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Background and Purpose: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. Materials and Methods: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. Results: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2–3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. Conclusion: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.

BackgroundAlthough clinical features of multi-parametric magnetic resonance imaging (mpMRI) have been associated with biochemical recurrence in localized prostate cancer, such features are subject to inter-observer variability.ObjectiveTo evaluate whether the volume of the dominant intraprostatic lesion (DIL), as provided by a deep learning segmentation algorithm, could provide prognostic information for patients treated with definitive radiation therapy (RT).Design, Setting, and ParticipantsRetrospective study of 438 patients with localized prostate cancer who underwent an endorectal coil, high B-value, 3-Tesla mpMRI and were treated with RT between 2010 and 2017.InterventionRT.Outcome Measurements and Statistical AnalysisBiochemical recurrence and metastasis risk, assessed with a cause-specific Cox regression and time-dependent receiver operating characteristic analysis.Results and LimitationsThe artificial intelligence (AI) model identified DILs with an area under the receiver operating characteristic curve (AUROC) of 0.827 at the patient level. For the 233 patients with available PI-RADS scores, with a median follow-up of 5.6 years, AI-defined DIL volume was significantly associated with biochemical failure (adjusted hazard ratio 1.54, 95% confidence interval 1.09-2.17, p=0.014) after adjustment for PI-RADS score. Among all 438 patients with a median follow-up of 6.9 years, the AUROC for predicting 7-year biochemical failure for AI volume (0.790) was similar to that for an expanded National Comprehensive Cancer Network (NCCN+) category (p=0.17). The AUROC for predicting 7-year metastasis for AI volume trended towards being higher compared to NCCN+ categories (0.854 vs 0.769, p=0.06).ConclusionsA deep learning algorithm could identify the DIL with good performance. AI-defined DIL volume may be able to provide prognostic information independent of the NCCN+ risk group or other radiologic factors for patients with localized prostate cancer treated with RT.

Interstitial and intracavitary gynecological HDR brachytherapy involve precise, localized delivery to targets with high dose gradients, sparing adjacent organs at risk (OAR). Due to the proximity of the rectum, bowel and bladder to the target, deviations in the applicator or catheter with respect to patient anatomy can significantly increase dose to OAR. The magnitude and direction of applicator and catheter migration at each fraction was assessed for template interstitial and tandem and ring (TR) cohorts. The cohort included twelve gynecological patients with intact cervical lesions treated with external beam and brachytherapy. Pre-treatment CT images were registered to the simulation CT with respect to the target. Treatment catheter positions transformed into the planning CT coordinate system to evaluate localized catheter displacement and dose distributions calculated at each fraction. Dose was evaluated on the planning CT with planning contours and dwell locations at treatment position. Absolute deviation, depth and deflection angle for all patients were 4.6 ± 4.2 mm, -1.4 ± 4.0 mm, and 3.1 ± 2.3° respectively (n = 516 catheter positions for all treatment fractions and patients, mean ± SD). Absolute catheter deviation and deflection magnitude for interstitial treatments increased overall with each subsequent fraction with an overall increase of catheter retraction at each fraction (p0.005, n = 492 catheters, Kruskal-Wallis). A target EQD2 D90 reduction of 10 ± 10% and 7.7 ± 8.7% of the planned dose for interstitial and TR cohorts respectively. There was an overall increase in bladder and rectal doses at each fraction. Catheter tracking in interstitial and intracavitary gynecological treatments with CT imaging revealed significant changes in catheter positioning with respect to the target volume. Overall deviations increased in magnitude with each subsequent fraction in the interstitial treatments. This caused patient dosimetry deviations, including target dose reduction and adjacent OAR doses changes.

Objective Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer associated with worse survival outcomes in African American (AA) patients. This study evaluated tumor miRNA expression by race, clinical and tumor characteristics, and survival outcomes. Methods FFPE tumor tissue from hysterectomy specimens was identified for 29 AA cases. Case matching was performed by computer-based random assignment in a 1:1 ratio with Caucasian controls based on age, stage and histologic subtype (pure vs. mixed). RNA was extracted from 77 specimens (54 tumors and 23 matched normal endometrium). MicroRNA array profiling was performed by microRNA Hi-Power Labeling (Hy3/Hy5) and hybridization to miRCURY LNA microRNA Array 7th Gen. Results Clinical and treatment characteristics were similar for cases and controls, although use of adjuvant radiation was less common in African Americans (p = 0.03). Of 968 miRNAs analyzed, 649 were differentially expressed in normal endometrium vs. tumor. When compared by race, histologic subtype, stage or presence of LVI, no differentially expressed miRNAs were identified. In patients with disease recurrence at 3 years, the three most upregulated miRNAs were miR-1, miR-21-5p and miR-223. Of these, increased miR-223 expression (>median) was associated with worse OS (p = 0.0496) in an independent dataset (TCGA dataset) comprising of 140 patients with USC (mixed or pure serous). After adjusting for age, ethnicity and BMI, upregulation of miR-223 remained risk factor for death (adjusted HR 2.87, 95% CI 1.00–8.27). Conclusions MiRNA profiling did not identify biological differences between AA and Caucasian patients with USC. Upregulation of miR-223 may be a prognostic factor in USC.

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.

Objective. The feasibility of MRI-only treatment planning (MRTP) for interstitial high-dose rate (HDR) brachytherapy (BT) was investigated for patients diagnosed with gynecologic cancer. Approach. A clinical MRTP workflow utilizing a ‘pointwise encoding time reduction with radial acquisition (PETRA)’ sequence was proposed. This is a clinically available MRI sequence optimized to improve interstitial catheter-tissue contrast. Interstitial needles outside the obturator region were reconstructed using MR images only. For catheters penetrating through the obturator, a library-based reconstruction was proposed. In this work, dwell coordinates from the clinical CT-based reconstruction were used as the surrogate for the library-based approach. For MR-only plan, dwell times were activated and assigned as in the clinical plans. The catheter reconstruction was assessed by comparing dwell position coordinates. The dosimetric comparisons between a clinical plan and MR-only plan were assessed for physical and EQD2 dose and volume parameters for D 90, D 50 and D 98 for clinical target volume (CTV) and D 2cc, D 0.1cc and D 5cc for OARs. Main results. Catheter reconstruction was possible using the optimized PETRA sequence on MR images. An overall reconstruction difference of 1.7 ± 0.5 mm, attributed to registration-based errors, was found compared to the CT-based reconstruction. The MRTP workflow has the potential to generate a treatment plan with an equivalent dosimetric quality compared to the conventional CT/MRI-based approach. For CTV D 90, physical and EQD2 dose and volume parameter differences were 1.5 ± 1.9% and 0.7 ± 1.0 Gy, respectively. For D 2cc OARs, DVH (EQD2) differences were −0.4 ± 1.1% (−0.2 ± 0.5 Gy), 0.5 ± 2.8% (0.2 ± 1.3 Gy) and −0.5 ± 1.4% (−0.2 ± 0.5 Gy) for rectum, bladder, and sigmoid, respectively. Significance. With the proposed MRTP approach, CT imaging may no longer be needed in HDR BT for interstitial gynecologic treatment. A proof-of-concept study was conducted to demonstrated that MRTP using PETRA is feasible, with comparable dosimetric results to the conventional CT/MRI-based approach.

