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Purpose Brachytherapy is an essential technique to deliver radiation therapy and is involved in the treatment of multiple disease sites as monotherapy or as an adjunct to external beam radiation therapy. With a growing focus on the cost and value of cancer treatments as well new payment models, it is essential that standardized quality measures and metrics exist to allow for straightforward assessment of brachytherapy quality and for the development of clinically significant and relevant clinical data elements. We present the American Brachytherapy Society consensus statement on quality measures and metrics for brachytherapy as well as suggested clinical data elements. Methods and Materials Members of the American Brachytherapy Society with expertise in disease site specific brachytherapy created a consensus statement based on a literature review and clinical experience. Results Key quality measures (ex. workup, clinical indications), dosimetric metrics, and clinical data elements for brachytherapy were evaluated for each modality including breast cancer, cervical cancer, endometrial cancer, prostate cancer, keratinocyte carcinoma, soft tissue sarcoma, and uveal melanoma. Conclusions This consensus statement provides standardized quality measures and dosimetric quality metrics as well as clinical data elements for each disease site to allow for standardized assessments of brachytherapy quality. Moving forward, a similar paradigm can be considered for external beam radiation therapy as well, providing comprehensive radiation therapy quality measures, metrics, and clinical data elements that can be incorporated into new payment models.

purpose This practice parameter aims to detail the processes, qualifications of personnel, patient selection, equipment, patient and personnel safety, documentation, and quality control and improvement necessary for an HDR brachytherapy program. Methods and Materials This practice parameter was revised collaboratively by the American College of Radiology (ACR), the American Brachytherapy Society (ABS), and the American Society for Radiation Oncology (ASTRO). Results Brachytherapy is a radiotherapeutic modality in which radionuclide or electronic sources are used to deliver a radiation dose at a distance of up to a few centimeters by surface, intracavitary, intraluminal, or interstitial application. Brachytherapy alone or combined with external beam radiotherapy plays an important role in the management and treatment of patients with cancer. High-dose-rate (HDR) brachytherapy uses radionuclides, such as iridium-192, at dose rates of ≥12 Gy/hr to a designated target point or volume, and it is an important treatment for a variety of malignant and benign conditions. Its use allows for application of high doses of radiation to defined target volumes with relative sparing of adjacent critical structures. Conclusions HDR brachytherapy requires detailed attention to personnel, equipment, patient and personnel safety, and continuing staff education. Coordination between the radiation oncologist and treatment planning staff and effective quality assurance procedures are important components of successful HDR brachytherapy programs.

From both a disease and management perspective, locally advanced gynecologic cancers present a significant challenge. Dose escalation with brachytherapy serves as a key treatment, providing conformal radiation while sparing at-risk organs. Intracavitary brachytherapy techniques have been shown to be effective, with improving tumor control and toxicity profiles with the advent of three-dimensional image planning. Despite this, the variations in tumor size, location, and pelvic anatomy may lead to suboptimal dosimetry with standard intracavitary applicators in some clinical scenarios. The addition of interstitial needles (interstitial brachytherapy (interstitial brachytherapy) can improve the conformality of brachytherapy treatments by adding needles to peripheral (and central) regions of the target volume, improving the ability to escalate doses in these undercovered regions while sparing organs at risk. Interstitial brachytherapy can be delivered by intracavitary and interstitial hybrid applicators (ICBT/ISBT), perineal template (P-ISBT), or by free-hand technique. ISBT has however yet to be widely available because of concerns of complications and toxicities from this specialized treatment. However, with the increasing use of three-dimensional image-guided brachytherapy, there is an opportunity to increase the level of expertise in the gynecologic radiation oncology community with an improved understanding of the potential complications and morbidity. In this article, we review the acute and long-term toxicity in both ICBT/ISBT and P-ISBT using image-guided brachytherapy.

DNA-damage repair (DDR) pathway mutations can sensitize cancer cells to a class of cancer therapeutics known as PARP inhibitors. Given that DDR alterations can be found in up to one-third of advanced prostate cancers, PARP inhibitors have recently been established in treatment-refractory settings. We provide an updated review of the clinical data supporting the 4 PARP inhibitors that have undergone the most investigation thus far in metastatic castrate-resistant prostate cancer (mCRPC). Two of these agents are currently approved for the treatment of DDR-altered mCRPC. We end with a discussion on integration of approved PARP inhibitors into advanced prostate cancer clinical practice.

Purpose High-dose-rate (HDR) brachytherapy as primary therapy (monotherapy) is a standard National Comprehensive Cancer Network (NCCN) endorsed treatment option for patients with localized prostate cancer. Thus far, most data are limited to single-institution experiences. Accordingly, we sought to systematically review rates of biochemical recurrence-free survival (bRFS) and toxicity associated with fractionated HDR monotherapy. Material and methods A systematic review was performed using PubMed and Embase databases for relevant articles published between January 1999 and December 2019, according to preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. Included studies were limited to fractionated HDR monotherapy publications in full manuscript form with at least 5-year median follow-up, at least 80 patients included, and adequate reporting of bRFS and toxicity data. Meta-analyses were performed with random-effect modeling. Extent of heterogeneity between studies was determined using I 2 and Cochran's Q tests. Results Seven unique studies were identified, including 2,123 patients. NCCN low-, intermediate-, and high-risk patients comprised 40%, 40%, and 20% of patients, respectively. Median follow-up at the study group level was 74 months (range, 60-131 months). The 5-year bRFS rate was 95% (95% confidence interval [CI]: 93-96%), and after adjusting to control for publication bias, it was 96% (95% CI: 94-99%). Estimated adjusted late grade ≥ 3 genitourinary and gastrointestinal toxicity rates were 2% (95% CI: 1-4%) and 0.3% (95% CI: 0-1.1%), respectively. Conclusions Fractionated HDR monotherapy is associated with high rates of disease control and low rates of toxicity. Future studies are needed to better define the value of this treatment modality relative to other options.

Purpose Brachytherapy (BT) after surgical resection of keloids reduces the risk of local recurrence, but standardization of dose/technique is lacking. Typical keloid BT treatment utilizes a single-channel source prescribed to 5-mm depth. We investigated the dosimetry of a volume-based target definition for interstitial high-dose-rate BT treatment of keloids. Methods and Materials We retrospectively identified consecutive 14 patients who had a total of 20 keloids treated with interstitial high-dose-rate BT for keloids at our institution between 2004 and 2014. Keloids were treated with a single 8 Gy fraction prescribed to 5 mm beneath the scar within 36 h of surgery. Retrospectively, a 3-mm skin high-risk clinical target volume (HR-CTV) was contoured under the scar for volume-based dose calculations. Results Mean (SD) HR-CTV was 3.91 cm3 (3.1) and mean (SD) HR-CTV dose was 11.3 Gy (3.6). Mean D90 (SD) was 62.9% (25.8) and mean V100 (SD) was 56.5% (26.4). The mean V150 (SD), V200 (SD), and V300 (SD) were as follows: 37.6% (19.9), 25.1% (14.4), and 11.3% (6.5), respectively. No local failures were reported at 9 months median followup. There were no Grade 2 or higher late toxicities. Conclusions Using a volume-based target definition, a wide range of target coverage was observed. This is likely a consequence of the curvature of the skin and the challenges of keeping the catheter equidistant from the skin across the target. Additional data are needed to define the potential clinical impact on outcomes/toxicities of dosimetric correlates with single-catheter BT keloid treatment.

Purpose Keratinocyte carcinoma (KC, previously nonmelanoma skin cancer) represents the most common cancer worldwide. While surgical treatment is commonly utilized, various radiation therapy techniques are available including external beam and brachytherapy. As such, the American Brachytherapy Society has created an updated consensus statement regarding the use of brachytherapy in the treatment of KCs. Methods Physicians and physicists with expertise in skin cancer and brachytherapy created a consensus statement for appropriate patient selection, data, dosimetry, and utilization of skin brachytherapy and techniques based on a literature search and clinical experience. Results Guidelines for patient selection, evaluation, and dose/fractionation schedules to optimize outcomes for patients with KC undergoing brachytherapy are presented. Studies of electronic brachytherapy are emerging, although limited long-term data or comparative data are available. Radionuclide-based brachytherapy represents an appropriate option for patients with small KCs with multiple techniques available. Conclusions Skin brachytherapy represents a standard of care option for appropriately selected patients with KC. Radionuclide-based brachytherapy represents a well-established technique; however, the current recommendation is that electronic brachytherapy be used for KC on prospective clinical trial or registry because of a paucity of mature data.

