has more miles of shoreline than Florida, herds of wild buffalo, the highest summit east of the Rockies, and more nurses per capita than all other states . Healthcare is one of the major industries in the Mount Rushmore State.
Haifa Abou Samra, dean and professor at the University of South Dakota School of Health Sciences, Vermillion, isn’t surprised that RNs want to call the state home.
“South Dakota is a nice place to live,” Samra said. “[The] schools are wonderful. If people are growing families, there is support; neighbors support their neighbors, and it’s a relatively safe community.”
South Dakota has 19 approved nursing education programs that graduated 878 RNs in 2022. Scholarships and student loan forgiveness programs have helped attract qualified RNs, and collaborations between education and industry have been instrumental in addressing the nursing shortage, Samra told this news organization.
Even though RNs earn less than the median wage ($87,070 per year/41.38 per hour), South Dakota has a low cost of living and no individual income tax, which helps stretch those earnings.
District of Columbia
RNs per 1000 residents: 15.39
Average wage: $105,220 or $50.59 per hour
Average rent in Washington, DC: $2485 per month
After a shift at some of the top-ranking hospitals in the nation, RNs working in the compact capital region can explore museums, monuments, and cultural sites; walk along the banks of the Potomac River; or grab a bite at award-winning restaurants.
Washington, a top-ranking metro area because of its growth, high wages, and access to economic opportunities, is also home to several top-tier hospitals and some of the best healthcare in the nation, and RNs who want to pursue continuing education have access to top-tier universities.
Nurses in Washington, DC, might make some of the highest wages in the nation, but the region also has the second-highest cost of living in the United States, with average rents topping $2400 per month and an average home price of $594,337.
North Dakota
RNs per 1000 residents: 12.99
Average wage: $74,930 or $36.03 per hour
Average rent in Fargo: $1051 per month
North Dakota projects a 10.4% increase in employment for RNs, which is higher than the national average, and the state has implemented several strategies to address chronic nursing shortages. The Nurse Staffing Clearinghouse connects nursing school graduates with local employers and created a statewide nursing staffing pool for in-state recruitment of travel nurses.
But it’s not just plentiful job opportunities and a low cost of living that attract nurses to the Peace Garden State. The state and its largest cities, Bismarck and Fargo, hold several “best of” accolades, including nods for the safest places to live and among the Best Places to Raise a Family, giving it high marks for quality of life.
Sure, the winters are cold, but the outdoor recreation can’t be beaten. RNs can bundle up and see the bighorn sheep in the Badlands at Theodore Roosevelt National Park or explore expansive terrain for skiing, snowboarding, and snowmobile trails.
States With the Lowest Number of Nurses Per Capita
Nevada
RNs per 1000 residents: 7.92
Average wage: $96,201 or $46.25 per hour
Average rent in Las Vegas: $1478 per month
Despite a projected 23% job growth for RNs between 2020 and 2030, the state has struggled to fill open positions. It might be the higher-than-average cost of living (9.7% higher than the US average) or higher-than-average crime rates that make RNs reluctant to gamble on a job in the Silver State. But there are some big wins for nurses in the state.
Salaries are higher than the national average, there is no state income tax, and some of the lowest property taxes in the nation. Thanks to new legislation, RNs with student loan debt won’t have to bet on black at the casino to make their payments. The Health Equity and Loan Assistance Program is a new initiative that offers up to $120,000 in loan repayment assistance to providers, including RNs, who commit to working in underserved and rural areas across the state for 5 years.
The state also has incredible attractions, from the neon lights and over-the-top architecture in Las Vegas to iconic red rock canyons, stunning state parks, and landmarks like Hoover Dam and Lake Tahoe.
Utah
RNs per 1000 residents: 7.05
Average wage: $79,790 or $38.36 per hour
Average rent in Salt Lake City: $1611 per month
Healthcare is one of the biggest employers in Utah, and nurses are the most in-demand healthcare workers in the state. But below-average wages and a cost of living that is a whopping 28% higher than the national average could be some reasons that the Beehive State is struggling to attract nurses.
A high number of job vacancies mean higher patient-to-nurse ratios, creating additional stress for a workforce prone to burnout. Much of the state is rural, public transportation is inadequate, and poor air quality causes frequent haze and smog.
The challenges are offset by some big benefits: Utah has been ranked as the “best state” thanks to the strong economy, infrastructure, and quality education — and it doesn’t hurt that Utah is home to myriad outdoor recreation opportunities and the stunning scenery at landmarks like Bryce Canyon and Arches National Park.
Moreover, Utah is hustling to boost its RN workforce. The University of Utah, Salt Lake City, has increased enrollment by 25% and hired additional faculty to help boost the nursing workforce — and those who work in hospitals and health clinics across the state benefit from a flat 4.55% individual income tax rate.
Idaho
RNs per 1000 residents: 7.02
Average wage: $80,130 or $38.53 per hour
Average rent in Boise: $1646 per month
Although the nursing workforce in Idaho has increased, it still ranks as the lowest in the nation. Teresa Stanfill, DNP, RN, executive director for the Idaho Center for Nursing, said that the number of new nurses is too low to replace the number of retiring nurses.
The state introduced loan repayment programs that award up to $25,000 to cover student loan debt, and hospitals and health systems often offer sign-on bonuses and relocation packages to attract RNs. But long winters, an isolated location, and limited cultural options can make it harder to attract nurses to the state.
It’s easier to recruit RNs to suburban areas like Boise, Meridian, and Nampa, but rural parts of the state struggle, Stanfill added. The nursing shortage is among the reasons that 11 hospitals and emergency departments closed in 2024, and healthcare organizations slashed services across the state.
Idaho has a lot to offer RNs, from small-town charm, reasonable cost of living, and gorgeous landscapes that make it one of the top 10 fastest-growing states in the nation. Collaboration between industry leaders and nursing programs is focused on finding creative solutions to boost the nursing workforce in Idaho.
A version of this article first appeared on Medscape.com.
During their 12-hour shifts, registered nurses (RNs) in Arizona and Arkansas perform many of the same tasks as RNs in Wisconsin and Wyoming: Assessing patients, monitoring vital signs, administering medications, and charting records to provide the best patient care. The work might be similar, but there are vast differences in the number of RNs in each state.
In states like Idaho, Utah, and Nevada, which have the lowest number of nurses per capita, there are as few as 7 nurses per 1000 residents, compared with South Dakota and the District of Columbia, which have double the number of nurses than underserved states — giving them the highest number of nurses per capita.
Even states with the largest number of nurses per capita are not immune to the nursing shortage. The National Bureau of Labor Statistics estimates that there will be 195,400 job openings for RNs from 2021 to 2031.
So, what makes it easier for some states to recruit and retain RNs than others?
States With the Highest Number of Nurses Per Capita
South Dakota
RNs per 1000 residents: 15.79
Average wage: $67,030 or $32.23 per hour
Average rent in Sioux Falls: $1192 per month
The Midwestern state has more miles of shoreline than Florida, herds of wild buffalo, the highest summit east of the Rockies, and more nurses per capita than all other states . Healthcare is one of the major industries in the Mount Rushmore State.
