Purpose/Objective(s) Post-mastectomy radiation therapy (PMRT) is integral in managing breast cancer patients. Several studies have validated the use of hypofractionation in the management of patients following breast conserving surgery, but less data to support hypofractionation are available for patients requiring adjuvant PMRT. In this retrospective study, we evaluated outcomes, toxicity, and cosmetic results in patients treated with hypofractionated PMRT (hfPMRT) at our center. Materials/Methods After obtaining IRB approval, we reviewed the patients who underwent mastectomy +/- reconstruction and were treated with adjuvant hfPMRT between 2016-2024. Reconstruction types were recorded. Ipsilateral chest wall recurrence (ICWR) and regional nodal recurrence (NR), overall survival (OS), disease-free survival (DFS) as well as complications and toxicity, and cosmetic outcomes were analyzed. T-test, Chi-square test and Kaplan-Meier analysis were performed, using data management and decision management software. Results A total of 58 patients were treated with PMRT to 4240 -5250 cGy in 16-20 fractions to the chest wall and comprehensive regional nodes. Median age 62 years (38 – 90 years). 29 (50%) patients had neoadjuvant chemo and 39 (67%) adjuvant chemo or endocrine therapy. 25 (43%) patients had axillary dissection. Of 26/56 (46%) patients who had reconstruction: 13 (50%) had immediate DIEP reconstruction and 13 (50%) had pre-RT expansion with an expander who went on to get post-RT exchange for a permanent implant, and 2 had post-RT DIEP. With median follow up of 24 months (1 - 96 months), there were 2 ICWR (3%), 2 ipsilateral axillary NR (3%), and 5 distant metastases (9%). The 2-year OS and DFS were 93%and 82%, respectively. Grade 2 acute skin toxicity, Grade 2 late skin toxicity, brachial plexopathy, lymphedema rate cosmesis (shrinkage/induration) were 14%, 2%, 0%, 12%, and 7%, respectively. There were no differences in acute or late toxicities, lymphedema, cosmesis in patients with reconstruction vs. without reconstruction (p = 0.45, 0.50, 0.45, 0.31). Among patients with reconstruction, there was no difference in acute, late toxicities, cosmesis or lymphedema for immediate DIEP vs. upfront expander (p = 0.48, 0.60, 1.00, 0.04). There were more Grade 2 acute skin toxicity (24% vs. 6%, p = 0.049) ALND compared to SLNB. Conclusion Adjuvant hfPMRT resulted in low rates of recurrence, toxicity and acceptable cosmetic results. hfPMRT may therefore provide a convenient, safe and effective option. Prospective data is awaited to validate these results.

Purpose/Objective(s) Radiotherapy (RT) is a mainstay of management of head and neck cancer (HNC) but is associated with high rates of severe toxicity. Currently there is a lack of objective criteria that can predict premature RT termination or delayed RT treatment completion. This study aims to evaluate objective criteria that can be used to identify patients who are less likely to tolerate an extended course of RT treatment. Materials/Methods A RT completion scoring system was developed based on patient characteristics (Table 1), which was used to assign patients with a total score. For validation of the scoring, patients with HNC treated with curative intent with RT at our tertiary care center from 2017 to 2023 were reviewed from a large departmental database (IRB approved). Patients were included if they had a diagnosis of primary HNC and were prescribed curative RT, either as primary treatment or post-operatively. Individual variables were scored and a total score was calculated for each patient. Early termination (ET) was defined as any non-completion of full radiation course. Prolonged treatment (PT) was defined as any radiation course >50 days. Chi-squares test / Fisher's exact test was used for categorical data. Univariable logistic regression was used for continuous data. Significance level was 0.05 for all tests unless otherwise specified. Data analysis was performed using SAS Version 9.4. Results Of 301 patients included, 182 (60%) were male and 119 (40%) were female. Median age was 66.9 years (range 20.3-96.0 years). 267 (89%) were treated with IMRT and 34 (11%) with SBRT. 150 (50%) had primary cancer in the oral cavity, 53 (18%) in the salivary glands, 45 (14%) in the oropharynx, 53 (18%) in the nasal cavity, sinuses, nasopharynx, larynx, hypopharynx and thyroid. 40 patients (13.3%) had PT and 14 (4.7%) had ET. For each unit increase in total score, there was significant increased risk of ET/PT (p value 0.002; odds ratio 1.17, 95% CI = 1.06-1.28). On multivariable analysis considering these covariates, patients with ECOG score 2-4 had higher risk of ET/PT than patients with ECOG score of 0-1 (odds ratio 3.63, 95% CI = 1.74-7.54, p value <0.001). Patients receiving >30 fractions had higher risk of ET/PT than those receiving <5 fractions (odds ratio 5.60, 95% CI = 1.09-28.71, p value = 0.039). Patients receiving concurrent chemotherapy had higher risk of ET/PT than patients receiving no systemic therapy (odds ratio 2.16, 95% CI = 1.08-4.34, p value = 0.030). Conclusion This novel radiation treatment score predicted ET/PT in RT treatment of HNC. Total score, ECOG score, total fractions and associated therapy were significantly associated with ET/PT. We plan to validate this score prospectively in patients with HNC being treated with RT.

