Use Of Adjuvant Radiotherapy Research Articles

NCOG-21. ADJUVANT RADIATION THERAPY IN ATYPICAL MENINGIOMA TREATMENT DOES NOT IMPROVE PROGRESSION FREE SURVIVAL OR OVERALL SURVIVAL: A RETROSPECTIVE COHORT STUDY

Abstract Treatment of atypical meningiomas (AMs) presents a challenge due to their aggressive nature and tendency to recur. While there is clear evidence for the role of surgical resection of AMs, the use of adjuvant radiation therapy (ART) is a topic of ongoing debate. The aim of this study is to explore the impact of ART following surgical resection of AMs. The primary outcomes of interest are progression free survival (PFS) and overall survival (OS). Records were reviewed for all patients treated for Ams at our institution between January 1, 2014 and January 1, 2024. Patients were grouped into two cohorts, those who were initially treated with surgical resection only and those who also received adjuvant RT. PFS and OS were compared between the two groups using Kaplan Meier curves and Log Rank test. Additionally, multivariable cox proportional hazard models were used to adjust for age, MIB, and resection Simpson grading. There were 76 patients who were initially treated with surgery only and 23 patients who had surgery and ART. No significant difference in PFS or OS was observed between the groups (p=0.3522 and p=0.3636, respectively); including after adjusting for age, MIB, and Simpson grading (HR= 1.55 [0.64-3.76], p= 0.330; and HR = 0.95 [0.31-2.93] p= 0.934, respectively). On multivariate analysis, MIB >10 was associated with a significant difference in PFS (HR=2.76 [1.15-6.59], p=0.023). With ART, PFS was 91% at 12 and 60% at 36 months (versus 89% and 57%, respectively, with surgery only). OS was 95% at 12 and 88% at 36 months (versus 91% and 85%, respectively, with surgery only). In this series, ART was not observed to significantly improve PFS or OS compared to surgery alone. Larger series are needed to determine if there is a subset of patients who benefit from ART.

A Nomogram Using Imaging Features to Predict Ipsilateral Breast Tumor Recurrence After Breast-Conserving Surgery for Ductal Carcinoma In Situ.

To develop a nomogram that integrates clinical-pathologic and imaging variables to predict ipsilateral breast tumor recurrence (IBTR) in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS). This retrospective study included consecutive women with DCIS who underwent BCS at two hospitals. Patients who underwent BCS between 2003 and 2016 in one hospital and between 2005 and 2013 in another were classified into development and validation cohorts, respectively. Twelve clinical-pathologic variables (age, family history, initial presentation, nuclear grade, necrosis, margin width, number of excisions, DCIS size, estrogen receptor, progesterone receptor, radiation therapy, and endocrine therapy) and six mammography and ultrasound variables (breast density, detection modality, mammography and ultrasound patterns, morphology and distribution of calcifications) were analyzed. A nomogram for predicting 10-year IBTR probabilities was constructed using the variables associated with IBTR identified from the Cox proportional hazard regression analysis in the development cohort. The performance of the developed nomogram was evaluated in the external validation cohort using a calibration plot and 10-year area under the receiver operating characteristic curve (AUROC) and compared with the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram. The development cohort included 702 women (median age [interquartile range], 50 [44-56] years), of whom 30 (4%) women experienced IBTR. The validation cohort included 182 women (48 [43-54] years), 18 (10%) of whom developed IBTR. A nomogram was constructed using three clinical-pathologic variables (age, margin, and use of adjuvant radiation therapy) and two mammographic variables (breast density and calcification morphology). The nomogram was appropriately calibrated and demonstrated a comparable 10-year AUROC to the MSKCC nomogram (0.73 vs. 0.66, P = 0.534) in the validation cohort. Our nomogram provided individualized risk estimates for women with DCIS treated with BCS, demonstrating a discriminative ability comparable to that of the MSKCC nomogram.

Abstract PO4-17-05: Patterns of care: radiotherapy after breast conserving surgery and the use of endocrine therapy for screen-detected ductal carcinoma in situ (DCIS) in the UK

Abstract Background The use of adjuvant radiotherapy (RT) and endocrine therapy (ET) in the management of pure ductal carcinoma in situ (DCIS) remains controversial. We investigate how the use of adjuvant RT after breast conserving surgery (BCS) and use of adjuvant ET (in BCS and mastectomy patients) has changed over time. Methods A prospective cohort SQL database of 11,284 patients (the Sloane Project) diagnosed 2003-2012 with screen-detected DCIS in the UK was interrogated for use of adjuvant RT and ET over time and association with factors reported to be predictive of recurrence (patient age, DCIS nuclear grade, size, comedo necrosis, resection margins), as well as institution of surgery, travel time to radiotherapy facility, Index of Multiple Deprivation and outcome (provided by the National Disease Registration Service, NDRS). RT data by site were confirmed with more recent data from the National Audit of Breast Cancer in Older Patients (NABCOP), which looked at patterns of care and outcomes for women aged 70 years and over, compared with those aged 50-64 in England and Wales. Results Among the 7,949 women (70.6%) treated by BCS, post-operative adjuvant RT was given to 4,939 (62.1%); RT use after BCS increased over time (R2 =0.92; p< 0.01). RT use was associated with year of diagnosis (p < 0.01), younger age at diagnosis (p < 0.01), larger DCIS size (p < 0.01), presence of comedo necrosis (p < 0.01), higher nuclear grade (p < 0.01) and presence of microinvasion (p < 0.01). Adjusted analyses showed the most significant factor for RT after BCS was the surgery institution. Travel time to RT facility, Index of Multiple Deprivation and final radial margin were not associated with RT use. When compared with the more recent data from the NABCOP, a marked variation in radiotherapy use across hospitals remains. Ipsilateral recurrence rate varied significantly by hospital, with some of the difference associated with RT utilisation. ET was prescribed in 1313 women (12%), more often following BCS than mastectomy (p < 0.001), with significant variation by institution and a decline in the use of ET over time. Conclusion Marked geographic variation in the use of RT and ET after surgery for DCIS persists in the UK and is likely due to physician choice rather than other factors such as travel times to RT facilities. This is contributing to geographic variation in ipsilateral recurrence rates, suggesting the need for adoption of more authoritative guidelines to support clinical decision-making. Consistent national practice could provide auditable performance standards for adjuvant therapy of screen detected DCIS and contribute to more uniform patient care. Citation Format: Karen Clements, David Dodwell, Elinor Sawyer, Ramsey Cutress, Nisha Sharma, Abeer Shaaban, Alastair Thompson. Patterns of care: radiotherapy after breast conserving surgery and the use of endocrine therapy for screen-detected ductal carcinoma in situ (DCIS) in the UK [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-05.

