Lester, Scott C.

7556 Background: The majority of R/R NHL progressions after CART involve pre-existing sites, suggesting a promising role for bridging radiotherapy (bRT). We assessed the local control rate of disease sites bridged with radiotherapy prior to CART and identified predictors of in-field recurrence. Methods: We retrospectively reviewed 35 patients with aggressive B-cell NHL who received bRT between leukapheresis and CART infusion between 2018 and 2021 at a multi-site single institution. bRT local control rate (LC), calculated based on the total number of irradiated sites, was defined from bRT end date. Progression-free survival (PFS) and overall-survival (OS) were defined from the date of CART infusion. In-field recurrence was defined as disease relapse occurring within the radiation planning target volume. Kaplan-Meier plots and cox regression modeling were used to estimate the desired output. Results: Median age of the cohort at time of CART infusion was 59 (range 19-73). The median equivalent 2 Gy dose (EQD2) administered was 23.3 Gy (range 4-41 Gy). The median time from end of bRT to CART infusion was 14 days (range 6-42). Five (14%) patients also received bridging chemotherapy with bRT. Among the 34 evaluable patients, 30 (88%) achieved an objective response (59% complete response and 29% partial response). At a median follow-up of 12 months, 1-year PFS was 48% and 1-year OS was 72%. No progression occurred beyond 240 days. On review of treatment plans and pre-treatment PET/CT scans, 59 sites were identified that received bRT prior to CART infusion. The median size and SUVmax of the irradiated sites were 8.7cm (range 1.5-22) and 13 (range 4-46), respectively. Of the 59 irradiated sites, 8 sites (13.6%) in 7 patients had in-field local recurrence, translating to 1-year LC of 84%. No in-field recurrence occurred beyond 180 days. Moreover, no local recurrence occurred in patients who received radiation to all known sites of active disease to EQD2> 30 Gy (n = 4 patients); these patients remained in remission except for 1 who experienced progression outside the bRT field. On univariate analysis, triple hit lymphoma (THL) (OR 22.8, 95% CI: 3.8-138.3; p < 0.001), tumor size (OR 1.25, 95% CI: 1.1-1.4; p < 0.001), specifically ≥ 9cm (OR 9.4, CI: 1.2-77.3; p = 0.036) and SUVmax (OR 1.1, CI: 1.02-1.15; p = 0.008), specifically ≥ 20 (OR 5.6, CI: 1.3-23.7; p = 0.018), were significantly associated with increased risk of in-field recurrence. On multivariate analysis, THL (OR 32.9, CI: 3.2-336.0; p = 0.03) and tumor size (OR 1.3, CI: 1.1-1.6; p = 0.01) retained significant association with in-field recurrence. Conclusions: Bridging radiotherapy prior to CART provides excellent and durable in-field local control for R/R B-cell NHL. Patients with triple hit histology and bulky disease are likely at higher risk of in-field recurrence and may benefit from higher doses of bRT.

Abstract Multiple clinical trials have assessed de-escalation strategies from combined modality therapy (CMT) to chemotherapy-alone for the treatment of early-stage classical Hodgkin lymphoma (cHL), confirming similar outcomes. The application of these data to the real-world is limited, however. We conducted a retrospective, multicenter cohort study comparing CMT vs chemotherapy-alone in patients with early-stage cHL (stage IA-IIB) treated between January 2010 and December 2020. Positron emission tomography (PET) scans after chemotherapy cycle 2 (PET2) were independently reviewed by a nuclear radiologist (Deauville score ≥4, positive; ≤3, negative). Patient outcomes were compared by using an intention-to-treat analysis. Among 125 patients (CMT, n = 63; chemotherapy-alone, n = 62) with a median follow-up of 59.8 months (95% CI, 48.6-71.0), no differences in overall survival were observed (5-year overall survival, CMT 98.0% vs chemotherapy-alone 95.1%; log-rank test, P = .38). However, there was reduced progression-free survival (PFS) with chemotherapy-alone among all patients (2-year PFS, CMT 95.1% vs chemotherapy-alone 75.3%; log-rank test, P = .005) and in those with bulky (n = 43; log-rank test, P &lt; .001), unfavorable (n = 81; log-rank test, P = .002), or PET2-positive (n = 15; log-rank test, P = .02) disease. No significant differences in PFS were seen for patients with non-bulky (log-rank test, P = .35), favorable (log-rank test, P = .62), or PET2-negative (log-rank test, P = .19) disease. Based on our real-world experience, CMT seems beneficial for patients with early-stage cHL, especially those with PET2-positive and unfavorable disease. Chemotherapy-alone regimens can lead to comparable outcomes for patients with favorable, non-bulky, or PET2-negative disease. We conclude that although results seen in clinical trials are replicated in certain patient subgroups, other subgroups not fitting trial criteria do poorly when radiotherapy is excluded.