Haifa Abou Samra, dean and professor at the University of South Dakota School of Health Sciences, Vermillion, isn’t surprised that RNs want to call the state home.
“South Dakota is a nice place to live,” Samra said. “[The] schools are wonderful. If people are growing families, there is support; neighbors support their neighbors, and it’s a relatively safe community.”
South Dakota has 19 approved nursing education programs that graduated 878 RNs in 2022. Scholarships and student loan forgiveness programs have helped attract qualified RNs, and collaborations between education and industry have been instrumental in addressing the nursing shortage, Samra told this news organization.
Even though RNs earn less than the median wage ($87,070 per year/41.38 per hour), South Dakota has a low cost of living and no individual income tax, which helps stretch those earnings.
District of Columbia
RNs per 1000 residents: 15.39
Average wage: $105,220 or $50.59 per hour
Average rent in Washington, DC: $2485 per month
After a shift at some of the top-ranking hospitals in the nation, RNs working in the compact capital region can explore museums, monuments, and cultural sites; walk along the banks of the Potomac River; or grab a bite at award-winning restaurants.
Washington, a top-ranking metro area because of its growth, high wages, and access to economic opportunities, is also home to several top-tier hospitals and some of the best healthcare in the nation, and RNs who want to pursue continuing education have access to top-tier universities.
Nurses in Washington, DC, might make some of the highest wages in the nation, but the region also has the second-highest cost of living in the United States, with average rents topping $2400 per month and an average home price of $594,337.
North Dakota
RNs per 1000 residents: 12.99
Average wage: $74,930 or $36.03 per hour
Average rent in Fargo: $1051 per month
North Dakota projects a 10.4% increase in employment for RNs, which is higher than the national average, and the state has implemented several strategies to address chronic nursing shortages. The Nurse Staffing Clearinghouse connects nursing school graduates with local employers and created a statewide nursing staffing pool for in-state recruitment of travel nurses.
But it’s not just plentiful job opportunities and a low cost of living that attract nurses to the Peace Garden State. The state and its largest cities, Bismarck and Fargo, hold several “best of” accolades, including nods for the safest places to live and among the Best Places to Raise a Family, giving it high marks for quality of life.
Sure, the winters are cold, but the outdoor recreation can’t be beaten. RNs can bundle up and see the bighorn sheep in the Badlands at Theodore Roosevelt National Park or explore expansive terrain for skiing, snowboarding, and snowmobile trails.
States With the Lowest Number of Nurses Per Capita
Nevada
RNs per 1000 residents: 7.92
Average wage: $96,201 or $46.25 per hour
Average rent in Las Vegas: $1478 per month
Despite a projected 23% job growth for RNs between 2020 and 2030, the state has struggled to fill open positions. It might be the higher-than-average cost of living (9.7% higher than the US average) or higher-than-average crime rates that make RNs reluctant to gamble on a job in the Silver State. But there are some big wins for nurses in the state.
Salaries are higher than the national average, there is no state income tax, and some of the lowest property taxes in the nation. Thanks to new legislation, RNs with student loan debt won’t have to bet on black at the casino to make their payments. The Health Equity and Loan Assistance Program is a new initiative that offers up to $120,000 in loan repayment assistance to providers, including RNs, who commit to working in underserved and rural areas across the state for 5 years.
The state also has incredible attractions, from the neon lights and over-the-top architecture in Las Vegas to iconic red rock canyons, stunning state parks, and landmarks like Hoover Dam and Lake Tahoe.
Utah
RNs per 1000 residents: 7.05
Average wage: $79,790 or $38.36 per hour
Average rent in Salt Lake City: $1611 per month
Healthcare is one of the biggest employers in Utah, and nurses are the most in-demand healthcare workers in the state. But below-average wages and a cost of living that is a whopping 28% higher than the national average could be some reasons that the Beehive State is struggling to attract nurses.
A high number of job vacancies mean higher patient-to-nurse ratios, creating additional stress for a workforce prone to burnout. Much of the state is rural, public transportation is inadequate, and poor air quality causes frequent haze and smog.
The challenges are offset by some big benefits: Utah has been ranked as the “best state” thanks to the strong economy, infrastructure, and quality education — and it doesn’t hurt that Utah is home to myriad outdoor recreation opportunities and the stunning scenery at landmarks like Bryce Canyon and Arches National Park.
Moreover, Utah is hustling to boost its RN workforce. The University of Utah, Salt Lake City, has increased enrollment by 25% and hired additional faculty to help boost the nursing workforce — and those who work in hospitals and health clinics across the state benefit from a flat 4.55% individual income tax rate.
Idaho
RNs per 1000 residents: 7.02
Average wage: $80,130 or $38.53 per hour
Average rent in Boise: $1646 per month
Although the nursing workforce in Idaho has increased, it still ranks as the lowest in the nation. Teresa Stanfill, DNP, RN, executive director for the Idaho Center for Nursing, said that the number of new nurses is too low to replace the number of retiring nurses.
The state introduced loan repayment programs that award up to $25,000 to cover student loan debt, and hospitals and health systems often offer sign-on bonuses and relocation packages to attract RNs. But long winters, an isolated location, and limited cultural options can make it harder to attract nurses to the state.
It’s easier to recruit RNs to suburban areas like Boise, Meridian, and Nampa, but rural parts of the state struggle, Stanfill added. The nursing shortage is among the reasons that 11 hospitals and emergency departments closed in 2024, and healthcare organizations slashed services across the state.
Idaho has a lot to offer RNs, from small-town charm, reasonable cost of living, and gorgeous landscapes that make it one of the top 10 fastest-growing states in the nation. Collaboration between industry leaders and nursing programs is focused on finding creative solutions to boost the nursing workforce in Idaho.
A version of this article first appeared on Medscape.com.
During their 12-hour shifts, registered nurses (RNs) in Arizona and Arkansas perform many of the same tasks as RNs in Wisconsin and Wyoming: Assessing patients, monitoring vital signs, administering medications, and charting records to provide the best patient care. The work might be similar, but there are vast differences in the number of RNs in each state.
In states like Idaho, Utah, and Nevada, which have the lowest number of nurses per capita, there are as few as 7 nurses per 1000 residents, compared with South Dakota and the District of Columbia, which have double the number of nurses than underserved states — giving them the highest number of nurses per capita.
Even states with the largest number of nurses per capita are not immune to the nursing shortage. The National Bureau of Labor Statistics estimates that there will be 195,400 job openings for RNs from 2021 to 2031.
So, what makes it easier for some states to recruit and retain RNs than others?
States With the Highest Number of Nurses Per Capita
South Dakota
RNs per 1000 residents: 15.79
Average wage: $67,030 or $32.23 per hour
Average rent in Sioux Falls: $1192 per month
The Midwestern state has more miles of shoreline than Florida, herds of wild buffalo, the highest summit east of the Rockies, and more nurses per capita than all other states . Healthcare is one of the major industries in the Mount Rushmore State.