Background Prostate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). However, relative SM probabilities following treatment with contemporary radiation techniques such as stereotactic body radiotherapy (SBRT) or moderately hypofractionated intensity modulated radiotherapy (HF-IMRT) remain unknown. Methods A cohort analysis was performed of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up comparing SM probability amongst men receiving either radical prostatectomy (RP), conventionally fractionated intensity-modulated radiotherapy (CF-IMRT), HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models, which were used to generate predicted probabilities. Additionally, propensity score-adjusted pairwise assessments of modalities were performed. Results For 303,432 patients included in the study, median follow-up was 9.08 years (IQR 7.01–11.21). Predicted rates of SM by treatment modality and adjusted odds ratios (AOR) for development of SM (referent: RP) were: 6.0% for RP (AOR n/a), 7.1% for CF-IMRT (AOR 1.20, 95%CI 1.14–1.25, P Conclusions Conventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy but not stereotactic body radiotherapy were associated with increased probability of a second malignancy compared to radical prostatectomy. Patients treated with SBRT may be at lower risk of second malignancy due to improved conformality, radiobiological differences or patient selection. The possibility that SBRT in select patients may minimize the probability of SM underscores the need for assessment of second malignancy risk in prospective studies of SBRT.

ImportanceHypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT.ObjectiveTo evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT.Design, Setting, and ParticipantsThis randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to μg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality.Main Outcomes and MeasuresFor the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%.ResultsOf the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% (P P = .01).Conclusions and RelevanceThe trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT.Trial RegistrationClinicalTrials.gov Identifier: NCT04189913

Purpose Brachytherapy is critical for the curative treatment of locally advanced cervical cancer. Although brachytherapy use is declining in the United States (U.S.), novel interstitial or intracavitary applicators and advances in image guidance for applicator placement and treatment planning have allowed for tumor dose escalation while reducing normal tissue toxicity. Recent survey data have suggested insufficient brachytherapy training for radiation oncology trainees in the United States. This study aimed to address these gaps by developing and piloting a simulation-based education (SBE) workshop for MR-guided cervical cancer brachytherapy. Methods and Materials An SBE workshop was developed for graduate medical education (GME) trainees focusing on MR-guided brachytherapy for cervical cancer. Four hands-on stations, simulating aspects of the procedure, were led by a team of gynecological brachytherapy experts. The learners were radiation oncology residents and fellows in a U.S. GME training program. The primary outcome was feasibility, assessed by completion of the workshop within the time constraints of the curriculum. Learners completed preworkshop and postworkshop surveys to provide information on efficacy. Results The workshop was successfully completed in a 1-h block of GME didactic time. Ten trainees completed all four stations, and all completed preworkshop and postworkshop surveys, which showed improvements in knowledge and technical proficiency. Feedback was positive, and trainees requested additional learning opportunities. Conclusions This study showed that GME-focused SBE in MR-guided cervical cancer brachytherapy was feasible. SBE provided a nonclinical environment in which to practice aspects of MR-guided brachytherapy. Ongoing work includes collaboration with other U.S. institutions. Future studies should focus on international adaptation.

To inform treatment decisions for patients with high-risk prostate cancer (PCa), we determined rates of adverse pathologic factors and overall survival (OS) among subgroups of high-risk men.Using the National Cancer Database, 89,450 patients with clinical N0M0 unfavorable intermediate-risk, favorable high-risk (cT1c, Gleason 6, prostate-specific antigen [PSA]20 ng/mL or cT1c, biopsy Gleason 8, PSA10 ng/mL), standard high-risk (all other cT3a, biopsy Gleason ≥ 8, or PSA20 ng/mL), or very high-risk (cT3b-T4 or biopsy primary Gleason pattern 5) PCa treated with radical prostatectomy were identified. Rates of adverse pathologic factors (positive surgical margins, T4 disease, or pathologic lymph node involvement) were compared across subgroups.Patients with unfavorable intermediate-risk (n = 31,381) and favorable high-risk (n = 10,296) disease had similar rates of adverse features (7.6% vs 8.2%, adjusted odds ratio 1.00, 95% confidence interval 0.92-1.08, P= .974). Patients with standard high-risk (n = 30,260) or very high-risk (n = 7513) disease were significantly more likely to have adverse pathologic factors (15.9% and 26.5%, P.001 for both). Patients with unfavorable intermediate-risk and favorable high-risk disease had similar 5-year OS (95.7% vs 95.1%, adjusted hazard ratio 1.06, 95% confidence interval 0.92-1.21, P = .411) but better OS compared to standard and very high-risk patients (93.4% and 88.1%, respectively; P.001).Unfavorable intermediate-risk or favorable high-risk PCa patients had low rates of adverse pathologic factors and similar OS. In contrast, standard and very high-risk PCa patients had significantly higher rates of adverse pathologic factors and worse OS. This 3-tiered subclassification of high-risk disease may allow for improved treatment selection among patients considering surgery.

BACKGROUND Comparative effectiveness research (CER) using national registries influences cancer clinical trial design, treatment guidelines, and patient management. However, the extent to which treatment selection bias (TSB) affects overall survival (OS) in cancer CER remains poorly defined. We sought to quantify the TSB effect on OS in the setting of low-risk prostate cancer, where 10-year prostate cancer-specific survival (PCSS) approaches 100% regardless of treatment modality. METHODS The Surveillance, Epidemiology, and End Results database was queried for patients with low-risk prostate cancer (cT1-T2a, PSA

Purpose To evaluate MRI characteristics in vaginal recurrence of endometrial cancer (EC) including tumor volume shrinkage during salvage radiotherapy, and to identify imaging features associated with survival. Methods Patients with vaginal recurrence of EC treated with external beam radiotherapy (EBRT) followed by brachytherapy (BT), and with available pelvic MRI at two time points: baseline and/or before BT were retrospectively identified from 2004 to 2017. MRI features including recurrence location and tissue characteristics on T2- and T1-weighted images were evaluated at baseline only. Tumor volumes were measured both at baseline and pre-BT. Survival rates and associations were evaluated by Cox regression and Fisher’s exact test, respectively. Results Sixty-two patients with 36 baseline and 50 pre-BT pelvic MRIs were included (24/62 with both MRIs). Vaginal recurrence of EC was most commonly located in the vaginal apex (27/36, 75%). Tumors with a post-contrast enhancing peripheral rim or low T2 signal rim at baseline showed longer recurrence-free survival (RFS) (HR 0.2, 95% CI 0.1–0.9, P P P Conclusion Vaginal recurrences with rim enhancement at baseline MRI predicted improved RFS, while tumor volume shrinkage at pre-BT did not. Distal vaginal recurrence was more common in patients with LVSI and adjuvant RT at EC diagnosis.

PURPOSE: The following is a summary of discussion at a United States FDA (Food and Drug Administration) public workshop reviewing potential trial designs and end points to develop therapies to treat localized prostate cancer. MATERIALS AND METHODS: The workshop focused on the challenge that drug and device development to treat localized prostate cancer has been limited by the large trial sizes and lengthy timelines required to demonstrate an improvement in overall or metastasis-free survival and by the lack of agreed on alternative end points. Additionally, evolving treatment paradigms in the management of localized prostate cancer include the widespread use of active surveillance of patients with low and some intermediate risk prostate cancer, and the availability of advances in imaging and genomics. RESULTS: The workshop addressed issues related to trial design in this setting. Attendees discussed several potential novel end points such as a delay of morbidity due to radiation or prostatectomy and pathological end points such as Gleason Grade Group upgrade. CONCLUSIONS: The workshop provided an open forum for multiple stakeholder engagement to advance the development of effective treatment options for men with localized prostate cancer.

