Breast Cancer

SAN ANTONIO – Swapping trastuzumab out for the drug-antibody conjugate trastuzumab emtansine (T-DM1; Kadcyla) as adjuvant therapy resulted in a halving in the risk of invasive disease or death in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy, including trastuzumab.

For the primary endpoint in the KATHERINE trial of invasive disease-free survival – defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – T-DM1 was associated with a hazard ratio of 0.50 (P less than .001).

The 3-year invasive disease-free survival rate for 743 patients treated with T-DMI 1 was 88.3%, compared with 77% for 743 patients treated with trastuzumab, reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond, at the San Antonio Breast Cancer Symposium.

In a video interview, Dr. Geyer discussed results of KATHERINE, which suggest that T-DM1 should be considered as a new standard of care in this patient population.

Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene.

SAN ANTONIO – Swapping trastuzumab out for the drug-antibody conjugate trastuzumab emtansine (T-DM1; Kadcyla) as adjuvant therapy resulted in a halving in the risk of invasive disease or death in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy, including trastuzumab.

For the primary endpoint in the KATHERINE trial of invasive disease-free survival – defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – T-DM1 was associated with a hazard ratio of 0.50 (P less than .001).

The 3-year invasive disease-free survival rate for 743 patients treated with T-DMI 1 was 88.3%, compared with 77% for 743 patients treated with trastuzumab, reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond, at the San Antonio Breast Cancer Symposium.

In a video interview, Dr. Geyer discussed results of KATHERINE, which suggest that T-DM1 should be considered as a new standard of care in this patient population.

Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene.

SAN ANTONIO – Swapping trastuzumab out for the drug-antibody conjugate trastuzumab emtansine (T-DM1; Kadcyla) as adjuvant therapy resulted in a halving in the risk of invasive disease or death in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy, including trastuzumab.

For the primary endpoint in the KATHERINE trial of invasive disease-free survival – defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – T-DM1 was associated with a hazard ratio of 0.50 (P less than .001).

The 3-year invasive disease-free survival rate for 743 patients treated with T-DMI 1 was 88.3%, compared with 77% for 743 patients treated with trastuzumab, reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond, at the San Antonio Breast Cancer Symposium.

In a video interview, Dr. Geyer discussed results of KATHERINE, which suggest that T-DM1 should be considered as a new standard of care in this patient population.

Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene.

While the majority of the presentations at this year’s San Antonio Breast Cancer Symposium, to be held Dec. 4-8, will focus on treatments, a few will focus on the treatment decisions. One such presentation will report on the findings of the phase 3 STIC CTC trial. This trial seeks to determine if circulating tumor cells (CTC) could serve as a tool to choose between first-line hormone therapy and chemotherapy for ER-positive HER2-negative metastatic breast cancer.

In the standard arm of the trial, treatment was decided by clinicians, taking into account the criteria usually used in this setting. In the CTC arm, the type of treatment was decided by CTC count: Hormone-therapy was chosen if there were fewer than 5 CTC/7.5 mL (CellSearch technique) or chemotherapy if there were 5 or more CTC/7.5 mL. The main objective was to demonstrate the noninferiority of the CTC-based strategy for progression-free survival. The secondary clinical objectives of the French trial were to compare toxicity, quality of life, and overall survival between the two arms. The cost per progression-free life-years gained will be compared in the two arms, as well.

The results and analysis of STIC CTC will be presented by Francois-Clement Bidard, MD, PhD, of Institut Curie, Paris, and the University of Versailles (France), on Thursday, Dec. 6 at 11 a.m. CST.




 

While the majority of the presentations at this year’s San Antonio Breast Cancer Symposium, to be held Dec. 4-8, will focus on treatments, a few will focus on the treatment decisions. One such presentation will report on the findings of the phase 3 STIC CTC trial. This trial seeks to determine if circulating tumor cells (CTC) could serve as a tool to choose between first-line hormone therapy and chemotherapy for ER-positive HER2-negative metastatic breast cancer.

In the standard arm of the trial, treatment was decided by clinicians, taking into account the criteria usually used in this setting. In the CTC arm, the type of treatment was decided by CTC count: Hormone-therapy was chosen if there were fewer than 5 CTC/7.5 mL (CellSearch technique) or chemotherapy if there were 5 or more CTC/7.5 mL. The main objective was to demonstrate the noninferiority of the CTC-based strategy for progression-free survival. The secondary clinical objectives of the French trial were to compare toxicity, quality of life, and overall survival between the two arms. The cost per progression-free life-years gained will be compared in the two arms, as well.

