Caleb Rans

Combining magnetic resonance imaging (MRI)–targeted biopsy and systematic biopsy improved detection of prostate cancer among men with MRI-visible lesions in a single-center study.

Compared with either method alone, a combination of the two biopsy methods resulted in 9.9% more prostate cancer diagnoses, explained study author Michael Ahdoot, MD, of the National Institutes of Health and colleagues. Their report was published in the New England Journal of Medicine.

“With the addition of MRI-targeted biopsy to systematic biopsy, we may have entered an era of increased diagnostic certainty in prostate cancer,” the researchers wrote.

Their single-center, comparative diagnostic study included 2,103 patients with MRI-visible prostate lesions who underwent both systematic and MRI-targeted biopsy. In cases of multiple biopsies, only the results of the initial biopsies were included.

Each individual specimen was assigned a Gleason score by a genitourinary pathologist and was subsequently categorized into a grade group on a scale of 1-5, with higher scores reflecting greater cancer risk. Grade group 1 was defined as clinically insignificant disease. Grade group 2 was defined as favorable intermediate-risk disease. Grade group 3 or higher was defined as unfavorable intermediate-risk disease or worse.

The primary endpoints were cancer detection rates for each biopsy method, based on grade group. “Among the men who underwent subsequent radical prostatectomy, upgrading and downgrading of grade group from biopsy to whole-mount histopathological analysis of surgical specimens [was also assessed],” the researchers explained.

Among patients who underwent combined biopsy, prostate cancer was identified in 62.4% of patients, and 19.2% underwent radical prostatectomy.

For grade groups 3-5, rates of cancer detection were significantly higher with MRI-targeted biopsy than with systematic biopsy (P less than .01 for all). For grade group 1, detection rates were significantly lower with MRI-targeted biopsy (P less than .01).

“Although many of [the] benefits resulted from MRI-targeted biopsy alone, omission of systematic biopsy would have led to missing the diagnosis of 8.8% of clinically significant cancers,” the researchers reported.

In addition, among patients who underwent radical prostatectomy, the rates of upgrading (grade group 3 or higher) on histopathological analysis were lower for combined biopsy (3.5%) than for MRI-targeted biopsy (8.7%) and systematic biopsy (16.8%).

The researchers acknowledged that a key limitation of this study was the single-center design. As a result, the findings may not be generalizable to other institutions.

However, the researchers concluded that “these findings suggest that combined biopsy provides improved diagnostic accuracy over either systematic or MRI-targeted biopsy alone and better predicts the results of final histopathological analysis.”

The study was funded by the National Institutes of Health, Philips, and the Dr. Mildred Scheel Foundation for Cancer Research. The authors disclosed financial affiliations with Philips, Biocompatibles UK, Boston Scientific, Celsion, and other companies.

SOURCE: Ahdoot M et al. N Engl J Med. 2020 Mar 4. doi: 10.1056/NEJMoa1910038.

Combining magnetic resonance imaging (MRI)–targeted biopsy and systematic biopsy improved detection of prostate cancer among men with MRI-visible lesions in a single-center study.

Compared with either method alone, a combination of the two biopsy methods resulted in 9.9% more prostate cancer diagnoses, explained study author Michael Ahdoot, MD, of the National Institutes of Health and colleagues. Their report was published in the New England Journal of Medicine.

“With the addition of MRI-targeted biopsy to systematic biopsy, we may have entered an era of increased diagnostic certainty in prostate cancer,” the researchers wrote.

Their single-center, comparative diagnostic study included 2,103 patients with MRI-visible prostate lesions who underwent both systematic and MRI-targeted biopsy. In cases of multiple biopsies, only the results of the initial biopsies were included.

Each individual specimen was assigned a Gleason score by a genitourinary pathologist and was subsequently categorized into a grade group on a scale of 1-5, with higher scores reflecting greater cancer risk. Grade group 1 was defined as clinically insignificant disease. Grade group 2 was defined as favorable intermediate-risk disease. Grade group 3 or higher was defined as unfavorable intermediate-risk disease or worse.

The primary endpoints were cancer detection rates for each biopsy method, based on grade group. “Among the men who underwent subsequent radical prostatectomy, upgrading and downgrading of grade group from biopsy to whole-mount histopathological analysis of surgical specimens [was also assessed],” the researchers explained.

Among patients who underwent combined biopsy, prostate cancer was identified in 62.4% of patients, and 19.2% underwent radical prostatectomy.

For grade groups 3-5, rates of cancer detection were significantly higher with MRI-targeted biopsy than with systematic biopsy (P less than .01 for all). For grade group 1, detection rates were significantly lower with MRI-targeted biopsy (P less than .01).

“Although many of [the] benefits resulted from MRI-targeted biopsy alone, omission of systematic biopsy would have led to missing the diagnosis of 8.8% of clinically significant cancers,” the researchers reported.

In addition, among patients who underwent radical prostatectomy, the rates of upgrading (grade group 3 or higher) on histopathological analysis were lower for combined biopsy (3.5%) than for MRI-targeted biopsy (8.7%) and systematic biopsy (16.8%).

The researchers acknowledged that a key limitation of this study was the single-center design. As a result, the findings may not be generalizable to other institutions.

However, the researchers concluded that “these findings suggest that combined biopsy provides improved diagnostic accuracy over either systematic or MRI-targeted biopsy alone and better predicts the results of final histopathological analysis.”

The study was funded by the National Institutes of Health, Philips, and the Dr. Mildred Scheel Foundation for Cancer Research. The authors disclosed financial affiliations with Philips, Biocompatibles UK, Boston Scientific, Celsion, and other companies.

SOURCE: Ahdoot M et al. N Engl J Med. 2020 Mar 4. doi: 10.1056/NEJMoa1910038.

Combining magnetic resonance imaging (MRI)–targeted biopsy and systematic biopsy improved detection of prostate cancer among men with MRI-visible lesions in a single-center study.

Compared with either method alone, a combination of the two biopsy methods resulted in 9.9% more prostate cancer diagnoses, explained study author Michael Ahdoot, MD, of the National Institutes of Health and colleagues. Their report was published in the New England Journal of Medicine.

“With the addition of MRI-targeted biopsy to systematic biopsy, we may have entered an era of increased diagnostic certainty in prostate cancer,” the researchers wrote.

Their single-center, comparative diagnostic study included 2,103 patients with MRI-visible prostate lesions who underwent both systematic and MRI-targeted biopsy. In cases of multiple biopsies, only the results of the initial biopsies were included.

Each individual specimen was assigned a Gleason score by a genitourinary pathologist and was subsequently categorized into a grade group on a scale of 1-5, with higher scores reflecting greater cancer risk. Grade group 1 was defined as clinically insignificant disease. Grade group 2 was defined as favorable intermediate-risk disease. Grade group 3 or higher was defined as unfavorable intermediate-risk disease or worse.

The primary endpoints were cancer detection rates for each biopsy method, based on grade group. “Among the men who underwent subsequent radical prostatectomy, upgrading and downgrading of grade group from biopsy to whole-mount histopathological analysis of surgical specimens [was also assessed],” the researchers explained.

Among patients who underwent combined biopsy, prostate cancer was identified in 62.4% of patients, and 19.2% underwent radical prostatectomy.

For grade groups 3-5, rates of cancer detection were significantly higher with MRI-targeted biopsy than with systematic biopsy (P less than .01 for all). For grade group 1, detection rates were significantly lower with MRI-targeted biopsy (P less than .01).

“Although many of [the] benefits resulted from MRI-targeted biopsy alone, omission of systematic biopsy would have led to missing the diagnosis of 8.8% of clinically significant cancers,” the researchers reported.

In addition, among patients who underwent radical prostatectomy, the rates of upgrading (grade group 3 or higher) on histopathological analysis were lower for combined biopsy (3.5%) than for MRI-targeted biopsy (8.7%) and systematic biopsy (16.8%).

The researchers acknowledged that a key limitation of this study was the single-center design. As a result, the findings may not be generalizable to other institutions.

However, the researchers concluded that “these findings suggest that combined biopsy provides improved diagnostic accuracy over either systematic or MRI-targeted biopsy alone and better predicts the results of final histopathological analysis.”

The study was funded by the National Institutes of Health, Philips, and the Dr. Mildred Scheel Foundation for Cancer Research. The authors disclosed financial affiliations with Philips, Biocompatibles UK, Boston Scientific, Celsion, and other companies.

SOURCE: Ahdoot M et al. N Engl J Med. 2020 Mar 4. doi: 10.1056/NEJMoa1910038.

Chlorotoxin (CLTX)-directed chimeric antigen receptor (CAR) T cells demonstrated activity against glioblastoma in a preclinical study and will soon be tested in a clinical trial.

“We sought to develop a CAR T cell using chlorotoxin peptide as the tumor-targeting domain,” wrote Dongrui Wang, a PhD candidate at City of Hope National Medical Center in Duarte, Calif., and colleagues. Their report is in Science Translational Medicine.

“CLTX has been established to bind broadly and specifically to glioblastoma and other neuroectodermal tumors while showing minimal cross-reactivity with nonmalignant cells,” the researchers noted.

The team evaluated CLTX binding capacity in 23 tumor samples from 15 glioblastoma patients, in patient-derived glioblastoma cell lines, and in orthotopic mouse xenograft models. These experiments showed that CLTX could bind to a high percentage of patient tumors as well as to most glioblastoma cells within a tumor.

In the design phase, the researchers engineered a peptide-bearing CAR, which overcame previous barriers of other glioblastoma-directed CARs, including antigen escape and tumor heterogeneity.