248 Background: Hypofractionated prostate cancer radiation has showed similar results in several prior phase III studies (PCG GU 003, PACE-B, and Hypo PC RT). However, prospective phase II-III clinical trial data testing 5 tx after prostatectomy is scarce. Methods: Between 2018 and 2019, 41 patients were treated after postprostatectomy for high risk features. 5 patients were treated adjuvantly, 36 for salvage including 8 with oligometastatic disease. Indications for adjuvant RT included a PSA < 0.2 and +margins, SVI, or EPE. Salvage RT was offered for PSA ≥0.2. Oligometastatic RT for patients with ≤5 RT targets. Staging included C11 PET for all cases. Total dose to the prostate bed was 30-32 Gy in 5tx QOD with IMRT, conebeam IGRT, and MRI registration. All salvage patients received ADT for 6 months and oligometastatic patients for 18 months. Dose to the metastatic sites was 30 in 5tx QOD. Of the 41 patients 8 also received SBRT to the sites of oligometastatic disease. We looked at clinical outcomes defining biochemical failure as a PSA > 0.2 after treatment, baseline adjusted CTC AE V5.0, baseline adjusted patient reported toxicities (PRO CTC AE), QOL (EPIC, PROMIS), and AUA was used for all cases. Results: Median follow up was 23 months (range 10-37). Pre-RT T stage was T2-T3b, with 47% being T3a-b; Pre RT Median PSA of 0.4 (range < 0.1-1.9); Median GS 8 (6-9); and (+) margins in 48.8%. Sites of oligometastatic disease radiated included the LN and bone. Treatment related AE were grade 0-1 in all cases, except for one patient with G2 GU incontinence. Overall QOL remained high during follow including Promis 10 overall, mental, and physical scores; urinary bother, irritative/obstructive, and AUA scores; bowel overall, bowel bother, and bowel function scores; and overall sexual, sexual function, and sexual bother scores remained at baseline levels during follow up. Only hormonal overall, hormonal function, and hormonal bother had lower scores at 3 months that recovered by 12 months in patients treated with ADT for 6 months and by 24 months in patients treated with ADT for 18 months. A total of 3 clinical failure have been seen; 2 patients with regional failures alone; and one with axial skeleton bony failures for 93% clinical control at median follow up of 23 months. All 3 patients with clinical failure were salvaged successfully with SBRT and all patients remain disease free at last follow up. A total 5 patients with raising PSAs alone have been seen. All patients have been re-staged with C11 PET. No failures in the prostate bed or previously radiated sites have been seen. Conclusions: Toxicity for RT over 5tx is lower than expected with only one case of grade 2 urinary incontinence. QOL scores remained high during follow up, minor changes in hormonal scores were seen during ADT, but recovered after. 30-32 Gy over 5 tx provided 100% control in radiated targets and metastatic sites. Clinical trial information: NCT03570827.

Abstract BACKGROUND Intensity‐modulated proton therapy (IMPT) demonstrates superior dose distribution over volumetric‐modulated arc therapy (VMAT) for sparing organs‐at‐risk (OARs) in ipsilateral radiotherapy. To determine a clinical benefit, assessment of patient‐reported outcomes (PRO) and physician‐reported toxicities alongside a dosimetric analysis is needed. METHODS Plans were analyzed for dosimetric differences. PROs were compared for patients undergoing ipsilateral curative‐intent radiotherapy for tonsil and salivary gland cancers with VMAT or IMPT from 2015 to 2020. Physician‐reported toxicities were compared. RESULTS In 40 patients, IMPT was associated with decreased dose to multiple OARs and less deterioration in the following PROs: pain, swallowing function, dry mouth, sticky saliva, sensory change, cough, speech, feeling ill, and social eating. Physician‐reported toxicities demonstrated less oral pain. CONCLUSION IMPT is associated with decreased dose to OARs and less patient‐reported acute deterioration in multiple head and neck domains. A strong consideration for IMPT in ipsilateral head and neck patients with cancer is warranted.