Abstract PS10-02: Association between Germline Mutation Status and Overall Survival among Women with Breast Cancer in Population-based Studies in the United States

Abstract Background: The influence of germline pathogenic variants (PVs) in breast cancer predisposition genes on overall survival (OS) after breast cancer diagnosis is not well defined, particularly for PVs in genes other than BRCA1 and BRCA2, and in the context of estrogen-receptor (ER) positive breast cancer. Even for BRCA1/2, OS estimates in women with breast cancer have primarily been derived from high-risk women qualifying for genetic testing due to young age at diagnosis or family history of cancer, and OS estimates by germline PV status from population-based studies are lacking. Methods: The study included 16,797 prospectively followed women with locoregional breast cancer within the population-based CARRIERS study who underwent surgical resection of the primary tumor. OS was compared between germline PV carriers and non-carriers (negative for germline PVs in 12 breast cancer predisposition genes) from the time of breast cancer diagnosis in a multivariable Cox proportional hazard regression analysis adjusting for age and menopausal status at diagnosis, race/ethnicity, ER status, type of surgery, use of adjuvant radiation, chemotherapy and endocrine agents, and prophylactic oophorectomy. Further subset analyses by race/ethnicity ER status of the primary tumor and adjusting for relevant covariates were also performed. Results: Germline PVs in ATM, BRCA1, BRCA2, CHEK2, or PALB2 were detected in 5.6% of the women in the study [ATM: 142 (0.8%), BRCA1: 206 (1.2%), BRCA2: 260 (1.5%), CHEK2:167 (1.0%) and PALB2:116 (0.7%)]. Compared to non-carriers, a significant difference in OS was not observed for germline PV carriers in ATM, BRCA1, BRCA2, or CHEK2 in the overall study population. However, a trend towards worse OS was noted for PALB2 PV carriers compared to non-carriers although this was not statistically significant (Hazard Ratio (HR): 1.36, 95%CI: 0.98 – 1.89, p=0.06). Further subset analysis by race/ethnicity demonstrated that the OS was significantly worse among Black PALB2 PV carriers (HR: 3.11, 95%CI: 1.74 – 5.55, p< 0.001) but not in non-Hispanic White PALB2 PV carriers (HR: 1.00, 95%CI: 0.59 – 1.70, p=0.98) compared to non-carriers within the same race/ethnicity. Among 12,780 women with ER+ breast cancer, compared to non-carriers, OS was significantly worse in BRCA2 PV carriers (HR: 1.51, 95%CI: 1.06 – 2.16, p=0.02) and a trend towards worse OS was observed in BRCA1 PV carriers (HR:1.53, 95%CI:0.93 – 2.51, p=0.09). Among women with ER-negative breast cancer, a significant difference in OS was not observed between PV carriers in each of the five genes and non-carriers. Conclusions: The differences in OS by race/ethnicity in PALB2 PV carriers and by ER status of the tumor in BRCA2 PV carriers warrant further investigation of underlying tumor biology and assessment of endocrine sensitivity of breast cancer in germline PV carriers. Citation Format: Fergus Couch. Association between Germline Mutation Status and Overall Survival among Women with Breast Cancer in Population-based Studies in the United States [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-02.

Abstract PO3-02-06: Predictive Factors for adjuvant radiation use in patients >70 years with pT1N0 HR+ breast cancers

Abstract Introduction: In 2004 the CALGB 9343 study reported that women >70 years of age with pT1NO hormone receptor positive breast cancer received no meaningful benefit from breast irradiation following lumpectomy. Although there was a modest reduction in local recurrence, there was no improvement in rates of mastectomy for local recurrence, distant metastases, 5-year overall survival (OS) and breast cancer specific survival therefore concluding that it was reasonable to omit radiation therapy in this group. An update of the CALGB 9343 study in 2013 with 10-year follow-up came to the same conclusion. Previous analysis of the National Cancer Database (NCDB) and the SEER database showed, however, that the majority of women with these characteristics were still receiving radiation therapy. We conducted this retrospective analysis from NCDB to identify factors associated with the use of radiation in this population. Methods: We reviewed the NCDB database and collected records of all breast cancer patients aged >70 years, who had hormone positive (HR+), pT1N0 disease between the years of 2004-2019. They were separated into radiation and non-radiation cohorts and then stratified based on ethnicity, age groups, insurance status, income quartiles, education quartiles, areas of residence, tumor size, comorbidities, diagnosis to treatment time, treatment facility type and geographic location. We then compared mortality between the two cohorts and completed a multivariate analysis to determine the demographic and clinical factors associated with the likelihood of receiving radiation. SAS was used for analysis and p-value < 0.05 was deemed as statistically significant. Results: 147,611 patients met the criteria of age > 70, pT1N0, HR+ treated with surgical lumpectomy. The majority of them were white, aged 70-75y, had Medicare, were in higher education and income quartiles and lived in metro areas (Table 1). 57.9% of the total study population received radiation. The possibility of receiving radiation decreased as age increased beyond 75 years. Uninsured patients, Medicare patients, those with comorbities, higher educational status as well as those who lived 20+ miles away from their treatment facility and treated at urban centers in central or south Atlantic areas were less likely to receive radiation. Those treated at Comprehensive community cancer programs and middle Atlantic areas were more likely to receive radiation. The possibility of radiation also progressively increased with tumor size. However, there were no differences observed when stratified by race, income status or chemotherapy use (Table 2). We also noted a small overall survival advantage for the radiation cohort (HR 0.77, p-value < 0.0001) which could be explained by the fact that patients without comorbidities were more likely to receive radiation. Discussion: Our results provide a real-world estimate of radiation use in pT1N0 HR+ early-stage breast cancer in women > 70 years. The major predictors of radiation use included younger age, low co-morbidities, insurance and institutions providing care. Lack of awareness about recent updates or concern about local recurrence could be contributing to the continued use of radiation. Although there are minor differences when stratified by demographics, it is concerning that the overall trend of radiation use has not significantly decreased over time. Since there is currently no data to support the routine use of radiation in this patient group as evidenced by randomized controlled trials, it is prudent to avoid radiation. This approach would help reduce healthcare costs, patient inconvenience and associated morbidity. Table 1 Baseline characteristics Table 2 Factors affecting radiation use Citation Format: Suma Sri Chennapragada, Runhua Shi, Shivani Sharma, Gary Burton. Predictive Factors for adjuvant radiation use in patients >70 years with pT1N0 HR+ breast cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-06.