178 Background: Intensification of systemic therapy beyond ADT, with use of novel hormonal agents (NHAs), and radiotherapy (RT) to the prostate have a proven survival benefit in mHSPC. MDT has shown benefit in delaying need for ADT in omHSPC in phase 2 trials. Combination of fixed-duration systemic therapy with MDT (and RT to the prostate in de novo mHSPC) may produce long-term remission and treatment-free survival in selected patients with omHSPC. Methods: Patients with de novo or recurrent omHSPC treated at our institution between 2010-2020 with MDT (+/- prostate RT if de novo) and a fixed duration of systemic therapy completed by September 2022 were identified. There was no limit on number of metastases as long as all sites could be treated with MDT in the view of the treating physician. Oligometastases were defined as bone or soft tissue lesions beyond the pelvic lymph nodes identified on conventional scans (CT, bone scan, MRI) or PET (fluciclovine or PSMA). The primary outcome was freedom from biochemical recurrence (BCR), defined as PSA of >0.02 (if the patient had undergone prior radical prostatectomy) or >2+nadir (if the patient underwent RT) after completion of systemic therapy. Testosterone recovery was defined as serum testosterone >150ng/dL attained after completion of systemic therapy. BCR-free survival after completion of systemic therapy was estimated using the Kaplan Meier method. Results: 32 patients were included. Median age at diagnosis of mHSPC was 67 (range 52-78). 12 patients (38%) had de novo mHSPC while 20 (63%) had oligorecurrent HSPC. Detection of omHSPC was by conventional scans in 23 patients (72%) and by PET only in 9 (28%), and median number of oligometastases was 1 (range 1-6). Median PSA at start of therapy for omHSPC was 8.2ng/mL (range 0.4-1244), with systemic therapy most commonly comprising of ADT and a NHA (abiraterone, enzalutamide, apalutamide, n=26 [82%]); 6 patients (19%) had ADT alone. Median duration of systemic therapy was 24 months (range 6-36), with 3 men (9%) having received prior systemic therapy for mHSPC. MDT consisted of external beam RT (EBRT, n=10, 31%), EBRT + stereotactic body radiotherapy (SBRT, n=8, 25%), or SBRT alone (n=14, 44%). At a median follow-up of 44 months (range 24-127) and 20 months (2-103) after start and completion of systemic therapy respectively, 9 patients (28%) had BCR and 23 (72%) remained free of BCR, of whom 13 (57%) had testosterone recovery. The estimated 2-year BCR-free survival after completion of systemic therapy was 73% (95% CI 51-86). Conclusions: In this carefully selected cohort of men with omHSPC, estimated 2-yr BCR-free survival after completion of therapy was >70% with ~2 years of ADT +/- NHA along with MDT +/- prostate RT (if de novo). Longer follow-up is needed to determine whether this translates to a durable treatment-free remission, and possibly cure, in these patients with omHSPC.

OBJECTIVES The objective of this study was to determine if deficiency of mismatch repair (dMMR) proteins in patients with early-stage favorable endometrial cancer treated with vaginal brachytherapy (VB) is associated with increased recurrence. MATERIALS AND METHODS A multi-institutional retrospective cohort study of 141 patients with stage I to II grade 1 and 2 endometrioid adenocarcinoma treated with surgery and adjuvant VB was performed to compare recurrence risk in dMMR (n=41) versus MMR-preserved (pMMR) (n=100). Additional clinical and pathologic risk factors were also collected. Univariate analysis and multivariable analysis Cox regression analysis was performed to identify factors associated with any recurrence. Kaplan-Meier method and log rank test were used to compare recurrence free survival and overall survival (OS). RESULTS Median follow up was 42 months. Forty-one patients (29%) were dMMR. There were 7 recurrences (17%) in dMMR versus 4 recurrences (4%) in pMMR (P=0.009). On univariate analysis of any recurrence, both dMMR (hazard ratio: 5.3, P=0.008) and stage (hazard ratio: 3.8, P=0.05) were statistically significantly associated with time to first recurrence. The 5-year recurrence free survival was 90% (95% CI: 73%-96%) in pMMR versus 61.0% (95% CI: 19%-86%) in dMMR (P=0.003). Five-year OS was 96% (95% CI: 76%-99%) in pMMR versus 86% (95% CI: 62%-95%) in dMMR (P=0.03). CONCLUSIONS MMR deficiency in stage I to II grade 1 to 2 endometrial cancer patients treated with adjuvant VB alone was associated with statistically significant increased risk for any recurrence and worse OS. MMR status may be an important prognosticator in this cohort of patients warranting adjuvant treatment intensification in the clinical trial setting.

A pointwise encoding time reduction with radial acquisition (PETRA) sequence was optimized to detect empty catheters in interstitial (HDR) brachytherapy with clinically acceptable spatial accuracy for the first time. Image quality and catheter detectability were assessed in phantoms, and the feasibility of PETRA's clinical implementation was assessed on a gynecological cancer patient.Empty catheters embedded in a gelatin phantom displayed positive signal on PETRA and more accurate cross-sections than on clinically employed T2-weighted sequences, differing by 0.4 mm on average from their nominal 2 mm diameter. PETRA presented minimal susceptibility differences and a symmetric metal artifact, contrary to the clinical sequences. The PETRA-CT catheter tip position differences assessed by a treatment planning system (TPS) were1 mm. PETRA also detected an interstitial template with empty catheters penetrating a poultry phantom and fused very well with CT. Interstitial catheter positional difference between PETRA and CT images was1 mm on average, increasing with distance from isocenter. All interstitial catheters and the employed interstitial template were detected on PETRA images of an endometrial adenocarcinoma patient. Empty needles were traceable using a TPS, with higher spatial resolution and more favorable contrast than on T2-weighted images used for contouring. A treatment plan could be produced by combining information from PETRA for catheter detection and from T2-weighted images for tumor and organs delineation.PETRA detected successfully and accurately interstitial catheters in phantoms. Its first clinical implementation shows a potential for MR-only treatment planning in interstitial HDR brachytherapy.

An 83-year-old woman presented with postmenopausal bleeding ultimately leading to surgery and a final diagnosis of stage IB grade 3 endometrioid endometrial adenocarcinoma. The tumor board reviewed current literature regarding the efficacy of sentinel lymph node dissection in appropriately allocating stage in high-grade endometrial cancer. The optimal role of adjuvant treatment in this setting is unclear. Current literature surrounding adjuvant radiation and chemotherapy, as well as current practices in molecular diagnostics for endometrial cancer were reviewed. The tumor board concluded that literature surrounding sentinel lymph node evaluation in high-grade endometrial cancers is robust enough to incorporate into clinical practice. Based on the best available evidence, a decision was made to treat with external beam radiotherapy and withhold chemotherapy.