Haifa Abou Samra, dean and professor at the University of South Dakota School of Health Sciences, Vermillion, isn’t surprised that RNs want to call the state home.
“South Dakota is a nice place to live,” Samra said. “[The] schools are wonderful. If people are growing families, there is support; neighbors support their neighbors, and it’s a relatively safe community.”
South Dakota has 19 approved nursing education programs that graduated 878 RNs in 2022. Scholarships and student loan forgiveness programs have helped attract qualified RNs, and collaborations between education and industry have been instrumental in addressing the nursing shortage, Samra told this news organization.
Even though RNs earn less than the median wage ($87,070 per year/41.38 per hour), South Dakota has a low cost of living and no individual income tax, which helps stretch those earnings.
District of Columbia
RNs per 1000 residents: 15.39
Average wage: $105,220 or $50.59 per hour
Average rent in Washington, DC: $2485 per month
After a shift at some of the top-ranking hospitals in the nation, RNs working in the compact capital region can explore museums, monuments, and cultural sites; walk along the banks of the Potomac River; or grab a bite at award-winning restaurants.
Washington, a top-ranking metro area because of its growth, high wages, and access to economic opportunities, is also home to several top-tier hospitals and some of the best healthcare in the nation, and RNs who want to pursue continuing education have access to top-tier universities.
Nurses in Washington, DC, might make some of the highest wages in the nation, but the region also has the second-highest cost of living in the United States, with average rents topping $2400 per month and an average home price of $594,337.
North Dakota
RNs per 1000 residents: 12.99
Average wage: $74,930 or $36.03 per hour
Average rent in Fargo: $1051 per month
North Dakota projects a 10.4% increase in employment for RNs, which is higher than the national average, and the state has implemented several strategies to address chronic nursing shortages. The Nurse Staffing Clearinghouse connects nursing school graduates with local employers and created a statewide nursing staffing pool for in-state recruitment of travel nurses.
But it’s not just plentiful job opportunities and a low cost of living that attract nurses to the Peace Garden State. The state and its largest cities, Bismarck and Fargo, hold several “best of” accolades, including nods for the safest places to live and among the Best Places to Raise a Family, giving it high marks for quality of life.
Sure, the winters are cold, but the outdoor recreation can’t be beaten. RNs can bundle up and see the bighorn sheep in the Badlands at Theodore Roosevelt National Park or explore expansive terrain for skiing, snowboarding, and snowmobile trails.
States With the Lowest Number of Nurses Per Capita
Nevada
RNs per 1000 residents: 7.92
Average wage: $96,201 or $46.25 per hour
Average rent in Las Vegas: $1478 per month
Despite a projected 23% job growth for RNs between 2020 and 2030, the state has struggled to fill open positions. It might be the higher-than-average cost of living (9.7% higher than the US average) or higher-than-average crime rates that make RNs reluctant to gamble on a job in the Silver State. But there are some big wins for nurses in the state.
Salaries are higher than the national average, there is no state income tax, and some of the lowest property taxes in the nation. Thanks to new legislation, RNs with student loan debt won’t have to bet on black at the casino to make their payments. The Health Equity and Loan Assistance Program is a new initiative that offers up to $120,000 in loan repayment assistance to providers, including RNs, who commit to working in underserved and rural areas across the state for 5 years.
The state also has incredible attractions, from the neon lights and over-the-top architecture in Las Vegas to iconic red rock canyons, stunning state parks, and landmarks like Hoover Dam and Lake Tahoe.
Utah
RNs per 1000 residents: 7.05
Average wage: $79,790 or $38.36 per hour
Average rent in Salt Lake City: $1611 per month
Healthcare is one of the biggest employers in Utah, and nurses are the most in-demand healthcare workers in the state. But below-average wages and a cost of living that is a whopping 28% higher than the national average could be some reasons that the Beehive State is struggling to attract nurses.
A high number of job vacancies mean higher patient-to-nurse ratios, creating additional stress for a workforce prone to burnout. Much of the state is rural, public transportation is inadequate, and poor air quality causes frequent haze and smog.
The challenges are offset by some big benefits: Utah has been ranked as the “best state” thanks to the strong economy, infrastructure, and quality education — and it doesn’t hurt that Utah is home to myriad outdoor recreation opportunities and the stunning scenery at landmarks like Bryce Canyon and Arches National Park.
Moreover, Utah is hustling to boost its RN workforce. The University of Utah, Salt Lake City, has increased enrollment by 25% and hired additional faculty to help boost the nursing workforce — and those who work in hospitals and health clinics across the state benefit from a flat 4.55% individual income tax rate.
Idaho
RNs per 1000 residents: 7.02
Average wage: $80,130 or $38.53 per hour
Average rent in Boise: $1646 per month
Although the nursing workforce in Idaho has increased, it still ranks as the lowest in the nation. Teresa Stanfill, DNP, RN, executive director for the Idaho Center for Nursing, said that the number of new nurses is too low to replace the number of retiring nurses.
The state introduced loan repayment programs that award up to $25,000 to cover student loan debt, and hospitals and health systems often offer sign-on bonuses and relocation packages to attract RNs. But long winters, an isolated location, and limited cultural options can make it harder to attract nurses to the state.
It’s easier to recruit RNs to suburban areas like Boise, Meridian, and Nampa, but rural parts of the state struggle, Stanfill added. The nursing shortage is among the reasons that 11 hospitals and emergency departments closed in 2024, and healthcare organizations slashed services across the state.
Idaho has a lot to offer RNs, from small-town charm, reasonable cost of living, and gorgeous landscapes that make it one of the top 10 fastest-growing states in the nation. Collaboration between industry leaders and nursing programs is focused on finding creative solutions to boost the nursing workforce in Idaho.
A version of this article first appeared on Medscape.com.
Bariatric Surgery: Nutrition’s Role in Patient Outcomes
, according to an updated clinical practice statement from the Obesity Medicine Association (OMA).
The update offers guidance on how to manage metabolic and bariatric surgery patients’ nutrition, from preoperative nutritional assessments through identification and treatment of the most common nutritional problems associated with bariatric procedures.
“The main takeaway really is that obesity is a complex and chronic disease. It requires the same model of care as diabetes or other chronic conditions,” said Rutuja Patel, DO, senior author and an obesity medicine specialist at Northwestern Medicine Regional Medical Group in Winfield, Illinois.
The development of an interdisciplinary team of medical providers with evidence-based nutrition knowledge and consistent information improves the quality of nutrition care provided to bariatric surgery patients, the authors wrote.
“Collaborative multidisciplinary care that takes into consideration the whole patient in a biopsychosocial way and uses multiple modalities — including medical, behavioral, nutritional, and others — leads to the best outcomes in these complex patients,” Patel said.
The updated statement, published online in Obesity Pillars, offers a variety of tools and checklists to aid clinicians, especially those who may not have access to a multidisciplinary team or dietitian knowledgeable about bariatric nutrition.