Purpose: In a single-institution phase II study, we evaluated the safety of a 5-day dose-equivalent neoadjuvant radiotherapy (RT) regimen for high-risk primary soft tissue sarcoma. Patients and Methods: Patients received neoadjuvant RT alone (30 Gy in five fractions) to the primary tumor with standard margins. The primary endpoint was grade ≥2 late-radiation toxicity. Major wound complications, local recurrences, and distant metastases were also examined. In exploratory analysis, we evaluated germline biomarkers for wound toxicity and the effects of the study on treatment utilization. Results: Over 2 years, 52 patients were enrolled with median follow-up of 29 months. Seven of 44 evaluable patients (16%) developed grade ≥2 late toxicity. Major wound complications occurred in 16 of 50 patients (32%); a signature defined by 19 germline SNPs in miRNA-binding sites of immune and DNA damage response genes, in addition to lower extremity tumor location, demonstrated strong predictive performance for major wound complications. Compared with the preceding 2-year period, the number of patients treated with neoadjuvant RT alone at our institution increased 3-fold, with a concomitant increase in the catchment area. Conclusions: A shorter 5-day neoadjuvant RT regimen results in favorable rates of wound complications and grade ≥2 toxicity after 2-year follow-up. Five-day RT significantly increased utilization of neoadjuvant RT at our high-volume sarcoma center. With further validation, a putative germline biomarker for wound complications may guide safer RT utilization.

PURPOSE: Cervical cancer (CC) disproportionately affects minorities who have higher incidence and mortality rates. Standard of care for locally advanced CC involves a multimodality approach including brachytherapy (BT), which independently improves oncologic outcomes. Here, we examine the impact of insurance status and race on BT utilization with the SEER database. MATERIALS AND METHODS: In total, 7,266 patients with stage I-IV CC diagnosed from 2007 to 2015 were included. BT utilization, overall survival (OS), and disease-specific survival (DSS) were compared. RESULTS: Overall, 3,832 (52.7%) received combined external beam radiation therapy (EBRT) + BT, whereas 3,434 (47.3%) received EBRT alone. On multivariate logistic regression analysis, increasing age (OR, 0.98; 95% CI, 0.98 to 0.99; P < .001); Medicaid (OR, 0.80; 95% CI, 0.72 to 0.88; P < .001), uninsured (OR, 0.67; 95% CI, 0.56 to 0.80; P < .001), and unknown versus private insurance (OR, 0.61; 95% CI, 0.43 to 0.86; P < .001); Black (OR, 0.68; 95% CI, 0.60 to 0.77; P < .001) and unknown versus White race (OR, 0.30; 95% CI, 0.13 to 0.77; P = .047); and American Joint Committee on Cancer stage II (OR, 1.07; 95% CI, 0.93 to 1.24; P = .36), stage III (OR, 0.82; 95% CI, 0.71 to 0.94; P = .006), stage IV (OR, 0.30; 95% CI, 0.23 to 0.40; P < .001), and unknown stage versus stage I (OR, 0.36; 95% CI, 0.28 to 0.45; P < .001) were associated with decreased BT utilization. When comparing racial survival differences, the 5-year OS was 44.2% versus 50.9% ( P < .0001) and the 5-year DSS was 55.6% versus 60.5% ( P < .0001) for Black and White patients, respectively. Importantly, the racial survival disparities resolved when examining patients who received combined EBRT + BT, with the 5-year OS of 57.3% versus58.5% ( P = .24) and the 5-year DSS of 66.3% versus 66.6% ( P = .53) for Black and White patients, respectively. CONCLUSION: This work demonstrates notable inequities in BT utilization for CC that particularly affects patients of lower insurance status and Black race, which translates into inferior oncologic outcomes. Importantly, the use of BT was able to overcome racial survival differences, thus highlighting its essential value.

Purpose: There is a paucity of data analyzing the anatomic locations and dose volume metrics achieved for surgically transposed ovaries in patients desiring fertility or hormonal preservation receiving pelvic radiation therapy (RT), which were examined herein. Methods and Materials: This is a retrospective study including women who underwent ovarian transposition before pelvic RT between 2010 to 2020. The craniocaudal (CC) distance of the ovary centroid to the (1) plane of the sacral promontory, (2) iliac crest, and (3) the nearest distance between the ovary edge and RT planning target volume (PTV) were measured (cm). The area under the receiver operating characteristic curve and cut-point analysis estimating ovary location outside the PTV was performed. Results: Thirty-one ovaries were analyzed from 18 patients. Thirteen (72.2%) were treated with intensity modulated RT, and 5 (27.8%) were treated with 3-dimensional conformal radiation therapy. Most ovaries were located above the sacral promontory (64.5%, n = 20), below the iliac crest (96.8%, n = 30), and outside the PTV (64.5%, n = 20). The median distance from the ovaries to the sacral promontory, iliac crest, and PTV was 0.8 cm (interquartile range [IQR], −0.83 to 1.59 cm), −3.22 cm (IQR, −5.12 to −1.84 cm), and 0.9 cm (IQR, −1.0 to 1.9 cm), respectively. The area under the receiver operating characteristic curve and cut-point analysis demonstrated that distance from the iliac crest predicted an ovary to be outside the PTV with an optimal cut-point of −3.0 cm (C-index = 0.82). The median mean and maximum (Dmax) ovary doses were 15.5 Gy (IQR, 9.6-20.2 Gy) and 32.2 Gy (IQR 24.8-46.5 Gy), respectively. Conclusions: Despite most transposed ovaries being located outside the PTV, nearly all remained below the iliac crest and received RT doses associated with a high risk of ovarian failure. These findings deepen our understanding of the spatial relationship between transposed ovaries and dose to inform surgical and pre-RT planning and suggest that more aggressive ovary-sparing strategies are warranted.

Purpose Brachytherapy is utilized in the treatment of many different malignancies; although traditionally performed with low-dose-rate or high-dose-rate techniques, more recently, electronic brachytherapy (EB) has emerged as a potential alternative. At this time, there are no evidence-based guidelines to assist clinicians in patient selection for EB and concerns exits regarding differences in dosimetry as compared to traditional brachytherapy techniques. As such, the American Brachytherapy Society appointed a group of physicians and physicists to create a consensus statement regarding the use of EB. Methods and Materials Physicians and physicists with expertise in brachytherapy created a site-directed consensus statement for appropriate patient selection and utilization of EB based on a literature search and clinical experience. Results EB has been utilized to deliver accelerated partial breast irradiation with, thus far acceptable local control and toxicity rates including a randomized trial that used EB to deliver intraoperative radiotherapy; however, prospective data with large patient numbers and long-term follow up are needed. Increasing numbers of patients have been treated with EB for nonmelanomatous skin cancers; although, preliminary data are promising, there is a lack of data comparing EB to traditional radiotherapy techniques as well as a lack of long-term follow up. For treatment of the vaginal cuff with EB, small retrospective studies have been reported without long-term follow up. Conclusions In light of a randomized trial in breast showing higher rates of recurrence and the lack of prospective data with mature follow up with other sites, as well as concerns regarding dosimetry, it is not recommended that EB be utilized for accelerated partial breast irradiation, nonmelanomatous skin cancers, or vaginal cuff brachytherapy outside prospective clinical trials at this time.

As brachytherapy utilization rates decline, we sought to evaluate the state of brachytherapy training during radiation oncology residency.US radiation oncology residents in the Association of Residents in Radiation Oncology database were sent an online questionnaire regarding brachytherapy training. Survey questions addressed a wide array of topics, and responses were often given on a 1 to 5 Likert-type scale that reflected strength of opinion. Postgraduate year (PGY) 4/5 respondents' answers were analyzed. Descriptive statistics were generated, and rank correlation analyses (Kendall's τ coefficient and Wilcoxon signed-rank test) were used for comparisons.The survey was completed by 145 of 567 residents (62% being PGY4/5). Of PGY4/5 respondents, 96% (86 of 90) believed learning brachytherapy during residency was important, and 72% (65 of 90) felt their program valued brachytherapy training. Resident brachytherapy comfort varied by site, decreasing as follows: gynecologic, prostate, breast, skin. The current intracavitary 15-case minimum was believed adequate by most, but only a minority believed the 5-case interstitial minimum was adequate. Most respondents (59%) believed that caseload was the greatest barrier to achieving independence in brachytherapy. Significant support exists for American Brachytherapy Society training courses and on-the-job education to enhance training, but enthusiasm about pursuing brachytherapy fellowship training was low. Most respondents expressed confidence in developing a brachytherapy practice (54%); however, this was significantly lower than the rate of those confident in developing a stereotactic body radiation therapy/stereotactic radiosurgery program (97%) (P .001). Furthermore, there was an association between aggregate number of brachytherapy cases performed and resident confidence in starting a brachytherapy practice (τ = 0.37; P .001).Brachytherapy is an important component of residency training that is valued by residents and programs. Because caseload was the greatest perceived barrier in brachytherapy training, with confidence correlated with case volume, attempts should be made to expand opportunities for training experiences that are feasible to complete during residency.