Purpose/Objective(s) Treatment failures with adjuvant radiation (RT) may not be identified for months after treatment and require invasive tests to confirm disease progression. This study assessed whether ctDNA is elevated in patients with vulvar cancer and whether it can be used as a non-invasive marker of response to RT. Materials/Methods After IRB approval, patients with advanced vulvar cancer treated with definitive RT at our institution 2022 - 2024 were assessed. ctDNA was obtained and measured using Signatera™ test (Natera Inc.) pre-, mid-way, pre-boost and at the end of RT and in follow up at 1, 3, 6 and every 6 months post-RT/, respectively. A detectable ctDNA was defined as any level above 0.00 mean tumor molecules (MTM)/ml, whereas 0.00MTM/ml was considered undetectable. During and after RT, ctDNA decline to 0.00MTM/ml was defined as complete metabolic response (cMR) but a reduction without achieving 0.00MTM/ml in ctDNA value was a partial metabolic response (pMR). Correlation between ctDNA levels and imaging (PET-CT, MRI, CT) was also assessed. Statistical analyses used were descriptive statistics, t-tests, and a Spearman correlation coefficient (ρ). Results At a median follow up of 8 months (range = 2-20 months), a total of 42 serial ctDNA blood draws were obtained. Median age was 63 (range = 40-90 years). Median radiation dose was 6600 cGy (range = 6400-7000 cGy). All patients with measurable disease on imaging and physical exam had median pre-RT ctDNA 1.63 MTM/ml (range = 1.20- 3.52 MTM/ml). There was a 100% reduction in all ctDNA values from pre-RT to mid-RT (mean 1.78 vs. 0.04, p = 0.02): 88% cMR and 12% pMR. A total of 100% cMR in ctDNA occurred from mid-RT to post-RT. All patients had 100% reduction in all ctDNA values from preRT- to post-RT (mean 1.78 vs. 0, p = 0.03). In patients who sustained complete response to RT, the mid-RT and end-RT ctDNA draws exhibited a cMR (ctDNA of 0.00MTM/ml), which was sustained in follow-up. In one patient with pMR at mid-RT (0.30MTM/ml), there was a rise of ctDNA at 9 mo post-RT (0.64MTM/ml) and progression of disease on PET-CT which led to a surgical excision. There was a strong correlation between elevated ctDNA and FDG uptake/measurable disease on imaging (PET/MRI) pre-treatment (ρ = 0.87, p < 0.0045), as well as between a ctDNA decline and decrease of disease on imaging post-RT/CRT (ρ = 1, p < 0.0001). Conclusion There was a reduction in ctDNA from pre- to mid- to post- RT. A mid-RT ctDNA identified responders to RT; hence, this finding may serve as an early predictive biomarker of response. Elevated ctDNA correlated with measurable disease on imaging. These early promising results suggest the need to study ctDNA in a larger cohort, prospectively.