It is a follow-up to the OMA’s 2022 clinical practice statement, which provided an overview of bariatric surgery, gastrointestinal hormones, and the microbiome in patients with obesity.
Presurgical Guidance
The new guidance lays out the various components of preoperative nutrition screenings, among which is a medication review to determine if the patient is taking drugs that may affect weight and calorie intake. These include antihypertensives, diabetes agents, hormonal contraceptives, antidepressants, migraine medications, and antipsychotics.
In taking a patient’s history, clinicians should ask about major events associated with weight changes, such as medication changes, illness, pregnancy, divorce, stressful employment, food insecurity, and periods of disordered eating.
The fundamental approach to conducting a nutrition assessment is an understanding of the role that various sections of the gastrointestinal tract play in micronutrient absorption, the authors wrote. As an educational tool, the update includes a diagram that indicates the areas of the stomach, duodenum, jejunum, and ileum that may be altered by bariatric surgery and how they factor into micronutrient absorption.
“It makes it easier to see why certain surgical procedures are more likely to cause certain deficiencies,” Patel said.
Postsurgery Patient Management
Post surgery, clinicians should monitor patients for other problems that could affect nutrient absorption, including food intolerances, drug-nutrient interactions, and increased gastrointestinal transit time.
Patel and coauthors discussed the pros and cons of multivitamin mineral supplement formulations as well as specific vitamin and mineral recommendations for patients undergoing certain metabolic or bariatric surgery procedures. They included three supplemental cases in the appendix to illustrate supplementation recommendations and long-term maintenance suggestions.
“It’s important to remember that most of these deficiencies present without many clinical symptoms, so it becomes essential to screen for them and repeat as needed,” Patel said.
The update also tackles postoperative nutritional assessments and diet progression. No evidence supports following one postsurgical diet progression protocol over another, but they generally proceed from a clear liquid diet to foods with normal textures, the authors noted. Clinicians should adapt them according to the procedure type, they added.
In addition, clinicians must troubleshoot any nutrition-related concerns, including constipation, dehydration, nausea, heartburn, and fatigue, for up to a year after surgery, they wrote.
Metabolic and bariatric surgery patients should be evaluated annually at a minimum, if not more frequently, to gauge nutritional health, the authors wrote. Treating obesity as a disease involves more than weight loss — instead, it’s about improving the quality of life of patients through procedures, medications, and lifestyle modifications, they added.
Track New Developments
With ongoing changes in the field of metabolic and bariatric surgery, it’s helpful for clinicians to remain updated about new approaches across various disciplines linked to obesity management and treatment, said Christina Poa-Li, MD, a surgeon at Huntington Health Medical Center, affiliated with Cedars-Sinai Health System, in Pasadena, California, who was not involved in developing the updated practice statement.
“For example, the rapidly growing prescription of anti-obesity medications and their use in both preoperative and postoperative surgical patients drastically affect their nutrition,” she said. “Providers of various backgrounds and specialties will benefit from the most updated guidance on evaluating patient nutrition.”
Clinicians should consider expanding their patient population to include those with metabolic dysfunction–associated steatohepatitis or metabolic dysfunction–associated steatotic liver disease, Poa-Li said.
“These patient subpopulations may not have been considered for bariatric surgery or even referral to a bariatric surgeon for consultation previously,” she said. “It is important to increase awareness among clinicians of the potential benefits for metabolic and bariatric surgery for these patients.”
The report didn’t receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Patel and Poa-Li reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to an updated clinical practice statement from the Obesity Medicine Association (OMA).
The update offers guidance on how to manage metabolic and bariatric surgery patients’ nutrition, from preoperative nutritional assessments through identification and treatment of the most common nutritional problems associated with bariatric procedures.
“The main takeaway really is that obesity is a complex and chronic disease. It requires the same model of care as diabetes or other chronic conditions,” said Rutuja Patel, DO, senior author and an obesity medicine specialist at Northwestern Medicine Regional Medical Group in Winfield, Illinois.
The development of an interdisciplinary team of medical providers with evidence-based nutrition knowledge and consistent information improves the quality of nutrition care provided to bariatric surgery patients, the authors wrote.
“Collaborative multidisciplinary care that takes into consideration the whole patient in a biopsychosocial way and uses multiple modalities — including medical, behavioral, nutritional, and others — leads to the best outcomes in these complex patients,” Patel said.
The updated statement, published online in Obesity Pillars, offers a variety of tools and checklists to aid clinicians, especially those who may not have access to a multidisciplinary team or dietitian knowledgeable about bariatric nutrition.
It is a follow-up to the OMA’s 2022 clinical practice statement, which provided an overview of bariatric surgery, gastrointestinal hormones, and the microbiome in patients with obesity.
Presurgical Guidance
The new guidance lays out the various components of preoperative nutrition screenings, among which is a medication review to determine if the patient is taking drugs that may affect weight and calorie intake. These include antihypertensives, diabetes agents, hormonal contraceptives, antidepressants, migraine medications, and antipsychotics.
In taking a patient’s history, clinicians should ask about major events associated with weight changes, such as medication changes, illness, pregnancy, divorce, stressful employment, food insecurity, and periods of disordered eating.
The fundamental approach to conducting a nutrition assessment is an understanding of the role that various sections of the gastrointestinal tract play in micronutrient absorption, the authors wrote. As an educational tool, the update includes a diagram that indicates the areas of the stomach, duodenum, jejunum, and ileum that may be altered by bariatric surgery and how they factor into micronutrient absorption.
“It makes it easier to see why certain surgical procedures are more likely to cause certain deficiencies,” Patel said.
Postsurgery Patient Management
Post surgery, clinicians should monitor patients for other problems that could affect nutrient absorption, including food intolerances, drug-nutrient interactions, and increased gastrointestinal transit time.
Patel and coauthors discussed the pros and cons of multivitamin mineral supplement formulations as well as specific vitamin and mineral recommendations for patients undergoing certain metabolic or bariatric surgery procedures. They included three supplemental cases in the appendix to illustrate supplementation recommendations and long-term maintenance suggestions.
“It’s important to remember that most of these deficiencies present without many clinical symptoms, so it becomes essential to screen for them and repeat as needed,” Patel said.
The update also tackles postoperative nutritional assessments and diet progression. No evidence supports following one postsurgical diet progression protocol over another, but they generally proceed from a clear liquid diet to foods with normal textures, the authors noted. Clinicians should adapt them according to the procedure type, they added.
In addition, clinicians must troubleshoot any nutrition-related concerns, including constipation, dehydration, nausea, heartburn, and fatigue, for up to a year after surgery, they wrote.
Metabolic and bariatric surgery patients should be evaluated annually at a minimum, if not more frequently, to gauge nutritional health, the authors wrote. Treating obesity as a disease involves more than weight loss — instead, it’s about improving the quality of life of patients through procedures, medications, and lifestyle modifications, they added.
Track New Developments
With ongoing changes in the field of metabolic and bariatric surgery, it’s helpful for clinicians to remain updated about new approaches across various disciplines linked to obesity management and treatment, said Christina Poa-Li, MD, a surgeon at Huntington Health Medical Center, affiliated with Cedars-Sinai Health System, in Pasadena, California, who was not involved in developing the updated practice statement.