Purpose Daily magnetic resonance (MR)–guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment. Methods and materials Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ2 test. Results The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively. Conclusions This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

Key Points Question What is the hemoglobin transfusion threshold and target recommended for patients with cervical cancer undergoing curative-intent radiotherapy (RT)? Findings In this international Delphi consensus study, 39 experts in gynecologic radiation oncology did not agree on a hemoglobin transfusion threshold, highlighting significant variability in clinical practice. For both external beam RT and brachytherapy, a hemoglobin transfusion target of 9 or more g/dL and less than 12 g/dL, respectively, was agreed on by an 89% consensus. Meaning A liberal packed red blood cell transfusion strategy was recommended by consensus to overcome hypoxia-induced radioresistance in patients with cervical cancer receiving curative RT., Importance Packed red blood cell (PRBC) transfusions are used to treat anemia in patients with cervical cancer undergoing radiotherapy (RT) owing to concerns of hypoxia-induced radioresistance. In the absence of high-quality evidence informing transfusion practices for patients receiving external beam RT (EBRT) and brachytherapy, various arbitrary hemoglobin target levels are used worldwide. Objective To develop consensus statements to guide PRBC transfusion practices in patients with cervical cancer receiving curative-intent RT with EBRT and brachytherapy. Design, Setting, and Participants This international Delphi consensus study was completed between November 1, 2019, and July 31, 2020. A total of 63 international clinical experts in gynecologic radiation oncology were invited; 39 (62%) accepted and consented to participate. Consensus building was achieved using a 3-round anonymous Delphi consensus method. Participants rated their agreement or disagreement with statements using a 5-point Likert scale. An a priori threshold of 75% or more was required for consensus. Main Outcomes and Measures The preplanned primary outcome of this study was to assess hemoglobin transfusion thresholds and targets for both EBRT and brachytherapy by expert consensus. Results Response rates of 100% (39 of 39), 92% (36 of 39), and 97% (35 of 36) were achieved for the first, second, and third rounds of surveys, respectively. Twenty-three experts (59%) practiced in Canada, 11 (28%) in the United States, 3 (8%) in South America, 1 (3%) in Europe, and 1 (3%) in Asia. Consensus was reached for 44 of 103 statements (43%), which were combined to form the final 27-statement consensus guideline. No specific hemoglobin transfusion threshold was agreed on by consensus for EBRT or brachytherapy. By consensus (89% [31 of 35]), a hemoglobin transfusion target for patients who receive a PRBC transfusion should be 9 g/dL or more and less than 12 g/dL. Conclusions and Relevance This study presents the first international expert consensus guideline informing PRBC transfusion practices for patients with cervical cancer undergoing EBRT and brachytherapy. A minimum hemoglobin transfusion target of 9 g/dL was endorsed to balance tumor radiosensitivity with appropriate use of a scarce resource. Randomized clinical trials are required to evaluate the optimal transfusion threshold and target that maximize clinical benefit in this patient population., This international Delphi consensus study developed consensus statements to guide packed red blood cell transfusion practices for patients with cervical cancer receiving curative-intent radiotherapy with external beam radiotherapy and brachytherapy.

PURPOSE/OBJECTIVE(S) National Comprehensive Cancer Network guidelines recommend adjuvant systemic therapy with or without external beam radiation and/or intravaginal brachytherapy for high-risk endometrial cancer histologies. Being able to estimate the risk of pelvic/para-aortic lymph node (LN) involvement could assist in making clinical decisions regarding whether to treat with external beam versus brachytherapy alone. The National Cancer Data Base was queried to develop predictive nomograms based on primary uterine factors to estimate the risk of pathologic LN involvement. MATERIALS/METHODS Patients diagnosed with pathologic T1-T2 clear cell, uterine papillary serous (UPS), carcinosarcoma, or mixed endometrial cancer between 2004-2016 undergoing primary surgery with at least 10 LNs sampled in the National Cancer Data Base were identified. Logistic regression was performed to identify primary pathologic tumor predictors of LN positivity. Pathologic variables assessed included primary tumor histology, pathologic tumor stage, tumor size, and presence/absence of lymphovascular invasion (LVI). Nomograms were created to predict overall, pelvic only, and paraaortic and/or pelvic LN involvement. RESULTS Among 7,918 patients included, 1,407 (18%) were node positive. On multivariable analysis, relative to carcinosarcoma, both clear cell (odds ratio [OR] 1.77, 95% confidence interval [CI] 1.34-2.32, P < 0.001) and UPS (OR 1.76, 95% CI 1.46-2.13, P < 0.001) histology were significantly associated with a higher risk of LN positivity while mixed histology was not (OR 1.14, 95% CI 0.95-1.37, P = 0.16). Furthermore, increasing pathologic tumor stage (pT2 versus pT1a, OR 3.62, 95% CI 3.04-4.28, P < 0.001), increase in tumor size per centimeter (OR 1.09, 95% CI 1.06-1.11, P < 0.001), and presence of LVI (OR 5.23, 95% CI 4.58-6.02, P < 0.001) were predictive of overall LN positivity. Nomograms demonstrated that the impact of primary tumor pathologic variables was comparable for predicting any LN involvement, pelvic only, and paraaortic with or without pelvic LN involvement. CONCLUSION Among endometrial cancer patients with high-risk histologies, predictors of LN positivity are similar to those with endometrial adenocarcinoma. Patients with carcinosarcoma are the least likely to be diagnosed with node positive disease relative to other high-risk histologies. Predictive nomograms can help to individualize the risk of pelvic and paraaortic LN involvement and may assist in adjuvant treatment decisions. AUTHOR DISCLOSURE E. Anderson: None. M. Luu: None. D.J. Lu: None. E.M. Chung: None. M. Kamrava: American Board of Radiology, Brachytherapy Journal, American Brachytherapy Society Board of Directors. Co-Editor; Journal of Contemporary Brachytherapy.

Objective To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer. Methods Patients received six cycles of chemotherapy with gemcitabine and cisplatin on day 1 and day 8 of a 21-day treatment cycle. Pembrolizumab was administered on day 1 of cycles 3–6 and as maintenance monotherapy in cycles 7–34. Palliative radiation to a non-target symptomatic lesion was allowed. The primary objective was overall response rate by RECIST 1.1 criteria. Secondary objectives included safety, progression-free survival, time to progression, duration of response and overall survival. Results An interim analysis for futility was performed at 18 evaluable patients. Overall response rate was 60%, duration of response was 4.9 months and time to progression was 5.2 months. Progression-free survival at 6 and 12 months was 43% and 5%. Median progression-free survival was 6.2 months and median overall survival was 11.3 months. In all patients, CA125 levels reflected response and progression. There were no pseudoprogression events. After receiving palliative radiation during pembrolizumab maintenance, a patient with recurrent ovarian clear cell carcinoma had an exceptional and durable response that is ongoing for greater than 2 years. After consultation with the sponsor, based on the modest duration of response observed at the interim analysis for futility, the decision was made to close the trial to further accrual. Conclusions The addition of pembrolizumab to cisplatin and gemcitabine did not appear to provide benefit beyond chemotherapy alone in patients with recurrent platinum-resistant ovarian cancer.

High Dose Rate (HDR) brachytherapy is a safe and effective method of treating men with prostate cancer. It is used in the definitive setting as monotherapy or in combination with hormonal therapy and/or external beam radiation therapy. It is also used in the salvage setting for local recurrence after primary radiotherapy. The best HDR brachytherapy treatments are performed by providers that understand ideal patient selection, appropriate operative practices, and optimal treatment planning. This chapter will discuss the history, rationale, pertinent anatomy, patient selection, operative procedure, treatment planning, clinical outcomes, and follow-up practices that will help ensure the reader is best positioned to leverage the benefits HDR brachytherapy can provide in treating prostate cancer.

Introduction The addition of brachytherapy (BT) in high risk prostate cancer is supported by Level 1 evidence. Whether all high risk patients benefit from BT to the same extent is unknown. The National Cancer Database (NCDB) was used to investigate overall survival (OS) differences between GS 8 and 9-10 treated with external beam radiation (EBRT) only or BT +/- EBRT. Materials and Methods We included localized prostate adenocarcinoma definitively treated with radiation between 2004-2014. Patients were stratified into various radiation treatment groups: EBRT 7560 - 8640 cGy, EBRT 5940 - 7540 cGy, and BT +/- EBRT. All EBRT only and BT +/- EBRT patients received ADT. A multivariable Cox proportional hazard model was used to assess OS. Propensity score matching was used to account for differences between groups. Median survival was determined based on Kaplan-Meier survival curves. Results 30,698 patients were included. On multivariable analysis among GS 8 patients, BT was associated with improved OS compared to 7560 - 8640 cGy (HR–0.80 (95% CI 0.70-0.92, P = 0.002). In Gleason 9-10 BT did not result in improved OS compared to 7560 – 8640 cGy (HR- 0.91 (95% CI 0.79 – 1.05, P = 0.212). Results remained significant with propensity score matching and removing patients with medical comorbidities. Conclusion BT was associated with improved OS when compared to 7560 – 8640 cGy in GS 8, but not in Gleason 9-10 disease. This hypothesis generating study suggests there may be variable benefit with BT in high risk prostate cancer patients on OS. Future prospective studies are needed to investigate whether the benefit of BT is similar across all high risk prostate cancer patients.

