The role of a radiopaque peri-rectal hydrogel spacer in aiding accurate daily image-guidance for prostate stereotactic radiotherapy.

Introduction: Precise patient positioning with image guidance (IGRT) is essential for safe prostate radiotherapy. We present the first report of utilizing a CT-visible hydrogel spacer, used to decrease rectal radiation dose, as a surrogate fiducial marker to aid in daily IGRT with cone-beam CT (CBCT) in stereotactic radiotherapy (SABR) for prostate cancer. Materials and methods: Prior to CT simulation, patients underwent placement of three intraprostatic gold fiducial markers and radiopaque hydrogel spacer per standard practice. At treatment, after initial setup, a CBCT was acquired and fused to the planning CT based on 3-dimensional matching of the spacer. A second alignment was then performed based on the fiducial markers. The six directional shifts (three linear and three rotational) were recorded, and the differences compared. Results: 140 individual fractions across 41 consecutive patients were evaluated. Mean/median differences between hydrogel spacer-based and fiducial-based alignment in linear (vertical, longitudinal, lateral) and rotational (rotation, pitch, roll) shifts were 0.9/0.6mm, 0.8/0.5mm, and 0.6/0.4mm, and 0.38/0, 0.62/0, and 0.35/0 degrees, respectively. No difference was observed in 9.9%, 22.9%, and 22.14% of linear shifts, and 65.7%, 65%, and 66.4% rotational shifts, respectively. Significantly smaller differences were observed in the latter 70 fractions vs. the former, and results were consistent across evaluators. Conclusions: For precise daily IGRT with CBCT for prostate SABR, alignment using a radiopaque hydrogel spacer was highly comparable to intraprostatic fiducial markers. This represents the first report supporting an additional indication of IGRT for a CT-visible hydrogel spacer, to further enhance treatment accuracy and potentially obviate the need for the additional fiducial marker procedure.

Gender Gap in Leadership of Clinical Trials.

This cross-sectional study investigates representation of women as principal investigators of clinical trials by study phase, medical specialty, and representation of women trial participants.

Comparison of intravenous 5-Fluorouracil with Oral Capecitabine in the Treatment of Anal Squamous Cell Carcinoma Using Modern Radiation Techniques.

BACKGROUND: Anal squamous cell carcinoma (ASqCC) is a rare malignancy, traditionally treated with combined chemoradiation, with a continuous infusion of 5-fluorouracil (5-FU) and mitomycin C (MMC). Replacing intravenous (IV) 5-FU with oral capecitabine (oral fluoropyrimidine) has been reported as a non-inferior treatment option. However, these data are scarce, with variable results. OBJECTIVES: To examine the outcome of patients with ASqCC treated with either IV 5-FU or capecitabine concomitantly with radiation therapy. To compare treatment side effects, local recurrence, and general outcome. METHODS: We reviewed charts of patients who were diagnosed with stage I-III ASqCC. All participating patients received chemoradiation at the Assuta Medical Center between 2011 and 2019. RESULTS: In this study, 43 patients with ASqCC were eligible; 14 received 5-FU and 29 were treated with capecitabine. Basic characteristics were similar between the two groups, with longer follow-up for the 5-FU group. Six months following treatment, 100% (13/13 with adequate follow-up) of the 5-FU group had complete clinical response, compared to 84% in the capecitabine group (21/24), P = 0.143. The local recurrence incidence was higher in the 5-FU group at 23% (7, 10, 26 months following therapy, and none in the capecitabine group (P = 0.088). Although local and hematological toxicities were similar between groups, one patient receiving capecitabine died during chemoradiotherapy. CONCLUSIONS: Oral capecitabine demonstrated non-inferior disease control in ASqCC treated with chemoradiotherapy. We recommend oral capecitabine over continuous IV 5-FU in locally and locally advanced ASqCC. Close monitoring of side effects is required to reduce major toxicity.

Trends in Women's Leadership of Oncology Clinical Trials.

It has been widely reported that women are underrepresented in leadership positions within academic medicine. This study aimed to assess trends in women representation as principal investigators (PIs) in oncology clinical trials and to characterize trends in women's leadership in such trials conducted between 1999 and 2019. The gender of 39,240 PIs leading clinical trials was determined using the gender prediction software Genderize.io. In total, 11,516 (27.7%) women served as PIs. Over the past 20 years, an annual increase of 0.65% in women PIs was observed. Analysis by geographic distribution revealed higher women representation among PIs in North America and Europe compared to Asia. Industry-funded trials were associated with lower women PI representation than academic-funded trials (31.4% vs. 18.8%, p<0.001). Also, women PIs were found to be underrepresented in late-phase as compared to early-phase studies (27.9%, 25.7%, 21.6%, and 22.4% in phase I, II, III, and IV, respectively; Cochran-Armitage test for trend, p<0.001). Furthermore, an association was found between the PI's gender and enrolment of female subjects (50% vs. 43% female participants led by women vs men PIs, respectively, p<0.001). Taken together, while the gender gap in women's leadership in oncology trials has been steadily closing, prominent inequalities remain in non-Western countries, advanced study phases, industry-funded trials and appear to be linked to a gender gap in patient accrual. These observations can serve for the development of strategies to increase women's representation and to monitor progress toward gender equality in PIs of cancer clinical trials.

Radiation-Associated Secondary Malignancies in BRCA Mutation Carriers Treated for Breast Cancer.

PURPOSE: Radiation therapy (RT), a standard breast cancer (BC) treatment modality, is associated with a small increased risk of in-field second primary malignancy (SPM). SPM rates after RT in BRCA mutation carriers have rarely been reported. An elevated risk of SPM would affect the safety of breast conservation for early BC or prophylactic radiation as a method of prevention. We analyzed a population of BRCA carriers irradiated for BC to determine whether there is an elevated rate of SPM. METHODS AND MATERIALS: Patients with BC who were BRCA1 or BRCA2 carriers and were treated with breast and/or chest wall RT with or without regional lymph nodes between 1991 and 2012 at a single institution were retrospectively identified. Only those with ≥5 years of follow-up with adequate demographic, tumor, and radiation data were included. SPMs were recorded, and previously delivered RT doses to the organ and site of malignancy were determined. RESULTS: Two hundred thirty women, of whom 80% carried an Ashkenazi Jewish founder mutation, met entry criteria with 3-dimensional RT delivered to 266 breasts or chest walls, including regional nodes in 110 (41%). With a median follow-up of 10 years (range, 5-27; mean 11.4) comprising 3042 person-years, 6 SPMs developed, of which only 1 (papillary thyroid carcinoma) was within the radiation field (crude rate of 0.38% of irradiated breasts or chest walls), diagnosed 17 years after RT. This corresponds to an incidence of 0.32 per 1000 woman-years. The Kaplan-Meier estimate of 20-year freedom from a radiation-induced SPM is 99.5%. Calculated dose exposure to the out-of-field SPMs ranged from 0.1 to 1 Gy. No patient developed an in-field skin cancer or sarcoma. CONCLUSIONS: In this largest cohort of women treated with radiation therapy for BRCA-associated breast cancer, we identified no signal for an increased risk of radiation-induced SPMs compared with the general BC population, and the risk is extraordinarily small. Although larger cohorts and longer follow-up are needed, these results support the safety of RT in BRCA carriers.