Black women have the highest incidence and mortality from cervical cancer in the United States. This study evaluated whether racial disparities in the receipt of brachytherapy (BT) for locally advanced cervical cancer mediate survival differences by race using the National Cancer Database.A retrospective cohort study was performed using 16,116 women with stage IB2-IVA cervical cancer treated from 2004 to 2014. Women who did not receive external beam radiation therapy, those with unknown survival data or stage, and those status post hysterectomy or pelvic exenteration were excluded. Multivariate logistic regression was performed to evaluate factors associated with BT use. Using a propensity score adjusted model with inverse probability treatment weighting, adjusted hazard ratios for overall survival were calculated, including an interaction term between BT and race.Of 16,116 patients, 19.2% were black and 55.8% received BT. Black women were significantly less likely to receive BT (AOR 0.87, 95% confidence interval [CI] 0.79-0.96, p = 0.007) and had worse all-cause mortality (median survival 3.9 years [95% CI 3.6-4.6] versus 5.2 years [95% CI 4.9-5.5] for non-black women, p 0.001). In the adjusted model, black patients had an increased risk of death compared to non-black patients (AHR 1.14, 95% CI 1.05-1.24; p = 0.002) among women who did not receive BT. However, there was no difference in survival by race when both groups received BT (AHR 1.04, 95% CI 0.95-1.13, p = 0.42; p-interaction = 0.005).Black women with locally advanced cervical cancer are less likely to receive brachytherapy, which mediates survival differences by race. Improving access to brachytherapy may improve overall survival.

IntroductionTo evaluate clinical outcomes for patients with localized recurrent ovarian cancer treated with salvage radiotherapy.MethodsIn a retrospective single institutional analysis, we identified 40 patients who received salvage radiotherapy for localized ovarian cancer recurrence from January 1995 to June 2011. Recurrent disease was categorized as: pelvic peritoneal (45%, 18), extraperitoneal/nodal (35%, 14), or vaginal (20%, eight). Actuarial disease-free and overall survival estimates were calculated by Kaplan–Meier and prognostic factors evaluated by the Cox proportional hazards model.ResultsMedian follow-up was 42 months. Median patient age was 54 years (range, 27–78). Histologic subtypes were: serous (58%, 23), endometrioid (15%, six), clear cell (13%, five), mucinous (8%, three), and other (8%, three). At the time of salvage radiotherapy, surgical cytoreduction was performed in 60% (24) and 68% (27) had platinum-sensitive disease. Most patients (63%, 25) received salvage radiotherapy at the time of first recurrence. Relapse after salvage radiotherapy occurred in 29 patients at a median time of 16 months and was outside the radiotherapy field in 62%. 18 At 3 years, disease-free and overall survival rates were 18% and 80%, respectively. On multivariate analysis, non-serous histology (hazards ratio 0.3, 95% CI 0.1–0.7) and platinum-sensitivity (hazards ratio 0.2, 95% CI 0.1–0.5) were associated with lower relapse risk. Platinum-sensitivity was also associated with overall survival (hazards ratio 0.4, 95% CI 0.1–1.0). Four patients (10%) were long-term survivors without recurrence 5 years after salvage radiotherapy. Of the five patients with clear cell histology, none experienced relapse at the time of last follow-up.DiscussionPatients with non-serous and/or platinum-sensitive ovarian cancer had the greatest benefit from salvage radiotherapy for localized recurrent disease. Although relapse was common, radiotherapy prolonged recurrence for > 1 year in most patients and four were long-term survivors.

Background While the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) is known to improve overall survival (OS) in Gleason 8–10 (Grade Group 4–5) prostate cancer (PCa), it has been hypothesized that Gleason 9–10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT. Objective To examine the association between ADT and OS for Gleason 8 versus Gleason 9–10 PCa. Design, setting, and participants A retrospective cohort study of 20 139 men from the National Cancer Database with localized or locally advanced, Gleason 8–10 PCa who received EBRT. Data were collected from 2004 to 2012. Intervention ADT. Outcome measurements and statistical analysis Cox proportional hazards regression was used to examine the association between ADT and OS. Results and limitations Overall, 9509 (78%) of the 12 160 men with Gleason 8 disease and 6908 (87%) of the 7979 men with Gleason 9–10 disease received ADT. On multivariable analysis, ADT was associated with a significant improvement in OS for Gleason 8 patients (adjusted hazard ratio 0.78, 95% confidence interval 0.70–0.87, p Conclusions In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results suggest that Gleason 9–10 disease derives less survival benefit from ADT and that a higher Gleason score predicts lesser benefit. Consideration should be given to treatment intensification for Gleason 9–10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings. Patient summary In this study, we examined the effect of androgen deprivation therapy (ADT) for Gleason 8 (Grade Group 4) versus Gleason 9–10 (Grade Group 5) prostate cancer. We found that Gleason 9–10 disease may derive a smaller survival benefit from ADT than Gleason 8 disease.

To report clinical outcomes and dosimetric predictors of late toxicity for patients with vaginal recurrence of endometrial cancer treated with brachytherapy in the re-irradiation setting.On retrospective review, 32 patients with vaginal recurrence of endometrial cancer received salvage brachytherapy with or without pelvic radiotherapy (RT) from 06/2003-12/2017. Prior RT modalities were vaginal brachytherapy (19, 59%), pelvic RT (7, 22%) or both (6, 19%). Image-guided brachytherapy was performed with CT- (25, 78%) or MR-guidance (7, 22%). Vaginal control, recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier method. Late toxicity was graded by Common Toxicity Criteria for Adverse Events.Median time from prior RT to re-irradiation was 22 months (range, 4-140). Salvage RT modalities were pelvic RT and brachytherapy (25, 78%) or brachytherapy alone (7, 22%). With median follow-up of 47 months, 3/5-year vaginal control, RFS and OS rates were 64/56%, 47/41% and 68/42%, respectively. Six patients (19%) had no evidence of disease at 85-155 months. Late grade 2/3 GI, GU and vaginal toxicity rates were 13%/16%, 19%/13%, and 9%/16%. Cumulative D2cc rectum (sum of prior and salvage RT courses) was predictive of grade 2+ and grade 3 GI toxicity. Cumulative D2cc rectum for an estimated 10% risk of late grade 2+ and 3 GI toxicity was 86 Gy and 92 Gy, respectively.Salvage image-guided brachytherapy in the re-irradiation setting results in modest local control and increased late toxicity for localized recurrent endometrial cancer. With long-term disease control, cumulative D2cc rectum may be used to reduce late GI complication risk.

PURPOSE The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. RESULTS LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen

PURPOSE/OBJECTIVE(S) Stereotactic body radiotherapy (SBRT) is increasingly being utilized in the management of localized prostate cancer. MR guided adaptive radiotherapy may be a valuable tool for delivery of prostate SBRT as it allows for MR based soft tissue contouring, real time MR motion management and daily plan adaptation to account for interfraction anatomic variability. The goal of the present study is to identify dosimetric gains that can be achieved with an MR guided adaptive prostate SBRT platform and describe acute clinical outcomes. MATERIALS/METHODS We reviewed our institutional experience treating patients with prostate cancer with MR guided adaptive SBRT to a dose of 36.25 Gy in 5 fractions. The adaptive workflow involves development of an "original" plan which is re-optimized daily based on anatomical variation for each fraction. "Predicted" plan dosimetry is generated for each fraction by re-calculating the original plan on the re-contoured daily anatomy, estimating what would have been delivered without adaptive capabilities. A "re-optimized" plan is developed based on the anatomy of the day to improve target coverage and organ-at-risk (OAR) metrics. Wilcoxon rank sum testing was used to compare predicted dosimetry to re-optimized dosimetry. Acute urinary and GI toxicity rates were assessed according to CTCAE v5. RESULTS A cohort of 16 patients treated was analyzed with median follow up time of 3 months. Acute G2+ GU toxicity was observed in 19% and acute G2+ GI toxicity in 6%. No G3+ events were noted. Comparison of dosimetry metrics for PTV coverage, urethra, rectum and bladder are shown in table 1; 100% of fractions required plan adaptation due to either exceeding OAR metrics (68%) or sub-optimal PTV coverage (33%). Adaptive planning increased the proportion of fractions meeting prescription metrics for PTV coverage (V34.44 from 71% to 100%), urethra (V38.78 from 58% to 100%) and rectum (V38.06 from 80% to 100%). Urethral metrics were most frequently violated in predicted plans (42% of fractions) and re-optimized to acceptable dosimetry in 100% of fractions. Re-optimization significantly improved PTV coverage, rectal metrics and urethral metrics. CONCLUSION Online adaptive re-optimization significantly improved plan dosimetry and achieved minimal acute toxicity. The clinical benefits of MR guided adaptive prostate SBRT for optimizing target coverage with urethral protection warrant further investigation.