The objective of this study was to explore radiomics features from longitudinal diffusion-weighted MRIs (DWIs) for pathologic treatment effect prediction in patients with localized soft tissue sarcoma (STS) undergoing hypofractionated preoperative radiotherapy (RT). Thirty patients with localized STS treated with preoperative hypofractionated RT were recruited to this longitudinal imaging study. DWIs were acquired at three time points using a 0.35 T MRI-guided radiotherapy system. Treatment effect score (TES) was obtained from the post-surgery pathology as a surrogate of treatment outcome. Patients were divided into two groups based on TES. Response prediction was first performed using a support vector machine (SVM) with only mean apparent diffusion coefficient (ADC) or delta ADC to serve as the benchmark. Radiomics features were then extracted from tumor ADC maps at each of the three time points. Logistic regression and SVM were constructed to predict the TES group using features selected by univariate analysis and sequential forward selection. Classification performance using SVM with features from different time points and with or without delta radiomics were evaluated. Prediction performance using only mean ADC or delta ADC was poor (area under the curve (AUC) < 0.7). For the radiomics study using features from all time points and corresponding delta radiomics, SVM significantly outperformed logistic regression (AUC of 0.91 ± 0.05 v.s. 0.85 ± 0.06). Prediction AUC values using single or multiple time points without delta radiomics were all below 0.74. Including delta radiomics of mid- or post-treatment relative to the baseline drastically boosted the prediction. In this work, an SVM model was built to predict the TES using radiomics features from longitudinal DWI. Based on this study, we found that use of mean ADC, delta ADC, or radiomics features alone was not sufficient for response prediction, and including delta radiomics features of mid- or post-treatment relative to the baseline can optimize the prediction of TES, a pathologic and clinical endpoint.

Introduction In response to the COVID-19 pandemic, there has been a rapid growth in the use of telehealth/telemedicine that will likely be sustained in the post-pandemic setting. Mobile health (mHealth) applications (apps) can be utilized as part of the telehealth encounter to monitor patient-reported outcomes (PROs) and enhance patient-provider communication. Methods A systematic review was performed of mHealth apps that include symptom trackers. We searched the iOS App Store and Andriod Google Play using the words “cancer,” “oncology,” and “symptom tracker.” Apps were included if they incorporated a symptom tracking function that could allow cancer patients to record symptoms and PROs. Apps were evaluated using the Mobile Apps Rating Scale (MARS), which includes engagement, functionality, aesthetics, information, and app subjective quality. Results The initial search yielded 1189 apps, with 101 apps eligible after title and description screening. A total of 41 apps met eligibility criteria and were included in this study. The majority of apps (73%, n=30) were general health/pain symptom trackers, while 27% (n=11) were cancer-specific. The app quality mean scores assessed using MARS ranged from 2.43 to 4.23 (out of 5.00). Only one app has been trialed for usability among cancer patients. Conclusion While various symptom tracking apps are available, cancer-specific apps remain limited. Future collaboration between oncologists, app developers, and patients to optimize PROs assessment and integration with telehealth/telemedicine encounters to increase symptom recognition and enhance patient-provider communication is urgently needed., In response to the COVID-19 pandemic, there has been an increase in the use of telehealth. mHealth apps can be utilized as part of the telehealth encounter to monitor patient-recorded outcomes and enhance patient-provider communication. We found 41 apps with symptom tracking functions relevant to oncology patients in the digital health market. However, cancer-specific apps remain limited. Future collaboration between oncologists, app developers, and patients is needed to optimize integration of mHealth apps within telehealth.

PURPOSE: In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT). PATIENTS AND METHODS: Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar’s test for rates > 0%. RESULTS: Of 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% (P < .0001), high-grade diarrhea 38.5% (P < .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference; P = .01), frequency of fecal incontinence (8.2% difference; P = .01), and interference of fecal incontinence (8.5% difference; P = .04). CONCLUSION: Patient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.

Purpose Multiple skin radiation therapy techniques exist including electron beam therapy, high-dose-rate (HDR) brachytherapy, superficial/orthovoltage, and electronic brachytherapy (EB). The purpose of this analysis was to compare reimbursement between these modalities by fractionation regimen. Methods and Materials Reimbursement was derived from the 2020 Medicare Physician Fee Schedule by fractionation schedule or from the 2020 Hospital Outpatient Prospective Payment national benchmarks. A secondary analysis evaluating incorporation of daily simulation codes was also performed to factor in coding heterogeneity. Results Superficial/orthovoltage was the least costly and EB the next least costly technique regardless of fractionation. When incorporating variations in coding of simulations, reimbursement with superficial/orthovoltage was still least costly, with a reduction in cost of $1,755, $2,715, $5,076, and $7,436 compared with HDR brachytherapy for 6, 10, 20, and 30 fractions, respectively, and a reduction in cost of $1,325, $2,170, $4,281, and $6,392 compared with EB. HDR brachytherapy and EB costs can increase by 63–110% based on nonrecommended variation in daily simulation billing, with superficial/orthovoltage experiencing the highest relative increase. Reimbursement per course can vary by a factor of 4.5–9.3x depending on the modality and fractionation scheme utilized. Conclusions Superficial/orthovoltage followed by EB were the least costly modalities with regard to reimbursement; however, costs can vary with frequency of simulation code billing. Consistency and standardization in skin radiation therapy reimbursement is needed, and case rates within a radiation oncology alternative payment model may help to minimize reimbursement heterogeneity among treatment options.

Purpose This guideline reviews the evidence and provides recommendations for the indications and appropriate techniques of radiation therapy (RT) in the treatment of nonmetastatic cervical cancer. Methods The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT in definitive and postoperative management of cervical cancer. These questions included the indications for postoperative and definitive RT, the use of chemotherapy in sequence or concurrent with RT, the use of intensity modulated radiation therapy (IMRT), and the indications and techniques of brachytherapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. Results The guideline recommends postoperative RT for those with intermediate risk factors, and chemoradiation for those with high-risk factors. In the definitive setting, chemoradiation is recommended for stages IB3-IVA, and RT or chemoradiation is conditionally recommended for stages IA1-IB2 if medically inoperable. IMRT is recommended for postoperative RT and conditionally recommended for definitive RT, for the purposes of reducing acute and late toxicity. Brachytherapy is strongly recommended for all women receiving definitive RT, and several recommendations are made for target dose and fractionation, the use of intraoperative imaging, volume-based planning, and recommendations for doses limits for organs at risk. Conclusions There is strong evidence supporting the use of RT with or without chemotherapy in both definitive and postoperative settings. Brachytherapy is an essential part of definitive management and volumetric planning is recommended. IMRT may be used for the reduction of acute and late toxicity. The use of radiation remains an essential component for women with cervical cancer to achieve cure.

Purpose To develop and evaluate a fast patient localization tool using megavoltage (MV)-topogram on helical tomotherapy. Methods and Materials Eighty-one MV-topogram pairs for 18 pelvis patients undergoing radiation were acquired weekly under an institutional review board–approved clinical trial. The MV-topogram imaging protocol requires 2 orthogonal acquisitions at static gantry angles of 0 degrees and 90 degrees for a programed scan length. A MATLAB based in-house software was developed to reconstruct the MV-topograms offline. Reference images (digitally reconstructed topograms, digitally reconstructed topograms) were generated using the planning computed tomography and tomotherapy geometry. The MV-topogram based alignment was determined by registering the MV-topograms to the digitally reconstructed topogram using bony landmark on commercial MIM software. The daily shifts in 3 translational directions determined from MV-topograms were compared with the megavoltage computed tomography (MVCT) based patient shifts. Linear-regression and two one-sided tests equivalence tests were performed to investigate the relation and equivalence between the 2 techniques. Seventy-eight MV-topogram pairs for 19 head and neck patients were included to validate the finding. Results The magnitudes of alignment differences of (MVCT − MV-topogram) (and standard deviations) were −0.3 ± 2.1, −0.8 ± 2.4, and 1.6 ± 1.7 mm for pelvis and 0.6 ± 1.2, 0.8 ± 4.2, 1.6 ± 2.6 mm for head and neck; the linear-regression coefficients between 2 imaging techniques were 1.18, 1.10, 0.94, and 0.86, 0.63, 0.38 in the lateral, longitudinal, vertical directions for pelvis and head and neck, respectively. The acquisition time for a pair of MV-topograms was up to 12.7 times less than MVCT scans (coarse scan mode) while covering longer longitudinal length. Conclusions MV-topograms showed equivalent clinical performance to the standard MVCT with significantly less acquisition time for pelvis and H&N patients. The MV-topogram can be used as an alternative or complimentary tool for bony landmark-based patient alignment on tomotherapy.