Adjuvant Chemoradiation in Resected Biliary Adenocarcinoma: Evaluation of SWOG S0809 with a Large National Database

BackgroundThere is a paucity of evidence supporting the use of adjuvant radiation therapy in resected biliary cancer. Supporting evidence for use comes mainly from the small SWOG S0809 trial, which demonstrated an overall median survival of 35 months. We aimed to use a large national database to evaluate the use of adjuvant chemoradiation in resected extrahepatic bile duct and gallbladder cancer.MethodsUsing the National Cancer Database, we selected patients from 2004 to 2017 with pT2-4, pN0-1, M0 extrahepatic bile duct or gallbladder adenocarcinoma with either R0 or R1 resection margins, and examined factors associated with overall survival (OS). We examined OS in a cohort of patients mimicking the SWOG S0809 protocol as a large validation cohort. Lastly, we compared patients who received chemotherapy only with patients who received adjuvant chemotherapy and radiation using entropy balancing propensity score matching.ResultsOverall, 4997 patients with gallbladder or extrahepatic bile duct adenocarcinoma with available survival information meeting the SWOG S0809 criteria were selected, 469 of whom received both adjuvant chemotherapy and radiotherapy. Median OS in patients undergoing chemoradiation was 36.9 months, and was not different between primary sites (p = 0.841). In a propensity score matched cohort, receipt of adjuvant chemoradiation had a survival benefit compared with adjuvant chemotherapy only (hazard ratio 0.86, 95% confidence interval 0.77–0.95; p = 0.004).ConclusionUsing a large national database, we support the findings of SWOG S0809 with a similar median OS in patients receiving chemoradiation. These data further support the consideration of adjuvant multimodal therapy in resected biliary cancers.

Abstract IA008: Racial disparities in guideline-concordant endometrial cancer treatment

Abstract Mortality associated with endometrial cancer is 98% higher among Black as compared with White women. A large body of literature has evaluated differential treatment patterns as a potential determinant of increased mortality among Black women. In most studies, receipt of individual endometrial cancer treatment components (i.e., surgery, radiation, chemotherapy) is compared between Black and White women. Moreover, individual treatment components are typically considered binary variables (received vs. not received) with the received category reflecting a wide spectrum of treatments received. For example, women who receive one vs. six cycles of chemotherapy would be similarly labeled as receiving chemotherapy, despite a clear difference in treatment intensity. In contrast, recent studies have begun to evaluate racial and ethnic differences in the complete course of treatment as a unit, within the context of established guidelines. The National Comprehensive Cancer Network guidelines provide evidence-based endometrial cancer treatment recommendations based on clinical trials and observational research. Surgery is the first step of guideline-concordant treatment and pathology factors captured from surgery inform adjuvant treatment recommendations. Since the distribution of tumor characteristics that guide treatment recommendations varies between Black and White women, we should expect racial differences in use of adjuvant radiation and chemotherapy. However, when conceptualizing treatment as guideline-concordant vs. discordant, racial and ethnic differences clearly signal disparate quality of care. In this presentation, we will discuss the need for research on endometrial cancer treatment disparities to shift from a paradigm of exploring individual treatment components to one in which receipt of guideline-concordant treatment is the focus. Moreover, through the lens of a recently funded grant, we will discuss the value of using an explicit disparities definition in analyses of guideline-concordant treatment, which allows for decomposition of the sources of racial and ethnic disparities. Differences in healthcare related to clinical need or preference are not considered sources of disparities, reflecting the normative view that these differences are acceptable, and therefore, just. On the other hand, unjust sources of disparities include the operation of healthcare systems, the legal and regulatory climate, and discrimination, among other factors. In addition to the selection of a rigorous and nuanced disparities definition, future research on guideline-concordant treatment disparities should investigate the role of multilevel factors that reflect the social determinants of health. Cancer health disparities are entrenched in the social determinants of health, which cannot be effectively addressed at the individual-level alone. Citation Format: Ashley S. Felix. Racial disparities in guideline-concordant endometrial cancer treatment [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA008.

