PD-L1 expression in rare and aggressive thyroid cancers: A preliminary investigation for a role of immunotherapy.

Background and Aim: Programmed cell death ligand-1 (PD-L1) immunoexpression status determines the response to immunotherapy in many cancers. Limited data exist on PD-L1 status in aggressive thyroid tumors. We investigated PD-L1 expression across thyroid cancers and correlated it with their molecular profile. Materials and Methods: Sixty-five cases of differentiated thyroid carcinoma, poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC) were assessed for PD-L1 expression (clone SP263, VENTANA). The differentiated cases encompassed the aggressive hobnail and tall cell subtypes of papillary thyroid carcinoma (PTC) besides classical PTC and follicular thyroid carcinoma (FTC). Ten nodular goiters (NG) were also evaluated. Tumor proportion score (TPS) and H-score were calculated. BRAFV600E and H-/K-/N-RAS were assessed using allele-specific real-time polymerase chain reaction (PCR). Fisher's exact and Kruskal-Wallis tests were used to investigate the associations between the categorical variables and compare PD-L1 scores with the mutation status. Results: Most PTC (87%) and ATC (73%) cases were PD-L1 positive (TPS ≥1%), with significantly higher positivity rates than NG (20%). TPS >50% was seen in 60% ATC and 7% PTC cases. The median TPS and H-score of ATC were 56 (0-96.6) and 168 (0-275), respectively, and of PTC were 9.6 (4-16.8) and 17.8 (6.6-38.6), respectively. The scores were similar across the PTC subtypes. Only one case each of FTC and PDTC was PD-L1 positive. PD-L1 expression correlated significantly with BRAFV600E, but not with RAS mutation. Conclusions: ATC showed intense and diffuse PD-L1 staining. Although most PTCs were PD-L1 positive, the expression was weaker and patchy, irrespective of the histological subtype. Results of this pilot study indicate that ATC is most likely to respond to immunotherapy. PTC, FTC, and PDTC may be less amenable to immunotherapy. PD-L1 expression correlated significantly with BRAFV600E, allowing for combined targeted therapy.

Compliance and outcomes of concurrent Chemo-radiation in patients with peri-ampullary cancer undergoing curative resections.

OBJECTIVES: We aimed to study the compliance and treatment outcome of patients who received adjuvant treatment following curative resection for periampullary cancers periampullary cancers. MATERIALS AND METHODS: Institute medical records of PAC treated during 2007-2014 were retrieved. Demographics, treatment, and outcome in patients who were intended to receive adjuvant chemoradiation after curative resection were analyzed. Patients received first cycle chemotherapy with 5-fluorouracil folinic acid/capecitabine, followed by external radiotherapy 45 Gy/25 fractions/5 weeks and second and third cycle concurrent chemotherapy. Fourth and fifth cycle chemotherapy were administered after radiotherapy). Various prognostic factors, disease-free survival (DFS), and overall survival (OS) were evaluated. RESULTS: Sixty-five patients were evaluated. Median age was 50 years. 96.9% patients completed the intended course of radiation and overall adherence to chemotherapy was 86.2%. Median follow-up and DFS were 20 and 29.64 months, respectively (range: 1.9-97.3 months). Estimated 1-, 2-, 5-year DFS was 77.8%, 59.3%, and 37.6%, respectively. One-year estimated OS was 92.7%. Median DFS for node-negative and node-positive patients was 88.6 and 24.33 months (P = 0.06). Grade ≥III hematological toxicity was 20%. CONCLUSION: Positive node indicated a trend toward poor survival. The study highlights high compliance to multimodal management of PAC with acceptable toxicity in and out of clinical trial setting in a tertiary cancer center in India.