Purpose To identify if baseline patient or magnetic resonance imaging (MRI) features can predict which women are at risk for inadequate tumor coverage with only intracavitary tandem and ovoid (T + O) brachytherapy and to correlate tumor coverage with clinical outcomes. Methods and Materials We performed a retrospective study of 50 women with cervical cancer treated with chemoradiation at a single institution between January 2014 and December 2015. All patients had a 3T-MRI performed at baseline (MRI1) and at the completion of external beam radiation therapy (MRI2). Gross tumor volume initial (GTV-Tinit) was measured on MRI1 and high-risk clinical tissue volume (CTVHR) on MRI2. CTVHR extending beyond point A was classified as too large for adequate coverage with T + O and requiring interstitial needles. Multivariate analysis was performed to determine predictive factors of inadequate coverage. Kaplan–Meier and Cox Regression were performed to correlate inadequate coverage with outcomes. Results Mean patient age was 49.2 ± 13.2 years, and 84% had Federation of Gynecology and Obstetrics IIB/IIIB disease. Forty-two percent of women were estimated to have inadequate tumor coverage with T + O brachytherapy. The GTV-Tinit volume and dimensions (superior-inferior, left-right, anterior-posterior) on MRI1 were all important predictive factors of inadequate coverage on multivariate analysis. Receiver operating characteristics curves identified optimal thresholds of superior-inferior ≥ 4.5 cm (area under the curve [AUC] = 0.718), left-right ≥ 4.5 cm (AUC = 0.745), anterior-posterior ≥ 5.0 cm (AUC = 0.767), and GTV-Tinit ≥ 85 cm3 (AUC = 0.842). Patients with inadequate coverage had worse clinical outcomes. Conclusions Baseline MRI tumor size may predict inadequate CTVHR coverage at the time of brachytherapy (i.e., the need for interstitial needles). This may help identify a subset of women requiring early referral to adequately resourced centers to improve clinical outcomes.

Myxofibrosarcoma (MFS) is reported to have a higher risk of local recurrence (LR) following definitive surgical excision relative to other soft tissue sarcomas. We reviewed our clinical experience treating MFS to investigate predictors of LR.We retrospectively reviewed treatment outcomes for MFS patients treated at our institution between 1999 and 2015. A total of 52 patients were identified. Median age was 65 years (range, 21 to 86 y). Site of disease was: upper extremity (27%), lower extremity (46%), trunk (15%), pelvic (8%), and head and neck (4%). Patients had low, intermediate, high-grade, and unknown grade in: 23%, 8%, 67%, and 2% of tumors, respectively. Tumors were categorized as ≤5 cm (35%),5 cm (56%), or unknown size (9%). In total, 71% received radiotherapy: 19% preoperative, 50% postoperative, and 2% both. All patients underwent surgery. Margins were negative in 71%, close/positive in 21%, and unknown in 8%. In total, 27% of patients received chemotherapy. Univariate Cox regression analysis was utilized to determine associations between clinical and treatment factors with LR.Median follow-up time was 2.9 years (range, 0.4 to 14.3 y). The 3-year actuarial LR, distant metastasis, and overall survival were: 31%, 15%, and 87%, respectively. Predictors of LR were patient age greater than or equal to the median of 65 years (hazard ratio, 13.46, 95% confidence interval, 1.71-106.18, P=0.013), and having close/positive tumor margins (hazard ratio, 3.4, 95% confidence interval, 1-11.53, P=0.049).In this institutional series of MFS older age and positive/close margins were significantly associated with a higher risk of LR.

To quantify Gleason score (GS) heterogeneity within multiparametric magnetic resonance imaging (MRI)-targeted prostate biopsies and to determine impact on National Comprehensive Cancer Network (NCCN) risk stratification. An Institutional Review Board-approved retrospective study was performed on men who underwent Artemis (MRI-transrectal–ultrasound fusion) targeted biopsy (TB) for suspected prostate cancer between 2012 and 2015. Intratarget heterogeneity was defined as a difference in GS between 2 cores within a single target in patients with ≥2 positive cores. Prostate specific antigen, maximum tumor diameter, apparent diffusion coefficient, MRI suspicion score, prostate volume, systematic biopsy (SB) GS, and T-stage were analyzed for correlation with heterogeneity. Changes in NCCN risk based on high versus low GS on TB, SB alone, and SB+TB were compared. Fifty-three patients underwent TB of 73 suspected lesions. Seventy percent (51/73) had ≥2 positive cores, thus meeting inclusion criteria for heterogeneity analysis. Fifty-five percent (28/51) of qualifying targets showed GS heterogeneity. None of the evaluated factors showed a significant relationship with heterogeneity. NCCN low-risk, intermediate-risk, and high-risk groups were 30%, 49%, and 21%, respectively, with SB alone. Adding low GS TB to SB resulted in 17%, 55%, 28% in each risk group, while using high GS+SB resulted in 4%, 54%, and 42%. Overall, the addition of TB resulted in higher NCCN risk groups in 38% of cases. Over half of multiparametric MRI-defined targets demonstrated GS heterogeneity. The addition of high GS from TB leads to risk inflation compared with using SB alone. Further research is needed on how to integrate these findings into current risk stratification models and clinical practice.

Objectives: To investigate biochemical relapse-free survival (BRFS) in men with National Comprehensive Cancer Network-defined intermediate-risk prostate cancer (PC) treated with either stereotactic body radiotherapy (SBRT) or high-dose-rate brachytherapy (HDR-B) monotherapy. Materials and methods: A retrospective, multi-institutional analysis of 437 patients with intermediate-risk PC treated with SBRT (N=300) or HDR-B (N=137) was performed. Men who underwent SBRT were treated to 35 to 40 Gy in 4 to 5 fractions. A total of 95.6% who underwent HDR-B were treated to 42 Gy in 6 fractions. Baseline patient characteristics were compared using a T test for continuous variables and the Mantel-Haenszel χ metric or Fisher exact test for categorical variables. Kaplan-Meier curves were generated to estimate 5-year actuarial BRFS. Multivariate analysis using a Cox proportional-hazards model was used to evaluate factors associated with biochemical failure. Results: The mean age at diagnosis was 68.4 (SD±7.8) years. T-category was T1 in 63.6% and T2 in 36.4%. Mean initial prostate-specific antigen was 7.4 (SD±3.4) ng/mL. Biopsy Gleason score was ≤3+4 in 82.8% and 4+3 in 17.2%. At a median of 4.1 years of follow-up, the BRFS rate (Phoenix definition) was 96.3%, with no difference when stratifying by treatment modality or biologically equivalent dose (BED1.5). On multivariate analysis, age (hazard ratio 1.08, P=0.04) and biopsy Gleason score (hazard ratio 2.48, P=0.03) were significant predictors of BRFS. Conclusions: With a median follow-up period of 4 years, SBRT and HDR-B monotherapy provide excellent BRFS in intermediate-risk PC. Longer-term follow-up is necessary to determine the ultimate efficacy of these hypofractionated approaches, but they appear promising relative to standard fractionation outcomes.

Background As high-dose-rate (HDR) brachytherapy can preferentially spare normal anatomic structures surrounding the radiation target, we report on our experience using this technique in head and neck cancer reirradiation. Methods Twenty patients received HDR brachytherapy reirradiation with curative or palliative intent from 2010-2015. Clinical and toxicity outcomes were recorded. Actuarial outcomes were calculated using Kaplan-Meier analysis. Results For curative treatment, actuarial 2-year rates of local control and overall survival (OS) were 73% and 56%, respectively. Palliatively, a 6-month local control rate of 65% was seen. Age >70 years was associated with poorer OS (P = .042). Prior salvage resection showed a trend toward improved local control and OS (P = .069 and P = .063, respectively). Thirty-three percent had grade 3 to 4 late toxicities. Conclusion Curative-intent HDR brachytherapy reirradiation can provide excellent local control and encouraging OS. Given the late toxicity rates, patient selection is essential, with particular utility for younger patients or those treated with salvage resection.