Impact of the COVID-19 Pandemic on Brachytherapy and Cancer Patient Outcomes: A Systematic Review

To assess the impact of the COVID-19 pandemic on the use of brachytherapy as a treatment modality in patients with gynecologic and prostate cancers including treatment delays, increased burden of mortality and associated clinical outcomes. 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 January 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. Data were extracted from two pairs of independent reviewers. Of the 292 screened records, 8 retrospective studies met the eligibility criteria and were selected. A total of 15,879 patients were included, of which 829 brachytherapy patients were identified. An Italian study reported an increase in the use of adjuvant radiation therapy (RT) in patients with uterine cancers during the lockdown period while the use of vaginal cuff brachytherapy remained stable. Hypofractionated regimens were the preferred approach in RT centers worldwide. Intracavitary brachytherapy for cervical cancer was limited to 3-4 fractions to limit personnel and patient exposure. RT treatment delay was the most common COVID-related care change ranging between 19% and 53% followed by treatment omission (2-28%). Causes of treatment delays and omissions were multifactorial: patient fear, COVID-19 infection, barriers to accessing care and operating room closures. Two studies reported modified brachytherapy approaches using single-application (SA) rather than multiple applications (MA) approaches with excellent local control, shorter overall treatment time, but at the expense of increased 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 with COVID-19 infection being the main cause of treatment delays of up to 3 weeks. 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 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.

Management of osteosarcoma of the head and neck.

There is no clear consensus guideline that specifies the optimum course of treatment for adult head and neck osteosarcoma (HNO) because of its rarity. The review's goal is to examine the most recent research on the presentation, diagnosis, prognosis, and therapy of head and neck osteosarcoma. Due to overlapping symptoms with various benign disorders of the lower jaw and midface bone, these patients present with a noticeable delay. The greatest results for these malignancies can be achieved with surgery with sufficient margins. However, it may not be able to achieve sufficient margins in tumours of the midface and skull base, and the significance of adjuvant radiation/chemotherapy needs to be investigated. The use of adjuvant radiation in instances with an advanced stage, poor prognostic indicators, and inadequate resection is supported by evidence. Nonetheless, there are divergent opinions regarding the advantages of chemotherapy in adjuvant and neoadjuvant conditions, and further multicentric randomized control trials are required to provide robust evidence. Multimodality treatments seem to yield better results for advanced HNO with adverse features and incomplete resections.

Adjuvant treatment decisions among adults aged 65 years and older with early-stage hormone receptor positive breast cancer seen in a simple multidisciplinary clinic versus standard consultation

IntroductionRandomized studies support de-escalation of adjuvant therapy for a target population of older adults ≥65 years with stage I, estrogen-receptor (ER) positive breast cancer after breast conserving surgery. We sought to evaluate the impact of a simplified multidisciplinary clinic (s-MDC) in this population by comparing treatment patterns and patient perceptions of adjuvant radiation therapy (RT) and hormone therapy (HT) between patients seen in s-MDC vs. standard consultations. Materials and MethodsMedical records were retrospectively reviewed for patients in the above target population who underwent surgery between August 2020 and May 2022 at our institution. Two cohorts were included: (1) patients seen in s-MDC, and (2) patients seen in standard clinic separately by medical and radiation oncology (non-s-MDC cohort). The non-s-MDC patients declined, could not attend, and/or were not referred to the s-MDC. Patients in the s-MDC cohort were prospectively administered validated questionnaires to evaluate patient reported data including the Decision Autonomy Preference Scale (DAPS), e-Prognosis, and Medical Maximizing-Minimizing Scale (MMS). Chi square, t-tests, and non-parametric equivalents compared demographics, and logistic regression evaluated RT and HT use and survey score outcomes between cohorts. ResultsA total of 127 patients met inclusion criteria, with 33 s-MDC and 94 non-s-MDC patients. There was no difference between the cohorts in age, margin status, histology, grade, or focality. In the s-MDC cohort there were significantly more patients without sentinel lymph node biopsy (71.3% vs 42.4%, p = 0.003) and mean tumor size was smaller (0.69 vs. 0.96 cm, p < 0.003), and Charlson comborbidity index (CCI) was higher (5.21 vs 4.96, p = 0.038). There was no significant difference in receipt of RT (65% s-MDC vs 77% standard; odds ratio [OR] = 0.55, p = 0.189), HT (78% ss-MDC vs 72% standard; OR = 1.36, p = 0.513), or both (50% s-MDC vs 59% standard; OR = 0.7, p = 0.429). The s-MDC cohort was significantly more likely to undergo accelerated (vs. standard hypofractionated) RT (70% vs 39%; OR = 3.59, p = 0.020). In s-MDC patients with completed questionnaires (n = 33), all whose selected “mostly patient (n=6)” based decision making by DAPS chose RT while all “mostly doctor (n=1)” chose no RT. Based on e-Prognosis, there were lower odds of RT for increasing Schonberg score/ higher 10 yr mortality risk (OR 0.600, p = 0.048). MMS score ≥ 40 (“maximizer”) was strongly linked with the use of RT (OR 18.57, p = 0.011). DiscussionFor adults ≥65 years with early stage, ER positive breast cancer, s-MDC participation was not significantly associated with lower use of adjuvant RT or HT versus standard consultation but was significantly associated with shorter RT courses. DAPS and MMS results indicate that patient treatment preference may be predictable, highlighting an opportunity to tailor consultation discussions and recommendations based on intrinsic patient preferences and individual goals.

Impact of the adjuvant management and risk factors on survival in FIGO stage 3 endometrial cancer patients.