“For example, the rapidly growing prescription of anti-obesity medications and their use in both preoperative and postoperative surgical patients drastically affect their nutrition,” she said. “Providers of various backgrounds and specialties will benefit from the most updated guidance on evaluating patient nutrition.”
Clinicians should consider expanding their patient population to include those with metabolic dysfunction–associated steatohepatitis or metabolic dysfunction–associated steatotic liver disease, Poa-Li said.
“These patient subpopulations may not have been considered for bariatric surgery or even referral to a bariatric surgeon for consultation previously,” she said. “It is important to increase awareness among clinicians of the potential benefits for metabolic and bariatric surgery for these patients.”
The report didn’t receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Patel and Poa-Li reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to an updated clinical practice statement from the Obesity Medicine Association (OMA).
The update offers guidance on how to manage metabolic and bariatric surgery patients’ nutrition, from preoperative nutritional assessments through identification and treatment of the most common nutritional problems associated with bariatric procedures.
“The main takeaway really is that obesity is a complex and chronic disease. It requires the same model of care as diabetes or other chronic conditions,” said Rutuja Patel, DO, senior author and an obesity medicine specialist at Northwestern Medicine Regional Medical Group in Winfield, Illinois.
The development of an interdisciplinary team of medical providers with evidence-based nutrition knowledge and consistent information improves the quality of nutrition care provided to bariatric surgery patients, the authors wrote.
“Collaborative multidisciplinary care that takes into consideration the whole patient in a biopsychosocial way and uses multiple modalities — including medical, behavioral, nutritional, and others — leads to the best outcomes in these complex patients,” Patel said.
The updated statement, published online in Obesity Pillars, offers a variety of tools and checklists to aid clinicians, especially those who may not have access to a multidisciplinary team or dietitian knowledgeable about bariatric nutrition.
It is a follow-up to the OMA’s 2022 clinical practice statement, which provided an overview of bariatric surgery, gastrointestinal hormones, and the microbiome in patients with obesity.
Presurgical Guidance
The new guidance lays out the various components of preoperative nutrition screenings, among which is a medication review to determine if the patient is taking drugs that may affect weight and calorie intake. These include antihypertensives, diabetes agents, hormonal contraceptives, antidepressants, migraine medications, and antipsychotics.
In taking a patient’s history, clinicians should ask about major events associated with weight changes, such as medication changes, illness, pregnancy, divorce, stressful employment, food insecurity, and periods of disordered eating.
The fundamental approach to conducting a nutrition assessment is an understanding of the role that various sections of the gastrointestinal tract play in micronutrient absorption, the authors wrote. As an educational tool, the update includes a diagram that indicates the areas of the stomach, duodenum, jejunum, and ileum that may be altered by bariatric surgery and how they factor into micronutrient absorption.
“It makes it easier to see why certain surgical procedures are more likely to cause certain deficiencies,” Patel said.
Postsurgery Patient Management
Post surgery, clinicians should monitor patients for other problems that could affect nutrient absorption, including food intolerances, drug-nutrient interactions, and increased gastrointestinal transit time.
Patel and coauthors discussed the pros and cons of multivitamin mineral supplement formulations as well as specific vitamin and mineral recommendations for patients undergoing certain metabolic or bariatric surgery procedures. They included three supplemental cases in the appendix to illustrate supplementation recommendations and long-term maintenance suggestions.
“It’s important to remember that most of these deficiencies present without many clinical symptoms, so it becomes essential to screen for them and repeat as needed,” Patel said.
The update also tackles postoperative nutritional assessments and diet progression. No evidence supports following one postsurgical diet progression protocol over another, but they generally proceed from a clear liquid diet to foods with normal textures, the authors noted. Clinicians should adapt them according to the procedure type, they added.
In addition, clinicians must troubleshoot any nutrition-related concerns, including constipation, dehydration, nausea, heartburn, and fatigue, for up to a year after surgery, they wrote.
Metabolic and bariatric surgery patients should be evaluated annually at a minimum, if not more frequently, to gauge nutritional health, the authors wrote. Treating obesity as a disease involves more than weight loss — instead, it’s about improving the quality of life of patients through procedures, medications, and lifestyle modifications, they added.
Track New Developments
With ongoing changes in the field of metabolic and bariatric surgery, it’s helpful for clinicians to remain updated about new approaches across various disciplines linked to obesity management and treatment, said Christina Poa-Li, MD, a surgeon at Huntington Health Medical Center, affiliated with Cedars-Sinai Health System, in Pasadena, California, who was not involved in developing the updated practice statement.
“For example, the rapidly growing prescription of anti-obesity medications and their use in both preoperative and postoperative surgical patients drastically affect their nutrition,” she said. “Providers of various backgrounds and specialties will benefit from the most updated guidance on evaluating patient nutrition.”
Clinicians should consider expanding their patient population to include those with metabolic dysfunction–associated steatohepatitis or metabolic dysfunction–associated steatotic liver disease, Poa-Li said.
“These patient subpopulations may not have been considered for bariatric surgery or even referral to a bariatric surgeon for consultation previously,” she said. “It is important to increase awareness among clinicians of the potential benefits for metabolic and bariatric surgery for these patients.”
The report didn’t receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Patel and Poa-Li reported no relevant disclosures.
A version of this article appeared on Medscape.com.
How Many Patients in Early Cancer Trials Get Drugs Ultimately Approved by FDA?
TOPLINE:
One in six patients in phase 2 cancer trials received treatments that were eventually approved by the Food and Drug Administration (FDA), a new analysis found. This proportion increased to 1 in 5 when considering National Comprehensive Cancer Network (NCCN) off-label recommendations and decreased to about 1 in 11 for approved regimens considered to have a substantial clinical benefit.
METHODOLOGY:
- Patients enroll in phase 2 oncology trials seeking access to promising new treatments, but the risk-benefit assessments and the likelihood of receiving a therapy that ultimately gains FDA approval remain unclear. Previous research suggests that the odds are 1 in 83 patients for those enrolled in a phase 1 cancer trial.
- Researchers randomly selected 400 phase 2 cancer trials initiated between November 2012 and November 2015 (to give enough time for an approval to occur); these trials included more than 25,000 patients across 608 specific treatment cohorts testing 332 drugs.
- The primary endpoint was the proportion of patients enrolled in phase 2 trials who received a treatment regimen that later attained FDA approval — defined as the “therapeutic proportion.”
- A secondary endpoint was determining the therapeutic proportion based on the therapeutic value of drugs. The three benchmarks were FDA approval alone, FDA approval plus NCCN off-label recommendations, and FDA approval for drugs considered to have a substantial clinical benefit, based on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).
TAKEAWAY:
- A total of 4045 patients received a treatment regimen that advanced to FDA approval, corresponding to a therapeutic proportion of 16.2%.
- The therapeutic proportion increased to 19.4% when considering NCCN off-label recommendations and decreased to 9.3% for FDA-approved regimens considered to have a substantial clinical benefit, based on the ESMO-MCBS.