Purpose Given the limited data using an interstitial approach with 3D-based planning for definitive cervical cancer utilizing the GEC-ESTRO defined high-risk clinical target volume (HR-CTV), we reviewed our institutional experience of cervical cancer patients with HR-CTVs ≥ 30 cc to determine whether our clinical and toxicity outcomes are acceptable. Methods A retrospective review of 37 cervical cancer patients with high-risk clinical target volumes (HR-CTVs) ≥30 cc treated with interstitial image-guided brachytherapy (IS IGBT) was performed. All patients received external beam radiotherapy to a median dose of 45 Gy, followed by IS IGBT delivered in a single implant to a median dose of 6 Gy × 5 fractions. Median HR-CTV was 59 cc. A median HR-CTV D90 of 87.44 Gy was achieved. Kaplan–Meier method was used to evaluate local control (LC), distant control, and overall survival (OS), with stratification by overall treatment time (OTT) ≤ 7 or >7 weeks. Results Median followup was 17 months. The estimated 2-year LC, distant control, and OS were 77.6% (confidence interval [CI]: 63.8–94.5%), 56.8% (CI: 41.3–78.1%), and 54.4% (CI: 39.4–75%), respectively. The 2-year LC for OTT ≤7 weeks and >7 weeks were 100% and 58.3%, respectively (p = 0.026). The 2-year OS for OTT ≤7 weeks and >7 weeks were 77.8% and 38%, respectively (p = 0.021). Discussions IS IGBT can achieve a high D90 to the HR-CTV even in the setting of large-volume disease and results in a favorable LC and toxicity profile. OTT > 7 weeks is associated with significant decrease in LC and OS. Conclusions Efforts should be made to complete whole treatment within 7 weeks as this is associated with improved clinical outcomes.

Purpose: National studies suggest over fifty percent of physicians have feelings of burnout (Shanafelt et. al. Mayo Clin Proc 2015). This can result in emotional exhaustion, depersonalization, and reduced personal accomplishment. Left unmanaged this can lead to depression, addiction, and suicidal ideation. Burnout rates are reported for radiation oncology residents, program directors, and academic chairs but not amongst radiation oncologists who practice brachytherapy. The purpose of this study was to determine the rates of burnout amongst physician members of the American Brachytherapy Society (ABS). Materials and Methods: An anonymous online cross-sectional survey was performed of ABS physician members from December 2020 to February 2021. The survey was initially emailed from the ABS to members, followed by two participation reminders. Burnout was assessed by the Maslach Burnout Inventory-Human Service Survey (MBI-HSS), a validated 22-question survey. Thirteen additional demographics questions were included. High emotional exhaustion (EE) was defined a score of at least 27, high depersonalization was defined as a score of at least 10, and low personal accomplishment (PA) was defined by a score of no more than 33 (Rotenstein et. al. JAMA 2018). This study was approved by the Institutional Review Board. Results: Overall, 51 out of 400 members responded to the survey (13% response rate). Respondents were predominantly male (69%), married (78%), had 1-5 full time faculty or partners (59%), worked 51-60 hours per week (61%), deliver 6-10 brachytherapy treatments per week (43%), and have a brachytherapy suite in their department (63%). Six percent of respondents met the strict MBI-HSS criteria for high burnout (as defined by high EE, high DP, and low PA). Fifty-seven percent of respondents reported at least one manifestation of professional burnout (either high EE or DP). Based on individual MBI-HSS subscale scores, 47% of respondents demonstrated high EE, 37% high DP, and 16% low PA. Compared to prior surveys of radiation oncology academic chairs, residency program directors, and residents, survey respondents consistently had higher mean scores for EE and higher scores for DP, but higher scores for PA (Table 1). The most common identified stressors were electronic medical records (EMR) and excessive workload. Forty-seven percent of respondents also reported that COVID-19 increased their feelings of burnout. Respondents from academic facilities were more likely to have increased feelings of burnout due to COVID-19 (odds ratio 6.8, 95% CI 1.8-25.7). Conclusions: Nearly 60% of ABS physician members who responded to this survey reported symptoms of professional burnout with 6% meeting strict criteria for high burnout. This is higher than that reported for radiation oncology residents, program directors, or academic chairs. Managing stressors related to the EMR and workload are potential areas for improvement.

PURPOSE/OBJECTIVE(S) The American Academy of Pediatrics (AAP) endorses 12-weeks of paid parental leave based on studies showing health benefits to parents and children. Parental leave policies can impact the distribution of child-rearing duties, which may influence gender equity and retention of women in medicine. However, there is a paucity of data describing paid parental leave for faculty/staff physicians. We sought to evaluate paid parental leave policies for physicians at top U.S. hospitals and cancer centers. MATERIALS/METHODS Parental leave policies for the 2020-2021 U.S. News Top 20 Best Hospitals and Best Hospitals for Cancer were reviewed from publicly accessible websites, yielding 27 unique institutions. Human resources offices were contacted to verify policies. Duration of paid child-bearing and parental leave, salary support, and related provisions were obtained. Parental leave included leave available post-childbirth/disability for birthing mothers and for non-birthing mothers, partners, and adoptive parents. Paid leave was defined as receiving ≥50% of base salary and excluded regular accrued paid time off (e.g., vacation). If unpaid parental leave was available (< 50% base salary), paid parental leave duration was considered to be zero. RESULTS Of 27 institutions, six (22%) offer longer leave and/or greater pay based on the extent of caregiving responsibility (e.g., primary vs. secondary; n = 2) or employment position (e.g., academic faculty vs. non-faculty staff physician; n = 4). The mean duration of paid leave for birthing mothers (childbirth plus parental leave) is 7.8 weeks (range, 0-14 weeks) and for parental leave is 3.6 weeks (range, 0-12 weeks), using benefits from primary caregiver and academic faculty status where institutional benefits differ. Conversely, using benefits from secondary caregiver or non-faculty status where benefits differ, the mean paid leave for birthing mothers is 6.8 weeks (range, 0-12 weeks) and for parental leave is 2.3 weeks (range, 0-8 weeks). While the majority of hospitals (n = 23, 85%) offer short-term disability for childbirth, pay varies markedly (range, 0%-100%). Four institutions (15%) do not provide paid leave for childbirth and more than half (n = 15, 56%) do not provide paid parental leave beyond childbirth (based on secondary caregiver or non-faculty status where benefits differ). CONCLUSION Despite AAP endorsement of 12-weeks paid parental leave given improved outcomes for parents and children, the mean duration of paid maternity and parental leave at 27 leading U.S. hospitals and cancer centers is only 7.8 weeks and 3.6 weeks, respectively, at maximal benefits estimates. Nearly one-fourth of institutions offer different leave benefits based on faculty status and/or extent of caregiving responsibility. Future longitudinal studies are needed to assess the effect of paid parental leave on career satisfaction, work-life integration, and gender equity.

PURPOSE/OBJECTIVE(S) To evaluate the clinical and patient-reported outcomes and toxicities in prostate cancer patients undergoing HDR brachytherapy after TURP. MATERIALS/METHODS Data was prospectively collected for patients undergoing HDR brachytherapy from October 1991 to March 2016. Patients were classified according to NCCN risk criteria. Implants were performed under ultrasound-guidance with CT based planning. Goal dosimetric constraints included V100 Prostate > 95%, D1cc Urethra < 105%, D1cc Bladder < 75%, and D1cc Rectum < 75%. Multivariate cox analysis (MVA) was performed and adjusted for age, T stage, Gleason score, initial PSA, and androgen deprivation therapy (ADT) use. Sexual health inventory for men (SHIM) score, International Prostate Symptom Score (IPSS), and CTCAE v5.0 graded toxicity were recorded. RESULTS 2266 patients underwent HDR brachytherapy. 228 underwent a prior TURP. The median follow-up was 61.1 months (range 3 - 257.4 mos). The median time from TURP to HDR was 52.5 months (range 0.17 - 392 mos). A total of 641, 431, 617, and 577 patients were low-, favorable intermediate-, unfavorable intermediate-, and high-risk, respectively, of which 41, 49, 53, and 85 patients with TURP were low-, favorable intermediate-, unfavorable intermediate-, and high-risk, respectively. Patients with a prior history of TURP were more advanced in age and had a higher incidence of high-risk disease (P < 0.001). Of the patients with history of prior TURP, 49 (22%) and 54 (24%) patients experienced Gr 1 and 2 GU toxicity. 8 patients (3.5%) experienced grade 3 GU toxicity with a median time to occurrence of 16 mo (0.2 - 57.7 mo), and 3 of the Grade 3 toxicities resolved. No grade ≥4 GU toxicity and significant differences in toxicity were observed between the cohorts (P = 0.108). Patient-reported SHIM scores were found to not be statistically significant between prior TURP and non-TURP patients, with average decreases in SHIM no greater than 5 points at all time points in the TURP cohort. No significant differences were observed in biochemical free survival, distant metastases free survival, and prostate cancer specific survival at 4 and 8 years between patients who did and did not receive a prior TURP (8-yr BCFS 84.7% (95% CI: 78.2%-91.8%) vs. 89.1% (95% CI: 87.3-91.0%), respectively; P = 0.16). The TURP cohort was found to have lower overall survival (8-yr OS 72.0% (95% CI 64.8%-79.9%) vs. 81.9% (95% CI: 80.0% - 84.1%) respectively; P = 0.041), and may be attributed to the older age of the TURP cohort (P < 0.001). CONCLUSION HDR brachytherapy is a safe and effective treatment modality with low toxicity for prostate cancer patients after a prior TURP.