Patients with FIGO stage III endometrial cancer routinely receive adjuvant therapy. The purpose of this study was to evaluate overall survival (OS) and disease-free survival (DFS) in patients with stage IIIA to IIIC2 patients by treatment modality received and risk factors. Patients with stage III endometrial cancer treated from 2000-2010 were identified in the provincial cancer registry. Clinicopathologic characteristics, adjuvant treatments and outcomes were compared using descriptive and multivariable analyses. 261 patients had stage 3 endometrial cancer, 132 with stage IIIA, 9 with IIIB, 85 with IIIC1 and 35 with IIIC2. 39 had FIGO grade 1 disease; 73, grade 2; 147, grade 3. 160 had endometrioid and 35 had serous carcinoma. 161 patients received sequential adjuvant chemotherapy (CT) and radiotherapy (RT); 33 received RT only; 32 received CT only; 35 received neither. 5-year (5Y) DFS and OS were similar among stage IIIA (DFS 46.7%, OS 58.5%), IIIB (DFS 50.8%, OS 58.5%), IIIC1 (DFS 44%, OS 49.9%) and IIIC2 (DFS 42%, OS 41.6%). Use of adjuvant RT was associated with improved median DFS (53.7 vs 14.7m, p<0.00001) and OS (61.9 vs 25.7m, p<0.00001) compared to no RT. Likewise, use of adjuvant CT was also associated with improved DFS (54.8 vs 16.5m, p<0.00001) and OS (62.9 vs 26.5m, p<0.00001) compared to no CT. Those who received both chemotherapy and radiotherapy had better outcomes with 5-year DFS (58.3%) and OS (65.2%), compared with those who received monotherapy. On multivariate analysis, grade 3 disease, deep myometrial invasion >50%, and no adjuvant RT or CT were identified as adversely impacting DFS and OS. In stage III endometrial cancer patients, use of both chemotherapy and radiation therapy was associated with improved DFS and OS and therefore should be recommended in all eligible patients after resection.

Factors associated with the use of adjuvant radiation therapy in stage III melanoma.

The role of radiation therapy (RT) in melanoma has historically been limited to palliative care, with surgery as the primary treatment modality. However, adjuvant RT can be a powerful tool in certain cases and its application in melanoma has been increasingly explored in recent years. The aim of this study is to explore national patterns of care and associations surrounding the use of adjuvant RT for stage III melanoma. The National Cancer Data Base (NCDB) was used to identify patients who were diagnosed with stage III melanoma between 2004 and 2014. Exclusion criteria included those with distant metastatic disease, in-situ histology, no confirmed positive nodes, palliative intent therapy, and dosing regimens inconsistent with National Comprehensive Cancer Network (NCCN) guidelines for adjuvant RT in melanoma. Patients treated with and without adjuvant RT were compared and factors associated with use of adjuvant RT were identified using multivariable logistic regression analyses. A total of 7,758 cases of stage III melanoma were analyzed, of which 11.7% received adjuvant RT. The mean age of the overall cohort was 58.5 years, and the majority of patients were male (64.7%), white (96.6%), on private insurance (51.3%), and presented to a non-high-volume facility (90.3%). Multivariable regression analyses revealed that patients who present to the hospital in 2009-2014 as compared to 2004-2008 (odds ratio [OR] 1.61, 95% confidence interval [CI] 1.36-1.92), had 4 or more positive nodes (OR 4.30, 95% CI 3.67-5.04), and had microscopic residual tumor (OR 2.11, 95% CI 1.46-3.04) were more likely to receive adjuvant RT. Factors that were negatively associated with receiving adjuvant RT included female gender (OR 0.72, 95% CI 0.61-0.85) and median income of at least $63,000 (OR 0.66, 95% CI 0.52-0.83). This study demonstrates the rising use of RT for stage III melanoma in recent years and identifies demographic, social, clinical, and hospital-specific factors associated with patients receiving adjuvant RT. Further investigation is needed to explore disease benefits to improve guidance on the utilization of RT in melanoma.

The relationship between adjuvant radiotherapy and survival of osteosarcoma: a case-control study

ABSTRACT To investigate whether adjuvant radiotherapy (RT) is associated with survival rate of osteosarcoma patients. A total of 3938 osteosarcoma patients between 1975 and 2016 from Surveillance, Epidemiology, and End Results (SEER) database were enrolled in this study. Survival rate was obtained by Kaplan-Meier method, with log-rank test identifying the difference. Multivariate Cox regression analysis was used to explore independent prognostic factors. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates in surgery plus adjuvant RT group and surgery alone group were 38.2%, 66.3% (OS), and 41.6%, 68% (CSS), respectively. Multivariate analysis showed that adjuvant RT served as the independent unfavorable prognostic factor for OS and CSS. Based on the propensity score matching (PSM) method, the patients who received adjuvant RT had a poorer prognosis. Adjuvant RT showed an association with survival of osteosarcoma. Patients who received adjuvant RT had poorer survival. In the clinical use of adjuvant RT for osteosarcoma, the potential for reduced survival should be considered.

PO32 Presentation Time: 10:30 AM: Outcomes After Adjuvant Radiation in Patients with Early-Stage Endometrial Cancer with Mismatch Repair Defects