PURPOSE/OBJECTIVE(S) Prostate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). Relative SM probabilities following stereotactic body radiotherapy (SBRT) or moderately hypofractionated radiation (HF-IMRT) remain unknown. We hypothesized that the probability of SM following SBRT or HF-IMRT would differ compared with conventionally fractionated intensity modulated radiotherapy (CF-IMRT). MATERIALS/METHODS Cohort analysis of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up compared SM probability amongst men receiving either radical prostatectomy (RP), CF-IMRT, HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models. Sensitivity analyses were conducted to evaluate differences in SM stratified by year of treatment and follow up length. Propensity score-adjusted pairwise assessments of modalities were also performed. RESULTS For 303,432 patients, median follow-up was 9.08 years (IQR 7.01 - 11.21), and median age was 64 years (IQR 58-69). Crude rates of SM by treatment modality were: 5.2% for RP, 8.9% for CF-IMRT, 7.7% for HF-IMRT, 7.9% for BT, and 5.3% for SBRT. Adjusted odds ratios (AOR) for development of SM (referent: RP) were: CF-IMRT vs. RP 1.20 (95% CI 1.14-1.25, P < 0.001), HF-IMRT vs. RP 1.25 (95% CI 1.01-1.55, P = 0.045), BT vs. RP 1.11 (95% CI 1.07-1.16, P < 0.001), and SBRT vs. RP 0.95 (95% CI 0.81-1.12, P = 0.567). Sensitivity analyses confirmed higher probability of SM comparing CF-IMRT to RP (P < 0.01 for all) and no statistically significant difference comparing SBRT to RP at all year and follow-up length groupings (P = NS for all). On propensity score-adjusted analysis, SBRT was associated with lower probability of SM compared to CF-IMRT (AOR 0.78, 95% CI 0.66-0.93, P = 0.005); no significant difference was found when SBRT was compared to RP (AOR 0.86, 95% CI 0.73-1.03, P = 0.102). CONCLUSION Conventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy, but not stereotactic body radiotherapy, were associated with increased probability of a second malignancy compared to radical prostatectomy. Our findings underscore the need for assessment of second malignancy risk in prospective studies of SBRT.

Purpose/Objective(s) In the last several decades, utilization of standard of care brachytherapy (BT) for locally advanced cervical cancer has declined, with increasing use of external alternatives associated with suboptimal outcomes. Emerging evidence implicates under-reimbursement but is incomplete, as prior studies have relied on surveys and lacked indirect costs. The impact of the upcoming Radiation Oncology Alternative Payment Model (RO-APM) on these trends is also unclear. This study used time-driven activity-based costing (TDABC) to compare the true cost of standard of care external beam radiotherapy (EBRT) plus BT boost with current and proposed reimbursement policy. We hypothesized that TDABC would reveal under-reimbursement of BT, which will be worsened under the RO-APM. Materials/Methods TDABC was used to map out the entire patient care cycle, accounting for both direct and indirect costs. Costs were estimated by multiplying prospectively collected timestamps from a 66-patient cohort with nationally derived capacity cost rates for personnel, space, equipment, consumables, and overhead. Current fee-for-service (FFS) and proposed RO-APM rates were derived from Current Procedural Terminology (CPT) codes and public notices and used to calculate reimbursement-cost ratios. Results The direct cost of standard of care radiotherapy was $16435. Indirect costs and MRI guidance added $6690 and $1280. BT and EBRT total costs were higher than previously estimated using direct cost, survey based TDABC ($13663 vs $8609 and $9462 vs $4090, respectively). Although BT cost 44% more than EBRT, under FFS policy, it was reimbursed 12% less ($16145 vs $19769; 45% vs 55% of total payment), resulting in a > 4-fold lower margin. The reimbursement-cost ratio for BT vs EBRT was 1.18 vs 2.09. Switching to the RO-APM reduced these ratios to 0.76 vs 1.34 (using the FFS 45% vs 55% split in payment). Physician payment was less than cost of care (BT = 0.70). Conclusion Unlike traditional measurements indexed on charges, TDABC more accurately estimates the true cost of care, particularly when using prospective timestamps and indirect costs. Current FFS rates undervalue the cost of BT relative to EBRT, which may be exacerbated by the RO-APM, incentivizing external alternatives (such as external boosts) over definitive care. TDABC can help policymakers align reimbursement with cost to mitigate declining BT usage, which may be worsening patient outcomes in an already underserved population.

Purpose: Outcomes of stereotactic body radiation therapy (SBRT) with respect to androgen receptor signaling inhibitors (ARSI) have not been characterized for oligometastatic prostate cancer. We sought to characterize prostate specific antigen (PSA) response and progression-free survival (PFS) after SBRT among men who have progressed on ARSI therapy in the oligometastatic castration-resistant setting. Methods and Materials: A single-institution retrospective analysis was performed for men with ARSI-resistant, oligometastatic, castrate-resistant prostate cancer (omCRPC). Intervention consisted of SBRT. PSA reduction greater than 50% and median PFS (PSA or radiographic progression) as determined by routine care comprised outcome measurements. Cox regression analysis was used to determine factors influencing PFS. Results: Thirty-five men with ARSI-resistant omCRPC and 65 lesions treated with SBRT were followed for a median of 17.2 months. In 63% of men PSA reduction greater than 50% was achieved. Median PFS was 9.0 months. Incomplete ablation (defined as the presence of untreated lesions after SBRT or receipt of prior palliative radiation therapy doses) was associated with worse PFS (hazard ratio 4.21 [1.74-10.19]; P < .01). For a subgroup of 22 men with complete ablation of metastatic sites with SBRT, the median PFS was 13.1 months. One-year overall survival was 93.1% (95% confidence interval, 84.4-100). Conclusions: SBRT may augment the efficacy of ARSI in omCRPC, provided that all lesions receive ablative radiation doses. Future prospective study of SBRT for men receiving ARSI is warranted.