Purpose/Objective(s) Radiotherapy (RT) causes toxicity and outcomes of treatment may not be known for months post-therapy. Early identification of response with a ctDNA blood draw may provide a non-invasive way to predict response to treatment. In this study, we used ctDNA to assess response to RT in patients with GYN cancers as early as mid-way during treatment. Materials/Methods After IRB approval, patients with vulvar, cervical, and recurrent endometrial cancer were treated with RT at our institution between 2022 and 2024. The ctDNA was obtained using personalized molecular residual disease assay pre-RT, mid-way through RT, pre-boost with brachytherapy or SBRT, at the end and in follow-up at 1, 3, 6, and every 6 months -post RT, respectively. A detectable value of ctDNA was defined as any level above 0.00 mean tumor molecules (MTM)/mL, whereas 0.00MTM/mL was undetectable. During and after RT, ctDNA of 0.00MTM/mL was defined as complete metabolic response (cMR) but a reduction without achieving the value 0.00MTM/mL in ctDNA was deemed partial metabolic response (pMR). Correlation between ctDNA levels and imaging (PET-CT, MRI, and CT) was also assessed. Statistical analyses used were descriptive statistics, t-test, Chi-square test and a spearman-rank correlation coefficient (ρ). Results A total of 105 serial ctDNA blood draws were obtained from 21 patients with 8 (38%) vulvar, 7 (33%) cervical, 2 (10%) neuroendocrine, and 3 (19%) recurrent endometrial cancers (reEMCa). Median age was 59 years (range = 35-90 years). Median number of ctDNA draws per patient was 6 (range = 1-9). Median radiation dose was 5900 cGy (range = 4500-7000 cGy), brachy boost of 28 Gy/4 fx T&O and SBRT 30 Gy/5 fx for 7 cervix cases, and SBRT boost 2750 cGy/5 fx for reEMCa. There was 100% reduction in ctDNA values (metabolic response) from pre-to post-RT (mean = 2.04 vs. 0, P = 0.03): 75% cMR and 25% pMR. In patients who sustained response to RT, mid- and end-RT ctDNA draw exhibited 0.00MT/ml (undetectable), which continued in follow-up. A strong correlation was observed between elevated ctDNA and SUV/measurable disease on imaging pre-treatment (ρ = 0.64, P = 0.01), as well as undetectable ctDNA and decline of SUV/complete resolution of SUV at 3-6 months following RT (P = 0.045). Conclusion The ctDNA in patients with gynecological malignancies drawn at pre-, mid- and post-RT sustained metabolic response and correlated with response to treatment by imaging and clinical examinations. Our early findings suggest that a mid-treatment ctDNA test identified responders to RT and thus may serve as an early predictive biomarker of response. A larger prospective evaluation is warranted.

Purpose/Objective(s) Ultra-hypofractionated radiotherapy (UHFRT) (1 week of RT in 5 fx) has been shown to be effective in controlling local recurrence in women with early-stage breast cancer as per the FAST-Forward trial. However, its role in the subset of older women was not specifically reported. Further, many older women have diminished compliance with endocrine therapy (ET). This study aims to investigate the initial outcomes of UHFRT in older patients with low-risk breast cancer who are potential candidates for omission of RT. Materials/Methods After IRB approval, we assessed outcomes of consecutive women treated in the department of radiation medicine at Northwell Health with breast conserving surgery and adjuvant 5-fx UHFRT regimens [whole breast 26Gy/5fx or accelerated partial breast irradiation (APBI) 26-30Gy/5fx] between Jan 2020 and Feb 2024. Inclusion criteria were age≥ 65 years, Grade 1 or 2, T1-T2 up to 3 cm invasive breast cancer, axillary node-negative, clear margins, hormone receptor-positive, Her-2 negative. Compliance with RT and ET, toxicity, cosmetic outcomes, and IBTR were analyzed. Descriptive statistics, t-test and Chi-square test were performed, using SAS OnDemand for academics 2024 version. Results Of 1258 women with early-stage breast cancer treated at our center, 71 women met low-risk inclusion criteria and were treated with UHFRT: 43 (61%) with whole breast and 28 (39%) with APBI. Median age was 73 years (range = 65 - 91 years). Median tumor size was 0.8cm (range = 0.12 – 2.8 cm). While compliance with UHFRT was 100%, compliance with ET was 24% (either due to refusal or termination of ET due to side effects). At a median follow up of 10 months (range = 1 - 37 months), there was no IBTR in the entire cohort. There were no Grades 3 or 4 toxicities. Grade 2 acute toxicities, late toxicities, and cosmetic outcomes (induration) with UHFRT+ET vs UHFRT alone were 2% vs. 0%, 2% vs. 0%, 0% vs. 5.9% respectively, and P = 0.28, 1.00, 0.24, respectively. Despite no significant difference in age and baseline performance status (P = 0.19 and 0.33), higher Grades 1 and 2 acute fatigue was observed in patients who were not compliant with ET after UHFRT (UHFRT vs UHFRT +ET 36% vs. 13%, P = 0.02). Conclusion These results demonstrate that UHFRT with FastForward and APBI regimens offer a convenient and easily tolerated treatment approach for older women who chose to reduce the rate of IBTR. Further, in women with diminished compliance with ET, there was 100% compliance with UHFRT. UHFRT resulted in encouraging local control, compliance, and cosmetic results (FAST-Forward showed 5.6% induration). Further prospective studies are necessary to confirm our initial findings.