The results and analysis of STIC CTC will be presented by Francois-Clement Bidard, MD, PhD, of Institut Curie, Paris, and the University of Versailles (France), on Thursday, Dec. 6 at 11 a.m. CST.




 

While the majority of the presentations at this year’s San Antonio Breast Cancer Symposium, to be held Dec. 4-8, will focus on treatments, a few will focus on the treatment decisions. One such presentation will report on the findings of the phase 3 STIC CTC trial. This trial seeks to determine if circulating tumor cells (CTC) could serve as a tool to choose between first-line hormone therapy and chemotherapy for ER-positive HER2-negative metastatic breast cancer.

In the standard arm of the trial, treatment was decided by clinicians, taking into account the criteria usually used in this setting. In the CTC arm, the type of treatment was decided by CTC count: Hormone-therapy was chosen if there were fewer than 5 CTC/7.5 mL (CellSearch technique) or chemotherapy if there were 5 or more CTC/7.5 mL. The main objective was to demonstrate the noninferiority of the CTC-based strategy for progression-free survival. The secondary clinical objectives of the French trial were to compare toxicity, quality of life, and overall survival between the two arms. The cost per progression-free life-years gained will be compared in the two arms, as well.

The results and analysis of STIC CTC will be presented by Francois-Clement Bidard, MD, PhD, of Institut Curie, Paris, and the University of Versailles (France), on Thursday, Dec. 6 at 11 a.m. CST.




 

Revisiting the old and enhancing with the new might describe the range of results in HER2+ breast cancer studies to be presented at the upcoming San Antonio Breast Cancer Symposium, which will be held Dec. 4-8 in San Antonio.

Since 2005, 12 months of trastuzumab added to chemotherapy alone has been the standard of care in patients with HER2-positive early breast cancer. PHARE (Protocol for Herceptin as Adjuvant Therapy With Reduced Exposure) was the first trial evaluating a reduced schedule of trastuzumab, a noninferiority trial comparing 6 with 12 months of adjuvant trastuzumab. Results published in 2013 in Lancet Oncology demonstrated a failure to prove that 6 months of treatment was non-inferior to 12 months. The final analysis of PHARE will be presented on Wednesday at SABCS 2018 by Xavier Pivot, MD, PhD, of Paul-Strauss Cancer Centre, Université de Strasbourg (France).

In a more recent study, trastuzumab emtansine (T-DM1) was pitted against trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab. The primary results of the phase 3 study (KATHERINE) will be presented by Charles E. Geyer, MD, of Virginia Commonwealth University and the Massey Cancer Center, both in Richmond.

As for the new, KATE2 is a phase 2 randomized trial evaluating the addition of checkpoint inhibitor atezolizumab to T-DM1 for patients with locally advanced or metastatic HER2-positive breast cancer who received prior trastuzumab and taxane-based therapy. Results will be presented by Leisha A. Emens, MD, PhD, professor at the University of Pittsburgh and director of translational immunotherapy for the Women’s Cancer Research Center there.




 

Revisiting the old and enhancing with the new might describe the range of results in HER2+ breast cancer studies to be presented at the upcoming San Antonio Breast Cancer Symposium, which will be held Dec. 4-8 in San Antonio.

Since 2005, 12 months of trastuzumab added to chemotherapy alone has been the standard of care in patients with HER2-positive early breast cancer. PHARE (Protocol for Herceptin as Adjuvant Therapy With Reduced Exposure) was the first trial evaluating a reduced schedule of trastuzumab, a noninferiority trial comparing 6 with 12 months of adjuvant trastuzumab. Results published in 2013 in Lancet Oncology demonstrated a failure to prove that 6 months of treatment was non-inferior to 12 months. The final analysis of PHARE will be presented on Wednesday at SABCS 2018 by Xavier Pivot, MD, PhD, of Paul-Strauss Cancer Centre, Université de Strasbourg (France).

In a more recent study, trastuzumab emtansine (T-DM1) was pitted against trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab. The primary results of the phase 3 study (KATHERINE) will be presented by Charles E. Geyer, MD, of Virginia Commonwealth University and the Massey Cancer Center, both in Richmond.