Purpose Clinical trials assessing evaluation prostate stereotactic body radiation therapy (SBRT) have used a wide range of allowed doses to the intraprostatic urethra, but the relationship between urethral dose and urinary toxicity has not been thoroughly evaluated. The goal of this study was to characterize urinary toxicity outcomes according to urethral dose administered during prostate SBRT. Methods and Materials The MEDLINE (PubMed) database was searched for published prospective studies of prostate SBRT through August 2020 that documented a maximum urethral dose metric (MUDM). Reported acute and late urinary toxicity rates were collected. Logistic regression and weighted Pearson correlation models were used to assess associations between urinary toxicity rates and MUDM. Results Twenty-three unique studies (n = 2232 patients) met the inclusion criteria and included a wide range of MUDMs (equivalent dose in 2 Gy fractions [EQD2]: 69-141.75 Gy; α/β = 3 Gy). The median follow-up ranged from 3 to 67 months (median, 32 months). On logistic regression analysis, the MUDM EQD2 was significantly associated with multiple urinary toxicity endpoints, including acute grade (G) 2+ (odds ratio [OR], 1.02; P Conclusions Radiation dose to the urethra correlates closely with urinary toxicity in patients with prostate cancer treated with SBRT. Attention should be paid to the urethral dose when delivering prostate SBRT to high doses, and approaches for urethral dose reduction warrant further investigation.

PROBLEM Cervical cancer screening strategies in the United States include cotesting (human papillomavirus (HPV) with cytology), primary HPV with genotyping and reflex cytology, and cytology alone. An ongoing challenge is the appropriate triage of patients to colposcopy to those at highest risk. We investigated whether incorporation of p16INK4a immunodetection by enzyme-linked immunosorbent assay (ELISA) on fresh cervical samples obtained at the time of screening could improve appropriate referral to colposcopy. METHOD OF STUDY A derivation group comprised of cervical swabs collected from subjects with high-grade dysplasia or cancer (positive control) and from subjects with negative screening history (negative control). Samples collected from colposcopy were used to evaluate the existing screening strategies individually and with incorporation of p16INK4a ELISA. Histology was used as the gold standard. RESULTS Among 163 subjects recruited, 138 were included. In the derivation group, mean p16INK4a level was 2.86 ng/mL (n = 31) and 0.58 ng/mL (n = 20) among positive and negative controls respectively (p = 0.002) with an area under the receiver operator characteristic curve of 0.79 (p

Purpose In patients with node-positive endometrial cancer, adjuvant radiation therapy with chemotherapy decreases local-regional recurrence compared with chemotherapy alone. However, the optimal radiation field borders and extent of nodal coverage have not been well studied. In a multi-institutional cohort, survival outcomes and sites of failure were analyzed for patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIIC endometrioid endometrial cancer treated with pelvic radiation therapy (PRT) versus extended-field radiation therapy (EFRT), which encompassed high para-aortic lymph nodes. Methods and Materials In a multi-institutional retrospective study, 143 patients with FIGO stage IIIC1 or IIIC2 endometrioid endometrial cancer treated with adjuvant radiation therapy from 2000 to 2016 were identified. Patient subgroups were classified by substage and radiation field extent: stage IIIC1 received EFRT, stage IIIC1 received PRT, and stage IIIC2 received EFRT. Recurrence-free survival (RFS), overall survival (OS), and out-of-field recurrence were calculated by the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards model. Sites of failure were categorized as within or outside the radiation field. Results The median follow-up was 59 months; 87% of patients received chemotherapy. The 5-year RFS and OS rates were 73% and 87%, respectively. By subgroup, 5-year RFS rates were 79% for stage IIIC1 EFRT, 73% for stage IIIC1 PRT, and 69% for stage IIIC2 EFRT (P = .4). On multivariate analysis, the recurrence risk was highest for stage IIIC2 EFRT, although this result was not statistically significant (adjusted hazard ratio, 2.0; P = .4). In-field vaginal and nodal recurrences were observed in 2 patients (1%) and 4 patients (3%), respectively. Of 78 patients with stage IIIC1 cancer treated with PRT, 5 (6%) had isolated para-aortic nodal relapse outside the radiation field; 3 were long-term survivors (more than 6 years after salvage therapy). For patients with para-aortic recurrence, 86% had lymphovascular invasion, 71% had myometrial invasion of ≥50%, and 57% had grade 3 disease. Conclusions Adjuvant chemoradiation therapy resulted in excellent survival outcomes for patients with FIGO stage IIIC endometrioid endometrial cancer. For patients with positive pelvic nodes, isolated para-aortic relapse outside the PRT field was uncommon and amenable to salvage therapy.

Treatment noncompletion may occur with radiation therapy (RT), especially with protracted treatment courses such as RT for prostate cancer, and may affect the efficacy of RT. For men with localized prostate cancer managed with primary RT, we evaluated associations between rates of treatment noncompletion and RT fractionation schedules.The National Cancer Database identified men diagnosed from 2004 to 2014 treated with primary RT. Patients receiving 180 cGy/fraction or 200 cGy/fraction were defined as having completed radiation therapy if they received ≥41 fractions of 180 cGy/fraction or ≥37 fractions of 200 cGy/fraction. Stereotactic body radiation therapy (SBRT) was defined as 5 to 8 fractions of 600 to 800 cGy/fraction. Odds ratios compared rates of treatment noncompletion, adjusting for sociodemographic covariates. A propensity-adjusted multivariable Cox regression assessed the association between treatment completion and overall survival.Of 157,657 patients, 95.7% (n = 150,847) received conventional fractionation and 4.3% (n = 6810) received SBRT. Rates of noncompletion were 12.5% (n = 18,803) among patients who received conventional fractionation and 1.9% (n = 131) among patients who received SBRT (odds ratio [OR] versus conventional, 0.21; 95% confidence interval [CI], 0.18-0.26; P.001). The rate of noncompletion among 25,727 African American patients was 12.8%, compared with 11.8% among 126,199 white patients (OR, 1.14; 95% CI, 1.09-1.19; P.001). In a subgroup analysis, the disparity in noncompletion persisted for conventional fractionation (13.2% vs 12.3%, respectively; OR, 1.09; 95% CI, 1.05-1.13; P.001), but not for SBRT (2.2% vs 1.8%, respectively; OR, 1.26; 95% CI, 0.79-2.00; P = .34). Noncompletion was associated with worse survival in a propensity-adjusted multivariable analysis (hazard ratio, 1.25; 95% CI, 1.22-1.29; P.001).SBRT was associated with lower rates of RT noncompletion among men with localized prostate cancer. African American race was associated with greater rates of treatment noncompletion, although the disparity may be decreased among men receiving SBRT.

Purpose High-dose-rate (HDR) brachytherapy is an alternative treatment to electron external beam radiation therapy (EBRT) of superficial skin lesions. The purpose of this study was to establish the selection criteria for HDR brachytherapy technique (HDR-BT) and EBRT in cutaneous oncology for various clinical scenarios. Material and methods The study consists of two parts: a) EBRT and HDR-BT treatment plans comparison analyzing clinical target volumes (CTVs) with different geometries, field sizes, and topologies, and b) development of a prediction model capable of characterization of dose distributions in HDR surface brachytherapy for various geometries of treatment sites. Results A loss of CTV coverage for the electron plans (D90, D95) was recorded up to 45%, when curvature of the applicator increased over 30°. Values for D2 cm3 for both plans were comparable, and they were in range of ±8% of prescription dose. An increase in higher doses (D0.5 cm3 and D0.1 cm3) was observed in HDR-BT plans, and it was greater for larger lesions. The average increase was 3.8% for D0.5 cm3 and 12.3% for D0.1 cm3. When CTV was approximately flat, electron plans were comparable with HDR-BT plans, having lower average D2 cm3, D0.5 cm3, and D0.1 cm3 of 7.7%. Degradation of quality of electron plans was found to be more dependent on target curvature than on CTV size. Conclusions Both EBRT and HDR-BT could be used in treatments of superficial lesions. HDR-BT revealed superior CTV coverage when the surface was very large, complex, curvy, or rounded, and when the topology was complicated. The prediction model can be used for an approximate calculation and quick assessment of radiation dose to organs-at-risk (OARs), at a depth or at a lateral distance from CTV.

