Outcomes after Salvage Therapy in Oral Cavity Squamous Cell Carcinoma (OCSCC) Patients Who Developed Locoregional Failure (LRF) after Definitive Surgery and Adjuvant (chemo)Radiotherapy: A Multi-Institutional Collaborative Study

Abstract

We conducted a multi-institutional study to review salvage therapy outcomes in OCSCC patients who developed LRF after upfront surgery and adjuvant (chemo)radiotherapy. A collaborative patient database with primary OCSCC stage I-IVB (AJCC 7th Ed) treated with primary surgical resection between 1/1/2005 and 1/1/2015 was collected from 6 academic centers. From a total of 1282 patients, we identified patients who developed LRF after primary surgery and adjuvant (chemo)radiotherapy. The exclusion criteria were: missing information on LRF, distant failure within 30 days of LRF, and LRF before completing initial adjuvant therapy. Cox proportional hazard analysis was performed to estimate hazard ratio (HR). 156 patients were selected: 60 females (38%), 126 Whites (81%), and 63 (40%) oral tongue primaries. Median age at initial diagnosis was 61 years. 152 (97%) smoked or chewed tobacco and 103 (66%) used alcohol. 54 (34 %) had pT4 and 76 (49%) pN2b-c disease. 33 (21%) had a positive margin at the initial surgery and 55 (15%) had extranodal spread. All received adjuvant radiation with a median dose of 60Gy and 66 (42%) patients also had concurrent chemotherapy. With a median follow up of 22.5 months, 82 (53%) developed only local failure, 39 (25%) had only neck failure, and 35 (22%) had both local and regional nodal failures. The median time to LRF was 13 months (range: 4-130). 104 of 156 (67%) underwent salvage surgery and 28 (27%) of surgically salvaged patients also received adjuvant re-irradiation. Patients who had any regional failure were more likely to receive adjuvant re-irradiation than those without (88% vs 11%, p=0.001). 49 (31%) patients received salvage chemotherapy. 38 (24%) patients had a 2nd LRF after salvage therapy. Median OS after 1st LRF for all patients was 7.7 months. Time from initial diagnosis to 1st LRF was not associated with OS. In multivariable analysis controlling for age, gender, re-irradiation, and salvage chemotherapy, lack of salvage surgery was independently associated with worse OS (HR=4.3, 95%CI=2.5-7.1). About 30% of surgically salvaged patients were alive at 125 months after 1st LRF. Among those who received salvage surgery, positive surgical margin (HR=2.3, 95%CI=1.1-4.8) and perineural invasion (PNI) (HR=2.3, 95%CI=1.1-4.6) were independently correlated with worse OS. Receipt of adjuvant re-irradiation showed a trend toward more favorable OS (HR=0.5, 95%CI=0.2-1.0) after further accounting for nodal failure status. Patients who were selected to receive salvage surgery had more favorable outcomes than those who were not. Positive salvage surgical margin and PNI were associated with worse OS. Adjuvant re-irradiation showed a trend towards improved OS after accounting for nodal failure status.