The team evaluated the antitumor activity of CLTX-CAR T cells in two orthotopic mouse xenograft models. Intracranial administration of CLTX-CAR T cells controlled tumor growth and extended survival in both models. All mice originally bearing PBT106-TS tumors became tumor-free and remained so for more than 170 days. However, only a subset of mice bearing PBT003-4-TS tumors experienced similar long-term tumor-free survival.

The researchers assessed potential off-target effects of CLTX-CAR T cells in normal human cells. The team observed limited binding of CLTX-CAR T cells to embryonic kidney cells, peripheral blood mononuclear cells, and neural progenitor cells, suggesting minimal off-target activity.

Further toxicity experiments demonstrated that, even at high doses, CLTX-CAR T cells were tolerated in mouse models, suggesting high potency for tumor cells and low risk of systemic toxicity.

Additional preclinical experiments elucidated mechanisms of CLTX-CAR T-cell function, namely the essential role of matrix metalloproteinase 2 expression for cell activation.

The researchers acknowledged that a key limitation of this study was the use of glioblastoma xenograft models, which may not fully represent tumor activity in glioblastoma patients.

Nevertheless, the researchers concluded that “CLTX-CAR T cells present a strategic combination of selective yet ubiquitous tumor targeting and are a candidate for clinical development as anti-glioblastoma immunotherapy.”

In fact, City of Hope is now screening patients for a clinical trial of CLTX-CAR T cells for the treatment of recurrent or progressive glioblastoma (NCT04214392).

The preclinical research was funded by the Ben and Catherine Ivy Foundation and the National Institutes of Health. Two authors disclosed financial affiliations with Mustang Bio.

SOURCE: Wang D et al. Sci Transl Med. 2020 Mar 4. doi: 10.1126/scitranslmed.aaw2672.

Chlorotoxin (CLTX)-directed chimeric antigen receptor (CAR) T cells demonstrated activity against glioblastoma in a preclinical study and will soon be tested in a clinical trial.

“We sought to develop a CAR T cell using chlorotoxin peptide as the tumor-targeting domain,” wrote Dongrui Wang, a PhD candidate at City of Hope National Medical Center in Duarte, Calif., and colleagues. Their report is in Science Translational Medicine.

“CLTX has been established to bind broadly and specifically to glioblastoma and other neuroectodermal tumors while showing minimal cross-reactivity with nonmalignant cells,” the researchers noted.

The team evaluated CLTX binding capacity in 23 tumor samples from 15 glioblastoma patients, in patient-derived glioblastoma cell lines, and in orthotopic mouse xenograft models. These experiments showed that CLTX could bind to a high percentage of patient tumors as well as to most glioblastoma cells within a tumor.

In the design phase, the researchers engineered a peptide-bearing CAR, which overcame previous barriers of other glioblastoma-directed CARs, including antigen escape and tumor heterogeneity.

The team evaluated the antitumor activity of CLTX-CAR T cells in two orthotopic mouse xenograft models. Intracranial administration of CLTX-CAR T cells controlled tumor growth and extended survival in both models. All mice originally bearing PBT106-TS tumors became tumor-free and remained so for more than 170 days. However, only a subset of mice bearing PBT003-4-TS tumors experienced similar long-term tumor-free survival.

The researchers assessed potential off-target effects of CLTX-CAR T cells in normal human cells. The team observed limited binding of CLTX-CAR T cells to embryonic kidney cells, peripheral blood mononuclear cells, and neural progenitor cells, suggesting minimal off-target activity.

Further toxicity experiments demonstrated that, even at high doses, CLTX-CAR T cells were tolerated in mouse models, suggesting high potency for tumor cells and low risk of systemic toxicity.

Additional preclinical experiments elucidated mechanisms of CLTX-CAR T-cell function, namely the essential role of matrix metalloproteinase 2 expression for cell activation.

The researchers acknowledged that a key limitation of this study was the use of glioblastoma xenograft models, which may not fully represent tumor activity in glioblastoma patients.

Nevertheless, the researchers concluded that “CLTX-CAR T cells present a strategic combination of selective yet ubiquitous tumor targeting and are a candidate for clinical development as anti-glioblastoma immunotherapy.”

In fact, City of Hope is now screening patients for a clinical trial of CLTX-CAR T cells for the treatment of recurrent or progressive glioblastoma (NCT04214392).

The preclinical research was funded by the Ben and Catherine Ivy Foundation and the National Institutes of Health. Two authors disclosed financial affiliations with Mustang Bio.

SOURCE: Wang D et al. Sci Transl Med. 2020 Mar 4. doi: 10.1126/scitranslmed.aaw2672.

Chlorotoxin (CLTX)-directed chimeric antigen receptor (CAR) T cells demonstrated activity against glioblastoma in a preclinical study and will soon be tested in a clinical trial.

“We sought to develop a CAR T cell using chlorotoxin peptide as the tumor-targeting domain,” wrote Dongrui Wang, a PhD candidate at City of Hope National Medical Center in Duarte, Calif., and colleagues. Their report is in Science Translational Medicine.

“CLTX has been established to bind broadly and specifically to glioblastoma and other neuroectodermal tumors while showing minimal cross-reactivity with nonmalignant cells,” the researchers noted.

The team evaluated CLTX binding capacity in 23 tumor samples from 15 glioblastoma patients, in patient-derived glioblastoma cell lines, and in orthotopic mouse xenograft models. These experiments showed that CLTX could bind to a high percentage of patient tumors as well as to most glioblastoma cells within a tumor.

In the design phase, the researchers engineered a peptide-bearing CAR, which overcame previous barriers of other glioblastoma-directed CARs, including antigen escape and tumor heterogeneity.

The team evaluated the antitumor activity of CLTX-CAR T cells in two orthotopic mouse xenograft models. Intracranial administration of CLTX-CAR T cells controlled tumor growth and extended survival in both models. All mice originally bearing PBT106-TS tumors became tumor-free and remained so for more than 170 days. However, only a subset of mice bearing PBT003-4-TS tumors experienced similar long-term tumor-free survival.

The researchers assessed potential off-target effects of CLTX-CAR T cells in normal human cells. The team observed limited binding of CLTX-CAR T cells to embryonic kidney cells, peripheral blood mononuclear cells, and neural progenitor cells, suggesting minimal off-target activity.

Further toxicity experiments demonstrated that, even at high doses, CLTX-CAR T cells were tolerated in mouse models, suggesting high potency for tumor cells and low risk of systemic toxicity.

Additional preclinical experiments elucidated mechanisms of CLTX-CAR T-cell function, namely the essential role of matrix metalloproteinase 2 expression for cell activation.

The researchers acknowledged that a key limitation of this study was the use of glioblastoma xenograft models, which may not fully represent tumor activity in glioblastoma patients.

Nevertheless, the researchers concluded that “CLTX-CAR T cells present a strategic combination of selective yet ubiquitous tumor targeting and are a candidate for clinical development as anti-glioblastoma immunotherapy.”

In fact, City of Hope is now screening patients for a clinical trial of CLTX-CAR T cells for the treatment of recurrent or progressive glioblastoma (NCT04214392).

The preclinical research was funded by the Ben and Catherine Ivy Foundation and the National Institutes of Health. Two authors disclosed financial affiliations with Mustang Bio.

SOURCE: Wang D et al. Sci Transl Med. 2020 Mar 4. doi: 10.1126/scitranslmed.aaw2672.

Preoperative chemoradiotherapy failed to improve overall survival among patients with resectable or borderline resectable pancreatic cancer, according to findings from a phase 3 trial.

On the other hand, preoperative chemoradiotherapy improved disease-free survival, locoregional failure-free interval, and other secondary endpoints, according to study author Eva Versteijne, MD, of the University of Amsterdam, and colleagues. Their findings were published in the Journal of Clinical Oncology.

The randomized, phase 3 study included 246 patients with borderline or resectable pancreatic ductal adenocarcinoma without distant metastases. Patients were randomized to receive preoperative chemoradiotherapy (n = 119) or immediate surgery (n = 127).

Patients in the preoperative chemoradiotherapy arm received three courses of gemcitabine at 1,000 mg/m², combined with 15 fractions of radiotherapy at 2.4 Gy during the second course. Explorative laparotomy with subsequent resection followed, in addition to four 4-week cycles of adjuvant gemcitabine at 1,000 mg/m². Following resection in the immediate surgery arm, patients received six 4-week cycles of adjuvant gemcitabine at the same dose.

The primary outcome was median overall survival in the intention-to-treat population. The median overall survival was 16.0 months in the preoperative chemoradiotherapy arm and 14.3 months in the immediate surgery arm (hazard ratio, 0.78; P = .096).

Secondary outcomes included disease-free survival, resection rate, R0 resection rate, and locoregional failure-free interval, among others.

The resection rate was 61% in the preoperative chemoradiotherapy arm and 72% in the immediate surgery arm (odds ratio, 0.58; P = .058). The R0 resection rates were 71% and 40%, respectively (OR, 3.61; P less than .001).

The median disease-free survival was 8.1 months in the preoperative chemoradiotherapy arm and 7.7 months in the immediate surgery arm (HR, 0.73; P = .032). The median locoregional failure-free interval was not reached and 13.4 months, respectively (HR, 0.56; P = .0034). The rate of serious adverse events was 52% and 41%, respectively (OR, 1.57; P = .096).

“Preoperative chemoradiotherapy was associated with significantly better [disease-free survival] and [locoregional failure-free interval] as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion,” the researchers noted.

They acknowledged that some findings, particularly the median overall survival in patients assigned to immediate surgery, require further investigation, as these data suggest the trial may have been underpowered.

“The consistent benefits for most secondary endpoints and the better compliance with preoperative chemoradiotherapy compared with postoperative adjuvant chemotherapy suggest superiority of the neoadjuvant approach,” the researchers concluded.