- The proportion of patients who participated in a trial in which the drug-indication pairing went on to phase 3 testing was 32.5%.
- Enrollment in a trial featuring biomarker enrichment, an immunotherapy drug, a large phase 2 cohort, and a nonrandomized, industry-sponsored trial all showed a trend toward a higher therapeutic proportion.
IN PRACTICE:
“By entering a phase 2 trial, a patient has a one in six chance of receiving a treatment that will later be approved for their condition,” the authors wrote. “The proportions described here, when juxtaposed with those estimated previously for phase 1 trials, suggest a striking improvement for a patient’s therapeutic prospects. This suggests that phase 1 trials do a good job at protecting patients downstream from unsafe and ineffective cancer treatments.”
In an editorial accompanying the study, Howard S. Hochster, MD, of the Rutgers Cancer Institute in New Brunswick, New Jersey, suggested that the 16.2% therapeutic proportion reported may be understated. For instance, “if using the criterion of drugs that were FDA approved in any indication and dose, the proportion of patient benefit in these trials rises to 38%, with a 51% benefit rate considering inclusion in NCCN guidelines,” he wrote.
SOURCE:
This study, led by Charlotte Ouimet, MSc, Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, Montréal, Québec, Canada, was published online in Journal of the National Cancer Institute.
LIMITATIONS:
The longitudinal design of this study required using a historical cohort of phase 2 clinical trials, which may not reflect current drug development patterns. This study was underpowered to determine trial characteristics that predicted higher therapeutic proportions. Furthermore, the exclusion of cytotoxic drugs from the analysis resulted in a somewhat restricted view of overall drug development.
DISCLOSURES:
This study was supported by the Canadian Institutes of Health Research. The authors reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
One in six patients in phase 2 cancer trials received treatments that were eventually approved by the Food and Drug Administration (FDA), a new analysis found. This proportion increased to 1 in 5 when considering National Comprehensive Cancer Network (NCCN) off-label recommendations and decreased to about 1 in 11 for approved regimens considered to have a substantial clinical benefit.
METHODOLOGY:
- Patients enroll in phase 2 oncology trials seeking access to promising new treatments, but the risk-benefit assessments and the likelihood of receiving a therapy that ultimately gains FDA approval remain unclear. Previous research suggests that the odds are 1 in 83 patients for those enrolled in a phase 1 cancer trial.
- Researchers randomly selected 400 phase 2 cancer trials initiated between November 2012 and November 2015 (to give enough time for an approval to occur); these trials included more than 25,000 patients across 608 specific treatment cohorts testing 332 drugs.
- The primary endpoint was the proportion of patients enrolled in phase 2 trials who received a treatment regimen that later attained FDA approval — defined as the “therapeutic proportion.”
- A secondary endpoint was determining the therapeutic proportion based on the therapeutic value of drugs. The three benchmarks were FDA approval alone, FDA approval plus NCCN off-label recommendations, and FDA approval for drugs considered to have a substantial clinical benefit, based on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).
TAKEAWAY:
- A total of 4045 patients received a treatment regimen that advanced to FDA approval, corresponding to a therapeutic proportion of 16.2%.
- The therapeutic proportion increased to 19.4% when considering NCCN off-label recommendations and decreased to 9.3% for FDA-approved regimens considered to have a substantial clinical benefit, based on the ESMO-MCBS.
- The proportion of patients who participated in a trial in which the drug-indication pairing went on to phase 3 testing was 32.5%.
- Enrollment in a trial featuring biomarker enrichment, an immunotherapy drug, a large phase 2 cohort, and a nonrandomized, industry-sponsored trial all showed a trend toward a higher therapeutic proportion.
IN PRACTICE:
“By entering a phase 2 trial, a patient has a one in six chance of receiving a treatment that will later be approved for their condition,” the authors wrote. “The proportions described here, when juxtaposed with those estimated previously for phase 1 trials, suggest a striking improvement for a patient’s therapeutic prospects. This suggests that phase 1 trials do a good job at protecting patients downstream from unsafe and ineffective cancer treatments.”
In an editorial accompanying the study, Howard S. Hochster, MD, of the Rutgers Cancer Institute in New Brunswick, New Jersey, suggested that the 16.2% therapeutic proportion reported may be understated. For instance, “if using the criterion of drugs that were FDA approved in any indication and dose, the proportion of patient benefit in these trials rises to 38%, with a 51% benefit rate considering inclusion in NCCN guidelines,” he wrote.
SOURCE:
This study, led by Charlotte Ouimet, MSc, Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, Montréal, Québec, Canada, was published online in Journal of the National Cancer Institute.
LIMITATIONS:
The longitudinal design of this study required using a historical cohort of phase 2 clinical trials, which may not reflect current drug development patterns. This study was underpowered to determine trial characteristics that predicted higher therapeutic proportions. Furthermore, the exclusion of cytotoxic drugs from the analysis resulted in a somewhat restricted view of overall drug development.
DISCLOSURES:
This study was supported by the Canadian Institutes of Health Research. The authors reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
One in six patients in phase 2 cancer trials received treatments that were eventually approved by the Food and Drug Administration (FDA), a new analysis found. This proportion increased to 1 in 5 when considering National Comprehensive Cancer Network (NCCN) off-label recommendations and decreased to about 1 in 11 for approved regimens considered to have a substantial clinical benefit.
METHODOLOGY:
- Patients enroll in phase 2 oncology trials seeking access to promising new treatments, but the risk-benefit assessments and the likelihood of receiving a therapy that ultimately gains FDA approval remain unclear. Previous research suggests that the odds are 1 in 83 patients for those enrolled in a phase 1 cancer trial.
- Researchers randomly selected 400 phase 2 cancer trials initiated between November 2012 and November 2015 (to give enough time for an approval to occur); these trials included more than 25,000 patients across 608 specific treatment cohorts testing 332 drugs.
- The primary endpoint was the proportion of patients enrolled in phase 2 trials who received a treatment regimen that later attained FDA approval — defined as the “therapeutic proportion.”
- A secondary endpoint was determining the therapeutic proportion based on the therapeutic value of drugs. The three benchmarks were FDA approval alone, FDA approval plus NCCN off-label recommendations, and FDA approval for drugs considered to have a substantial clinical benefit, based on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).
TAKEAWAY:
- A total of 4045 patients received a treatment regimen that advanced to FDA approval, corresponding to a therapeutic proportion of 16.2%.
- The therapeutic proportion increased to 19.4% when considering NCCN off-label recommendations and decreased to 9.3% for FDA-approved regimens considered to have a substantial clinical benefit, based on the ESMO-MCBS.
- The proportion of patients who participated in a trial in which the drug-indication pairing went on to phase 3 testing was 32.5%.
- Enrollment in a trial featuring biomarker enrichment, an immunotherapy drug, a large phase 2 cohort, and a nonrandomized, industry-sponsored trial all showed a trend toward a higher therapeutic proportion.