Comparative effectiveness research (CER) using national registries influences cancer clinical trial design, treatment guidelines, and patient management. However, the extent to which treatment selection bias (TSB) affects overall survival (OS) in cancer CER remains poorly defined. We sought to quantify the TSB effect on OS in the setting of low-risk prostate cancer, where 10-year prostate cancer-specific survival (PCSS) approaches 100% regardless of treatment modality.The Surveillance, Epidemiology, and End Results database was queried for patients with low-risk prostate cancer (cT1-T2a, PSA 10, and Gleason 6) who received radical prostatectomy (RP), brachytherapy (BT), or external beam radiotherapy (EBRT) from 2005 to 2015. The TSB effect was defined as the unadjusted 10-year OS difference between modalities that was not due to differences in PCSS. Propensity score matching was used to estimate the TSB effect on OS due to measured confounders (variables present in the database and associated with OS) and unmeasured confounders.A total of 50,804 patients were included (8845 RP; 18,252 BT; 23,707 EBRT) with a median follow-up of 7.4 years. The 10-year PCSS for the entire cohort was 99%. The 10-year OS was 92.9% for RP, 83.6% for BT, and 76.9% for EBRT (p 0.001). OS differences persisted after propensity score matching of RP vs. EBRT (7.4%), RP vs. BT (4.6%), and BT vs. EBRT (3.7%) (all p 0.001). The TSB effect on 10-year OS was estimated to be 15.0% for RP vs. EBRT (8.6% measured, 6.4% unmeasured), 8.5% for RP vs. BT (4.8% measured, 3.7% unmeasured), and 6.5% for BT vs. EBRT (3.1% measured, 3.4% unmeasured).Patients with low-risk prostate cancer selected for RP exhibited large OS differences despite similar PCSS compared to radiotherapy, suggesting OS differences are almost entirely driven by TSB. The quantities of these effects are important to consider when interpreting prostate cancer CER using national registries.

Purpose The role of multimodality therapy (MMT) in the treatment of Gleason 8–10 prostate cancer remains controversial. We sought to evaluate factors associated with MMT utilization for primary radical prostatectomy (RP) and primary radiation therapy (RT). Methods and Materials From the National Cancer Database, we conducted a retrospective review of 81,528 men with National Cancer Center Network Gleason 8–10 prostate cancer diagnosed between 2004 and 2015, who underwent (1) primary RP with or without early postoperative external beam RT (EBRT) or (2) primary RT (androgen deprivation therapy + EBRT) with or without brachytherapy (BT) boost. Using multivariable logistic regression models, we evaluated factors associated with the utilization of MMT, defined as early postoperative EBRT for primary RP or BT boost for primary RT. Results For primary RP, the percentages of men who underwent MMT for Gleason 8 and 9–10 disease were 12.2% and 24.1%, respectively. On multivariable logistic regression, men with Gleason 9–10 were more likely to undergo MMT (odds ratio 1.03 [1.02, 1.04]), although adverse pathologic features such as T3b-4 (1.24 [1.23, 1.25]) disease demonstrated the strongest associations. For primary RT, the percentages of men who underwent BT boost for Gleason 8 and 9–10 disease were 11.8% and 9.8%, respectively. On multivariable logistic regression, men with Gleason 9–10 disease were less likely to receive BT boost (0.99 [0.98, 0.99]). Conclusions Men with more aggressive Gleason 9 disease were more likely to undergo MMT if they underwent primary RP but not primary RT. Further blood-based or imaging biomarkers may aid in identifying optimal candidates for MMT, especially for primary RT.

Background: Although the incidence of cervical cancer among younger Black women is now equivalent to that of White women, it is unknown whether the reduced incidence has affected survival rates among younger Black women. The goal of this study was to assess differences in survival by age and race. Patients and Methods: A retrospective cohort study was performed using the National Cancer Database to analyze women with nonmetastatic cervical cancer diagnosed between 2004 and 2014. Women with unknown survival data and those who died within 3 months of diagnosis were excluded. Multivariable logistic regression models evaluated interactions between age and race (Black vs non-Black) for presentation with stage I disease and receipt of optimal treatment. A multivariable Cox regression model was used to evaluate survival differences by age and race. Results: Of 55,659 women included, 16.4% were Black. Compared with their non-Black counterparts, fewer Black women presented with stage I disease (37.8% vs 47.8%; PPPP=.43). According to multivariable logistic regression, Black women aged ≤39 years were less likely to present with stage I disease, with a significant interaction term between age and race (PPPConclusions: Younger Black women with cervical cancer are at risk for presenting with higher-stage disease and having worse overall survival. These findings may be related to insurance-related disparities and inadequate follow-up for abnormal Papanicolaou test results. Younger Black women with cervical cancer may be a particularly vulnerable population.

ObjectiveThe aim of this study was to evaluate recurrence patterns and survival outcomes for patients with early-stage non-endometrioid endometrial adenocarcinoma treated with adjuvant high-dose rate vaginal brachytherapy with a low-dose scheme.MethodsA retrospective review was performed of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I–II non-endometrioid endometrial cancer who received adjuvant vaginal brachytherapy with a low-dose regimen of 24 Gy in six fractions from November 2005 to May 2017. All patients had >6 months of follow-up. Rates of recurrence-free survival, overall survival, vaginal, pelvic, and distant recurrence were calculated by the Kaplan–Meier method. Prognostic factors for recurrence and survival were evaluated by Cox proportional hazards modeling.ResultsA total of 106 patients were analyzed. Median follow-up was 49 months (range 9–119). Histologic subtypes were serous (47%, n=50), clear cell (10%, n=11), mixed (27%, n=29), and carcinosarcoma (15%, n=16). Most patients (79%) had stage IA disease, 94% had surgical nodal assessment, and 13% had lymphovascular invasion. Adjuvant chemotherapy was delivered to 75%. The 5-year recurrence-free and overall survival rates were 74% and 83%, respectively. By histology, 5-year recurrence-free/overall survival rates were: serous 73%/78%, clear cell 68%/88%, mixed 88%/100%, and carcinosarcoma 56%/60% (p=0.046 and pConclusionsAdjuvant high-dose rate brachytherapy with a low-dose scheme is effective for most patients with early-stage non-endometrioid endometrial cancer, particularly stage IA disease and no lymphovascular invasion. Pelvic radiation therapy should be considered for those with carcinosarcoma, lymphovascular invasion and/or stage IB/II disease.

INTRODUCTION AND OBJECTIVE:For men with Gleason score 9-10 prostate cancer, studies have demonstrated conflicting results on the outcomes from combination radiation therapy (ComboRT) with external ...