The study was funded by the Dutch Cancer Society. The authors disclosed financial affiliations with Bristol-Myers Squibb, Eisai, Ipsen, Merck Serono, and several other companies.

SOURCE: Versteijne E et al. J Clin Oncol. 2020 Feb 27. doi: 10.1200/JCO.19.02274.

Preoperative chemoradiotherapy failed to improve overall survival among patients with resectable or borderline resectable pancreatic cancer, according to findings from a phase 3 trial.

On the other hand, preoperative chemoradiotherapy improved disease-free survival, locoregional failure-free interval, and other secondary endpoints, according to study author Eva Versteijne, MD, of the University of Amsterdam, and colleagues. Their findings were published in the Journal of Clinical Oncology.

The randomized, phase 3 study included 246 patients with borderline or resectable pancreatic ductal adenocarcinoma without distant metastases. Patients were randomized to receive preoperative chemoradiotherapy (n = 119) or immediate surgery (n = 127).

Patients in the preoperative chemoradiotherapy arm received three courses of gemcitabine at 1,000 mg/m², combined with 15 fractions of radiotherapy at 2.4 Gy during the second course. Explorative laparotomy with subsequent resection followed, in addition to four 4-week cycles of adjuvant gemcitabine at 1,000 mg/m². Following resection in the immediate surgery arm, patients received six 4-week cycles of adjuvant gemcitabine at the same dose.

The primary outcome was median overall survival in the intention-to-treat population. The median overall survival was 16.0 months in the preoperative chemoradiotherapy arm and 14.3 months in the immediate surgery arm (hazard ratio, 0.78; P = .096).

Secondary outcomes included disease-free survival, resection rate, R0 resection rate, and locoregional failure-free interval, among others.

The resection rate was 61% in the preoperative chemoradiotherapy arm and 72% in the immediate surgery arm (odds ratio, 0.58; P = .058). The R0 resection rates were 71% and 40%, respectively (OR, 3.61; P less than .001).

The median disease-free survival was 8.1 months in the preoperative chemoradiotherapy arm and 7.7 months in the immediate surgery arm (HR, 0.73; P = .032). The median locoregional failure-free interval was not reached and 13.4 months, respectively (HR, 0.56; P = .0034). The rate of serious adverse events was 52% and 41%, respectively (OR, 1.57; P = .096).

“Preoperative chemoradiotherapy was associated with significantly better [disease-free survival] and [locoregional failure-free interval] as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion,” the researchers noted.

They acknowledged that some findings, particularly the median overall survival in patients assigned to immediate surgery, require further investigation, as these data suggest the trial may have been underpowered.

“The consistent benefits for most secondary endpoints and the better compliance with preoperative chemoradiotherapy compared with postoperative adjuvant chemotherapy suggest superiority of the neoadjuvant approach,” the researchers concluded.

The study was funded by the Dutch Cancer Society. The authors disclosed financial affiliations with Bristol-Myers Squibb, Eisai, Ipsen, Merck Serono, and several other companies.

SOURCE: Versteijne E et al. J Clin Oncol. 2020 Feb 27. doi: 10.1200/JCO.19.02274.

Preoperative chemoradiotherapy failed to improve overall survival among patients with resectable or borderline resectable pancreatic cancer, according to findings from a phase 3 trial.

On the other hand, preoperative chemoradiotherapy improved disease-free survival, locoregional failure-free interval, and other secondary endpoints, according to study author Eva Versteijne, MD, of the University of Amsterdam, and colleagues. Their findings were published in the Journal of Clinical Oncology.

The randomized, phase 3 study included 246 patients with borderline or resectable pancreatic ductal adenocarcinoma without distant metastases. Patients were randomized to receive preoperative chemoradiotherapy (n = 119) or immediate surgery (n = 127).

Patients in the preoperative chemoradiotherapy arm received three courses of gemcitabine at 1,000 mg/m², combined with 15 fractions of radiotherapy at 2.4 Gy during the second course. Explorative laparotomy with subsequent resection followed, in addition to four 4-week cycles of adjuvant gemcitabine at 1,000 mg/m². Following resection in the immediate surgery arm, patients received six 4-week cycles of adjuvant gemcitabine at the same dose.

The primary outcome was median overall survival in the intention-to-treat population. The median overall survival was 16.0 months in the preoperative chemoradiotherapy arm and 14.3 months in the immediate surgery arm (hazard ratio, 0.78; P = .096).

Secondary outcomes included disease-free survival, resection rate, R0 resection rate, and locoregional failure-free interval, among others.

The resection rate was 61% in the preoperative chemoradiotherapy arm and 72% in the immediate surgery arm (odds ratio, 0.58; P = .058). The R0 resection rates were 71% and 40%, respectively (OR, 3.61; P less than .001).

The median disease-free survival was 8.1 months in the preoperative chemoradiotherapy arm and 7.7 months in the immediate surgery arm (HR, 0.73; P = .032). The median locoregional failure-free interval was not reached and 13.4 months, respectively (HR, 0.56; P = .0034). The rate of serious adverse events was 52% and 41%, respectively (OR, 1.57; P = .096).

“Preoperative chemoradiotherapy was associated with significantly better [disease-free survival] and [locoregional failure-free interval] as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion,” the researchers noted.

They acknowledged that some findings, particularly the median overall survival in patients assigned to immediate surgery, require further investigation, as these data suggest the trial may have been underpowered.

“The consistent benefits for most secondary endpoints and the better compliance with preoperative chemoradiotherapy compared with postoperative adjuvant chemotherapy suggest superiority of the neoadjuvant approach,” the researchers concluded.

The study was funded by the Dutch Cancer Society. The authors disclosed financial affiliations with Bristol-Myers Squibb, Eisai, Ipsen, Merck Serono, and several other companies.

SOURCE: Versteijne E et al. J Clin Oncol. 2020 Feb 27. doi: 10.1200/JCO.19.02274.

The presence of HLA-B27 may predict the radiographic phenotype of patients with axial spondyloarthritis (axSpA), according to recent research.

The findings suggest HLA-B27-positive patients have worse radiographic damage, more typical marginal syndesmophytes, and a greater number of bilateral fused sacroiliac joints in the spine, reported Laura C. Coates, MBChB, PhD, of the University of Oxford (England) and colleagues. Their report was published in Arthritis Care & Research.

“In order to achieve phenotypic diversity, we studied patients with PsA [psoriatic arthritis] and axial involvement (a group of patients recognized to have less frequent carriage of HLA-B27), and AS [ankylosing spondylitis],” they wrote.

The researchers conducted a multicenter, cross-sectional cohort study involving 198 patients with AS and 244 with PsA. Various clinical, radiographic, and laboratory data were collected from databases in Ireland, Spain, Germany, Russia, Canada, and Italy.

HLA-B27-positive patients were older (mean 49.1 years vs. 53.8 years), were more often male (73% vs. 59%), and had longer disease duration (mean 13.6 years vs. 11.0 years).

The team compared HLA-B27 carriers and noncarriers on syndesmophyte morphology, the symmetry of the sacroiliac joints and syndesmophytes, in addition to radiographic damage, as measured by the modified Stoke Ankylosing spondylitis spinal score (mSASSS) and PsA Spondylitis Radiology Index (PASRI).

After analysis, the researchers found that HLA-B27 positivity was associated with higher median mSASSS (6 vs. 2; P = .04) and PASRI scores (12 vs. 6; P less than .0001), marginal syndesmophytes (odds ratio, 1.97; 95% confidence interval, 1.16-3.36), and syndesmophyte symmetry (OR, 3.02; 95% CI, 1.38-6.61).

“[Our] study [showed] no difference in sacroiliac symmetry, and no difference in nonmarginal syndesmophytes, according to HLA-B27 status,” they reported.

In addition, they reported that male sex (OR, 1.66; 95% CI, 1.04-2.66) and age (OR, 1.08; 95% CI, 1.05-1.10) were positive predictors of marginal syndesmophytes.

In contrast, only male sex (OR, 2.55; 95% CI, 1.46-4.64) and age (OR, 1.05; 95% CI, 1.03-1.07) predicted the presence of nonmarginal syndesmophytes.

The researchers acknowledged that two key limitations of the study were the absence of disease-group matching and lack of independent central reading of radiographs.

“This analysis suggests less difference in radiographic phenotype between AS and axial PsA than previously found but emphasizes the importance of HLA-B27 status in severity and the phenotypic expression of disease radiographically,” they concluded.

The study was funded by the Academy of Medical Sciences (U.K.). The authors reported having no conflicts of interest.

SOURCE: Coates LC et al. Arthritis Care Res. 2020 Feb 26. doi: 10.1002/acr.24174.

The presence of HLA-B27 may predict the radiographic phenotype of patients with axial spondyloarthritis (axSpA), according to recent research.

The findings suggest HLA-B27-positive patients have worse radiographic damage, more typical marginal syndesmophytes, and a greater number of bilateral fused sacroiliac joints in the spine, reported Laura C. Coates, MBChB, PhD, of the University of Oxford (England) and colleagues. Their report was published in Arthritis Care & Research.

“In order to achieve phenotypic diversity, we studied patients with PsA [psoriatic arthritis] and axial involvement (a group of patients recognized to have less frequent carriage of HLA-B27), and AS [ankylosing spondylitis],” they wrote.

The researchers conducted a multicenter, cross-sectional cohort study involving 198 patients with AS and 244 with PsA. Various clinical, radiographic, and laboratory data were collected from databases in Ireland, Spain, Germany, Russia, Canada, and Italy.

HLA-B27-positive patients were older (mean 49.1 years vs. 53.8 years), were more often male (73% vs. 59%), and had longer disease duration (mean 13.6 years vs. 11.0 years).