IN PRACTICE:
“By entering a phase 2 trial, a patient has a one in six chance of receiving a treatment that will later be approved for their condition,” the authors wrote. “The proportions described here, when juxtaposed with those estimated previously for phase 1 trials, suggest a striking improvement for a patient’s therapeutic prospects. This suggests that phase 1 trials do a good job at protecting patients downstream from unsafe and ineffective cancer treatments.”
In an editorial accompanying the study, Howard S. Hochster, MD, of the Rutgers Cancer Institute in New Brunswick, New Jersey, suggested that the 16.2% therapeutic proportion reported may be understated. For instance, “if using the criterion of drugs that were FDA approved in any indication and dose, the proportion of patient benefit in these trials rises to 38%, with a 51% benefit rate considering inclusion in NCCN guidelines,” he wrote.
SOURCE:
This study, led by Charlotte Ouimet, MSc, Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, Montréal, Québec, Canada, was published online in Journal of the National Cancer Institute.
LIMITATIONS:
The longitudinal design of this study required using a historical cohort of phase 2 clinical trials, which may not reflect current drug development patterns. This study was underpowered to determine trial characteristics that predicted higher therapeutic proportions. Furthermore, the exclusion of cytotoxic drugs from the analysis resulted in a somewhat restricted view of overall drug development.
DISCLOSURES:
This study was supported by the Canadian Institutes of Health Research. The authors reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Bariatric Surgery Lowers Risk for Long-Term Liver Complications in MASH-Related Cirrhosis
according to a recent study by Cleveland Clinic researchers.
Compared with patients who received medical therapy alone, those who underwent bariatric surgery had a 72% lower risk of developing serious complications of liver disease and an 80% lower risk for progression to decompensated cirrhosis.
The results could have major implications for patients with metabolic dysfunction–associated steatohepatitis (MASH), particularly given that about 20% of patients with MASH progress to cirrhosis, the researchers said.
“Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis,” said Steven Nissen, MD, the senior author and chief academic officer of the Miller Family Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Ohio.
“However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population,” he said. “This study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”
The study was published online in Nature Medicine.
Significantly Reduced Risks
As part of the Surgical Procedures Eliminate Compensated Cirrhosis in Advancing Long-Term (SPECCIAL) observational study, Nissen and colleagues compared the long-term effects of metabolic surgery and medical treatment in patients with obesity and compensated, biopsy-proven MASH-related cirrhosis. They looked for six major adverse liver outcomes (MALO): ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and all-cause mortality.
Among nearly 37,000 patients who underwent liver biopsy at the Cleveland Clinic Health System between 1995 and 2020, the research team identified 168 patients (69.6% women) with MASH-related cirrhosis, Child-Pugh class A, and model for end-stage liver disease scores ≤ 10. Among those, 62 underwent metabolic surgery (37 Roux-en-Y gastric bypass and 25 sleeve gastrectomy) and 106 had nonsurgical treatment.
After overlap weighting, the groups had balanced baseline characteristics, including mean body mass index of 42.7, Fibrosis-4 score of 2.1, albumin of 4.1 g/dL, bilirubin of 0.6 mg/dL, and Elixhauser comorbidity index of 9. In each group, 84.5% had type 2 diabetes and 79.1% had Ishak fibrosis stage 6.
Overall, the 15-year cumulative incidence of MALO was 20.9% in the surgical group and 46.4% in the nonsurgical group (adjusted hazard ratio [aHR], 0.28; P = .003), with MALO occurring in 10 surgical patients and 42 nonsurgical patients.
Assuming a causal effect, the number needed to treat with metabolic surgery to avoid one incidence of MALO over a 15-year timespan was 4.5.
The 15-year incidence of MALO was similar between surgical methods, with 20.1% for Roux-en-Y gastric bypass and 19.9% for sleeve gastrectomy.
In addition, the 15-year cumulative incidence of progression to decompensated cirrhosis was 15.6% in the surgical group and 30.7% in the nonsurgical group (aHR, 0.2; P = .01), with decompensation occurring in four surgical patients and 33 nonsurgical patients.
At 15 years, patients in the surgical group lost 31.6 kg or about 26.6% of their weight, and those in the nonsurgical group lost 10.7 kg or 9.8%.
Among patients with type 2 diabetes at baseline, metabolic surgery was associated with a reduction in hemoglobin A1c levels, as well as diabetes remission for some patients.
Potential to Fill an Unmet Need
Previous studies have indicated that bariatric surgery can effectively treat noncirrhotic MASH and lead to histologic resolution of MASH. In a 2021 study, Nissen and colleagues found bariatric surgery was associated with a lower risk for MALO and major adverse cardiovascular events in patients with biopsy-proven MASH without cirrhosis. Now, Nissen said, the SPECCIAL study indicates surgery may be a good option for MASH-related cirrhosis as well.
The study authors also noted that similar findings are theoretically possible from medical therapies, given the emergence of a new generation of anti-obesity medications. In this study, 16.8% of the surgical group and 14.3% of the nonsurgical group took semaglutide or tirzepatide at some point during the follow-up period.
“Patients with MASH-related cirrhosis have extremely limited treatment options,” said Sobia Laique, MD, study coauthor and a transplant hepatologist at the Cleveland Clinic who specializes in MASH-related cirrhosis. She cofounded the Cleveland Clinic’s task force on metabolic dysfunction–associated steatotic liver disease (MASLD) to improve screening, management, and patient outcomes for MASLD and related comorbidities.
“No therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications for these patients,” she said. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”
No funding was reported for this study. Several authors reported receiving grant funding, consultant fees, and advisory roles for various pharmaceutical companies.
A version of this article appeared on Medscape.com.
according to a recent study by Cleveland Clinic researchers.
Compared with patients who received medical therapy alone, those who underwent bariatric surgery had a 72% lower risk of developing serious complications of liver disease and an 80% lower risk for progression to decompensated cirrhosis.
The results could have major implications for patients with metabolic dysfunction–associated steatohepatitis (MASH), particularly given that about 20% of patients with MASH progress to cirrhosis, the researchers said.
“Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis,” said Steven Nissen, MD, the senior author and chief academic officer of the Miller Family Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Ohio.
“However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population,” he said. “This study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”
The study was published online in Nature Medicine.
Significantly Reduced Risks
As part of the Surgical Procedures Eliminate Compensated Cirrhosis in Advancing Long-Term (SPECCIAL) observational study, Nissen and colleagues compared the long-term effects of metabolic surgery and medical treatment in patients with obesity and compensated, biopsy-proven MASH-related cirrhosis. They looked for six major adverse liver outcomes (MALO): ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and all-cause mortality.
Among nearly 37,000 patients who underwent liver biopsy at the Cleveland Clinic Health System between 1995 and 2020, the research team identified 168 patients (69.6% women) with MASH-related cirrhosis, Child-Pugh class A, and model for end-stage liver disease scores ≤ 10. Among those, 62 underwent metabolic surgery (37 Roux-en-Y gastric bypass and 25 sleeve gastrectomy) and 106 had nonsurgical treatment.
