Objectives The benefit of adjuvant chemotherapy in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) and surgery is controversial. We examined the association of perineural invasion (PNI) with outcomes to determine whether PNI could be used to risk-stratify patients. Materials and Methods We performed a retrospective study of 110 patients treated with nCRT and surgery for LARC at our institution from 2004 to 2011. Eighty-seven patients were identified in our final analysis. We evaluated the association of PNI with locoregional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival, using log-rank and Cox proportional hazard modeling. Results Fourteen patients (16%) were PNI + and 73 patients (84%) were PNI−. The median follow-up was 27 months (range, 0.9 to 84 mo). The median DMFS was 13.5 months for PNI + and median not reached (> 40 mo) for PNI− (P < 0.0001). The median DFS was 13.5 months for PNI + and 39.8 months for PNI− (P < 0.0001). In a multivariate model including 7 pathologic variables, type of surgery, time to surgery from end of nCRT, and use of adjuvant chemotherapy, PNI remained a significant independent predictor of DMFS (hazard ratio 9.79; 95% confidence interval, 3.48–27.53; P < 0.0001) and DFS (hazard ratio 5.72; 95% confidence interval, 2.2–14.9; P = 0.0001). Conclusions For patients with LARC treated with nCRT, PNI found at the time of surgery is significantly associated with worse DMFS and DFS. Our data support testing the role of adjuvant chemotherapy in patients with PNI and perhaps other high-risk features.

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Background In patients with stage III melanoma, the use of adjuvant radiation therapy (RT) after lymph node dissection (LND) may be currently considered in selected high-risk patients to improve tumor control. Melanomas harbor BRAF mutations (BRAF+) in 40–50% of cases, the majority of which are on the V600E residue. This study sought to compare the clinical outcomes after RT between patients with BRAF+ and BRAF− melanoma. Methods This was a retrospective review of 105 Stage III melanoma patients treated at our institution with LND followed by adjuvant RT from 2006 to 2019. BRAF mutational status was determined on the primary skin or nodal tissue samples from all patients. We compared characteristics of the BRAF+ and BRAF− groups using Fisher’s exact test and Wilcoxon rank sum test and performed univariate and multivariate analysis using Kaplan–Meier estimates, log-rank tests, and Cox proportional hazards modeling with the clinical outcomes of local–regional lymph node control, distant metastasis-free survival (DMFS), recurrence-free survival (RFS), and overall survival (OS). Results Fifty-three (50%) patients harbored a BRAF mutation (92%, pV600E). BRAF+ patients were younger and had primary tumors more commonly found in the trunk vs head and neck compared to BRAF- patients (p < 0.05). The 5 year local–regional control in the BRAF + patients was 60% compared to 81% in the BRAF- patients (HR 4.5, 95% CI 1.3–15.5, p = 0.02). There were no significant differences in 5-year DMFS, RFS, and OS rates between the two BRAF patient groups. The presence of 4 or more positive LNs remained a significant prognostic factor for local–regional lymph node control, RFS, and OS in multivariate analysis. Conclusions Stage III melanoma patients with BRAF mutation treated with adjuvant RT had > 4 times increased risk of local recurrence or regional lymph node recurrence. These results could be useful for adjuvant RT consideration in lymph node positive melanoma patients and supports other data that BRAF mutation confers radiation resistance.

2592 Background: Pembrolizumab (pembro) is an intravenous immune checkpoint inhibitor used for anti-cancer treatment, with equivalent monotherapy dosing options of 200 mg every 3 weeks (Q3W) or 400 mg every 6 weeks (Q6W). Pembro Q6W dosing was approved for use in April 2020 after the Q3W dose had already been established. As pembro dosing patterns in real-world practice are not well-described, we evaluated this in a large cancer center network consisting of a central site (CS) and 36 community network sites (NS). Methods: We retrospectively reviewed the charts of all patients who received pembro monotherapy for cancer treatment between 4/2020 – 4/2022 at UPMC Hillman Cancer Center sites across the state of Pennsylvania, as well as sites in New York and Ohio. We performed statistical comparisons using the Fisher’s exact test and Wilcoxon rank-sum test. Results: We identified 1,640 patients who received pembro monotherapy, including 377 patients at the CS and 1,263 patients in the NS, with characteristics displayed. Pembro Q6W dosing was significantly more common at the CS than in the NS (42% vs. 15%, p<0.0001). When analyzed by tumor type, pembro Q6W dosing was significantly more common at the CS than in the NS for head & neck (53% vs. 11%, p<0.0001), thoracic (49% vs. 15%, p<0.0001), skin (60% vs. 19%, p<0.0001), and genitourinary (30% vs. 16%, p=0.015) cancers, but not for other tumor types. Within the NS, 30% (11/36) of sites only utilized pembro Q3W dosing and never administered Q6W dosing to patients. Of note, some patients who received pembro Q6W dosing received pembro Q3W dosing initially, either as part of a pembro-containing multidrug regimen or as monotherapy. Excluding patients initially treated with a multidrug regimen to reduce confounding factors, we found that of the patients who received pembro Q6W dosing, 47% (65/137) at the CS and 28% (48/169) in the NS were initially treated with pembro Q3W monotherapy before transitioning to Q6W monotherapy (p=0.0008). Conclusions: In our large cancer center network, pembro Q6W dosing was significantly more common at the CS than in the NS. Switching from pembro Q3W to Q6W dosing was also significantly more common at the CS. Further work is needed to clarify the patient, provider, and institutional factors influencing differences in pembro dosing patterns in real-world practice, as well as the impact of dosing patterns on care delivery outcomes such as cost and accessibility. [Table: see text]

We found that delaying surgical resection longer than 8 weeks after nCRT was associated with an increased risk of DF. This study, in combination with a recent larger study, questions the recent trend in promoting surgical delay beyond the traditional 6 to 10 weeks. Larger, prospective databases or randomized studies may better clarify surgical timing following nCRT in rectal adenocarcinoma.