As for the new, KATE2 is a phase 2 randomized trial evaluating the addition of checkpoint inhibitor atezolizumab to T-DM1 for patients with locally advanced or metastatic HER2-positive breast cancer who received prior trastuzumab and taxane-based therapy. Results will be presented by Leisha A. Emens, MD, PhD, professor at the University of Pittsburgh and director of translational immunotherapy for the Women’s Cancer Research Center there.




 

Revisiting the old and enhancing with the new might describe the range of results in HER2+ breast cancer studies to be presented at the upcoming San Antonio Breast Cancer Symposium, which will be held Dec. 4-8 in San Antonio.

Since 2005, 12 months of trastuzumab added to chemotherapy alone has been the standard of care in patients with HER2-positive early breast cancer. PHARE (Protocol for Herceptin as Adjuvant Therapy With Reduced Exposure) was the first trial evaluating a reduced schedule of trastuzumab, a noninferiority trial comparing 6 with 12 months of adjuvant trastuzumab. Results published in 2013 in Lancet Oncology demonstrated a failure to prove that 6 months of treatment was non-inferior to 12 months. The final analysis of PHARE will be presented on Wednesday at SABCS 2018 by Xavier Pivot, MD, PhD, of Paul-Strauss Cancer Centre, Université de Strasbourg (France).

In a more recent study, trastuzumab emtansine (T-DM1) was pitted against trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab. The primary results of the phase 3 study (KATHERINE) will be presented by Charles E. Geyer, MD, of Virginia Commonwealth University and the Massey Cancer Center, both in Richmond.

As for the new, KATE2 is a phase 2 randomized trial evaluating the addition of checkpoint inhibitor atezolizumab to T-DM1 for patients with locally advanced or metastatic HER2-positive breast cancer who received prior trastuzumab and taxane-based therapy. Results will be presented by Leisha A. Emens, MD, PhD, professor at the University of Pittsburgh and director of translational immunotherapy for the Women’s Cancer Research Center there.




 

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.

In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.

“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.

Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.

The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.

The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.

The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.

Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.

One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.

Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.

“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”

The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”

However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.

“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.

The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.

SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
 

Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.

In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.

“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.

Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.

The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.

The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.

The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.

Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.

One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.

Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.

“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”

The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”

However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.

“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.

The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.

SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
 

Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.

In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.

“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.

Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.

The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.

The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.

The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.

Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.

One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.

Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.

“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”

The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”

However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.

“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.

The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.

SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
 

BOSTON – For women undergoing nipple-sparing mastectomy, advanced age and neoadjuvant chemotherapy are not associated with increased postoperative complications, results of recent studies suggest.

Andrew D. Bowser/MDedge News

The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.

“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.

The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.

“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.

Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.

The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.

Andrew D. Bowser/MDedge News

SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018

BOSTON – For women undergoing nipple-sparing mastectomy, advanced age and neoadjuvant chemotherapy are not associated with increased postoperative complications, results of recent studies suggest.

Andrew D. Bowser/MDedge News

The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.

“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.

The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.

“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.

Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.

The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.

Andrew D. Bowser/MDedge News

SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018

BOSTON – For women undergoing nipple-sparing mastectomy, advanced age and neoadjuvant chemotherapy are not associated with increased postoperative complications, results of recent studies suggest.

Andrew D. Bowser/MDedge News

The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.

“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.

The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.

“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.

Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.

The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.

Andrew D. Bowser/MDedge News

SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018

The Food and Drug Administration has approved a second biosimilar to pegfilgrastim (Neulasta) to decrease the chance of infection in patients with nonmyeloid cancer who are receiving myelosuppressive chemotherapy and are at risk of febrile neutropenia.

Approval of pegfilgrastim-cbqv, previously known as CHS-1701, was based on analyses establishing biosimilarity, including pharmacokinetic, pharmacodynamic, and immunogenicity studies. Clinical trial results were presented at the 2017 ASCO Annual Meeting.

The most common adverse reactions with pegfilgrastim-cbqv are bone pain and pain in extremities.

The FDA approved the first pegfilgrastim biosimilar, pegfilgrastim-jmdb (Fulphila) in June.

Pegfilgrastim-cbqv will be marketed as Udenyca by Coherus BioSciences.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” Barbara Finck, MD, chief medical officer of Coherus BioSciences, said in a press release.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

Coherus BioSciences plans to provide details about pricing and the launch of pegfilgrastim-cbqv during an earnings call on Nov. 8.

The Food and Drug Administration has approved a second biosimilar to pegfilgrastim (Neulasta) to decrease the chance of infection in patients with nonmyeloid cancer who are receiving myelosuppressive chemotherapy and are at risk of febrile neutropenia.