The team compared HLA-B27 carriers and noncarriers on syndesmophyte morphology, the symmetry of the sacroiliac joints and syndesmophytes, in addition to radiographic damage, as measured by the modified Stoke Ankylosing spondylitis spinal score (mSASSS) and PsA Spondylitis Radiology Index (PASRI).

After analysis, the researchers found that HLA-B27 positivity was associated with higher median mSASSS (6 vs. 2; P = .04) and PASRI scores (12 vs. 6; P less than .0001), marginal syndesmophytes (odds ratio, 1.97; 95% confidence interval, 1.16-3.36), and syndesmophyte symmetry (OR, 3.02; 95% CI, 1.38-6.61).

“[Our] study [showed] no difference in sacroiliac symmetry, and no difference in nonmarginal syndesmophytes, according to HLA-B27 status,” they reported.

In addition, they reported that male sex (OR, 1.66; 95% CI, 1.04-2.66) and age (OR, 1.08; 95% CI, 1.05-1.10) were positive predictors of marginal syndesmophytes.

In contrast, only male sex (OR, 2.55; 95% CI, 1.46-4.64) and age (OR, 1.05; 95% CI, 1.03-1.07) predicted the presence of nonmarginal syndesmophytes.

The researchers acknowledged that two key limitations of the study were the absence of disease-group matching and lack of independent central reading of radiographs.

“This analysis suggests less difference in radiographic phenotype between AS and axial PsA than previously found but emphasizes the importance of HLA-B27 status in severity and the phenotypic expression of disease radiographically,” they concluded.

The study was funded by the Academy of Medical Sciences (U.K.). The authors reported having no conflicts of interest.

SOURCE: Coates LC et al. Arthritis Care Res. 2020 Feb 26. doi: 10.1002/acr.24174.

The presence of HLA-B27 may predict the radiographic phenotype of patients with axial spondyloarthritis (axSpA), according to recent research.

The findings suggest HLA-B27-positive patients have worse radiographic damage, more typical marginal syndesmophytes, and a greater number of bilateral fused sacroiliac joints in the spine, reported Laura C. Coates, MBChB, PhD, of the University of Oxford (England) and colleagues. Their report was published in Arthritis Care & Research.

“In order to achieve phenotypic diversity, we studied patients with PsA [psoriatic arthritis] and axial involvement (a group of patients recognized to have less frequent carriage of HLA-B27), and AS [ankylosing spondylitis],” they wrote.

The researchers conducted a multicenter, cross-sectional cohort study involving 198 patients with AS and 244 with PsA. Various clinical, radiographic, and laboratory data were collected from databases in Ireland, Spain, Germany, Russia, Canada, and Italy.

HLA-B27-positive patients were older (mean 49.1 years vs. 53.8 years), were more often male (73% vs. 59%), and had longer disease duration (mean 13.6 years vs. 11.0 years).

The team compared HLA-B27 carriers and noncarriers on syndesmophyte morphology, the symmetry of the sacroiliac joints and syndesmophytes, in addition to radiographic damage, as measured by the modified Stoke Ankylosing spondylitis spinal score (mSASSS) and PsA Spondylitis Radiology Index (PASRI).

After analysis, the researchers found that HLA-B27 positivity was associated with higher median mSASSS (6 vs. 2; P = .04) and PASRI scores (12 vs. 6; P less than .0001), marginal syndesmophytes (odds ratio, 1.97; 95% confidence interval, 1.16-3.36), and syndesmophyte symmetry (OR, 3.02; 95% CI, 1.38-6.61).

“[Our] study [showed] no difference in sacroiliac symmetry, and no difference in nonmarginal syndesmophytes, according to HLA-B27 status,” they reported.

In addition, they reported that male sex (OR, 1.66; 95% CI, 1.04-2.66) and age (OR, 1.08; 95% CI, 1.05-1.10) were positive predictors of marginal syndesmophytes.

In contrast, only male sex (OR, 2.55; 95% CI, 1.46-4.64) and age (OR, 1.05; 95% CI, 1.03-1.07) predicted the presence of nonmarginal syndesmophytes.

The researchers acknowledged that two key limitations of the study were the absence of disease-group matching and lack of independent central reading of radiographs.

“This analysis suggests less difference in radiographic phenotype between AS and axial PsA than previously found but emphasizes the importance of HLA-B27 status in severity and the phenotypic expression of disease radiographically,” they concluded.

The study was funded by the Academy of Medical Sciences (U.K.). The authors reported having no conflicts of interest.

SOURCE: Coates LC et al. Arthritis Care Res. 2020 Feb 26. doi: 10.1002/acr.24174.

New research suggests the incidence of death from unintentional injury is higher among patients with cancer than among those in the general U.S. population.

The findings highlight the need for more initiatives to help recognize patients at risk of death from this category of injury, which is the third leading cause of death in the country, according to the study authors.

“The purpose of our study was to present a comprehensive analysis of death from unintentional injury among patients with cancer using a large population-based cohort,” wrote Kunyu Yang, MD, of Huazhong University of Science and Technology in China, and colleagues. Their report is in JAMA Network Open.

The retrospective study included 8,271,020 patients with cancer, 40,599 of whom died from unintentional injury. The researchers identified patients who received a new diagnosis of primary cancer between Jan. 1, 1973, and Dec. 31, 2015, from the Surveillance, Epidemiology, and End Results (SEER) database.

The mean age of study participants was 63.0 years, and most were diagnosed in the 2000-2009 period (41.6%) or the 2010-2015 period (27.6%).

The SEER data was compared with mortality data representative of the general U.S. population obtained from the National Center for Health Statistics. Standardized mortality ratios and rates of death from unintentional injury were measured in both groups.

The rates of death from unintentional injury were 81.90 per 100,000 person-years in cancer patients and 51.21 per 100,000 person-years in the general population. The standardized mortality ratio was 1.60 (95% confidence interval, 1.58-1.61).

Factors associated with higher rates of death from unintentional injury among cancer patients included male sex (relative risk, 1.69; P less than .001), age greater than 80 years at diagnosis (RR, 2.91; P less than .001), and being unmarried (RR, 1.23; P less than .001).

“Rates of death from unintentional injury were the highest in patients with cancers of the liver (200.37 per 100,000 person-years), brain (175.04 per 100,000 person-years), larynx (148.78 per 100,000 person-years), and esophagus (144.98 per 100,000 person-years),” the researchers reported.

They acknowledged that a key limitation of this study was the potential role of reporting bias in death certificate analyses. As a result, death due to unintentional injury and death from suicide and homicide could have been misclassified.

“Cancer-related suicides, like all suicides, are preventable and should be viewed as cancer-related mortality. It is a silent killer with a peak incidence weeks after diagnosis – an undeniably hectic time for most patients and clinicians getting to know their patients,” said Daniel C. McFarland, DO, of Memorial Sloan Kettering Cancer Center in New York. He was not involved in this study.

“Suicide screening with appropriate systems in place to address suicidal thoughts and behavior is crucial for cancer patients throughout the trajectory of their care,” he added.

As with death from unintentional injury, higher rates of suicide have been reported among cancer patients in comparison to the general population (Nat Commun. 2019;10[1]:207).

No funding sources were reported for this study. The authors and Dr. McFarland disclosed no conflicts of interest.

SOURCE: Yang K et al. JAMA Netw Open. 2020 Feb 21. doi: 10.1001/jamanetworkopen.2019.21647.

New research suggests the incidence of death from unintentional injury is higher among patients with cancer than among those in the general U.S. population.

The findings highlight the need for more initiatives to help recognize patients at risk of death from this category of injury, which is the third leading cause of death in the country, according to the study authors.

“The purpose of our study was to present a comprehensive analysis of death from unintentional injury among patients with cancer using a large population-based cohort,” wrote Kunyu Yang, MD, of Huazhong University of Science and Technology in China, and colleagues. Their report is in JAMA Network Open.

The retrospective study included 8,271,020 patients with cancer, 40,599 of whom died from unintentional injury. The researchers identified patients who received a new diagnosis of primary cancer between Jan. 1, 1973, and Dec. 31, 2015, from the Surveillance, Epidemiology, and End Results (SEER) database.

The mean age of study participants was 63.0 years, and most were diagnosed in the 2000-2009 period (41.6%) or the 2010-2015 period (27.6%).

The SEER data was compared with mortality data representative of the general U.S. population obtained from the National Center for Health Statistics. Standardized mortality ratios and rates of death from unintentional injury were measured in both groups.

The rates of death from unintentional injury were 81.90 per 100,000 person-years in cancer patients and 51.21 per 100,000 person-years in the general population. The standardized mortality ratio was 1.60 (95% confidence interval, 1.58-1.61).

Factors associated with higher rates of death from unintentional injury among cancer patients included male sex (relative risk, 1.69; P less than .001), age greater than 80 years at diagnosis (RR, 2.91; P less than .001), and being unmarried (RR, 1.23; P less than .001).

“Rates of death from unintentional injury were the highest in patients with cancers of the liver (200.37 per 100,000 person-years), brain (175.04 per 100,000 person-years), larynx (148.78 per 100,000 person-years), and esophagus (144.98 per 100,000 person-years),” the researchers reported.

They acknowledged that a key limitation of this study was the potential role of reporting bias in death certificate analyses. As a result, death due to unintentional injury and death from suicide and homicide could have been misclassified.

“Cancer-related suicides, like all suicides, are preventable and should be viewed as cancer-related mortality. It is a silent killer with a peak incidence weeks after diagnosis – an undeniably hectic time for most patients and clinicians getting to know their patients,” said Daniel C. McFarland, DO, of Memorial Sloan Kettering Cancer Center in New York. He was not involved in this study.