Abstract Purpose: Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy utilized for patients with non-Hodgkin lymphoma (NHL) refractory to at least 2 lines of therapy. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is used to evaluate disease extent prior to CAR-T infusion at two time points: pre-leukapheresis (pre-leuk) approximately 6 weeks prior to CAR-T infusion, and pre-lymphodepletion chemotherapy (pre-LD) approximately 1 week prior to CAR-T infusion. We hypothesized that PET/CT characteristics beyond Lugano criteria, such as metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUV maximum (SUVMax), and changes in these parameters from pre-leuk to pre-LD, may predict for progressive disease (PD), death, and treatment toxicity after CAR-T infusion. Methods: Patients with NHL who received axi-cel on a prospective registry at Mayo Clinic Rochester were included. Lesions on pre-leuk and pre-LD PET/CT scans were segmented with a fixed absolute SUVMax threshold of 2.5 using a semi-automated workflow (LesionID, MIM Software Inc.) with manual modification to exclude physiologic uptake as needed. MTV, TLG, SUVMax, number of lesions, and other lesion characteristics were assessed for each PET/CT, and changes from pre-leuk to pre-LD were calculated. Lesions were categorized as either nodal, spleen, bone, parenchymal (i.e. liver, lung), or soft tissue (i.e. subcutaneous, muscle), and MTV was calculated for each category. Univariate Cox modeling was used to associate relative and directional change in metabolic and volumetric PET/CT characteristics with PD and death, after adjusting for bridging therapy. LASSO method was used for multivariable model selection. Pre-LD PET/CT characteristics were also assessed for association with presence and duration of cytokine release syndrome (CRS), grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS), tocilizumab (toci) use, and corticosteroid use. Results: From 2018-2020, axi-cel was delivered to 69 patients. Histology included diffuse large B-cell lymphoma (57%), transformed follicular lymphoma (23%), or high-grade lymphoma (19%). Pre-leuk and pre-LD PET/CT scans were performed a median of 46 days and 7 days prior to CAR-T infusion, respectively. Forty patients (58%) received bridging therapy between scans, including 9 (13%) receiving radiotherapy. At a median follow-up of 13 months, 39 (57%) had died and 46 (67%) had PD. Sixty patients (87%) developed CRS following CAR-T infusion for a median duration of 5 days. Presence of pre-LD parenchymal disease was associated with longer duration CRS (p=0.032). Thirty-seven patients (54%) developed ICANS for a median duration of 4.5 days, including 12 (32%) with grade 3+ ICANS. Greater pre-LD total MTV was associated with higher risk of grade 3+ ICANS (p=0.042). Greater pre-LD SUVMax was associated with longer duration ICANS (p=0.032). Nineteen (28%) patients required toci. Greater pre-LD total MTV, SUVMax, TLG, and volume of the largest lesion were associated with increased use of toci (p&lt;0.05 for all). Greater pre-LD total MTV and TLG of the largest lesion were associated with increased use of corticosteroid (p&lt;0.05 for each). While no individual pre-leuk or pre-LD PET/CT characteristics were associated with risk of PD or death, increases from pre-leuk to pre-LD in total MTV, total TLG, parenchymal MTV, and nodal MTV were associated with increased risk of PD (Figure 1). Similarly, increases from pre-leuk to pre-LD in parenchymal MTV, nodal MTV, TLG of the largest lesion, and total number of lesions were associated with increased risk of death (p&lt;0.05 for all). LASSO analysis identified increasing extranodal MTV (≥25% increase) and increasing TLG of the largest lesion (≥10% increase) as strong predictors of death (AUC 0.74, Table 1). Kaplan-Meier plots were generated for overall and progression-free survival using these risk factors (Figure 2). Additional patients and follow-up will be presented. Conclusions: Patients with greater pre-LD MTV had higher risk of grade 3+ ICANS and use of toci or corticosteroids. Increasing metabolic disease burden during CAR-T manufacturing is associated with increased risk of PD and death. A two variable risk score using increasing extranodal disease and increasing TLG of the largest lesion may stratify prognosis prior to CAR-T and inform treatment paradigms. Figure 1 Figure 1. Disclosures Bennani: Verastem: Other: Advisory Board; Purdue Pharma: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Vividion: Other: Advisory Board; Kymera: Other: Advisory Board. Paludo: Karyopharm: Research Funding. Wang: Genentech: Research Funding; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; InnoCare: Research Funding; Novartis: Research Funding; MorphoSys: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Lin: Gamida Cell: Consultancy; Janssen: Consultancy, Research Funding; Legend: Consultancy; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Sorrento: Consultancy; Bluebird Bio: Consultancy, Research Funding; Takeda: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Merck: Research Funding; Vineti: Consultancy; Juno: Consultancy.

