TP53 structure-function relationships in metastatic castrate-sensitive prostate cancer and the impact of APR-246 treatment.

PURPOSE: Despite well-informed work in several malignancies, the phenotypic effects of TP53 mutations in metastatic castration-sensitive prostate cancer (mCSPC) progression and metastasis are not clear. We characterized the structure-function and clinical impact of TP53 mutations in mCSPC. PATIENTS AND METHODS: We performed an international retrospective review of men with mCSPC who underwent next-generation sequencing and were stratified according to TP53 mutational status and metastatic burden. Clinical outcomes included radiographic progression-free survival (rPFS) and overall survival (OS) evaluated with Kaplan-Meier and multivariable Cox regression. We also utilized isogenic cancer cell lines to assess the effect of TP53 mutations and APR-246 treatment on migration, invasion, colony formation in vitro, and tumor growth in vivo. Preclinical experimental observations were compared using t-tests and ANOVA. RESULTS: Dominant-negative (DN) TP53 mutations were enriched in patients with synchronous (vs. metachronous) (20.7% vs. 6.3%, p < 0.01) and polymetastatic (vs. oligometastatic) (14.4% vs. 7.9%, p < 0.01) disease. On multivariable analysis, DN mutations were associated with worse rPFS (hazards ratio [HR] = 1.97, 95% confidence interval [CI]: 1.31-2.98) and overall survival [OS] (HR = 2.05, 95% CI: 1.14-3.68) compared to TP53 wild type (WT). In vitro, 22Rv1 TP53 R175H cells possessed stronger migration, invasion, colony formation ability, and cellular movement pathway enrichment in RNA sequencing analysis compared to 22Rv1 TP53 WT cells. Treatment with APR-246 reversed the effects of TP53 mutations in vitro and inhibited 22Rv1 TP53 R175H tumor growth in vivo in a dosage-dependent manner. CONCLUSIONS: DN TP53 mutations correlated with worse prognosis in prostate cancer patients and higher metastatic potential, which could be counteracted by APR-246 treatment suggesting a potential future therapeutic avenue.

Disparities in brachytherapy utilization in cervical cancer in the United States: A comprehensive literature review.

Brachytherapy (BT) is an integral component of treatment for patients with locally advanced cervical cancer, significantly improving local control and overall survival. There is an overall trend of decreased utilization of BT in United States (US) in the last few decades with around 50% of patients being treated without BT. The cause of decreased utilization is multifactorial including physician comfort, facility volume, low reimbursements rates and costs of starting and maintaining a brachytherapy program. This decrease coincides with an increase in the use of newer advanced techniques like intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) boost resulting in inferior oncological outcomes and increased toxicity. Moreover, racial and socioeconomic disparities in BT utilization have been widely reported in the US. Various factors including age, race, socio-economic status, location, facility type, facility volume and insurance status result in limited access to brachytherapy, which jeopardizes oncologic outcomes. This comprehensive review discusses the BT utilization in the US, examines the impact of race and socioeconomic factors on BT utilization, and highlights its impact on outcomes.

Metastasis-Directed Therapy for Oligometastatic Castration-Sensitive Prostate Cancer: An Alternative to ADT?

PURPOSE OF REVIEW: The standard treatment of patients with metastatic prostate cancer is systemic treatment with androgen-deprivation therapy (ADT). The spectrum-based model of metastatic disease includes the presence of an oligometastatic state, an intermediary between localized and widespread metastatic disease, in which radical local treatment might improve systemic control. Our purpose is to review the literature on metastasis-directed therapy in the treatment of oligometastatic prostate cancer. RECENT FINDINGS: Several prospective clinical trials have reported improvements in ADT-free survival and progression-free survival with metastasis-directed therapy of oligometastatic prostate cancer. Retrospective studies have found improvements in oncologic outcomes for patients with oligometastatic prostate cancer undergoing metastasis-directed therapy, and several recent prospective clinical trials have confirmed these results. Advancements in imaging as well as an understanding of the genomics of oligometastatic prostate cancer may allow for better patient selection for metastasis-directed therapy and the potential for cure in selected patients.

The clinical impact of removing rectal gas on high-dose-rate brachytherapy dose distributions for gynecologic cancers.

PURPOSE: To evaluate the impact of gas removal on bladder and rectal doses during intracavitary and interstitial high-dose-rate brachytherapy (HDRB) for gynecologic cancers. MATERIAL AND METHODS: Fifteen patients treated with definitive external beam radiation followed by HDRB for gynecologic cancers for a total of 21 fractions, presented with a significant amount of rectal gas at initial CT imaging (CTGAS ) after implantation. The gas was removed via rectal tubing followed by subsequent scan acquisition (CTCLINICAL ), which was used for planning and treatment delivery. To assess the effect of gas removal on dosimetry, both bladder and rectum volumes were recontoured on CTGAS . In order to evaluate the clinical impact on the total Equivalent-Dose-in-2Gy-fraction (EQD2 ), each fraction was also replanned to maintain clinically delivered target coverage (HRCTV D90). EQD2 D2cm3 for bladder and rectum were compared between plans. The Wilcoxon signed rank test was performed to evaluate statistically significant differences for all comparisons (P < 0.05). RESULTS: Mean rectum and bladder Dmax , D0.1cm3 , D1cm3 , D2cm3 , and D5cm3 were significantly different between CTGAS and CTCLINICAL . The mean percent increases on CTGAS for bladder were 12.3, 8.4, 9.9, 10.2, and 9.5% respectively and for rectum were 27.0, 19.6, 18.1, 18.5, and 19.4%, respectively. After replanning with CTGAS to maintain HRCTV D90 EQD2 , bladder and rectum EQD2 D2 cm3 resulted in significantly higher doses. The mean EQD2 D2 cm3 difference was 2.4 and 4.1 Gy for bladder and rectum, revealing a higher impact of gas removal on rectal DVH. CONCLUSION: Rectal gas removal resulted in statistically significant differences for both bladder and rectum. The resulting larger EQD2 D2 cm3 for bladder and rectum demonstrates that if patients were treated without removing gas, target coverage would need to be sacrificed to satisfy the rectum constraints and prevent toxicities. Therefore, this study demonstrates the importance of gas removal for gynecologic HDRB patients.

The combined use of 2D scout and 3D axial CT images to accurately determine the catheter tips for high-dose-rate brachytherapy plans.

PURPOSE: To develop a method combining CT scout images with axial images to improve the localization accuracy of catheter tips in high-dose-rate (HDR) brachytherapy treatments. MATERIALS AND METHODS: CT scout images were utilized along with conventionally reconstructed axial images to aid the localization of catheter tips used during HDR treatment planning. A method was developed to take advantage of the finer image resolution of the scout images to more precisely identify the tip coordinates. The accuracies of this method were compared with the conventional method based on the axial CT images alone, for various slice thicknesses, in a computed tomography dose index (CTDI) head phantom. A clinical case which involved multiple interstitial catheters was also selected for the evaluation of this method. Locations of the catheter tips were reconstructed with the conventional CT-based method and this newly developed method, respectively. Location coordinates obtained via both methods were quantitatively compared. RESULTS: Combination of the scout and axial CT images improved the accuracy of identification and reconstruction of catheter tips along the longitudinal direction (i.e., head-to-foot direction, more or less parallel to the catheter tracks), compared to relying on the axial CT images alone. The degree of improvement was dependent on CT slice thickness. For the clinical patient case, the coordinate differences of the reconstructed catheter tips were 2.6 mm ± 0.9 mm in the head-to-foot direction, 0.4 mm ± 0.2 mm in the left-to-right direction, and 0.6 mm ± 0.2 mm in the anterior-to-posterior direction, respectively. CONCLUSION: Combining CT scout and axial images demonstrates the ability to provide a more accurate identification and reconstruction of the interstitial catheter tips for HDR brachytherapy treatment, especially in the longitudinal direction. The method developed in this work has the potential to be implemented clinically together with automatic segmentation in modern brachytherapy treatment planning systems, in order to improve the reconstruction accuracy of HDR catheters.

Stereotactic body radiation therapy for oligometastatic gynecologic malignancies: A systematic review.

OBJECTIVE: To assess the efficacy and safety of stereotactic body radiation therapy (SBRT) for oligometastatic gynecologic malignancies. METHOD: A comprehensive search of the PubMed, Medline, and EMBASE databases was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. "Oligometastatic" was defined as a limited number of uncontrolled/untreated metastatic lesions (typically ≤ 5), including regional nodal metastases. Primary outcomes were response rate (complete response or partial response), local control of oligometastatic lesions, and toxicity. RESULTS: Of 716 screened records, 17 studies (13 full length articles, 4 conference abstracts) were selected and analyzed as 16 unique studies. A total of 667 patients were treated with ~1071 metastatic lesions identified. Primary sites included ovarian (57.6%), cervical (27.1%), uterine (11.1%), vaginal (0.4%), vulvar (0.3%), and other/unspecified (3.4%). Most patients (65.4%) presented with a single metastatic lesion. Metastatic lesion sites included the abdomen (44.2%), pelvis (18.8%), thorax (15.5%), neck (4.6%), central nervous system (4.3%), bone (1.6%), and other/unspecified (11%). Of the lesions, 64% were nodal. Response rate (among 8 studies) ranged from 49% to 97%, with 7/8 studies reporting > 75% response rate. Local control ranged from 71% to 100%, with 14/16 studies reporting ≥ 80% local control. No grade ≥ 3 toxicities were observed in 9/16 (56%) studies. Median progression-free survival (PFS) (among 10 studies) ranged from 3.3 months to 21.7 months. Disease progression most commonly occurred outside of the SBRT radiation field (79% to 100% of failures). CONCLUSIONS: SBRT for oligometastatic gynecologic malignancies is associated with favorable response and local control rates but a high rate of out-of-field progression and heterogeneous PFS. Additional study into rational combinations of SBRT and systemic therapy appears warranted to further improve patient outcomes.

Revisiting Milan cervical cancer study: Do the original findings hold in the era of chemotherapy?

BACKGROUND: The primary treatment of early stage cervical carcinoma (IB-IIA) is either surgery or radiation therapy based on the pivotal Milan randomized study published twenty years ago. In the presence of high-risk features, the gold standard treatment is concurrent chemotherapy and radiation therapy (CRT) whether it is the in the postoperative or the definitive setting. Using the National Cancer Data Base (NCDB), the goal of our study is to compare the outcomes of surgery and radiation therapy in the chemotherapy era. METHODS: Between 2004 and 2013, 5478 patients diagnosed with early stage cervical cancer were divided into 2 groups based on their primary treatment: non-surgical (n=1980) and surgical groups (n=3498). The distribution of patient/tumor characteristics and treatment variables with their relation to overall survival and proportional regression models were assessed to investigate the superiority of one approach over the other. Propensity score analysis adjusted for imbalance of covariates to create a well-matched-patient cohort. FINDINGS: At 46months median follow-up, the 5-year overall survival was similar between both groups (73·8% vs. 75.7%; p=0.619) after applying propensity score analysis. On multivariate analysis, high Charlson comorbidity score, stage IIA disease, larger tumor size, positive lymph nodes and high-grade disease were significant predictors of poor outcome while older age and treatment approach were not. INTERPRETATION: Our analysis suggests that surgery (followed by adjuvant RT or CRT) and definitive radiotherapy (with or without chemotherapy) result in equivalent survival. Prospective studies are warranted to establish this paradigm in the chemotherapy era.

Can chemotherapy boost the survival benefit of adjuvant radiotherapy in early stage cervical cancer with intermediate risk factors? A population based study.

PURPOSE: The Gynecologic Oncology group (GOG) 0263 trial is currently exploring whether adding chemotherapy to adjuvant radiotherapy improves recurrence-free and/or overall survival in stage IB-IIA cervical cancer patients with pathologic intermediate-risk factors. Using the National Cancer Data Base, we evaluated the benefit of adjuvant chemoradiotherapy over adjuvant radiotherapy alone in the community practice setting. MATERIALS: The analysis included 869 stage IB-IIA cervical cancer patients who underwent radical hysterectomy retrieving intermediate-risk factors justifying adjuvant therapy. Adjuvant chemoradiotherapy and adjuvant radiotherapy were delivered in 440 and 429 patients, respectively. Chi-square test assessed the distribution of variables in each group and the overall survival was estimated using the Kaplan-Meier method. Proportional hazard models were performed to evaluate the impact of the different prognostic factors on survival and propensity score analysis adjusted variables imbalanced distribution. RESULTS: Adding chemotherapy to ART did not show a survival benefit at 48months median follow-up; the 5-year overall survival was 87% and 81% (p=0.6) in the adjuvant chemoradiotherapy and adjuvant radiotherapy groups, respectively. On univariate analysis, age older than 60, a higher comorbidity score, and stage IIA were significantly associated with worse survival, while none of the other covariates were significant prognosticator on multivariate analysis. The same findings held after propensity score analysis. CONCLUSION: Our analysis could not detect a significant survival benefit for adjuvant chemoradiotherapy over adjuvant radiotherapy in women with intermediate-risk factors. Until GOG 0263 results become available, the benefits of adjuvant chemoradiotherapy should be considered on an individual basis within a multidisciplinary approach.

High-dose-rate brachytherapy for vaginal rhabdomyosarcoma using a personalized mold in a 20-month old patient.

Treatment of vaginal rhabdomyosarcoma (RMS) with conservative approaches is presently the standard of care. Intravaginal high-dose rate brachytherapy is a very effective treatment while sparing the normal tissue to preserve growth, fertility and prevent organ dysfunction. In this report, we describe the management of an infant with Stage I vaginal RMS, treated with chemotherapy, maximal safe resection and intravaginal brachytherapy using a customized mold and MRI and CT-based three-dimensional (3D) conformal planning, followed by a critical review of the literature.

Impact of the COVID-19 pandemic on brachytherapy and cancer patient outcomes: A systematic review.

PURPOSE/OBJECTIVE(S): To assess the impact of the COVID-19 pandemic on the use of brachytherapy in patients with gynecologic and prostate cancers including treatment delays, increased burden of mortality, and associated clinical outcomes. MATERIALS/METHODS: A comprehensive search of PubMed, Cochrane Library, CINAHL, Scopus, and Web of Science was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for studies published through September 2023 using MeSH terms and keywords related to "COVID and brachytherapy." Inclusion criteria included all studies reporting on the impact of COVID-19 on treatment delay, treatment omission, recurrence rates, and clinical outcomes in patients requiring brachytherapy for prostate or gynecologic cancers from December 2019 to September 2023. Data were extracted by two independent reviewers (LH, IV). RESULTS: Of the 292 screened records, 10 studies (9 retrospective, 1 prospective single-arm exploratory noninferiority) were included. Hypofractioned regimens were the preferred approach in radiation treatment (RT) centers, with 6 of 10 studies noting shift towards hypofractionation. For cervical cancer, intracavitary brachytherapy was limited to 3-4 fractions, reducing personnel and patient exposure. Treatment delays influenced by COVID-19 ranged between 19% and 53% and treatment omissions ranged between 2% and 28%. These disruptions arose from factors such as patient fear of contracting COVID-19, COVID-19 infection, barriers to accessing care, and operating room closures. Three studies reported on a single-application (SA) rather than a multiple application (MA) approach for cervical cancer. They reported excellent local control, shorter overall treatment time at the expense of higher grade ≥2 vaginal, genitourinary, and gastrointestinal events. For cervical cancer patients, overall treatment time (OTT) was significantly impacted by COVID-19 as reported by 2 studies from India. OTT > 60 days occurred in 40-53% of patients. CONCLUSION: This is the first systematic review to assess the impact of the COVID-19 pandemic on brachytherapy in patients with gynecologic and prostate cancers. Although many expert consensus recommendations have been published during the pandemic regarding radiation therapy, few studies evaluated its clinical impact on brachytherapy delivery and patient outcomes. The COVID-19 pandemic resulted in treatment delays, omissions in brachytherapy, and further adoption of hypofractionated regimens. Early results demonstrate that despite increased toxicities, local control rates with hypofractionated treatment are similar to standard fractionation. The impact of the pandemic on gynecologic and prostate cancers is yet to be determined as well as the long-term outcomes on patients treated during the lockdown period.

Prognostic Effect of Mismatch Repair Status in Early-Stage Endometrial Cancer Treated With Adjuvant Radiation: A Multi-institutional Analysis.

PURPOSE: The aim of this work was to report the effect of mismatch repair (MMR) status on outcomes of patients with stage I-II endometrioid endometrial adenocarcinoma (EEC) who receive adjuvant radiation therapy. METHODS AND MATERIALS: This is a multi-institutional retrospective cohort study across 11 institutions in North America. Patients with known MMR status and stage I-II EEC status postsurgical staging were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated via the Kaplan-Meier method. Univariable and multivariable analyses were performed via Cox proportional hazard models for RFS and OS. Statistical analyses were conducted using SPSS version 27. RESULTS: In total, 744 patients with a median age at diagnosis of 65 years (IQR, 58-71) were included. Most patients were White (69.4%) and had Federation of Obstetrics and Gynecology 2009 stage I (84%) and Federation of Obstetrics and Gynecology grade 1 to 2 (73%). MMR deficiency was reported in 234 patients (31.5%), whereas 510 patients (68.5%) had preserved MMR. External beam radiation therapy with or without vaginal brachytherapy was delivered to 186 patients (25%), whereas 558 patients (75%) received vaginal brachytherapy alone. At a median follow-up of 43.5 months, the estimated crude OS and RFS rates for the entire cohort were 92.5% and 84%, respectively. MMR status was significantly correlated with RFS. RFS was inferior for MMR deficiency compared with preserved MMR (74.3% vs 88.6%, P < .001). However, no difference in OS was seen (90.8% vs 93.2%, P = .5). On multivariable analysis, MMR deficiency status was associated with worse RFS (hazard ratio, 1.86; P = .001) but not OS. CONCLUSIONS: MMR status was independently associated with RFS but not OS in patients with early-stage EEC who were treated with adjuvant radiation therapy. These findings suggest that differential approaches to surveillance and/or treatment based on MMR status could be warranted.

Prostate-Specific Membrane Antigen PET Response Associates with Metastasis-Free Survival After Stereotactic Ablative Radiation in Oligometastatic Prostate Cancer.

Purpose: Emerging data suggest that metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can detect occult metastatic disease, and PSMA response has been proposed as a biomarker for treatment response. Herein, we identify and validate a PSMA-PET biomarker for metastasis-free survival (MFS) following MDT in omCSPC. Methods and Materials: We performed an international multi-institutional retrospective study of patients with omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation who underwent PSMA-PET/computed tomography (CT) before and after (median, 6.2 months; range, 2.4-10.9 months) treatment. Pre- and post-MDT PSMA-PET/CT maximum standardized uptake value (SUVmax) was measured for all lesions, and PSMA response was defined as the percent change in SUVmax of the least responsive lesion. PSMA response was both evaluated as a continuous variable and dichotomized into PSMA responders, with a complete/partial response (at least a 30% reduction in SUVmax), and PSMA nonresponders, with stable/progressive disease (less than a 30% reduction in SUVmax). PSMA response was correlated with conventional imaging-defined metastasis-free survival (MFS) via Kaplan-Meier and Cox regression analysis. Results: A total of 131 patients with 261 treated metastases were included in the analysis, with a median follow-up of 29 months (IQR, 18.5-41.3 months). After stereotactic ablative radiation, 70.2% of patients were classified as PSMA responders. Multivariable analysis demonstrated that PSMA response as a continuous variable was associated with a significantly worse MFS (hazard ratio = 1.003; 95% CI, 1.001-1.006; P = .016). Patients classified as PSMA responders were found to have a significantly improved median MFS of 39.9 versus 12 months (P = .001) compared with PSMA nonresponders. Our study is limited as it is a retrospective review of a heterogenous population. Conclusions: After stereotactic ablative radiation, PSMA-PET response appears to be a radiographic biomarker that correlates with MFS in omCSPC. This approach holds promise for guiding clinical management of omCSPC and should be validated in a prospective setting.

Stereotactic Body Radiation Therapy in Gynecologic Oligometastases: An Effective but Underutilized Approach.

Historically, the role of radiation in gynecological metastatic disease involved palliation for pain or bleeding. Stereotactic Body Radiation Therapy (SBRT) has shown survival benefits in oligometastatic disease from varying primary histologies in recent randomized trials. However, gynecologic primary oligometastases have been underrepresented in these trials. Recent studies across gynecological malignancy types have similarly shown favorable outcomes and acceptable toxicities from treating recurrent or oligometastatic gynecologic cancer (ROMGC) patients with definitive radiation therapy. The largest body of literature reported on the use of SBRT in ovarian cancer, which was found to be an effective option, especially in the setting of chemo-resistant disease. Despite the encouraging outcomes using SBRT in oligometastatic gynecologic malignancies, SBRT remains underutilized given the lack of randomized studies studying ROMGC with long term follow-up. While waiting for future prospective trials to establish the role of SBRT as the standard of care in ROMGC patients, this review focuses on reporting the advantages and drawbacks of this technique and examines the current literature to help guide patient centered treatment decisions.

Reconstructive complications and early toxicity in breast cancer patients treated with proton-based postmastectomy radiation therapy.

Background: Postmastectomy radiation therapy (PMRT) decreases the risk of locoregional recurrence and increases overall survival rates in patients with high-risk node positive breast cancer. While the number of breast cancer patients treated with proton-based PMRT has increased in recent years, there is limited data on the use of proton therapy in the postmastectomy with reconstruction setting. In this study, we compared acute toxicities and reconstructive complications in patients treated with proton-based and photon-based PMRT. Methods: A retrospective review of our institutional database was performed to identify breast cancer patients treated with mastectomy with implant or autologous reconstruction followed by PMRT from 2015 to 2020. Baseline clinical, disease, and treatment related factors were compared between the photon-based and proton-based PMRT groups. Early toxicity outcomes and reconstructive complications following PMRT were graded by the treating physician. Results: A total of 11 patients treated with proton-based PMRT and 26 patients treated with photon-based PMRT were included with a median follow-up of 7.4 months (range, 0.7-33 months). Six patients (55%) in the proton group had a history of breast cancer (3 ipsilateral and 3 contralateral) and received previous RT 38 months ago (median, range 7-85). There was no significant difference in mean PMRT (p = 0.064) and boost dose (p = 0.608) between the two groups. Grade 2 skin toxicity was the most common acute toxicity in both groups (55% and 73% in the proton and photon group, respectively) (p = 0.077). Three patients (27%) in the proton group developed grade 3 skin toxicity. No Grade 4 acute toxicity was reported in either group. Reconstructive complications occurred in 4 patients (36%) in the proton group and 8 patients (31%) in photon group (p = 0.946). Conclusions: Acute skin toxicity remains the most frequent adverse event in both proton- and photon-based PMRT. In our study, reconstructive complications were not significantly higher in patients treated with proton- versus photon-based PMRT. Longer follow-up is warranted to assess late toxicities.

Radiation therapy for prostate cancer in Syrian refugees: facing the need for change.

Purpose: To report the utilization of radiation therapy in Syrian refugee patients with prostate cancer residing in Turkey. Methods and materials: A multi-institutional retrospective review including 14 cancer centers in Turkey was conducted to include 137 Syrian refugee patients with prostate cancer treated with radiation therapy (RT). Toxicity data was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Noncompliance was defined as a patient missing two or more scheduled RT appointments. Results: Advanced disease, defined as stage III or IV, was reported in 64.2% of patients while androgen deprivation therapy (ADT) was only administrated to 20% of patients. Conventionally fractionated RT with a median number of 44 fractions was delivered to all patients with curative intent (n = 61) while palliative RT (n = 76) was delivered with a median number of 10 fractions. The acute grade 3-4 toxicity rate for the entire cohort was 16%. Noncompliance rate was 42%. Conclusion: Most Syrian refugee prostate cancer patients presented with advanced disease however ADT was seldom used. Despite the low treatment compliance rate, conventional fractionation was used in all patients. Interventions are critically needed to improve screening and increase the use of standard-of-care treatment paradigms, including hypofractionated RT and ADT.

Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline.

PURPOSE: With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling. METHODS: The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. RESULTS: The task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy. CONCLUSIONS: These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.

The Impact of Racial Disparities on Outcome in Patients With Stage IIIC Endometrial Carcinoma: A Pooled Data Analysis.

OBJECTIVE: To report the impact of race on clinical outcomes in patients with stage IIIC endometrial carcinoma. MATERIALS AND METHODS: A retrospective multi-institutional study included 90 black and 568 non-black patients with stage IIIC endometrial carcinoma who received adjuvant chemotherapy and radiation treatments. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan-Meier method. Propensity score matching (PSM) was conducted. Statistical analyses were conducted using SPSS version 27. RESULTS: The Median follow-up was 45.3 months. black patients were significantly older, had more nonendometrioid histology, grade 3 tumors, and were more likely to have >1 positive paraaortic lymph nodes compared with non-black patients (all P <0.0001). The 5-year estimated OS and RFS rates were 45% and 47% compared with 77% and 68% for black patients versus non-black patients, respectively ( P <0.001). After PSM, the 2 groups were well-balanced for all prognostic covariates. The estimated hazard ratios of black versus non-black patients were 1.613 ( P value=0.045) for OS and 1.487 ( P value=0.116) for RFS. After PSM, black patients were more likely to receive the "Sandwich" approach and concurrent chemoradiotherapy compared with non-black ( P =0.013) patients. CONCLUSIONS: Black patients have higher rates of nonendometrioid histology, grade 3 tumors, and number of involved paraaortic lymph nodes, worse OS, and RFS, and were more likely to receive the "Sandwich" approach compared with non-black patients. After PSM, black patients had worse OS with a nonsignificant trend in RFS. Access to care, equitable inclusion on randomized trials, and identification of genomic differences are warranted to help mitigate disparities.

Adjuvant Radiation in Early Stage Vulvar Cancer: A Review of Indications and Optimal Dose.

Vulvar cancer is a relatively rare gynecologic malignancy for which surgery remains the cornerstone of treatment. A wide local excision is the goal for treatment with curative intent in patients with early stage vulvar cancer, given that there are adverse pathologic features shown to increase risk of local recurrence. Specifically, the presence of positive or close margins of < 8 mm or 2 or more positive nodes have been shown to significantly increase the risk of recurrence and have informed guidelines for risk-adapted adjuvant radiation, although the optimal dose for adjuvant radiation is yet to be established. Given the rarity of vulvar cancer, guidelines regarding the indications and dose for adjuvant radiation are based largely on retrospective studies. The purpose of this review is to summarize the evidence underlying the current indications for adjuvant radiation in early stage vulvar cancer as well as to determine the optimal dose for adjuvant radiation.

Benign metastasizing leiomyoma in retroperitoneal lymph nodes with concurrent early stage cervical cancer.

Extrauterine leiomyomas can present as benign metastasizing leiomyoma involving lymph nodes, which can be mistaken for metastatic malignancy. We report a case of a 52-year-old female who presented with postmenopausal bleeding and was found to have an endocervical mass. Imaging demonstrated retroperitoneal lymphadenopathy and biopsy of the cervical mass showed adenocarcinoma of either uterine or cervical origin. Patient underwent hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy for bulky pelvic and para-aortic lymph nodes. Final pathology was consistent with FIGO 2019 stage IB2 adenocarcinoma of the cervix with concurrent and benign metastasizing leiomyomas involving retroperitoneal lymph nodes.

Does the Use of BioZorb® Result in Smaller Breast Seroma Volume?

AIM: To evaluate the impact of BioZorb®, a 3D-bioabsorbable marker, on the tumor-bed boost volume and dosimetric parameters in adaptive boost planning for breast cancer. PATIENTS AND METHODS: Records were reviewed for 51 breast-cancer patients who underwent breast-conserving surgery and adjuvant whole-breast irradiation between January 2017 and October 2018. Changes in lumpectomy boost volume (LBV), doses to organs at risk, toxicity and cosmesis were compared between patients with and without BioZorb® Chi-square test and paired and independent t-tests were used for comparisons of variables. RESULTS: Median follow-up was 35.5 months. Mean LBV on initial CT (LBV1; 32.2 vs. 33.8 cc, p=0.74) and on boost computed tomography (CT) (LBV2; 25.3 vs. 24.8 cc, p=0.87) were similar with and without BioZorb® The mean decrease from LBV1 to LBV2 was 9.0 cc and 6.8 cc with and without BioZorb®, respectively (p=0.42). LBV1 was significantly positively correlated with a 20% reduction in LBV (p=0.02). Mean heart and lung doses on adaptive boost planning CT were slightly lower compared to initial planning CT in both groups. Acute breast pain was reported in 18/51 patients, 9 of whom had BioZorb® (p=0.24). Grade-2 pain was reported in 5/51 patients, 3 of whom had BioZorb® (p=0.11). Excellent or good cosmesis was reported in 36/41 patients. Fair cosmesis was reported in 5/41 patients, of whom 2 had BioZorb® (p=0.64). CONCLUSION: BioZorb® placement does not impact the tumor-bed boost volume nor the variation of seroma volume within the period of treatment. More data and longer follow-up are needed to identify a measurable clinical impact of BioZorb® placement.