PURPOSE In situ drug release concurrent with radiation therapy has been proposed to enhance the therapeutic ratio of permanent prostate brachytherapy. Both brachytherapy sources and brachytherapy spacers have been proposed as potential eluters to release compounds, such as nanoparticles or chemotherapeutic agents. The relative effectiveness of the approaches has not been compared yet. This work models the physical dose enhancement of implantable eluters in conjunction with brachytherapy to determine which delivery mechanism provides greatest opportunity to enhance the therapeutic ratio. MATERIALS AND METHODS The combined effect of implanted eluters and radioactive sources were modeled in a manner that allowed the comparison of the relative effectiveness of different types of implantable eluters over a range of parameters. Prostate geometry, source, and spacer positions were extracted from treatment plans used for 125 I permanent prostate implants. Compound concentrations were calculated using steady-state solution to the diffusion equation including an elimination term characterized by the diffusion-elimination modulus (ϕb ). Does enhancement was assumed to be dependent on compound concentration up to a saturation concentration (csat ). Equivalent uniform dose (EUD) was used as an objective to determine the optimal configuration of eluters for a range of diffusion-elimination moduli, concentrations, and number of eluters. The compound delivery vehicle that produced the greatest enhanced dose was tallied for points in parameter space mentioned to determine the conditions under whether there are situations where one approach is preferable to the other. RESULTS The enhanced effect of implanted eluters was calculated for prostate volumes from 14 to 45 cm3 , ϕb from 0.01 to 4 mm-1 , csat from 0.05 to 7.5 times the steady-state compound concentration released from the surface of the eluter. The number of used eluters (ne ) was simulated from 10 to 60 eluters. For the region of (csat , Φ)-space that results in a large fraction of the gland being maximally sensitized, compound eluting spacers or sources produce equal increase in EUD. In the majority of the remaining (csat , Φ)-space, eluting spacers result in a greater EUD than sources even where sources often produce greater maximal physical dose enhancement. Placing eluting implants in planned locations throughout the prostate results in even greater enhancement than using only source or spacer locations. CONCLUSIONS Eluting brachytherapy spacers offer an opportunity to increase EUD during the routine brachytherapy process. Incorporating additional needle placements permits compound eluting spacer placement independent of source placement and thereby allowing a further increase in the therapeutic ratio. Additional work is needed to understand the in vivo spatial distribution of compound around eluters, and to incorporate time dependence of both compound release and radiation dose.

BACKGROUND Partial prostate treatment has emerged as a potential method for treating patients with favorable-risk prostate cancer while minimizing toxicity. The authors previously demonstrated poor rates of biochemical disease control for patients with National Comprehensive Cancer Network (NCCN) intermediate-risk disease using partial gland treatment with brachytherapy. The objective of the current study was to estimate the rates of distant metastasis and prostate cancer-specific mortality (PCSM) for this cohort. METHODS Between 1997 and 2007, a total of 354 men with clinical T1c disease, a prostate-specific antigen (PSA) level

Purpose Although level 1 evidence has demonstrated a survival benefit from the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) for patients with high-risk prostate cancer, the benefits of ADT with combined EBRT and brachytherapy for high-risk patients are unclear. We examined the association between ADT and overall survival in a national cohort of high-risk patients treated with EBRT with or without brachytherapy. Methods and Materials We identified 46,325 men in the National Cancer Database with a diagnosis of high-risk prostate cancer (Gleason score 8-10, clinical stage T3-T4, or prostate-specific antigen >20 ng/mL) who were treated with EBRT with or without brachytherapy and ADT from 2004 through 2011. Multivariable Cox regression analysis adjusting for sociodemographic and clinicopathologic factors was used to identify the association between ADT and overall survival. Results The median follow-up period was 48.6 and 59.2 months for patients treated with EBRT only and combined modality RT, respectively. ADT was associated with an improvement in overall survival for the 85.0% (39,361) of the study cohort who underwent EBRT alone (adjusted hazard ratio 0.91, P =.001) but not for patients treated with combined modality RT (adjusted hazard ratio 1.05, P =.496), with a significant interaction ( P interaction =.036). Conclusions In contrast to the known survival benefit when ADT is given with EBRT, our results suggest that ADT might not improve survival for high-risk patients who undergo combined EBRT and brachytherapy. Given the significant adverse effects of ADT, in particular, with long-term therapy, a randomized controlled trial of combined EBRT and brachytherapy with or without ADT for select high-risk patients using a noninferiority design should be undertaken.

Active Surveillance among Blacks with Low-Risk Prostate Cancer Between 2010 and 2015, use of active surveillance or watchful waiting as a management strategy for low-risk prostate cancer increased ...

PURPOSE/OBJECTIVE(S) Clinical trials of prostate SBRT have utilized a wide range of allowed doses to the intraprostatic urethra but the relationship between urethral dose and urinary toxicity has not been thoroughly evaluated. We aimed to characterize urinary toxicity outcomes according to urethral dose administered during prostate SBRT. MATERIALS/METHODS We searched MEDLINE (PubMed) for published prospective studies of prostate SBRT through August 2020 that documented a maximum urethral dose metric (MUDM). Reported acute and late urinary toxicity rates were collected. Weighted correlation and weighted linear regression models were used to assess the associations between urinary toxicity rates and MUDM. RESULTS Twenty-three unique studies (n = 2232 patients) met the inclusion criteria and included a wide range of MUDMs (EQD2 69 Gy to 141.75 Gy, a/b = 3). Median follow up ranged from 3-67 months (median 32 months). MUDM was strongly associated with urinary toxicity and was more closely associated with toxicity than prescription dose, including acute G2+ (r = 0.51, P = 0.02), late G2+ (r = 0.9, P < 0.0001) and late G3+ toxicity (r = 0.7, P = 0.003). Weighted linear regression accounting for age, prostate size and baseline urinary function confirmed association between urinary outcomes and MUDM. The weighted correlation model predicted late grade 2+ urinary toxicity rates of 2.5%, 5%, 10% and 15% corresponding to MUDMs of 34.2 Gy, 37.7 Gy, 43.9 Gy and 49.4 Gy, respectively, for 5 fraction regimens. Within the studied dose range, each increase of 1 Gy to the MUDM corresponded to a 0.8% and 0.9% increase in acute G2+ and late G2+ toxicity, respectively. CONCLUSION Radiation dose to the urethra correlates closely with urinary toxicity in prostate cancer patients treated with SBRT. Attention should be paid to urethral dose when delivering prostate SBRT to high doses and approaches for urethral dose reduction warrant further investigation. These techniques may be facilitated by online adaptive planning with daily urethral delineation.

Objectives: Disparities among Black women with cervical cancer in the United States are well known; however, the etiology is not fully understood. Access to oncologic care and adequate insurance coverage likely affect these racial disparities. The aim of this study was to describe factors affecting the ability to receive oncologic care in cervical cancer as a function of race among different regions in the U.S. Methods: A retrospective cohort study was performed using the National Cancer Database (NCDB) among women with stage I-IVA cervical cancer from 2004-2014. To identify factors associated with the receipt of optimal treatment, multivariate logistic regression was used, including an interaction term to determine the relationship of race and region. To evaluate overall survival, a Cox multivariate proportional hazards model was performed, including a similar interaction term. Publicly available data from the NCI, the Society of Gynecologic Oncology, and the United States Census were utilized to compile data regarding availability of cancer centers, gynecologic oncologists, and insurance status by region. Results: A total of 55,659 women with cervical cancer were identified, of whom 9,153 were Black (16.4%). Fewer Black women presented with stage I disease (37.8% versus 47.8%, p Download : Download high-res image (149KB) Download : Download full-size image Conclusions: Black women living in the South of the United States are at particular risk of both inadequate treatment and worse overall survival for cervical cancer after controlling for confounding factors. Population-level data suggests that women in the South may be underinsured and lack access to cancer centers and gynecologic oncologists.