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.

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.

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.

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.

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.

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.

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.

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.

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.

Inflammatory bowel disease-associated malignancies and considerations for radiation impacting bowel: a scoping review.

Background: Inflammatory bowel disease (IBD), subdivided into Crohn's disease (CD) and ulcerative colitis (UC), is an auto-inflammatory gastrointestinal condition with an established increased risk of certain malignancies. Compared to sporadic cancers in the general population, IBD-associated malignancies present unique challenges to providing quality care. Radiation therapy (RT) targeting IBD-associated malignancies may directly impact inflamed bowel, with special considerations for the risk of toxicities. Historically, patients with IBD have been less likely to receive radiotherapy in proximity to bowel due to a poor understanding of the potential for acute and chronic toxicities and unclear treatment outcomes. We present a scoping review, to more fully assess IBD-associated malignancies and their treatment. As opposed to a systematic review, this approach allows us to analyze the broadest range of literature, including experimental and non-experimental research, and reflect on current guidelines and practices. Methods: Literature search: a systematic, scoping search of published literature was conducted using applicable PRISMA scoping review (ScR) guidelines. The literature search was conducted on PubMed and was searched systematically by screening all publications from January 1990 to June 2021. Citations from the included articles were also manually searched. Relevant National Comprehensive Cancer Network guidelines were reviewed. Final query was December 2021 in editing. Articles were selected for full text reading if the abstract reported on malignancy in IBD or bowel toxicities. Results: The pelvic malignancies found in the IBD patient population, including colorectal carcinoma, anal carcinoma, lymphoma, small bowel adenocarcinoma (SBA), and prostate cancer (PCa) are outlined in this scoping review. Additional cancers that have a contested relationship with IBD, including cervical, bladder, and upper GI cancers, are also explored. This review provides literature guided recommendations on the eligibility of patients with IBD to receive RT, management of IBD during and after treatment, and counseling for radiation-induced toxicities. Conclusions: After review of the literature, IBD should not be considered an absolute contraindication to radiation therapy, given the lack of evidence for increased toxicities, and the evolution of RT techniques which limit radiation dose to the bowel.

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.

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.

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.

Does Prophylactic Paraortic Lymph Node Irradiation Improve Outcomes in Women With Stage IIIC1 Endometrial Carcinoma?

PURPOSE: To evaluate the impact of prophylactic paraortic lymph node (PALN) radiation therapy (RT) on clinical outcomes in patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 endometrial cancer (EC). METHODS AND MATERIALS: A multi-institutional retrospective study included patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 EC lymph node assessment, status postsurgical staging, followed by adjuvant chemotherapy and RT using various sequencing regimens. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. In addition, propensity score matching was used to estimate the effect of the radiation field extent on survival outcomes. RESULTS: A total of 378 patients were included, with a median follow-up of 45.8 months. Pelvic RT was delivered to 286 patients, and 92 patients received pelvic and PALN RT. The estimated OS and RFS rates at 5 years for the entire cohort were 80% and 69%, respectively. There was no difference in the 5-year OS (77% vs 87%, P = .47) and RFS rates (67% vs 70%, P = .78) between patients treated with pelvic RT and those treated with pelvic and prophylactic PALN RT, respectively. After propensity score matching, the estimated hazard ratios (HRs) of prophylactic PALN RT versus pelvic RT were 1.50 (95% confidence interval, 0.71-3.19; P = .28) for OS and 1.24 (95% confidence interval, 0.64-2.42; P = .51) for RFS, suggesting that prophylactic PALN RT does not improve survival outcomes. Distant recurrence was the most common site of first recurrence, and the extent of RT field was not associated with the site of first recurrence (P = .79). CONCLUSIONS: Prophylactic PALN RT was not significantly associated with improved survival outcomes in stage IIIC1 EC. Distant metastasis remains the most common site of failure despite routine use of systemic chemotherapy. New therapeutic approaches are necessary to optimize the outcomes for women with stage IIIC1 EC.