After overlap weighting, the groups had balanced baseline characteristics, including mean body mass index of 42.7, Fibrosis-4 score of 2.1, albumin of 4.1 g/dL, bilirubin of 0.6 mg/dL, and Elixhauser comorbidity index of 9. In each group, 84.5% had type 2 diabetes and 79.1% had Ishak fibrosis stage 6.
Overall, the 15-year cumulative incidence of MALO was 20.9% in the surgical group and 46.4% in the nonsurgical group (adjusted hazard ratio [aHR], 0.28; P = .003), with MALO occurring in 10 surgical patients and 42 nonsurgical patients.
Assuming a causal effect, the number needed to treat with metabolic surgery to avoid one incidence of MALO over a 15-year timespan was 4.5.
The 15-year incidence of MALO was similar between surgical methods, with 20.1% for Roux-en-Y gastric bypass and 19.9% for sleeve gastrectomy.
In addition, the 15-year cumulative incidence of progression to decompensated cirrhosis was 15.6% in the surgical group and 30.7% in the nonsurgical group (aHR, 0.2; P = .01), with decompensation occurring in four surgical patients and 33 nonsurgical patients.
At 15 years, patients in the surgical group lost 31.6 kg or about 26.6% of their weight, and those in the nonsurgical group lost 10.7 kg or 9.8%.
Among patients with type 2 diabetes at baseline, metabolic surgery was associated with a reduction in hemoglobin A1c levels, as well as diabetes remission for some patients.
Potential to Fill an Unmet Need
Previous studies have indicated that bariatric surgery can effectively treat noncirrhotic MASH and lead to histologic resolution of MASH. In a 2021 study, Nissen and colleagues found bariatric surgery was associated with a lower risk for MALO and major adverse cardiovascular events in patients with biopsy-proven MASH without cirrhosis. Now, Nissen said, the SPECCIAL study indicates surgery may be a good option for MASH-related cirrhosis as well.
The study authors also noted that similar findings are theoretically possible from medical therapies, given the emergence of a new generation of anti-obesity medications. In this study, 16.8% of the surgical group and 14.3% of the nonsurgical group took semaglutide or tirzepatide at some point during the follow-up period.
“Patients with MASH-related cirrhosis have extremely limited treatment options,” said Sobia Laique, MD, study coauthor and a transplant hepatologist at the Cleveland Clinic who specializes in MASH-related cirrhosis. She cofounded the Cleveland Clinic’s task force on metabolic dysfunction–associated steatotic liver disease (MASLD) to improve screening, management, and patient outcomes for MASLD and related comorbidities.
“No therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications for these patients,” she said. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”
No funding was reported for this study. Several authors reported receiving grant funding, consultant fees, and advisory roles for various pharmaceutical companies.
A version of this article appeared on Medscape.com.
according to a recent study by Cleveland Clinic researchers.
Compared with patients who received medical therapy alone, those who underwent bariatric surgery had a 72% lower risk of developing serious complications of liver disease and an 80% lower risk for progression to decompensated cirrhosis.
The results could have major implications for patients with metabolic dysfunction–associated steatohepatitis (MASH), particularly given that about 20% of patients with MASH progress to cirrhosis, the researchers said.
“Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis,” said Steven Nissen, MD, the senior author and chief academic officer of the Miller Family Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Ohio.
“However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population,” he said. “This study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”
The study was published online in Nature Medicine.
Significantly Reduced Risks
As part of the Surgical Procedures Eliminate Compensated Cirrhosis in Advancing Long-Term (SPECCIAL) observational study, Nissen and colleagues compared the long-term effects of metabolic surgery and medical treatment in patients with obesity and compensated, biopsy-proven MASH-related cirrhosis. They looked for six major adverse liver outcomes (MALO): ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and all-cause mortality.
Among nearly 37,000 patients who underwent liver biopsy at the Cleveland Clinic Health System between 1995 and 2020, the research team identified 168 patients (69.6% women) with MASH-related cirrhosis, Child-Pugh class A, and model for end-stage liver disease scores ≤ 10. Among those, 62 underwent metabolic surgery (37 Roux-en-Y gastric bypass and 25 sleeve gastrectomy) and 106 had nonsurgical treatment.
After overlap weighting, the groups had balanced baseline characteristics, including mean body mass index of 42.7, Fibrosis-4 score of 2.1, albumin of 4.1 g/dL, bilirubin of 0.6 mg/dL, and Elixhauser comorbidity index of 9. In each group, 84.5% had type 2 diabetes and 79.1% had Ishak fibrosis stage 6.
Overall, the 15-year cumulative incidence of MALO was 20.9% in the surgical group and 46.4% in the nonsurgical group (adjusted hazard ratio [aHR], 0.28; P = .003), with MALO occurring in 10 surgical patients and 42 nonsurgical patients.
Assuming a causal effect, the number needed to treat with metabolic surgery to avoid one incidence of MALO over a 15-year timespan was 4.5.
The 15-year incidence of MALO was similar between surgical methods, with 20.1% for Roux-en-Y gastric bypass and 19.9% for sleeve gastrectomy.
In addition, the 15-year cumulative incidence of progression to decompensated cirrhosis was 15.6% in the surgical group and 30.7% in the nonsurgical group (aHR, 0.2; P = .01), with decompensation occurring in four surgical patients and 33 nonsurgical patients.
At 15 years, patients in the surgical group lost 31.6 kg or about 26.6% of their weight, and those in the nonsurgical group lost 10.7 kg or 9.8%.
Among patients with type 2 diabetes at baseline, metabolic surgery was associated with a reduction in hemoglobin A1c levels, as well as diabetes remission for some patients.
Potential to Fill an Unmet Need
Previous studies have indicated that bariatric surgery can effectively treat noncirrhotic MASH and lead to histologic resolution of MASH. In a 2021 study, Nissen and colleagues found bariatric surgery was associated with a lower risk for MALO and major adverse cardiovascular events in patients with biopsy-proven MASH without cirrhosis. Now, Nissen said, the SPECCIAL study indicates surgery may be a good option for MASH-related cirrhosis as well.
The study authors also noted that similar findings are theoretically possible from medical therapies, given the emergence of a new generation of anti-obesity medications. In this study, 16.8% of the surgical group and 14.3% of the nonsurgical group took semaglutide or tirzepatide at some point during the follow-up period.
“Patients with MASH-related cirrhosis have extremely limited treatment options,” said Sobia Laique, MD, study coauthor and a transplant hepatologist at the Cleveland Clinic who specializes in MASH-related cirrhosis. She cofounded the Cleveland Clinic’s task force on metabolic dysfunction–associated steatotic liver disease (MASLD) to improve screening, management, and patient outcomes for MASLD and related comorbidities.
“No therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications for these patients,” she said. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”
No funding was reported for this study. Several authors reported receiving grant funding, consultant fees, and advisory roles for various pharmaceutical companies.
A version of this article appeared on Medscape.com.
FROM NATURE MEDICINE
Open Clinical Trials for Patients With Prostate Cancer
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA