Impact of Clinical Trial Design on Recruitment of Racial and Ethnic Minorities.

Knowledge related to how oncology treatment trial design influences enrollment of racial and ethnic minorities is limited. Rigorous identification of clinical trial design parameters that associate favorably with minority accrual provides educational opportunities for individuals interested in designing more representative treatment trials. We identified oncology trials with a minimum of 10 patients at an NCI-Designated Comprehensive Cancer Center from 2010 to 2021. We defined a study endpoint of racial and ethnic minority accrual greater than zero. Multivariable logistic regression was used to determine whether co-variables predicted our study endpoint. P-values of less than 0.05 were considered significant. A total of 352 cancer trials met eligibility criteria. These studies enrolled a total of 7981 patients with a total of 926 racial and ethnic minorities leading to a median enrollment of 10%. Trials open in community sites (yes versus no) were more likely to have a minority patient (OR, 2.21; 95% CI, 1.02-4.96) as well as pilot/phase I studies compared to phase II/III (OR, 3.19; 95% CI, 1.34-8.26). Trials incorporating immunotherapy (yes versus no) were less likely to have a minority patient (OR, 0.47; 95% CI, 0.23-0.94). Trials open in community sites as well as early phase treatment studies were more likely to accrue minority patients. However, studies including immunotherapy were less likely to accrue racial and ethnic minorities. Knowledge gained from our analysis may help individuals design oncology treatment trials that are representative of more diverse populations.

Neoadjuvant Reirradiation for Radiation Therapy-Associated Angiosarcoma of the Breast.

PURPOSE: Radiation-associated angiosarcoma of the breast (RAASB) is a rare side effect after breast radiation and has been associated with poor outcomes. At this time, there is no consensus regarding management of RAASB, and the role of reirradiation remains controversial. We present our modern institutional outcomes in managing RAASB with incorporation of neoadjuvant hyperfractionated reirradiation. METHODS AND MATERIALS: Patients identified were treated between 2016 and 2020 with inclusion of any histologically proven RAASB without metastatic disease at diagnosis, while excluding those with a history of radiation therapy outside of the breast/chest wall or other sarcoma histologies. Major wound complications were defined as requiring wound care and/or wound vacuum or return to the operating room for wound repair at any time after surgery. RESULTS: Eight patients were identified, and the median follow-up was 34 months. Median time to RAASB development was 8 years from initial radiation therapy. With respect to RAASB management, all underwent surgery and neoadjuvant reirradiation therapy, and all but 1 patient received taxol-based chemotherapy. At last follow-up, 7 patients remained free of disease, and 1 patient died with distant disease. With respect to acute toxicity after reirradiation, all patients developed at least acute grade 2 toxicities. Five of the 8 patients developed a major wound complication. CONCLUSIONS: Our institutional analysis suggests excellent local control and survival outcomes for RAASB treated with neoadjuvant hyperfractionated reirradiation, surgery, and taxol-based chemotherapy. However, major wound complications represent a major challenge with this approach. Future studies should consider how best to improve the therapeutic ratio while maintaining high rates of local control and survival.

Five Fraction Accelerated Partial Breast Irradiation Versus Intraoperative Radiation Therapy for Early-Stage Breast Cancer.

PURPOSE/OBJECTIVE(S): Accelerated partial breast irradiation (PBI) delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable clinical outcomes to whole breast irradiation with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were promising, concerns exist regarding long-term rates of local recurrence after IORT. We present a comparison of 5 fraction PBI versus IORT. MATERIALS/METHODS: We performed a retrospective review of 473 patients with early-stage breast cancer treated at a single institution from 2011 to 2021 with 258 receiving PBI and 215 receiving IORT. PBI patients received 30 Gy in 5 fractions delivered with IMRT. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface at surgery using the low-energy TARGIT technique. RESULTS: Mean age was 71 years old (IQR:67-74) for IORT patients and 67 years old (IQR:62-72) for PBI patients. Median follow up was 5.7 years (IQR:4.2-7.0) for IORT patients and 2.4 years (IQR:1.8-3.3) for PBI patients (P < .001). Recurrence at any time (locoregional and distant) was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving PBI. IORT was associated with reduced rates of locoregional relapse free survival at 5 years (93.6% vs. 99.4%, P = .05) with no difference in overall survival(92.8% vs. 95.1%, P = .99). CONCLUSION: Low-energy TARGIT IORT was associated with higher rates of locoregional recurrence compared to PBI. These outcomes, consistent with other series and current guidelines, suggest a limited role for low-energy IORT as monotherapy.

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: Updated Outcomes from a Single-Institution Experience.

BACKGROUND: Increasingly, data have supported the use of partial-breast irradiation (PBI) for low-risk patients after breast-conserving surgery, with techniques allowing for completion of treatment in 1-3 weeks. Intraoperative radiation therapy (IORT) is an alternative to PBI. Our institution had used low-energy photon IORT (TARGIT) for more than a decade. The initial results demonstrated a 2% local recurrence rate with a short follow-up period of 2 years. This report presents updated outcomes during with 5-year follow-up. METHODS: A review of an institutional review board (IRB)-approved institutional registry was performed. The review identified 215 patients with early-stage breast cancer (stages 0-IIA) who received IORT. At the time of surgery, IORT was delivered with 20 Gy in a single fraction, with 5.1% (n = 11) of patients receiving additional whole-breast irradiation (WBI). RESULTS: The mean age at diagnosis was 71 years (range, 49-98 years), and the median follow-up was 5.7 years (interquartile range [IQR], 4.2-7.0 years). Of the 215 patients, 2.8% (n = 6) had ductal carcinoma in situ (DCIS), 90.7% (n = 195) had T1 disease, and 6.5% (n = 14) had T2 disease. Endocrine therapy was prescribed for 79% and chemotherapy for 1.4% of the patients. The 5-year rates were 5.3% for local recurrence, 6.4% for locoregional recurrence, and 2.7% for distant metastases. At 5 years, 93% of the patients were alive. CONCLUSIONS: The 5-year outcomes with TARGIT IORT demonstrated high rates of local recurrence, exceeding those seen with alternative modern approaches. The local recurrence outcomes with IORT are more consistent with studies omitting radiation following breast-conserving surgery, using endocrine therapy alone. Consistent with current guidelines and previous data, TARGIT IORT should not be used as monotherapy outside prospective clinical trials.

Factors associated with matching into research-focused dermatology residency programs.

Although dermatology is one of the most competitive specialties to match into, there is limited transparency in the residency match process. In this retrospective cohort study of 2234 allopathic medical graduates, we identify applicant characteristics associated with matching into research oriented dermatology programs. Many of the statistically significant variables in our study, including PhD/MD status, graduating from a Top-25 NIH funded medical school, increasing total number of pre-residency publications (PRPs), and increasing number of high-impact PRPs, correlate with future academic employment. Although literature shows an association between an increasing number of first author PRPs and future academic employment, we did not find number of first or last author PRPs to be predictive of matching into a research oriented residency program. A more comprehensive evaluation of an applicant's research output, considering both the final products of an applicant's research endeavors and an applicant's role in various projects, may better approximate an applicant's commitment to academics.

Delivery of Adjuvant Radiation in 5 Days or Less After Lumpectomy for Breast Cancer: A Systematic Review.

PURPOSE: Recent data have been published supporting the application of ultrashort radiation therapy (RT) regimens for women with early stage breast cancer after breast conserving surgery. What has remained controversial is whether and how to apply accelerated whole breast irradiation (AWBI) or accelerated partial breast irradiation (APBI) approaches in these patients, as well as the consideration of intraoperative RT (IORT). METHODS AND MATERIALS: We performed a systematic review of the literature searching for randomized and prospective data published evaluating ultrashort RT delivered in 5 days or less with APBI, AWBI, or IORT. RESULTS: We identified 2 randomized studies evaluating AWBI (n = 5,011 patients) with 5 to 10 year follow-up, which supported the use of ultrashort course AWBI compared with hypofractionated whole breast irradiation (WBI). We identified 7 randomized trials evaluating APBI (compared with WBI) in 5 days or less (n = 8528) with numerous (n = 55) prospective studies as well, with the data supporting short course APBI. Finally, we identified 2 randomized trials evaluating IORT; however, both trials demonstrated elevated rates of recurrence with IORT compared with WBI. CONCLUSIONS: The current body of data available for ultrashort adjuvant RT regimens delivered in 5 days or less after breast conserving surgery overwhelmingly support their utilization. Although data for both exist, APBI regimens have, by far, greater numbers of patients and longer follow-up compared with AWBI. Also, given increased rates of recurrence seen with IORT with long-term follow-up, this should not be considered a standard approach at this time.

Trends of Research Output of Allopathic Medical Students Matching Into Dermatology, 2007-2018.

IMPORTANCE: According to the National Residency Matching Program's biennial Charting Outcomes in the Match (NRMP ChOM) reports, the mean number of research items of matched allopathic dermatology applicants has nearly tripled since 2007, rising from 5.7 to 14.7. Research items are self-reported by applicants and serve as an approximation of research output. Because the NRMP research items field is unverified and reported as an aggregate of several different research pursuits, it may not be an accurate representation of applicant research output. OBJECTIVE: To determine if the rise in NRMP-reported data is associated with a rise in verifiable, indexed publications from matched allopathic dermatology applicants from 2007 to 2018. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study including a bibliometric analysis on accepted applicant research output among 2234 matched allopathic dermatology applicants, with a total of 6229 publications, in dermatology residency programs for the years 2007, 2009, 2011, 2014, 2016, and 2018. MAIN OUTCOME AND MEASURES: The primary outcomes were the mean number of peer-reviewed indexed publications and mean number of NRMP ChOM research items. Secondary outcomes assessed the quality of indexed publications by analyzing article type and journal of publication. RESULTS: From 2007 to 2018, the mean number of indexed publications per matched dermatology applicant increased from 1.6 to 4.7 (203% increase). Indexed publications consistently compose a minority of NRMP ChOM research items (28.8% across the 6 years of the study). Nonindexed research items increased at more than double the rate of indexed publications. Bibliometric analysis showed that all other types of publications are increasing at a rate of 6 to 9 times that of basic science publications, dermatology-related publications increased at 5 times the rate of non-dermatology publications, and publications in lower-impact factor dermatology journals increased at 4 times the rate of publications in higher-impact factor dermatology journals. CONCLUSIONS AND RELEVANCE: This cross-sectional study provides data on the research output of matched dermatology applicants. Indexed publications compose a minority of NRMP research items. Medical student self-reports of research output may emphasize research quantity over quality.

Outcomes with intraoperative radiation therapy for early-stage breast cancer.

Adjuvant radiation therapy has been associated with improved local control following breast-conserving surgery. Traditionally, treatment has been delivered with whole breast irradiation over 3-6 weeks or partial breast irradiation over 1-3 weeks. However, intraoperative radiation therapy (IORT) has emerged as a technique that delivers a single dose of radiotherapy at the time of surgery for early-stage breast cancers. We report initial outcomes and acute toxicities with intraoperative radiation from a single institution. Patients with DCIS or Stage I-II breast cancer who underwent lumpectomy and sentinel lymph node biopsy (nodal sampling excluded in some cases) were included. All patients in this analysis were treated with IORT as at the time of surgery, 20 Gy in 1 fraction with 50 kV x-ray. Patients were treated at a single institution between 2011 and 2019. Follow-up was per standard institutional protocol. Two hundred and one patients were included in the analysis, with a median follow-up of 23 months (range: 0-73 months). Median age was 71 years old. Overall, 4 (2.0%) patients had DCIS, 186 (92.5%) patients had Stage 1 disease, and 11 patients had (5.5%) Stage 2 disease. All patients were estrogen receptor-positive, 175 (87.9%) progesterone receptor-positive, and 1 (0.5%) HER2 amplified. The crude rate of local recurrence was 2.0% (n = 4) and distant metastasis rate was 0.5% (n = 1). The rate of arm lymphedema was 0.5% (n = 1) and chronic telangiectasia rate was 1.1% (n = 2). Intraoperative radiation therapy, in a cohort of low-risk patients, demonstrated low rates of recurrence and reproducibility in a multi-disciplinary setting. Further follow-up, analysis of patient satisfaction and cosmesis, and comparison to whole breast irradiation and partial breast techniques is necessary in order to further validate these findings.

Initial outcomes with image-guided partial breast irradiation delivered with intensity-modulated radiation therapy.

Patients were treated at a single institution to a dose of 30 Gy in five fractions delivered every other day using image-guided intensity modulated radiation therapy (IMRT) partial breast irradiation. A total of 34 patients were treated with a median follow-up of 4.6 months. The rate of acute Grade 1 dermatitis was 23.5% (n = 8), and Grade 1 fatigue was 17.6% (n = 6), with no Grade 2 or higher acute toxicities. The rate of chronic Grade 1 dermatitis was 25.0% (n = 6), Grade 1 fat necrosis 4.2% (n=1), with no patients demonstrating other chronic toxicities. Image-guided APBI delivered with IMRT is associated with low rates of acute and chronic toxicity though additional follow-up is warranted.