Purpose/Objective(s) Preoperative radiation therapy (RT) is an integral component of local control in soft tissue sarcoma (STS), but the conventional 5-week treatment course is burdensome for patients (pts). We conducted a single-institution phase 2 study of 5-day dose-equivalent preoperative RT for high-risk primary STS, which demonstrated acceptable rates of wound complications and 2-year toxicity. Here, we present results with longer follow-up, including additional pts from an expansion cohort. Materials/Methods The initial cohort accrued between April 2016 and May 2018 and included 52 pts with histologically confirmed extremity or trunk STS planning to undergo preoperative RT followed by surgery. The primary endpoint of the initial cohort was the rate of grade ≥2 radiation morbidity (fibrosis, lymphedema, or joint stiffness) at 2-years. An expansion cohort opened in October 2018 to compare wound complication rates between preoperative RT alone versus chemoRT and has enrolled an additional 47 pts. Patients received 30 Gy (RT alone) or 25 Gy (chemoRT) over 5 daily fractions to the primary tumor with standard margins. Here we report on pts with primary localized STS who completed preoperative RT and surgery in the initial and expansion cohorts (N = 79; chemoRT excluded). We assessed disease outcomes (local control, distant metastasis, and survival rates) and toxicity (grade ≥2 fibrosis, lymphedema, or joint stiffness) after minimum 2-year follow-up (N = 52). Fibrosis and joint stiffness were graded using RTOG/EORTC criteria, and lymphedema by Stern's scale. We also updated the major wound complication rate (defined per established criteria) after minimum 1-year follow up (N = 60). Results Of the 52 pts with minimum 2-year follow-up, predominant histologic subtypes included undifferentiated pleomorphic sarcoma, spindle cell sarcoma or sarcoma NOS (N = 24), myxofibrosarcoma (N = 8), and myxoid liposarcoma (N = 12). Median tumor size was 6.9 cm, and 15 pts had tumors ≥10 cm. At a median follow-up of 3 years, the local recurrence, distant metastasis and all-cause mortality rates were 6.5% (3 of 46 evaluable pts), 20.8% (10 of 48 evaluable pts), and 21.2% (11 of 52). Two of 3 pts (66%) with a local recurrence had undergone R1 resections, compared to 9 of 46 (19.5%) overall. The rate of overall grade ≥2 radiation morbidity in this same group was 13.0% (fibrosis: 5 pts, joint stiffness: 5 pts, lymphedema: 2 pts). Major wound complications were observed in 16 out of 60 (26.7%) evaluable pts. Conclusion Longer follow-up of a phase 2 study of 5-day pre-operative RT for pts with extremity/trunk STS demonstrates excellent local control. Rates of radiation fibrosis, joint stiffness and lymphedema, as well as wound complications, remain acceptable. We have also developed a web-based, interactive user interface for data visualization, which can help providers identify and understand relationships between baseline characteristics and clinical outcomes in our study.

PURPOSE/OBJECTIVE(S) Nodal staging systems vary substantially across solid tumors, which implies significant heterogeneity in the behavior of nodal variables across cancers. We hypothesized, in contradiction to this, that quantitative metastatic lymph node (LN) burden is a universal and dominant predictor of mortality across solid cancers, and therefore is capable of both simplifying and improving nodal staging for many cancers. MATERIALS/METHODS Retrospective cohort analysis of 1,304,498 patients in the National Cancer Database with solid cancers undergoing surgery between 2004-2015 across the 16 most common cancer sites in the United States (bladder, breast, cervix, colorectal, endometrium, esophagus, gastric, head and neck, hepatobiliary, lung, melanoma, ovary, pancreas, prostate, renal, thyroid). Restricted cubic spline modeling was used to assess the independent association of LN number and survival across a continuous nonlinear spectrum. Recursive partitioning analysis (RPA) was used to develop 16 nodal classification systems based on quantitative nodal burden. The reproducibility of these findings was assessed in 1,969,727 patients from SEER-18. RESULTS Consistently across all disease sites and without exception, mortality risk increased continuously and steeply with each +LN to a change point of ≤5 LN, and continued to increase more modestly without plateau beyond this (P < 0.001 for all hazard ratios [HRs] per LN of the initial and secondary spline segments). Disease sites with the highest HR per LN of the initial spline segment were melanoma (1.92/LN), bladder (1.66/LN) and renal (1.57/LN). Conversely, sites with the lowest HR per LN of the initial spline segment were thyroid (1.13/LN), ovary (1.19/LN) and endometrium (1.21/LN). RPA-derived nodal classification systems for all 16 disease sites universally produced multiple prognostic groups (between 3-8 depending on site) with non-overlapping survival curves that captured a wide spectrum of mortality risk (all P < 0.001). These RPA-derived systems demonstrated improved concordance with mortality compared to current AJCC nodal staging systems in disease sites without pathologic nodal classification based on number of positive LNs including bladder, cervix, endometrium, lung, ovary, prostate, and renal. The RPA-derived systems were also validated in an independent database, producing groups with distinct all-cause mortality and cause-specific mortality (all P < 0.001). Defining high nodal burden as the RPA-derived group with the highest number of +LNs, this factor conveyed markedly higher mortality (HR range: 1.8-4.6) than any other nodal covariate, including extranodal extension, size, and location (HR range: 0.9-1.5) in multivariable analysis across all organ sites. CONCLUSION Quantitative metastatic LN burden is a fundamental driver of mortality across solid cancers. Given its reproducibility and objectiveness, +LN number should serve as a foundation for pathologic nodal staging across all solid tumors.

To develop a consensus report for the quality practice of accelerated partial breast irradiation (APBI) using interstitial multicatheter brachytherapy (IMB).The American Brachytherapy Society Board appointed an expert panel with clinical and research experience with breast brachytherapy to provide guidance for the current practice of IMB. This report is based on a comprehensive literature review with emphasis on randomized data and expertise of the panel.Randomized trials have demonstrated equivalent efficacy of APBI using IMB compared with whole breast irradiation for select patients with early-stage breast cancer. Several techniques for placement of interstitial catheters are described, and importance of three-dimensional planning with appropriate optimization is reviewed. Optimal target definition is outlined. Commonly used dosing schemas include 50 Gy delivered in pulses of 0.6-0.8 Gy/h using pulsed-dose-rate technique and 34 Gy in 10 fractions, 32 Gy in eight fractions, or 30 Gy in seven fractions using high-dose-rate technique. Potential toxicities and strategies for toxicity avoidance are described in detail. Dosimetric constraints include limiting whole breast volume that receives ≥50% of prescription dose to60%, skin dose to ≤100% of prescription dose (≤60-70% preferred), chest wall dose to ≤125% of prescription dose, Dose Homogeneity Index to0.75 (0.85 preferred), VIMB is an effective technique to deliver APBI for appropriately selected women with early-stage breast cancer. This consensus report has been created to assist clinicians in the appropriate practice of APBI using IMB.

Introduction To identify differences in acute urinary and sexual toxicity between a 6-fraction and 2-fraction high-dose-rate brachytherapy monotherapy regimen and correlate dosimetric constraints to short-term toxicity. Methods A single institution retrospective study of 116 men with prostate cancer treated with HDR monotherapy from 2010 to 2015 was conducted. Eighty-one men had 7.25 Gy × 6-fractions and 35 men had 13.5 Gy × 2-fractions. Patients had two CT-planned implants spaced 1–2 weeks apart. Patient baseline characteristics, International Prostate Symptom Scores (IPSS) and Sexual Health Inventory for Men (SHIM) scores were collected pre-treatment and 3, 6 and 12 months post-implantation. Mixed effect modelling was undertaken to compare baseline, 1–6 month and 7–12 month scores between groups. Poisson regression analysis was performed to correlate dosimetric constraints with acute toxicity. Results There was no difference between baseline and post-implantation IPSS scores between 6-fraction and 2-fraction groups. SHIM scores for men treated with 6-fractions had a steeper decline at 1–6 months, but resolved at 7–12 months. Pre-treatment alpha-blocker use correlated with worse short-term acute urinary toxicity. Worsened SHIM score correlated with increasing age, diabetes mellitus and androgen-deprivation therapy. In a dosimetric analysis of outcomes, prostate V150 dose and bladder wall (D01.cc, D1cc, D2cc) dose correlated with increased IPSS score. Conclusion No increased acute genitourinary or sexual dysfunction has been observed in men when transitioning from 6-fraction to 2-fraction HDR monotherapy. A dosimetric correlation was found between the V150 and bladder wall doses for acute urinary toxicity. Future research should continue to standardize and validate dose constraints for prostate HDR monotherapy patients.

