K. Liang1, G. Gauvin1, K. Ruth2, E. McGillivray1, C. Mayemura1, K. Loo1, H. Wu3, J. D’Souza4, A. Olszanski5, S. Movva5, S. Reddy1, J. Farma1 1Fox Chase Cancer Center,Department Of Surgical Oncology,Philadelphia, PA, USA 2Fox Chase Cancer Center,Department Of Biostatistics,Philadelphia, PA, USA 3Fox Chase Cancer Center,Department Of Pathology,Philadelphia, PA, USA 4Fox Chase Cancer Center,Molecular Therapeutics Program,Philadelphia, PA, USA 5Fox Chase Cancer Center,Department Of Hematology/Oncology,Philadelphia, PA, USA
Introduction: Staging for melanoma continues to evolve. Although the prognostic value of tumor thickness and presence of ulceration is widely accepted, the clinical role of tumor infiltrating lymphocytes (TILs) is not as clear. The development of targeted immunotherapy may enlighten the role of TILs, which is easily evaluated at the time of initial biopsy. In this study, we investigated the prognostic value of TILs in non-metastatic melanoma patients and its relationship to recurrence.
Methods: A retrospective chart review of patient with melanoma from 2003 and 2017 was conducted at our NCI designated cancer center. Non-metastatic patients who underwent surgery and had a documented presence or absence of TIL on initial pathology were included. Cumulative incidence of recurrence including cause-specific mortality (CSM) was calculated. Survival distributions were compared using Gray’s test, and subdistribution hazard ratios adjusting for covariates were estimated using Fine and Gray competing risk regression methods.
Results: Of 645 patients, 341 had TILs (present, brisk or non-brisk) and 304 did not have TILs (n=304). Fifty five percent were male with a median age of 63 (range 21-99). Patients were pathologically staged with stage I (n=339), II (n=171) or III (n=135) disease. Forty-six patients received adjuvant therapy (stage II n=5, stage III n= 41), of which 22 received interferon, 20 immunotherapy (anti-CTLA4 antibody, PD-1 inhibitor), 3 chemotherapy, and 1 vaccine trial. During follow-up, 83 patients died, 75% from their melanoma (n=62); median follow-up was 18.2 months for those alive. Ninety-seven patients recurred. In stage III patients, the cumulative probability of recurrence/CSM was lower for patients with TIL (p=0.035); at 36 months, the cumulative probability was 0.33 (95% CI 0.20-0.47) for patients with TILs present compared to 0.50 (95%CI 0.37-0.62) for TILs absent. Recurrence did not differ by TIL status in stage I and stage II patients. For stage III patients, cumulative incidence of recurrence/CSM did not differ by adjuvant therapy status (p=0.116); at 36 months this was 0.41 for adjuvant compared to 0.43 for non-adjuvant patients. Competing risk regression was used to adjust for age, adjuvant therapy use, and pathologic staging. With adjustment, patients with TILs were less likely to have recurrence (subHR=0.71, 95% CI=0.49-1.03, p=0.067).
Conclusion: This study shows that the presence of tumor infiltrating lymphocytes (TILs) is associated with lower probability for recurrence, especially in stage III patients. This is an important finding that warrants further evaluation in a larger cohort.