Approval of pegfilgrastim-cbqv, previously known as CHS-1701, was based on analyses establishing biosimilarity, including pharmacokinetic, pharmacodynamic, and immunogenicity studies. Clinical trial results were presented at the 2017 ASCO Annual Meeting.

The most common adverse reactions with pegfilgrastim-cbqv are bone pain and pain in extremities.

The FDA approved the first pegfilgrastim biosimilar, pegfilgrastim-jmdb (Fulphila) in June.

Pegfilgrastim-cbqv will be marketed as Udenyca by Coherus BioSciences.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” Barbara Finck, MD, chief medical officer of Coherus BioSciences, said in a press release.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

Coherus BioSciences plans to provide details about pricing and the launch of pegfilgrastim-cbqv during an earnings call on Nov. 8.

The Food and Drug Administration has approved a second biosimilar to pegfilgrastim (Neulasta) to decrease the chance of infection in patients with nonmyeloid cancer who are receiving myelosuppressive chemotherapy and are at risk of febrile neutropenia.

Approval of pegfilgrastim-cbqv, previously known as CHS-1701, was based on analyses establishing biosimilarity, including pharmacokinetic, pharmacodynamic, and immunogenicity studies. Clinical trial results were presented at the 2017 ASCO Annual Meeting.

The most common adverse reactions with pegfilgrastim-cbqv are bone pain and pain in extremities.

The FDA approved the first pegfilgrastim biosimilar, pegfilgrastim-jmdb (Fulphila) in June.

Pegfilgrastim-cbqv will be marketed as Udenyca by Coherus BioSciences.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” Barbara Finck, MD, chief medical officer of Coherus BioSciences, said in a press release.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

Coherus BioSciences plans to provide details about pricing and the launch of pegfilgrastim-cbqv during an earnings call on Nov. 8.

American Indian/Alaska Native (AI/AN) women face the same barriers as all low-income minority women face in accessing preventive care, but according to researchers from Rutgers University in New Jersey and University of Arizona, they also face “unique challenges and circumstances.” The researchers reviewed 18 studies to find out more about facilitators of, and barriers to, breast cancer screening.

Low-income women are more likely to be diagnosed at a later stage and to die of breast cancer, one study found. The factors are well known: cost, lack of a usual source of care, lack of insurance, distance from a facility, and lack of transportation.

However, the researchers of the meta-analysis say, “compounding these barriers,” AI/AN women expressed the belief that preventive care is not a priority, especially when it is their own preventive care. Moreover, some barriers that might be unique to the AI/AN women included concern with “manifest destiny”: the assumption that thinking or talking about breast cancer can cause it, for instance. One study examined “traditionality” and found women who could be seen as more traditional, defining themselves as living an “Indian way of life,” were less likely to be current with screening. Other women expressed mistrust in the technology of screening or spoke about perception of discrimination in the health care system.

Although this population has access to screening through IHS facilities, women who also have insurance (typically Medicaid) are more likely to get screened. Women in rural areas who lived near an IHS facility were more likely than were urban women to get mammograms. The researchers suggest this could be because rural women are more likely to be isolated from other mammogram facilities. Too, the IHS is “chronically underfunded,” the researchers note, likely a cause of the health disparities and limiting scope of services.

Their review made clear that efforts to intervene with AI/AN women to increase breast cancer screening have been limited, the researchers say. The intervention studies they reviewed “were not successful in improving screening rates or adherence.” The qualitative studies, on the other hand, suggest that women may be more responsive to locally supportive, targeted, and culturally appropriate interventions that respect traditionality yet encourage trust in the medical system.

American Indian/Alaska Native (AI/AN) women face the same barriers as all low-income minority women face in accessing preventive care, but according to researchers from Rutgers University in New Jersey and University of Arizona, they also face “unique challenges and circumstances.” The researchers reviewed 18 studies to find out more about facilitators of, and barriers to, breast cancer screening.

Low-income women are more likely to be diagnosed at a later stage and to die of breast cancer, one study found. The factors are well known: cost, lack of a usual source of care, lack of insurance, distance from a facility, and lack of transportation.

However, the researchers of the meta-analysis say, “compounding these barriers,” AI/AN women expressed the belief that preventive care is not a priority, especially when it is their own preventive care. Moreover, some barriers that might be unique to the AI/AN women included concern with “manifest destiny”: the assumption that thinking or talking about breast cancer can cause it, for instance. One study examined “traditionality” and found women who could be seen as more traditional, defining themselves as living an “Indian way of life,” were less likely to be current with screening. Other women expressed mistrust in the technology of screening or spoke about perception of discrimination in the health care system.

Although this population has access to screening through IHS facilities, women who also have insurance (typically Medicaid) are more likely to get screened. Women in rural areas who lived near an IHS facility were more likely than were urban women to get mammograms. The researchers suggest this could be because rural women are more likely to be isolated from other mammogram facilities. Too, the IHS is “chronically underfunded,” the researchers note, likely a cause of the health disparities and limiting scope of services.

Their review made clear that efforts to intervene with AI/AN women to increase breast cancer screening have been limited, the researchers say. The intervention studies they reviewed “were not successful in improving screening rates or adherence.” The qualitative studies, on the other hand, suggest that women may be more responsive to locally supportive, targeted, and culturally appropriate interventions that respect traditionality yet encourage trust in the medical system.

American Indian/Alaska Native (AI/AN) women face the same barriers as all low-income minority women face in accessing preventive care, but according to researchers from Rutgers University in New Jersey and University of Arizona, they also face “unique challenges and circumstances.” The researchers reviewed 18 studies to find out more about facilitators of, and barriers to, breast cancer screening.

Low-income women are more likely to be diagnosed at a later stage and to die of breast cancer, one study found. The factors are well known: cost, lack of a usual source of care, lack of insurance, distance from a facility, and lack of transportation.

However, the researchers of the meta-analysis say, “compounding these barriers,” AI/AN women expressed the belief that preventive care is not a priority, especially when it is their own preventive care. Moreover, some barriers that might be unique to the AI/AN women included concern with “manifest destiny”: the assumption that thinking or talking about breast cancer can cause it, for instance. One study examined “traditionality” and found women who could be seen as more traditional, defining themselves as living an “Indian way of life,” were less likely to be current with screening. Other women expressed mistrust in the technology of screening or spoke about perception of discrimination in the health care system.

Although this population has access to screening through IHS facilities, women who also have insurance (typically Medicaid) are more likely to get screened. Women in rural areas who lived near an IHS facility were more likely than were urban women to get mammograms. The researchers suggest this could be because rural women are more likely to be isolated from other mammogram facilities. Too, the IHS is “chronically underfunded,” the researchers note, likely a cause of the health disparities and limiting scope of services.

Their review made clear that efforts to intervene with AI/AN women to increase breast cancer screening have been limited, the researchers say. The intervention studies they reviewed “were not successful in improving screening rates or adherence.” The qualitative studies, on the other hand, suggest that women may be more responsive to locally supportive, targeted, and culturally appropriate interventions that respect traditionality yet encourage trust in the medical system.

Moderate application of topical therapies directly prior to radiotherapy (RT) treatment sessions may be safe and might exhibit minimal effects on delivered treatment dose, investigators report.

The researchers found that although avoiding topical agents prior to radiation treatments was widespread, preclinical data indicate that there is no difference in the radiation dose on the skin with or without a 1- to 2-mm-thick layer of topical agent.

In an online survey, which queried 133 patients and 108 clinicians in relation to existing practices surrounding topical agent use, 83.4% of patients were informed to discontinue application of topical therapies directly before RT treatment sessions. In addition, 54.1% were told to clean and remove any enduring topical agents before treatment. Among clinicians, 91.4% reported to have received or given advice to stop application of topicals before obtaining RT treatment, Brian C. Baumann, MD, and his associates reported in JAMA Oncology.

However, in a preclinical study using a mouse- and tissue-equivalent phantom model to determine the dosimetric effects of concomitant topical agent use with daily RT treatments, Dr. Baumann, of Washington University in St. Louis, and his colleagues determined that when a topical agent was given prior to RT at a thickness below 2 mm, no changes were seen in radiation treatment dose, irrespective of depth, photon and electron energy level, or beam angle.

However, a proportionally thicker covering (3 mm or more) caused a bolus effect at the surface, which resulted in electron dose increases of 2%-5%, and photon increases of 15%-35%, when compared with controls.

Investigators measured radiation dose and photon beam intensity at various surface depths after applying two commonly used topical therapies, a healing ointment of 41% petrolatum or silver sulfadiazine cream 1%. The agents were administered using a thick (1-2 mm) application and proportionally thicker (3 mm or more) covering.

“Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence,” the investigators wrote. However, the findings do suggest that “applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided,” they said.

The authors reported that the study was funded by development funds from the University of Pennsylvania, Philadelphia. One of the coauthors, James M. Metz, MD, disclosed service on advisory boards for Ion Beam Applications and Varian Medical Systems for proton therapy; however, these roles were not relevant to this study.
 

SOURCE: Baumann BC et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4292.

Moderate application of topical therapies directly prior to radiotherapy (RT) treatment sessions may be safe and might exhibit minimal effects on delivered treatment dose, investigators report.

The researchers found that although avoiding topical agents prior to radiation treatments was widespread, preclinical data indicate that there is no difference in the radiation dose on the skin with or without a 1- to 2-mm-thick layer of topical agent.

In an online survey, which queried 133 patients and 108 clinicians in relation to existing practices surrounding topical agent use, 83.4% of patients were informed to discontinue application of topical therapies directly before RT treatment sessions. In addition, 54.1% were told to clean and remove any enduring topical agents before treatment. Among clinicians, 91.4% reported to have received or given advice to stop application of topicals before obtaining RT treatment, Brian C. Baumann, MD, and his associates reported in JAMA Oncology.

However, in a preclinical study using a mouse- and tissue-equivalent phantom model to determine the dosimetric effects of concomitant topical agent use with daily RT treatments, Dr. Baumann, of Washington University in St. Louis, and his colleagues determined that when a topical agent was given prior to RT at a thickness below 2 mm, no changes were seen in radiation treatment dose, irrespective of depth, photon and electron energy level, or beam angle.

However, a proportionally thicker covering (3 mm or more) caused a bolus effect at the surface, which resulted in electron dose increases of 2%-5%, and photon increases of 15%-35%, when compared with controls.

Investigators measured radiation dose and photon beam intensity at various surface depths after applying two commonly used topical therapies, a healing ointment of 41% petrolatum or silver sulfadiazine cream 1%. The agents were administered using a thick (1-2 mm) application and proportionally thicker (3 mm or more) covering.

“Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence,” the investigators wrote. However, the findings do suggest that “applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided,” they said.

The authors reported that the study was funded by development funds from the University of Pennsylvania, Philadelphia. One of the coauthors, James M. Metz, MD, disclosed service on advisory boards for Ion Beam Applications and Varian Medical Systems for proton therapy; however, these roles were not relevant to this study.
 

SOURCE: Baumann BC et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4292.

Moderate application of topical therapies directly prior to radiotherapy (RT) treatment sessions may be safe and might exhibit minimal effects on delivered treatment dose, investigators report.

The researchers found that although avoiding topical agents prior to radiation treatments was widespread, preclinical data indicate that there is no difference in the radiation dose on the skin with or without a 1- to 2-mm-thick layer of topical agent.

In an online survey, which queried 133 patients and 108 clinicians in relation to existing practices surrounding topical agent use, 83.4% of patients were informed to discontinue application of topical therapies directly before RT treatment sessions. In addition, 54.1% were told to clean and remove any enduring topical agents before treatment. Among clinicians, 91.4% reported to have received or given advice to stop application of topicals before obtaining RT treatment, Brian C. Baumann, MD, and his associates reported in JAMA Oncology.

However, in a preclinical study using a mouse- and tissue-equivalent phantom model to determine the dosimetric effects of concomitant topical agent use with daily RT treatments, Dr. Baumann, of Washington University in St. Louis, and his colleagues determined that when a topical agent was given prior to RT at a thickness below 2 mm, no changes were seen in radiation treatment dose, irrespective of depth, photon and electron energy level, or beam angle.

However, a proportionally thicker covering (3 mm or more) caused a bolus effect at the surface, which resulted in electron dose increases of 2%-5%, and photon increases of 15%-35%, when compared with controls.

Investigators measured radiation dose and photon beam intensity at various surface depths after applying two commonly used topical therapies, a healing ointment of 41% petrolatum or silver sulfadiazine cream 1%. The agents were administered using a thick (1-2 mm) application and proportionally thicker (3 mm or more) covering.

“Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence,” the investigators wrote. However, the findings do suggest that “applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided,” they said.

The authors reported that the study was funded by development funds from the University of Pennsylvania, Philadelphia. One of the coauthors, James M. Metz, MD, disclosed service on advisory boards for Ion Beam Applications and Varian Medical Systems for proton therapy; however, these roles were not relevant to this study.
 

SOURCE: Baumann BC et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4292.