Purpose Patients with prostate cancer (PCa) containing Gleason pattern (GP) 5 disease experience a greater and earlier incidence of prostate cancer-specific mortality (PCSM) than general PCa patients. This affords the statistical power to compare PCSM outcomes among different treatment modalities even when restricting the analysis to patients treated in the modern era. The purpose of the present study was to compare the survival outcomes among patients with GP 5 PCa on needle core biopsy or transurethral resection of the prostate who underwent extremely dose-escalated radiation therapy (RT; exemplified by external beam RT with a brachytherapy boost [EBRT + BT]) versus radical prostatectomy (RP) in the modern era. Methods and Materials A total of 7669 men with a diagnosis of GP 5 PCa from 2004 to 2013 who had undergone EBRT + BT or RP were identified using the Surveillance, Epidemiology, and End Results database. After propensity score matching to balance the patient characteristics, PCSM was compared between modalities using a multivariate Fine and Gray competing risk model that accounted for other-cause mortality, with adjustment for age, race, GP, and clinical T stage. Results Patients treated with RP were younger and had a lower burden of GP 5, lower T stage, and lower other-cause mortality than patients who underwent EBRT + BT. After propensity score matching, no difference was found in PCSM between the RP and EBRT + BT groups (adjusted hazard ratio 1.018; P =.910). The cumulative 5-year PCSM incidence rates were 5.6% and 6.1% for patients undergoing RP and EBRT + BT, respectively. Patients with primary GP 5 experienced significantly greater PCSM than those with secondary GP 5, regardless of the treatment modality. Conclusions For patients with GP 5 PCa found on needle core biopsy or transurethral resection of the prostate, RP and EBRT + BT offer equivalent PCSM in a competing risk model after propensity score matching to balance the differences in patient characteristics.

BackgroundThe long natural history of prostate cancer (CaP) limits comparisons of efficacy between radical prostatectomy (RP) and external beam radiotherapy (EBRT), since patients treated years ago received treatments considered suboptimal by modern standards (particularly with regards to androgen deprivation therapy [ADT] and radiotherapy dose-escalation]. Gleason score (GS) 9-10 CaP is particularly aggressive, and clinically-relevant endpoints occur early, facilitating meaningful comparisons.ObjectiveTo compare outcomes of patients with GS 9-10 CaP following EBRT, extremely-dose escalated radiotherapy (as exemplified by EBRT+brachytherapy [EBRT+BT]), and RP.Design, setting, participantsRetrospective analysis of 487 patients with biopsy GS 9-10 CaP treated between 2000 and 2013 (230 with EBRT, 87 with EBRT+BT, and 170 with RP). Most radiotherapy patients received ADT and dose-escalated radiotherapy.Outcome measurements and statistical analysisKaplan-Meier analysis and multivariate Cox regression estimated and compared 5-yr and 10-yr rates of distant metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS).Results and limitationsThe median follow-up was 4.6 yr. Local salvage and systemic salvage were performed more frequently in RP patients (49.0% and 30.1%) when compared with either EBRT patients (0.9% and 19.7%) or EBRT+BT patients (1.2% and 16.1%, p

Background and purpose Second malignancies (SM) after external beam radiotherapy (EBRT) or brachytherapy (BT) for prostate cancer (PCa) are rare but serious sequelae. Materials and methods The Surveillance, Epidemiology, and End Results (SEER) database was used to identify men diagnosed with cT1-2N0M0 PCa between 1999 and 2005, who underwent EBRT, BT or radical prostatectomy (RP). Patients with time interval to second malignancy or follow-up shorter than five and two years were excluded for solid and hematopoietic SM analyses respectively. Risks for solid and hematopoietic SM were evaluated via the multivariate Fine and Gray proportional hazards model. Results EBRT and BT resulted in similar increases in solid and hematopoietic SM compared to RP. In subgroup analysis stratified by treatment modality, only the EBRT cohort demonstrated significantly decreased solid and hematopoietic SM in years 2002–2005 compared to years 1999–2001, with adjusted-hazard ratios of 0.752 ( p =0.001) and 0.815 ( p =0.018) respectively. Conclusions EBRT and BT resulted in statistically equivalent increase in both solid and hematopoietic SM compared to RP. EBRT in more recent years resulted in significantly decreased solid and hematopoietic SM, coinciding with increased utilization of IMRT.

Purpose Outcomes using high-dose-rate (HDR) brachytherapy monotherapy (without androgen deprivation therapy or external beam radiation therapy) for National Comprehensive Cancer Network–defined intermediate-risk (IR) patients are limited. We report our long-term data using HDR monotherapy for this patient population. Methods and Materials One-hundred ninety IR prostate cancer patients were treated 1996–2013 with HDR monotherapy. Biochemical prostate-specific antigen (PSA) failure was per the Phoenix definition. Acute and late genitourinary and gastrointestinal toxicities were graded according to Common Toxicity Criteria of Adverse Events, version 4. Kaplan–Meier (KM) biochemical progression-free survival (BPFS), cause-specific survival, and overall survival rates were calculated. Univariate analyses were performed to determine relationships with BPFS. The median patient age was 66 years (43–90), and the median initial PSA was 7.4 ng/mL. The Gleason score was ≤6 in 26%, 3 + 4 in 62%, and 4 + 3 in 12%. The median treatment BED 1.5 was 254 Gy; 83% of patients were treated with a dose of 7.25 Gy × six fractions delivered in two separate implants. Results With a median follow-up of 6.2 years, KM BPFS at 5/8 years was 97%/90%, cause-specific survival at 8 years was 100%, and overall survival at 5/8 years was 93%/88%. Late genitourinary toxicities were 36.3% Grade 1, 18.9% Grade 2, and 3.7% Grade 3. Late gastrointestinal toxicities were 6.3% Grade 1, 1.1% Grade 2, and no Grade ≥3. Of the patients with no sexual dysfunction before treatment, 68% maintained potency. Age, initial PSA, T stage, Gleason score, prostate volume, and percent positive cores did not correlate with BPFS. Stratifying by favorable vs. unfavorable IR groups did not affect BPFS. Conclusions HDR brachytherapy monotherapy represents a safe and highly effective treatment for IR prostate cancer patients with long-term follow-up.

ObjectivesWe report single-institution clinical outcomes of women treated with stereotactic ablative radiotherapy (SABR) for oligometastatic or progressive gynecological malignancies.Materials and MethodsFrom 2009 to 2015, 47 lesions from 28 patients were treated with SABR and retrospectively analyzed. All patients had oligometastatic (93%) or oligoprogressive (7%) disease. Primary cancer diagnoses were 15 ovarian, 8 endometrial, 2 cervical, 2 vaginal, and 1 uterine carcinosarcoma. Treatment was delivered using a median of 5 fractions to a median total dose of 40 Gy. Targets were grouped by treatment site and assessed for response using Response Evaluation Criteria in Solid Tumors v1.1. Mean biologically effective dose and pre-SABR tumor size were compared with response. Progression-free survival (PFS) was determined using Kaplan-Meier analysis, and toxicity outcomes were graded using Common Terminology Criteria for Adverse Events version 4.03.ResultsMedian follow-up was 12.8 months. Target locations were 17% liver, 21% lung, 17% paraaortic node, 26% other node, and 19% pelvic soft tissue. After treatment, 34% of targets were stable (SD), 32% had a partial response (PR), 17% had a complete response (CR), and 17% had progressive disease (PD). No failures occurred in lung or nodal targets. Mean ± standard deviation pre-SABR tumor diameter was 24 ± 22 mm. There was a significant difference in mean size between lesions that had a favorable (SD, PR, and CR) versus unfavorable response (PD) (17.2 vs 57.6 mm,P= 0.0044). Lesions that responded favorably were also more likely to have received a higher biologically effective dose (79.0 vs 59.6 Gy,P= 0.027). Median PFS was 10.8 months, and 1 patient experienced grade 3 toxicity.ConclusionsThe SABR is a safe and effective local treatment modality in patients with oligometastatic gynecological disease. Distant progression remains the primary mode of failure in this patient population. In carefully selected patients, a combination of systemic treatment and SABR may offer long-term PFS.

Purpose The American Brachytherapy Society (ABS) consensus guidelines for high-dose-rate (HDR) prostate brachytherapy suggest 11 different dose constraints for the urethra. The purpose of this study is to evaluate whether a single urethral constraint of D0.1 cm3 Methods This is a retrospective study of 18 consecutively treated HDR prostate brachytherapy patients treated between May 2018 to November 2018. Nine patients underwent HDR brachytherapy combined with external beam radiation therapy, and nine underwent HDR brachytherapy as monotherapy. Additional DVH values were extracted for the whole, proximal, middle, and distal urethra and compared for differences. Results None of the ABS suggested constraints were violated when optimizing the urethra D0.1 cm3 dose to be less than 110% of the prescription. An evaluation of the DVHs for the whole, proximal, middle, and distal urethra showed a large variation in the shape of the remainder of the DVH for all parts of the urethra. The largest standard deviations in dose to the whole and middle urethra were at the V14 dose level, and that to the proximal and distal urethra were at the V10 dose level. Conclusion A single urethral dose constraint of D0.1 cm3