Tolerability and Outcomes after Neoadjuvant and Definitive Radiation of Elderly Patients with Localized Pancreatic Cancer.

664 Background: Multimodal therapy for pancreatic cancer (PC) may be challenging in older adults with comorbidities or limited performance status (PS). Methods: This is a retrospective review of patients (pts) age 70 and older with localized PC treated with neoadjuvant or definitive radiation (RT) at the Massachusetts General Hospital from 2016-2024. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) calculated from RT start. The Cox model was used to assess predictors of survival: age (>75 vs ≤75), ECOG PS (1+ vs 0), NCCN Stage (resectable vs not), ypT (2+ vs 0/1) and N (1 vs 0), and resection (yes vs no). Results: 366 pts met inclusion criteria with a median follow-up of 13 mo (range 0.2-102.2). Median age was 75 (range 70-95). 339 pts (93%) were deemed medically fit for surgery of whom 153 had resectable, 58 had borderline, and 128 had locally advanced disease. 317 of the 339 pts (94%) received induction chemotherapy (INCT), including: FOLFIRINOX (n=249), gemcitabine/nab-paclitaxel (n=61), and gemcitabine (n=29). 27 pts were deemed medically inoperable, of whom 11 were treated with INCT and RT and 16 with RT alone. RT regimens included: 50.4-58.8 Gy/28 fractions (fx) (n=223), 40 Gy/10 fx (n=2), 30 Gy/10 fx (n=52), 33-40 Gy/5 fx (n=28), or other (n=61). 3 discontinued RT due to toxicity (n=2) or progression (n=1). Of the 339 pts deemed medically fit, 206 (61%) had resection. The R0 resection rate was 86%. Median OS of the entire, medically operable and inoperable cohorts was 18.9 (95% CI 16.2-22.7), 20.3 (95% CI 17-25.4), and 10.1 (95% CI 7.5-17.1) mo. Median PFS of the entire, medically operable and inoperable cohorts was 9.6 (95% CI 8.3-11.5), 10.1 (95% CI 8.8-12.2), and 6.9 (95% CI 4.8-9.1) mo. Table 1 shows PFS and OS by NCCN categories. Univariate predictors of PFS and OS included age (HR 1.31 (p=0.029); HR 1.46 (p<0.01)), PS (HR 1.54 (p<0.001); HR 1.84 (p<0.001)), NCCN stage (HR 0.64 (p<0.001); HR 0.69 (p<0.01)), ypT (HR 1.78 (p<0.01); HR 1.58 (p=0.048)), N stage (HR 2.07 (p<0.001); HR 2.33 (p<0.001)), and resection (HR 0.33 (p<0.001); HR 0.33 (p<0.001)). Conclusions: RT was well tolerated in this elderly population. Among well-selected elderly pts, favorable outcomes can be achieved in those who undergo NT and resection, including borderline and locally advanced patients. For medically inoperable pts, further work is needed to investigate the optimal regimen. Clinical outcomes of elderly patients with PC. Median PFS (months) Median OS (months) Resectable (N=167) Neoadjuvant Therapy (NT) + resection (N=128) NT - no resection (N=25)Medically Inoperable (N=14) 17.3 2.3 6.2 29.8 8.2 10.3 Borderline (N=61) NT + resection (N=37) NT – no resection (N=21)Medically Inoperable (N=3) 20.8 2.4 7 31.3 13 7 Locally Advanced (N=138) NT + resection (N=41) NT – no resection (N=87) Medically Inoperable (N=10) 12.56.77.5 30.2 2.58