Abstract Primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL, LT) is a rare, aggressive lymphoma characterized by skin involvement predominantly in the lower extremities. Immunochemotherapy with or without involved‐site radiation therapy (ISRT) is considered standard front‐line therapy. Over‐expression of PD‐L1/PD‐L2 is seen in a high proportion of PCDLBCL, LT cases, but efficacy of immune checkpoint inhibitors (ICI) in relapsed/refractory, PCDLBCL, LT has not been thoroughly studied. We conducted a retrospective cohort study of patients diagnosed with PCDLBCL, LT seen at Mayo Clinic from 1 January 2000 to 31 December 2020. Using the Kaplan–Meier method, we calculated progression‐free survival, duration of response, and overall survival in patients who received front‐line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) with and without ISRT, and salvage ICI therapy for relapsed/refractory disease. A total of 28 patients with PCDLBCL, LT were identified. The median PFS in patients treated with R‐CHOP plus ISRT was 58 months (95% CI: 18–112) compared to 14 months (95% CI: 5–not reached; p = 0.04) in those treated with R‐CHOP without ISRT. The median PFS from salvage ICI therapy was 10 months (95% CI: 4–not reached), and median DOR from salvage ICI therapy was 23 months [95% CI: 4–26]. R‐CHOP with ISRT had a significantly longer median PFS compared to R‐CHOP without ISRT as front‐line therapy for PCDLBCL, LT. ICIs may have a role in treating relapsed/refractory disease as reasonable activity in heavily pre‐treated patients was observed in this study.

Abstract The coronavirus disease-2019 (COVID-19) pandemic caused by SARS-CoV-2 has exacted an enormous toll on healthcare systems worldwide. The cytokine storm that follows pulmonary infection is causally linked to respiratory compromise and mortality in the majority of patients. The sparsity of viable treatment options for this viral infection and the sequelae of pulmonary complications have fueled the quest for new therapeutic considerations. One such option, the long-forgotten idea of using low-dose radiation therapy, has recently found renewed interest in many academic centers. We outline the scientific and logistical rationale for consideration of this option and the mechanistic underpinnings of any potential therapeutic value, particularly as viewed from an immunological perspective. We also discuss the preliminary and/or published results of prospective trials examining low-dose radiation therapy for COVID-19.

131 Background: Trimodality therapy is the standard of care for patients with resectable cancer of the esophagus. However, patients ≥75 years have been underrepresented or excluded from landmark clinical trials to date. We investigated the feasibility and safety of treatment of esophageal cancer with trimodality therapy in patients’ ≥ 75 years. Methods: We performed a retrospective review of all patients ≥75 years who received trimodality therapy for esophageal cancer in 3 high volume tertiary cancer institutions from June 2007 to June 2013. All patients received neoadjuvant radiation with concomitant chemotherapy followed by esophagectomy. Toxicities and clinical outcomes were abstracted from the electronic medical record and partially from a prospectively maintained database. Overall and disease-free survival were estimated using the Kaplan-Meier method. Results: Five hundred seventy patients were treated with trimodality therapy for esophageal cancer from 2007-2013. Of these, 38 patients (7%) were 75 or older at the time of diagnosis. At diagnosis, comorbidities included coronary artery disease (32%), atrial fibrillation (11%) and COPD (13%). The majority of patients (87%) received 50.4Gy/28 fractions. 5-fluorouracil (5-FU)/cisplatin was the most common chemotherapy regimen (37%), followed by 5-FU/docetaxel (24%). A total of 13 patients (34%) developed acute grade ≥3 toxicity associated with neoadjuvant therapy. The most common acute grade 3 toxicities were haematological (10%), nausea (8%), esophagitis (5%) and fatigue (5%). Significant postoperative complications included respiratory (empyema, ARDS, pleural effusion) (39%), arrhythmia (32%), anastomotic leak (5%), and ileus (5%). There were 2 deaths (5%) within 90 days of surgery: one was secondary to empyema, the other developed DIC and sepsis. Median overall survival and disease free survival were 4.4 and 2.3 years respectively. Conclusions: Trimodality treatment is a reasonable approach for management of carefully selected elderly patients with esophageal cancer, with similar rates of cancer outcomes, and treatment related morbidity and mortality as compared to younger patients.