“Suicide screening with appropriate systems in place to address suicidal thoughts and behavior is crucial for cancer patients throughout the trajectory of their care,” he added.

As with death from unintentional injury, higher rates of suicide have been reported among cancer patients in comparison to the general population (Nat Commun. 2019;10[1]:207).

No funding sources were reported for this study. The authors and Dr. McFarland disclosed no conflicts of interest.

SOURCE: Yang K et al. JAMA Netw Open. 2020 Feb 21. doi: 10.1001/jamanetworkopen.2019.21647.

New research suggests the incidence of death from unintentional injury is higher among patients with cancer than among those in the general U.S. population.

The findings highlight the need for more initiatives to help recognize patients at risk of death from this category of injury, which is the third leading cause of death in the country, according to the study authors.

“The purpose of our study was to present a comprehensive analysis of death from unintentional injury among patients with cancer using a large population-based cohort,” wrote Kunyu Yang, MD, of Huazhong University of Science and Technology in China, and colleagues. Their report is in JAMA Network Open.

The retrospective study included 8,271,020 patients with cancer, 40,599 of whom died from unintentional injury. The researchers identified patients who received a new diagnosis of primary cancer between Jan. 1, 1973, and Dec. 31, 2015, from the Surveillance, Epidemiology, and End Results (SEER) database.

The mean age of study participants was 63.0 years, and most were diagnosed in the 2000-2009 period (41.6%) or the 2010-2015 period (27.6%).

The SEER data was compared with mortality data representative of the general U.S. population obtained from the National Center for Health Statistics. Standardized mortality ratios and rates of death from unintentional injury were measured in both groups.

The rates of death from unintentional injury were 81.90 per 100,000 person-years in cancer patients and 51.21 per 100,000 person-years in the general population. The standardized mortality ratio was 1.60 (95% confidence interval, 1.58-1.61).

Factors associated with higher rates of death from unintentional injury among cancer patients included male sex (relative risk, 1.69; P less than .001), age greater than 80 years at diagnosis (RR, 2.91; P less than .001), and being unmarried (RR, 1.23; P less than .001).

“Rates of death from unintentional injury were the highest in patients with cancers of the liver (200.37 per 100,000 person-years), brain (175.04 per 100,000 person-years), larynx (148.78 per 100,000 person-years), and esophagus (144.98 per 100,000 person-years),” the researchers reported.

They acknowledged that a key limitation of this study was the potential role of reporting bias in death certificate analyses. As a result, death due to unintentional injury and death from suicide and homicide could have been misclassified.

“Cancer-related suicides, like all suicides, are preventable and should be viewed as cancer-related mortality. It is a silent killer with a peak incidence weeks after diagnosis – an undeniably hectic time for most patients and clinicians getting to know their patients,” said Daniel C. McFarland, DO, of Memorial Sloan Kettering Cancer Center in New York. He was not involved in this study.

“Suicide screening with appropriate systems in place to address suicidal thoughts and behavior is crucial for cancer patients throughout the trajectory of their care,” he added.

As with death from unintentional injury, higher rates of suicide have been reported among cancer patients in comparison to the general population (Nat Commun. 2019;10[1]:207).

No funding sources were reported for this study. The authors and Dr. McFarland disclosed no conflicts of interest.

SOURCE: Yang K et al. JAMA Netw Open. 2020 Feb 21. doi: 10.1001/jamanetworkopen.2019.21647.

Combination pembrolizumab and chemoradiotherapy appears safe and active for patients with locally advanced non–small cell lung cancer (NSCLC), results from a phase 1 trial suggest.

Nearly 90% of evaluable patients responded to the combination, and the 12-month progression-free survival rate was 69.7%. Pneumonitis was common, but most patients responded to high-dose corticosteroids.

Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey, in New Brunswick, and colleagues reported these results in JAMA Oncology.

The phase 1 study included 21 patients with locally advanced, unresectable, stage III NSCLC. Planned treatment consisted of pembrolizumab (Keytruda) at various dosing schedules, chemotherapy (weekly carboplatin and paclitaxel), and radiation (2 Gy/day, 60 Gy total).

The researchers used a standard 3 + 3 design to evaluate the safety and tolerability of pembrolizumab in five dosing cohorts.

In cohort 1, patients received pembrolizumab at 200 mg every 21 days within 2-6 weeks of completing chemoradiotherapy. In cohort 2, patients received pembrolizumab at 100 mg every 21 days, starting on day 29 of chemoradiotherapy. Cohort 3 received the 200 mg dose of pembrolizumab, starting on day 29.

Pembrolizumab was started on day 1 of chemoradiotherapy at the 100-mg dose in cohort 4 and at the 200-mg dose in cohort 5. An additional six-patient safety expansion cohort received the same treatment as cohort 5.

The median follow-up was 16 months. There was one dose-limiting toxicity – grade 5 pneumonitis, which occurred in the safety expansion cohort.

Grade 2 or higher immune-related toxicities were observed in 14 patients (67%), and grade 2 or higher pneumonitis occurred in 7 patients (33%).

“Although we observed an increased rate of pneumonitis, most patients had pneumonitis that responded to high-dose corticosteroid treatment,” the researchers noted.

There were 19 patients who received at least two cycles of pembrolizumab and were evaluable for response. The best response was complete response in 3 patients (16%), partial response in 14 patients (74%), and stable disease in 1 patient (5%).

The progression-free survival rate was 81.0% at 6 months and 69.7% at 12 months. The overall survival rate was 95.2% at 6 months and 85.2% at 12 months.

The researchers acknowledged that two key limitations of this study were the small sample size and short duration of follow-up.

“Pembrolizumab with concurrent chemoradiotherapy is tolerable for patients with locally advanced, unresectable NSCLC, although the risk of pneumonitis and long-term outcomes should be evaluated in additional studies,” commented Enriqueta Felip, MD, PhD, of Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in this study.

The study was funded by Merck. The authors and Dr. Felip disclosed relationships with Merck and other companies.

SOURCE: Jabbour SK et al. JAMA Oncol. 2020 Feb 20. doi: 10.1001/jamaoncol.2019.6731.

Combination pembrolizumab and chemoradiotherapy appears safe and active for patients with locally advanced non–small cell lung cancer (NSCLC), results from a phase 1 trial suggest.

Nearly 90% of evaluable patients responded to the combination, and the 12-month progression-free survival rate was 69.7%. Pneumonitis was common, but most patients responded to high-dose corticosteroids.

Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey, in New Brunswick, and colleagues reported these results in JAMA Oncology.

The phase 1 study included 21 patients with locally advanced, unresectable, stage III NSCLC. Planned treatment consisted of pembrolizumab (Keytruda) at various dosing schedules, chemotherapy (weekly carboplatin and paclitaxel), and radiation (2 Gy/day, 60 Gy total).

The researchers used a standard 3 + 3 design to evaluate the safety and tolerability of pembrolizumab in five dosing cohorts.

In cohort 1, patients received pembrolizumab at 200 mg every 21 days within 2-6 weeks of completing chemoradiotherapy. In cohort 2, patients received pembrolizumab at 100 mg every 21 days, starting on day 29 of chemoradiotherapy. Cohort 3 received the 200 mg dose of pembrolizumab, starting on day 29.

Pembrolizumab was started on day 1 of chemoradiotherapy at the 100-mg dose in cohort 4 and at the 200-mg dose in cohort 5. An additional six-patient safety expansion cohort received the same treatment as cohort 5.

The median follow-up was 16 months. There was one dose-limiting toxicity – grade 5 pneumonitis, which occurred in the safety expansion cohort.

Grade 2 or higher immune-related toxicities were observed in 14 patients (67%), and grade 2 or higher pneumonitis occurred in 7 patients (33%).

“Although we observed an increased rate of pneumonitis, most patients had pneumonitis that responded to high-dose corticosteroid treatment,” the researchers noted.

There were 19 patients who received at least two cycles of pembrolizumab and were evaluable for response. The best response was complete response in 3 patients (16%), partial response in 14 patients (74%), and stable disease in 1 patient (5%).

The progression-free survival rate was 81.0% at 6 months and 69.7% at 12 months. The overall survival rate was 95.2% at 6 months and 85.2% at 12 months.

The researchers acknowledged that two key limitations of this study were the small sample size and short duration of follow-up.

“Pembrolizumab with concurrent chemoradiotherapy is tolerable for patients with locally advanced, unresectable NSCLC, although the risk of pneumonitis and long-term outcomes should be evaluated in additional studies,” commented Enriqueta Felip, MD, PhD, of Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in this study.

The study was funded by Merck. The authors and Dr. Felip disclosed relationships with Merck and other companies.

SOURCE: Jabbour SK et al. JAMA Oncol. 2020 Feb 20. doi: 10.1001/jamaoncol.2019.6731.

Combination pembrolizumab and chemoradiotherapy appears safe and active for patients with locally advanced non–small cell lung cancer (NSCLC), results from a phase 1 trial suggest.

Nearly 90% of evaluable patients responded to the combination, and the 12-month progression-free survival rate was 69.7%. Pneumonitis was common, but most patients responded to high-dose corticosteroids.

Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey, in New Brunswick, and colleagues reported these results in JAMA Oncology.

The phase 1 study included 21 patients with locally advanced, unresectable, stage III NSCLC. Planned treatment consisted of pembrolizumab (Keytruda) at various dosing schedules, chemotherapy (weekly carboplatin and paclitaxel), and radiation (2 Gy/day, 60 Gy total).

The researchers used a standard 3 + 3 design to evaluate the safety and tolerability of pembrolizumab in five dosing cohorts.

In cohort 1, patients received pembrolizumab at 200 mg every 21 days within 2-6 weeks of completing chemoradiotherapy. In cohort 2, patients received pembrolizumab at 100 mg every 21 days, starting on day 29 of chemoradiotherapy. Cohort 3 received the 200 mg dose of pembrolizumab, starting on day 29.