<h3>Purpose</h3> Although mismatch repair (MMR) deficiency is commonly identified in endometrial cancers, its significance on outcomes remains unknown. Our study aims to determine if MMR status affects clinical outcomes in early-stage endometrial cancer patients treated with adjuvant radiation therapy. <h3>Methods/Materials</h3> We identified 194 patients with FIGO 2009 stage I-II endometrioid endometrial cancer who underwent surgical resection followed by adjuvant radiation therapy at our institution with available MMR status. Locoregional recurrence (LRR) and distant metastases were analyzed using competing risk methods, and overall survival (OS) and progression free survival (PFS) were analyzed using Kaplan-Meier. <h3>Results</h3> The median age was 65 years, and the median follow-up time was 38 months. There were 73 patients (37.6%) with an MMR deficiency, and 121 (62.4%) patients with intact MMR. Eleven patients (5.7%) experienced LRR, and 14 patients (7.2%) experienced distant recurrence. The median OS and PFS of the cohort was not reached and MMR status was not associated with OS or PFS. MMR deficiency was significantly associated with the grade of the tumor (17.1% of grade 1 versus 54.4% of grade 2 and 46.9% of grade 3 patients (<i>p</i><0.01)), the depth of myometrial invasion (<i>p</i><0.01), and the presence of LVSI (<i>p</i><0.01). MMR status was not associated with the type of radiation delivered. In the entire cohort, patients who received external beam radiation therapy had significantly worse PFS than patients who underwent brachytherapy (<i>p</i>=0.03). In patients whose tumors were MMR deficient, there was also a significant difference in PFS based on the type of radiation delivered. Patients who underwent external beam radiation therapy (EBRT) had shorter PFS versus patients who underwent brachytherapy only (<i>p</i>=0.02). In patients with MMR deficient tumors, there was a significant correlation between radiation type and stage; patients with stage II disease were more likely to undergo both EBRT and brachytherapy (<i>p</i><0.01). After adjusting for stage, type of radiation delivered was trending towards significance (p=0.07). Greater depth of myometrial invasion was also associated with the use of both EBRT and brachytherapy (<i>p</i>=0.03). <h3>Conclusions</h3> Patients with stage I-II endometrial cancer have excellent oncologic outcomes with the use of adjuvant radiation therapy, regardless of MMR status.

Omission of Radiation in Elderly Patients in a Predominantly Minority Population

<h3>Purpose/Objective(s)</h3> The omission of radiation (RT) has increased among elderly patients following the results of CALGB C9343 and more recently PRIME II demonstrating low local recurrence (LR) risk with adjuvant endocrine therapy (ET) alone for women over 70 with estrogen receptor positive (ER+) Stage I breast cancer. However, these trials were conducted in predominantly Caucasian populations and may not be generalizable to more diverse populations. The aim of this study was to evaluate the risk factors for LR without RT in ER+ Stage I disease among elderly women in a largely minority patient population. <h3>Materials/Methods</h3> This study is a retrospective analysis of elderly patients (≥70) with Stage I ER+ breast cancer who underwent lumpectomy and were considered for RT at an urban, academic institution between 2006 to 2020. The primary endpoint was mammographic LR at 5 years, stratified by use of adjuvant RT. Demographic and clinical variables, including pathology (grade, LVI, Her2 status), compliance with ET (defined as at least 1 year), imaging, and follow-up information were obtained from the electronic medical record. Fisher's exact test was used for categorical variables. <h3>Results</h3> Three hundred and sixty-nine patients were included in the initial analysis with a median follow-up time of 6.2 years. Median age was 75.8 years (interquartile range [IQR] 72.4-79.5), with 78% identifying as either Hispanic or non-Hispanic black. 33% of patients omitted adjuvant RT, and 89% were compliant with adjuvant ET. There was a total of 18 LRs at a median of 4.1 years (IQR: 2.3 – 5.5 years). Of these, 13 omitted RT, 2 were LVI+, 3 were grade 3, 2 were Her2+, 11 were non-compliant with ET, and 0 identified as non-Hispanic Caucasian. 11 patients who had a LR omitted both RT and ET. Amongst those with follow-up of at least 5 years (225 patients), there were 11 LRs. The use of RT led to a significant reduction in 5-year LR (1.4% vs 14%, p <0.001). There was a trend toward increased LR in minority patients (6.7% vs 0%, p=0.125) regardless of receipt of RT. <h3>Conclusion</h3> In this retrospective analysis of elderly, mostly minority, stage I post-lumpectomy ER+ breast cancer patients, we observed a significant reduction of LR with the use of adjuvant RT in line with prior studies. However, omission of RT led to higher than anticipated LR likely due to adjuvant ET non-adherence. Whether ethnicity is a truly factor in LR would require larger confirmatory studies.

Adjuvant Treatment Decisions among Older Women with Early-Stage Breast Cancer Seen in Multidisciplinary Consultation vs. Standard Consultation

<h3>Purpose/Objective(s)</h3> Randomized studies and national guidelines support de-escalation of adjuvant therapy for a target population of woman ≥65 years with Stage I, ER positive breast cancer after breast conserving surgery. We sought to evaluate the impact of a multidisciplinary clinic (MDC) in this population by comparing treatment patterns and patient perceptions of adjuvant radiation therapy (RT) and hormone therapy (HT) between patients seen in MDC vs. standard consultation. <h3>Materials/Methods</h3> Medical records were retrospectively reviewed for women in the above target population who underwent surgery between 8/2020-11/2021 at our institution. Two cohorts were included: (1) patients seen in MDC, and 2) patients seen in standard clinic separately by medical and radiation oncology (non-MDC cohort). The non-MDC patients either declined MDC, could not attend an MDC clinic day, and/or were not referred to the MDC. Patients in the MDC cohort were also prospectively administered validated questionnaires to evaluate patient treatment preferences including the Decision Autonomy Preference Scale (DAPS) and Medical Maximizing-Minimizing Scale (MMS). Chi square, t-tests, and non-parametric equivalents compared demographics and logistic and linear regression evaluated RT and HT use and survey score outcomes between cohorts. <h3>Results</h3> A total of 90 patients met inclusion criteria, with 23 MDC and 67 non-MDC patients. There was no difference between the cohorts in age, Oncotype Recurrence Score, margin status, or tumor histology, grade, or focality. For the MDC cohort, there were significantly fewer sentinel lymph node biopsies performed (44% vs. 74%, p=0.006), and tumor size was smaller (0.6 vs. 1.1 cm, p<0.005), although all tumors were pT1c or less. Significantly fewer MDC patients received RT (61% vs. 82%, OR=0.34, p=0.046). The MDC cohort was more likely to undergo accelerated (vs. standard hypofractionated) RT (57% vs. 27%, OR 3.61, p=0.039). There was no difference in use of HT between cohorts (75% vs 76%, OR 1.08, p=0.885). Among the MDC cohort, all who preferred decisions be made "mostly by the patient" on the DAPS elected RT. Increasing MMS total score was associated with higher odds of RT (OR 1.43, p=0.027), with no "minimizers" (score <40) electing RT. <h3>Conclusion</h3> For women ≥65 years with early stage, ER positive breast cancer, MDC participation was associated with lower use of adjuvant RT and selection of shorter RT regimens versus standard consultation. These results support the role of the MDC in facilitating shared decision-making, perhaps enhancing patient comfort with forgoing more aggressive therapies. Responses from the DAPS and MMS tools indicate that patient treatment preference may be predictable, highlighting an opportunity to better tailor consultation discussions and recommendations based on intrinsic patient preferences and individual goals.