Pembrolizumab was started on day 1 of chemoradiotherapy at the 100-mg dose in cohort 4 and at the 200-mg dose in cohort 5. An additional six-patient safety expansion cohort received the same treatment as cohort 5.

The median follow-up was 16 months. There was one dose-limiting toxicity – grade 5 pneumonitis, which occurred in the safety expansion cohort.

Grade 2 or higher immune-related toxicities were observed in 14 patients (67%), and grade 2 or higher pneumonitis occurred in 7 patients (33%).

“Although we observed an increased rate of pneumonitis, most patients had pneumonitis that responded to high-dose corticosteroid treatment,” the researchers noted.

There were 19 patients who received at least two cycles of pembrolizumab and were evaluable for response. The best response was complete response in 3 patients (16%), partial response in 14 patients (74%), and stable disease in 1 patient (5%).

The progression-free survival rate was 81.0% at 6 months and 69.7% at 12 months. The overall survival rate was 95.2% at 6 months and 85.2% at 12 months.

The researchers acknowledged that two key limitations of this study were the small sample size and short duration of follow-up.

“Pembrolizumab with concurrent chemoradiotherapy is tolerable for patients with locally advanced, unresectable NSCLC, although the risk of pneumonitis and long-term outcomes should be evaluated in additional studies,” commented Enriqueta Felip, MD, PhD, of Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in this study.

The study was funded by Merck. The authors and Dr. Felip disclosed relationships with Merck and other companies.

SOURCE: Jabbour SK et al. JAMA Oncol. 2020 Feb 20. doi: 10.1001/jamaoncol.2019.6731.

Implementing a more stringent treat‐to‐target strategy could provide better outcomes for patients with early RA, according to a recent comparative study.

The findings confirm the feasibility of adopting a treat‐to‐target approach to ensure optimal outcomes are achieved for patients with early-stage disease.

“The objective of the present study was to compare achievement of remission during 2 years of follow-up in two early RA cohorts implementing different treat‐to‐target strategies,” wrote Vibeke Norvang, MD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, and colleagues. The findings were published in Arthritis & Rheumatology.

The researchers performed a pooled analysis of data from the randomized ARCTIC trial and the Norwegian Very Early Arthritis Clinic (NOR-VEAC) observational study. The combined cohort included a total of 429 disease-modifying antirheumatic drug (DMARD)–naive early RA patients, 189 and 330 from each study, respectively.

The American College of Rheumatology/European League Against Rheumatism Boolean remission criteria differed between the two cohorts, with more stringent criteria in ARCTIC than in NOR-VEAC. Remission was defined as scores of less than 1.6 and 2.6 on the Disease Activity Scores in 44 joints and 28 joints, respectively.

At 12- and 24-month follow-up, the researchers found that the odds of achieving remission were greater in ARCTIC than in NOR-VEAC (odds ratios, 1.97; 95% confidence interval, 1.21-3.20 vs. OR, 1.82; 95% CI, 1.05-3.16).

“We found that more than half of patients in each cohort had reached the study-specific remission targets at 6 months, and this increased to more than 60% in each cohort at 12 and 24 months,” they reported.

With respect to drug therapy, all study patients started with methotrexate monotherapy at a mean dose of 16.0 mg and 15.5 mg in ARCTIC and NOR-VEAC, respectively. In addition, similar rates of escalation to a biologic DMARD were observed in both studies (25.6% vs. 25.4%) at 24 months.

The researchers acknowledged that a key limitation of the study was comparing outcomes in two cohorts with different study designs; hence, the risk of bias in estimates of effect cannot be excluded.

“Targeting a more stringent remission and implementing more frequent visits provide further potential for favorable outcomes of a treat‐to‐target strategy,” they concluded.

The study was supported by legacy funds provided to the department of rheumatology at Diakonhjemmet Hospital. Three authors reported financial relationships with AbbVie, Amgen, Corrona, Genentech, Janssen, Mylan, Pfizer, and other companies.

SOURCE: Norvang V et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41232.

Implementing a more stringent treat‐to‐target strategy could provide better outcomes for patients with early RA, according to a recent comparative study.

The findings confirm the feasibility of adopting a treat‐to‐target approach to ensure optimal outcomes are achieved for patients with early-stage disease.

“The objective of the present study was to compare achievement of remission during 2 years of follow-up in two early RA cohorts implementing different treat‐to‐target strategies,” wrote Vibeke Norvang, MD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, and colleagues. The findings were published in Arthritis & Rheumatology.

The researchers performed a pooled analysis of data from the randomized ARCTIC trial and the Norwegian Very Early Arthritis Clinic (NOR-VEAC) observational study. The combined cohort included a total of 429 disease-modifying antirheumatic drug (DMARD)–naive early RA patients, 189 and 330 from each study, respectively.

The American College of Rheumatology/European League Against Rheumatism Boolean remission criteria differed between the two cohorts, with more stringent criteria in ARCTIC than in NOR-VEAC. Remission was defined as scores of less than 1.6 and 2.6 on the Disease Activity Scores in 44 joints and 28 joints, respectively.

At 12- and 24-month follow-up, the researchers found that the odds of achieving remission were greater in ARCTIC than in NOR-VEAC (odds ratios, 1.97; 95% confidence interval, 1.21-3.20 vs. OR, 1.82; 95% CI, 1.05-3.16).

“We found that more than half of patients in each cohort had reached the study-specific remission targets at 6 months, and this increased to more than 60% in each cohort at 12 and 24 months,” they reported.

With respect to drug therapy, all study patients started with methotrexate monotherapy at a mean dose of 16.0 mg and 15.5 mg in ARCTIC and NOR-VEAC, respectively. In addition, similar rates of escalation to a biologic DMARD were observed in both studies (25.6% vs. 25.4%) at 24 months.

The researchers acknowledged that a key limitation of the study was comparing outcomes in two cohorts with different study designs; hence, the risk of bias in estimates of effect cannot be excluded.

“Targeting a more stringent remission and implementing more frequent visits provide further potential for favorable outcomes of a treat‐to‐target strategy,” they concluded.

The study was supported by legacy funds provided to the department of rheumatology at Diakonhjemmet Hospital. Three authors reported financial relationships with AbbVie, Amgen, Corrona, Genentech, Janssen, Mylan, Pfizer, and other companies.

SOURCE: Norvang V et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41232.

Implementing a more stringent treat‐to‐target strategy could provide better outcomes for patients with early RA, according to a recent comparative study.

The findings confirm the feasibility of adopting a treat‐to‐target approach to ensure optimal outcomes are achieved for patients with early-stage disease.

“The objective of the present study was to compare achievement of remission during 2 years of follow-up in two early RA cohorts implementing different treat‐to‐target strategies,” wrote Vibeke Norvang, MD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, and colleagues. The findings were published in Arthritis & Rheumatology.

The researchers performed a pooled analysis of data from the randomized ARCTIC trial and the Norwegian Very Early Arthritis Clinic (NOR-VEAC) observational study. The combined cohort included a total of 429 disease-modifying antirheumatic drug (DMARD)–naive early RA patients, 189 and 330 from each study, respectively.

The American College of Rheumatology/European League Against Rheumatism Boolean remission criteria differed between the two cohorts, with more stringent criteria in ARCTIC than in NOR-VEAC. Remission was defined as scores of less than 1.6 and 2.6 on the Disease Activity Scores in 44 joints and 28 joints, respectively.

At 12- and 24-month follow-up, the researchers found that the odds of achieving remission were greater in ARCTIC than in NOR-VEAC (odds ratios, 1.97; 95% confidence interval, 1.21-3.20 vs. OR, 1.82; 95% CI, 1.05-3.16).

“We found that more than half of patients in each cohort had reached the study-specific remission targets at 6 months, and this increased to more than 60% in each cohort at 12 and 24 months,” they reported.

With respect to drug therapy, all study patients started with methotrexate monotherapy at a mean dose of 16.0 mg and 15.5 mg in ARCTIC and NOR-VEAC, respectively. In addition, similar rates of escalation to a biologic DMARD were observed in both studies (25.6% vs. 25.4%) at 24 months.

The researchers acknowledged that a key limitation of the study was comparing outcomes in two cohorts with different study designs; hence, the risk of bias in estimates of effect cannot be excluded.

“Targeting a more stringent remission and implementing more frequent visits provide further potential for favorable outcomes of a treat‐to‐target strategy,” they concluded.

The study was supported by legacy funds provided to the department of rheumatology at Diakonhjemmet Hospital. Three authors reported financial relationships with AbbVie, Amgen, Corrona, Genentech, Janssen, Mylan, Pfizer, and other companies.

SOURCE: Norvang V et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41232.

The topoisomerase I (TOP1) inhibitor irinotecan could be effective in treating triple-negative breast cancer (TNBC), according to results from a preclinical study published in Science Translational Medicine.

Florence Coussy, MD, PhD, of Institut Curie, Paris, and colleagues evaluated the antitumor activity of the Food and Drug Administration–approved TOP1 inhibitor irinotecan in 40 patient-derived xenografts (PDXs) of TNBC.

Other treatments, such as noncamptothecin TOP1 inhibitors (indotecan and indimitecan) and irinotecan plus VE-822 (an ataxia telangiectasia and Rad3-related protein [ATR] inhibitor), were also evaluated in the PDX models.

Tumor samples were collected from patients with primary breast cancer at the time of surgery (55%), residual breast cancer after neoadjuvant treatment (40%), or axillary lymph node metastases (5%). The patients had a mean age of 56 years (range, 29-89 years).