Considerations in Treatment Planning and Dosimetric Specifications of Permanent 131Cs Brachytherapy Implantation in Treatment of Brain Tumor – An Institutional Experience

<h3>Purpose/Objective(s)</h3> Local recurrence after the operative management of several types of brain tumors remains common and is the rationale for the frequent use of adjuvant radiation. This report details the dosimetry and normal tissue exposure to organs at risk (OARs) for patients with brain tumors treated with a novel strategy of maximum safe resection (MSR) and permanent ¹³¹Cs brachytherapy implantation. <h3>Materials/Methods</h3> From 01/2019 to 02/2022, thirty-two patients with 35 brain tumors underwent MSR followed by permanent ¹³¹Cs source implantation using a collagen tile brachytherapy device. The pre-op GTV delineated on MRI within 30 days was used to estimate the number of tiles needed. The post-operative thin-slice (1 mm) CT and contrast-enhanced MRI were obtained within 24 hours of surgery. Dosimetry analysis was performed using a brachytherapy planning tool. A dose of 60 Gy was prescribed to the high-risk clinical target volume (HR-CTV), defined as the brain parenchyma within 5 mm isotropic expansion from the resection cavity, respecting unviolated anatomical borders. Implant quality was evaluated with the D₉₀, V₅₀, V₁₀₀, V₁₅₀, V₂₀₀ metrics for the HR-CTV; D_max and D_mean OAR metrics were recorded. When applicable, the residual gross tumor volume (GTV_r), defined as persistent, nodular contrast enhancement on post-operative T1-weighted MRI, was delineated, and the D₉₀ to GTV_r was recorded. <h3>Results</h3> The median volume was 17.8 cc (2.3-119.2 cc) for the pre-op GTV, 15.8 cc (4.6-78.3 cc) for the resection cavity, 21.2 cc (9.5-58.3 cc) for HR-CTV, and 1.2 cc (0.2-28.9 cc) for GTV_r. 36% (16/35) cavities were larger than pre-op GTV by an average of 9.1 cc (<0.1-31.3 cc). The median D₉₀ was 63.4 Gy to HR-CTV (n=35, 31.7- 148.3 Gy), and 68.7 Gy to GTV_r (n=24, 22.8-113.8 Gy). The median V₅₀, V₁₀₀, V₁₅₀, V₂₀₀ of HRCTV were 100% (91.1-100%), 93.2% (41.9-100%), 11.1 cc (3.7-51.9 cc), and 4.7 cc (1.2-43.7 cc). The dosimetric objective D₉₀ ≥ 54 Gy to the HR-CTV was met in 69% (24/35) of cavities; the objectives V₅₀ ≥ 99% and V₁₀₀ ≥ 90% were met in 83% (29/35) and 54% (19/35) of cavities. OAR metrics were summarized in Table 1. <h3>Conclusion</h3> Permanent ¹³¹Cs brachytherapy implantation can provide adequate dosimetric coverage of the HR-CTV and selective sparing of OARs after MSR.

Role of Adjuvant Regional Nodal Irradiation in Resected Melanoma: A Secondary Analysis of SWOG S1404

<h3>Purpose/Objective(s)</h3> Results from TROG 02.01 demonstrated that adjuvant radiotherapy (RT) in high-risk melanoma patients is associated with improved locoregional control (LRC). The aim of our study is to evaluate the role of adjuvant RT in standard risk (SR), high risk (HR) and ultra-high risk (UHR) melanoma patients in the immunotherapy era. S1404 randomized resected stage III and stage IV melanoma patients to standard of care adjuvant immunotherapy or pembrolizumab after surgery. <h3>Materials/Methods</h3> We retrospectively analyzed the data for 1239 patients enrolled in S1404. We stratified the patients according to SR (no high-risk features), HR (defined according to TROG 02.01 trial) and UHR (extracapsular extension with 5 or more positive nodes or 4 cm or greater nodal size). Recurrence free survival (RFS) and time to regional recurrence (TtRR) were primary outcomes; distant metastasis free survival (DMFS) was a secondary outcome. RFS was estimated using the Kaplan-Meier method and associations with the outcome were evaluated using Cox regression models. TtRR and DMFS were estimated with cumulative incidence curves and associations with the outcome were evaluated using cause-specific regression models. <h3>Results</h3> Of 1239 patients analyzed, 136 patients (11%) completed RT. The most common RT regimen used was 30 Gy/5 fractions (37%) followed by 48 Gy/20 fractions (31%). Fifty three percent of patients were HR per TROG02.01. More HR patients received RT compared to SR (16 % versus 6%; p-value <= 0.001). Among the patients who received RT 76/136 (56%) were advanced stage (Stage IIIC/ resected Stage IV) compared with those who did not 390/1103 (35%); p value <= 0.001. Similarly macroscopic lymph node involvement was significantly higher in RT group, 89/136 (65%) versus 457/1103 (41%); p value <=0.001. TtRR was significantly longer for patients who completed RT (all comers: 9% RR @ 4 year no RT vs 1% @ 4 year with RT; p value = 0.015). For high-risk patients, TtRR was longer for patients who received RT regardless of PD1 status (12% RR @ 4 year no RT vs 2% @ 4 year with RT; p value = 0.009). No significant difference in value of RT was seen based on anatomic nodal site, study arm or BRAF mutation status. Among patients treated with pembrolizumab, a trend toward RFS benefit was seen in patients treated with RT (HR = 1.54, 95% confidence interval 0.94-2.53; p=0.085). There was no significant difference in DMFS between those who completed RT versus not. <h3>Conclusion</h3> Our study validated the results of previous studies and suggests consideration of adjuvant RT in high-risk patients regardless of planned adjuvant immunotherapy for improved LRC. We recommend the use of adjuvant RT in patients with macroscopic nodal involvement with extracapsular extension or with heavy nodal burden even in the immunotherapy era.

Adjuvant radiation therapy improves survival in stage IIIA (N2) non-small cell lung cancer with persistent N2 disease after neoadjuvant chemotherapy

ObjectivesRole of adjuvant radiation therapy in stage III (N2) non-small cell lung cancer has been controversial over the decades. Recent large, randomized trials have demonstrated that adjuvant radiation did not improve overall survival or disease-free survival; however, the trials either excluded or enrolled very few cases that have undergone neoadjuvant chemotherapy. Role of adjuvant radiation after neoadjuvant chemotherapy remains unclear. Whether the use of adjuvant radiation is associated with improved overall survival in those who have received neoadjuvant chemotherapy, especially in a subgroup of patients with persistent N2, is unknown. Materials and methodsPatients with clinical stage III (N2) non-small cell lung cancer diagnosed from 2004 through 2017 were queried to National Cancer Database. Eligibility criteria included completely resected (R0), pathological diagnosis, neoadjuvant multi-agent chemotherapy, information regarding post-surgical N2 status (persistent versus downstaged to pN0-1), adjuvant radiation (45 Gy+ versus none), and American Joint Commission on Cancer staging version (6th versus 7th). Those who have received neoadjuvant radiation with any dose or adjuvant radiation with less than 45 Gy total dose were excluded. Kaplan-Meier and log-rank tests were used for survival analyses. Propensity-score matching analysis was used for validation. All statistical analyses were two-sided, and p < 0.05 was required for statistical significance. ResultsA total of 1,855 patients met the eligibility criteria for analysis. In the overall cohort, there was a significant difference in overall survival between persistent N2 (Cohort P: N = 854, median survival 50.7 months) and downstaged N (Cohort D: N = 1,001, median survival 82.7 months). The use of adjuvant radiation showed a non-significant detrimental effect in overall survival in the overall and Cohort D (univariate p-values 0.27 and 0.077, respectively); however, both univariate and multivariate analyses demonstrated a significant improvement in overall survival in Cohort P (p = 0.004 and 0.028, respectively). These findings are also verified by propensity-score matching analysis (p = 0.0347). ConclusionsThis large-scale retrospective analysis suggests that adjuvant radiation may still have a role in persistent N2 disease after neoadjuvant chemotherapy. Further investigations are warranted.

Adjuvant treatment decisions among women age &gt; 65 with early-stage, hormone-receptor breast cancer seen in multidisciplinary clinic versus standard consultation.

281 Background: Randomized studies and national guidelines support de-escalation of adjuvant therapy for a target population of woman &gt;65 years with Stage I, ER positive breast cancer after breast conserving surgery. We sought to evaluate the impact of a multidisciplinary clinic (MDC) in this population by comparing treatment patterns and patient perceptions of adjuvant radiation therapy (RT) and hormone therapy (HT) between patients seen in MDC vs. standard consultation. Methods: Medical records were retrospectively reviewed for women in the above target population who underwent surgery between 8/2020- 5/2022at our institution. Two cohorts were included: (1) patients seen in MDC, and 2) patients seen in standard clinic separately by medical and radiation oncology (non-MDC cohort). The non-MDC patients declined, could not attend, and/or were not referred to the MDC. Patients in the MDC cohort were prospectively administered validated questionnaires to evaluate patient reported data including the Decision Autonomy Preference Scale (DAPS), e-Prognosis, and Medical Maximizing-Minimizing Scale (MMS). Chi square, t-tests, and non-parametric equivalents compared demographics and logistic and linear regression evaluated RT and HT use and survey score outcomes between cohorts. Results: A total of 128 patients met inclusion criteria, with 33 MDC and 94 non-MDC patients. There was no difference between the cohorts in age, margin status, histology, grade, or focality. In the MDC cohort there were significantly fewer sentinel lymph node biopsies (42.4% vs. 71.3%, p = 0.003) and mean tumor size was smaller (0.69 vs. 0.96 cm, p &lt; 0.003). There was no significant difference in receipt of RT (65% MDC vs 77% standard; OR = 0.55, p = 0.189, HT (78% MDC vs 72% standard; OR = 1.36, p = 0.534), or both (65% MDC vs 77% standard; OR = 0.7, p = 0.430). The MDC cohort was significantly more likely to undergo accelerated (vs. standard hypofractionated) RT (70% vs 39%; OR = 3.60, p = 0.020). In MDC patients with completed questionnaires (n = 33), by DAPS, all “mostly patient (n = 8)” chose RT while all “mostly doctor (n = 1)” chose no RT (p = 0.063). Based on e-Prognosis, there were lower odds of RT for increasing Schonberg score/ higher 10yr mortality risk (OR 0.600, p = 0.048). MIMS score &gt; 40 (“maximizer”) was strongly correlated with the use of RT (OR 18.57, p = 0.011). Conclusions: For women &gt; 65 years with early stage, ER positive breast cancer, MDC participation was not associated with lower use of adjuvant RT or HT versus standard consultation but was significantly associated with shorter RT courses. DAPS and MMS results indicate that patient treatment preference may be predictable, highlighting an opportunity to tailor consultation discussions and recommendations based on intrinsic patient preferences and individual goals.