The researchers assessed BRCAness using the homologous recombination deficiency–large-scale state transition assay. Additional potential markers of response, including expression of retinoblastoma transcriptional corepressor 1 (RB1) and Schlafen family member 11 (SLFN11), were detected on transcriptomic analysis and validated using immunohistochemistry analyses.

The researchers found that 37.5% (n = 15) of TNBC PDX models achieved a partial or complete response to irinotecan therapy, while 22.5% (n = 9) of models had stable disease. BRCAness, RB1 loss, and high SLFN11 expression were deemed potential markers of response to irinotecan and other clinical TOP1 inhibitors.

The researchers then evaluated 250 breast cancer patients treated with anthracycline-based chemotherapy and found that lower expression of SLFN11 was associated with worse survival.

“We also [found] that, in the absence of SLFN11, response to irinotecan can be increased by adding an ATR inhibitor and that the clinical TOP1 inhibitors are highly efficient in BRCA1-mutant and BRCAness-positive TNBC PDXs,” the researchers reported.

They acknowledged that a key limitation of this study was the absence of tumor samples from patients who had received a TOP1 inhibitor.

“Overall, our findings are in line with the notion that concomitant defects in DNA repair and checkpoints render cancer cells highly vulnerable to TOP1 inhibitors,” the researchers concluded.

The study was funded by the National Cancer Institute, PIC3i NCI-Curie, and Site de Recherche Intégrée sur le Cancer. One author is an inventor of indotecan and indimitecan. Two authors are coinventors of the method used to detect inactivation of the homologous recombination pathway, which is licensed to Myriad Genetics.

SOURCE: Coussy F et al. Sci Transl Med. 2020 Feb 19. doi: 10.1126/scitranslmed.aax2625.

The topoisomerase I (TOP1) inhibitor irinotecan could be effective in treating triple-negative breast cancer (TNBC), according to results from a preclinical study published in Science Translational Medicine.

Florence Coussy, MD, PhD, of Institut Curie, Paris, and colleagues evaluated the antitumor activity of the Food and Drug Administration–approved TOP1 inhibitor irinotecan in 40 patient-derived xenografts (PDXs) of TNBC.

Other treatments, such as noncamptothecin TOP1 inhibitors (indotecan and indimitecan) and irinotecan plus VE-822 (an ataxia telangiectasia and Rad3-related protein [ATR] inhibitor), were also evaluated in the PDX models.

Tumor samples were collected from patients with primary breast cancer at the time of surgery (55%), residual breast cancer after neoadjuvant treatment (40%), or axillary lymph node metastases (5%). The patients had a mean age of 56 years (range, 29-89 years).

The researchers assessed BRCAness using the homologous recombination deficiency–large-scale state transition assay. Additional potential markers of response, including expression of retinoblastoma transcriptional corepressor 1 (RB1) and Schlafen family member 11 (SLFN11), were detected on transcriptomic analysis and validated using immunohistochemistry analyses.

The researchers found that 37.5% (n = 15) of TNBC PDX models achieved a partial or complete response to irinotecan therapy, while 22.5% (n = 9) of models had stable disease. BRCAness, RB1 loss, and high SLFN11 expression were deemed potential markers of response to irinotecan and other clinical TOP1 inhibitors.

The researchers then evaluated 250 breast cancer patients treated with anthracycline-based chemotherapy and found that lower expression of SLFN11 was associated with worse survival.

“We also [found] that, in the absence of SLFN11, response to irinotecan can be increased by adding an ATR inhibitor and that the clinical TOP1 inhibitors are highly efficient in BRCA1-mutant and BRCAness-positive TNBC PDXs,” the researchers reported.

They acknowledged that a key limitation of this study was the absence of tumor samples from patients who had received a TOP1 inhibitor.

“Overall, our findings are in line with the notion that concomitant defects in DNA repair and checkpoints render cancer cells highly vulnerable to TOP1 inhibitors,” the researchers concluded.

The study was funded by the National Cancer Institute, PIC3i NCI-Curie, and Site de Recherche Intégrée sur le Cancer. One author is an inventor of indotecan and indimitecan. Two authors are coinventors of the method used to detect inactivation of the homologous recombination pathway, which is licensed to Myriad Genetics.

SOURCE: Coussy F et al. Sci Transl Med. 2020 Feb 19. doi: 10.1126/scitranslmed.aax2625.

The topoisomerase I (TOP1) inhibitor irinotecan could be effective in treating triple-negative breast cancer (TNBC), according to results from a preclinical study published in Science Translational Medicine.

Florence Coussy, MD, PhD, of Institut Curie, Paris, and colleagues evaluated the antitumor activity of the Food and Drug Administration–approved TOP1 inhibitor irinotecan in 40 patient-derived xenografts (PDXs) of TNBC.

Other treatments, such as noncamptothecin TOP1 inhibitors (indotecan and indimitecan) and irinotecan plus VE-822 (an ataxia telangiectasia and Rad3-related protein [ATR] inhibitor), were also evaluated in the PDX models.

Tumor samples were collected from patients with primary breast cancer at the time of surgery (55%), residual breast cancer after neoadjuvant treatment (40%), or axillary lymph node metastases (5%). The patients had a mean age of 56 years (range, 29-89 years).

The researchers assessed BRCAness using the homologous recombination deficiency–large-scale state transition assay. Additional potential markers of response, including expression of retinoblastoma transcriptional corepressor 1 (RB1) and Schlafen family member 11 (SLFN11), were detected on transcriptomic analysis and validated using immunohistochemistry analyses.

The researchers found that 37.5% (n = 15) of TNBC PDX models achieved a partial or complete response to irinotecan therapy, while 22.5% (n = 9) of models had stable disease. BRCAness, RB1 loss, and high SLFN11 expression were deemed potential markers of response to irinotecan and other clinical TOP1 inhibitors.

The researchers then evaluated 250 breast cancer patients treated with anthracycline-based chemotherapy and found that lower expression of SLFN11 was associated with worse survival.

“We also [found] that, in the absence of SLFN11, response to irinotecan can be increased by adding an ATR inhibitor and that the clinical TOP1 inhibitors are highly efficient in BRCA1-mutant and BRCAness-positive TNBC PDXs,” the researchers reported.

They acknowledged that a key limitation of this study was the absence of tumor samples from patients who had received a TOP1 inhibitor.

“Overall, our findings are in line with the notion that concomitant defects in DNA repair and checkpoints render cancer cells highly vulnerable to TOP1 inhibitors,” the researchers concluded.

The study was funded by the National Cancer Institute, PIC3i NCI-Curie, and Site de Recherche Intégrée sur le Cancer. One author is an inventor of indotecan and indimitecan. Two authors are coinventors of the method used to detect inactivation of the homologous recombination pathway, which is licensed to Myriad Genetics.

SOURCE: Coussy F et al. Sci Transl Med. 2020 Feb 19. doi: 10.1126/scitranslmed.aax2625.

Researchers have identified 24 common genetic variants that may be associated with a greater risk of developing endometrial cancer.

SilverV/Thinkstock

The 24 single-nucleotide polymorphisms (SNPs) were detected in genes that function in transcriptional regulation, cell survival, and estrogen metabolism.

“Understanding genetic predisposition to endometrial cancer could facilitate personalized risk assessment with a view to targeted prevention and screening interventions,” wrote Cemsel Bafligil, of the University of Manchester (England) and her coinvestigators. The group’s findings were published in the Journal of Medical Genetics.

The researchers searched major databases for primary studies that evaluated associations between endometrial cancer and SNPs. After applying the search criteria, 453 eligible records were found, and 149 of these were included in the study.

The majority of records were genome-wide association studies, case-control studies, and meta-analyses. Various data, including study type, ethnicity, and endometrial cancer type, were extracted and included in the qualitative synthesis.

After analysis, the researchers identified 24 independent genetic variants associated with a higher risk of developing endometrial cancer, and SNPs in 6 genes – CYP19A1, SOX4, HNF1B, MYC, KLF, and EIF2AK – showed a strong association.

The researchers also estimated the predictive value of the identified SNPs using a theoretical polygenic risk score model. They found that women with genome-wide significant SNPs had double the risk of developing endometrial cancer (relative risk, 2.09), and women with all 24 SNPs had a three-fold greater risk of developing the disease (RR, 3.16).

“The importance of these variants and relevance of the proximate genes in a functional or biological context is challenging to evaluate,” the researchers noted.

They also acknowledged that a key limitation of this study was the ethnic homogeneity of the cohort, with most patients being of European descent. As a result, the findings may not be fully representative of other ethnic groups.

“The multiplicative effects of these SNPs could be used in a PRS [polygenic risk score] to allow personalised risk prediction models to be developed for targeted screening and prevention interventions for women at greatest risk of endometrial cancer,” the researchers concluded.

The National Institute for Health Research Manchester Biomedical Research Centre funded the study. The authors reported having no conflicts of interest.

SOURCE: Bafligil C et al. J Med Genet. 2020 Feb 17. doi: 10.1136/jmedgenet-2019-106529.

Researchers have identified 24 common genetic variants that may be associated with a greater risk of developing endometrial cancer.

SilverV/Thinkstock

The 24 single-nucleotide polymorphisms (SNPs) were detected in genes that function in transcriptional regulation, cell survival, and estrogen metabolism.

“Understanding genetic predisposition to endometrial cancer could facilitate personalized risk assessment with a view to targeted prevention and screening interventions,” wrote Cemsel Bafligil, of the University of Manchester (England) and her coinvestigators. The group’s findings were published in the Journal of Medical Genetics.

The researchers searched major databases for primary studies that evaluated associations between endometrial cancer and SNPs. After applying the search criteria, 453 eligible records were found, and 149 of these were included in the study.

The majority of records were genome-wide association studies, case-control studies, and meta-analyses. Various data, including study type, ethnicity, and endometrial cancer type, were extracted and included in the qualitative synthesis.

After analysis, the researchers identified 24 independent genetic variants associated with a higher risk of developing endometrial cancer, and SNPs in 6 genes – CYP19A1, SOX4, HNF1B, MYC, KLF, and EIF2AK – showed a strong association.

The researchers also estimated the predictive value of the identified SNPs using a theoretical polygenic risk score model. They found that women with genome-wide significant SNPs had double the risk of developing endometrial cancer (relative risk, 2.09), and women with all 24 SNPs had a three-fold greater risk of developing the disease (RR, 3.16).

“The importance of these variants and relevance of the proximate genes in a functional or biological context is challenging to evaluate,” the researchers noted.

They also acknowledged that a key limitation of this study was the ethnic homogeneity of the cohort, with most patients being of European descent. As a result, the findings may not be fully representative of other ethnic groups.

“The multiplicative effects of these SNPs could be used in a PRS [polygenic risk score] to allow personalised risk prediction models to be developed for targeted screening and prevention interventions for women at greatest risk of endometrial cancer,” the researchers concluded.

The National Institute for Health Research Manchester Biomedical Research Centre funded the study. The authors reported having no conflicts of interest.

SOURCE: Bafligil C et al. J Med Genet. 2020 Feb 17. doi: 10.1136/jmedgenet-2019-106529.

Researchers have identified 24 common genetic variants that may be associated with a greater risk of developing endometrial cancer.

SilverV/Thinkstock

The 24 single-nucleotide polymorphisms (SNPs) were detected in genes that function in transcriptional regulation, cell survival, and estrogen metabolism.

“Understanding genetic predisposition to endometrial cancer could facilitate personalized risk assessment with a view to targeted prevention and screening interventions,” wrote Cemsel Bafligil, of the University of Manchester (England) and her coinvestigators. The group’s findings were published in the Journal of Medical Genetics.

The researchers searched major databases for primary studies that evaluated associations between endometrial cancer and SNPs. After applying the search criteria, 453 eligible records were found, and 149 of these were included in the study.

The majority of records were genome-wide association studies, case-control studies, and meta-analyses. Various data, including study type, ethnicity, and endometrial cancer type, were extracted and included in the qualitative synthesis.

After analysis, the researchers identified 24 independent genetic variants associated with a higher risk of developing endometrial cancer, and SNPs in 6 genes – CYP19A1, SOX4, HNF1B, MYC, KLF, and EIF2AK – showed a strong association.

The researchers also estimated the predictive value of the identified SNPs using a theoretical polygenic risk score model. They found that women with genome-wide significant SNPs had double the risk of developing endometrial cancer (relative risk, 2.09), and women with all 24 SNPs had a three-fold greater risk of developing the disease (RR, 3.16).

“The importance of these variants and relevance of the proximate genes in a functional or biological context is challenging to evaluate,” the researchers noted.

They also acknowledged that a key limitation of this study was the ethnic homogeneity of the cohort, with most patients being of European descent. As a result, the findings may not be fully representative of other ethnic groups.

“The multiplicative effects of these SNPs could be used in a PRS [polygenic risk score] to allow personalised risk prediction models to be developed for targeted screening and prevention interventions for women at greatest risk of endometrial cancer,” the researchers concluded.

The National Institute for Health Research Manchester Biomedical Research Centre funded the study. The authors reported having no conflicts of interest.

SOURCE: Bafligil C et al. J Med Genet. 2020 Feb 17. doi: 10.1136/jmedgenet-2019-106529.

A higher lifetime number of sexual partners was associated with a greater risk of being diagnosed with cancer in older adults, according to a recent study.

Additionally, among women, having had more lifetime partners was linked to higher odds of reporting a limiting long-standing condition.

Igor Grabovac, MD, of the Medical University of Vienna, and colleagues reported these results in BMJ Sexual & Reproductive Health.

The exploratory analysis included 2,537 men and 3,185 women, aged 50 years and older, who were a part of the English Longitudinal Study of Ageing. The mean age of study subjects was 64 years in men and 65 years in women, and most were either married or cohabitating.

Researchers collected data on sexual history using a self-administered questionnaire, which privately recorded the lifetime number of sexual partners among study participants. Data on other health outcomes, such as limiting long-standing illness and cancer diagnoses, were also self-reported.

Among male participants, 28.5% reported a history of 0-1 lifetime sexual partners, 29.0% had 2-4 partners, 20.2% had 5-9 partners, and 22.2% had 10 or more partners. The respective measures in women were 40.8%, 35.5%, 15.8%, and 7.8%.

Among all participants, a greater number of sexual partners was associated with being single, younger age, and being in the least or greatest brackets of household income.

The researchers found that, compared with having 0-1 sexual partners, a lifetime history of 10 or more sexual partners was associated with a greater risk of reported cancer in both men (odds ratio, 1.69; P = .047) and women (OR, 1.91; P = .038).

In addition, women with a lifetime history of 10 or more sexual partners had greater odds of reporting a limiting long-standing condition (OR, 1.64; P = .007).

“We observed no statistically significant association between number of lifetime sexual partners and self-rated health, CHD [coronary heart disease], or stroke in either sex, or with limiting long-standing illness in men,” the researchers explained.

They acknowledged that a key limitation of the study was the self-reported nature of the data. As a result, further studies are required to establish causality.

“Sexual history may be a relevant clinical indicator for cancer risk in older patients,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.
 

SOURCE: Grabovac I et al. BMJ Sex Reprod Health. 2020 Feb 13. doi: 10.1136/bmjsrh-2019-200352.

A higher lifetime number of sexual partners was associated with a greater risk of being diagnosed with cancer in older adults, according to a recent study.

Additionally, among women, having had more lifetime partners was linked to higher odds of reporting a limiting long-standing condition.

Igor Grabovac, MD, of the Medical University of Vienna, and colleagues reported these results in BMJ Sexual & Reproductive Health.

The exploratory analysis included 2,537 men and 3,185 women, aged 50 years and older, who were a part of the English Longitudinal Study of Ageing. The mean age of study subjects was 64 years in men and 65 years in women, and most were either married or cohabitating.

Researchers collected data on sexual history using a self-administered questionnaire, which privately recorded the lifetime number of sexual partners among study participants. Data on other health outcomes, such as limiting long-standing illness and cancer diagnoses, were also self-reported.

Among male participants, 28.5% reported a history of 0-1 lifetime sexual partners, 29.0% had 2-4 partners, 20.2% had 5-9 partners, and 22.2% had 10 or more partners. The respective measures in women were 40.8%, 35.5%, 15.8%, and 7.8%.

Among all participants, a greater number of sexual partners was associated with being single, younger age, and being in the least or greatest brackets of household income.

The researchers found that, compared with having 0-1 sexual partners, a lifetime history of 10 or more sexual partners was associated with a greater risk of reported cancer in both men (odds ratio, 1.69; P = .047) and women (OR, 1.91; P = .038).

In addition, women with a lifetime history of 10 or more sexual partners had greater odds of reporting a limiting long-standing condition (OR, 1.64; P = .007).

“We observed no statistically significant association between number of lifetime sexual partners and self-rated health, CHD [coronary heart disease], or stroke in either sex, or with limiting long-standing illness in men,” the researchers explained.

They acknowledged that a key limitation of the study was the self-reported nature of the data. As a result, further studies are required to establish causality.

“Sexual history may be a relevant clinical indicator for cancer risk in older patients,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.
 

SOURCE: Grabovac I et al. BMJ Sex Reprod Health. 2020 Feb 13. doi: 10.1136/bmjsrh-2019-200352.

A higher lifetime number of sexual partners was associated with a greater risk of being diagnosed with cancer in older adults, according to a recent study.

Additionally, among women, having had more lifetime partners was linked to higher odds of reporting a limiting long-standing condition.

Igor Grabovac, MD, of the Medical University of Vienna, and colleagues reported these results in BMJ Sexual & Reproductive Health.

The exploratory analysis included 2,537 men and 3,185 women, aged 50 years and older, who were a part of the English Longitudinal Study of Ageing. The mean age of study subjects was 64 years in men and 65 years in women, and most were either married or cohabitating.

Researchers collected data on sexual history using a self-administered questionnaire, which privately recorded the lifetime number of sexual partners among study participants. Data on other health outcomes, such as limiting long-standing illness and cancer diagnoses, were also self-reported.

Among male participants, 28.5% reported a history of 0-1 lifetime sexual partners, 29.0% had 2-4 partners, 20.2% had 5-9 partners, and 22.2% had 10 or more partners. The respective measures in women were 40.8%, 35.5%, 15.8%, and 7.8%.

Among all participants, a greater number of sexual partners was associated with being single, younger age, and being in the least or greatest brackets of household income.

The researchers found that, compared with having 0-1 sexual partners, a lifetime history of 10 or more sexual partners was associated with a greater risk of reported cancer in both men (odds ratio, 1.69; P = .047) and women (OR, 1.91; P = .038).

In addition, women with a lifetime history of 10 or more sexual partners had greater odds of reporting a limiting long-standing condition (OR, 1.64; P = .007).

“We observed no statistically significant association between number of lifetime sexual partners and self-rated health, CHD [coronary heart disease], or stroke in either sex, or with limiting long-standing illness in men,” the researchers explained.

They acknowledged that a key limitation of the study was the self-reported nature of the data. As a result, further studies are required to establish causality.

“Sexual history may be a relevant clinical indicator for cancer risk in older patients,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.
 

SOURCE: Grabovac I et al. BMJ Sex Reprod Health. 2020 Feb 13. doi: 10.1136/bmjsrh-2019-200352.