Induction Chemotherapy Followed by Concurrent Chemoradiation versus Concurrent Chemoradiation Alone in the Definitive Management of p16-positive Oropharyngeal Cancer with Low-neck or N3 Disease

Abstract

The role of induction chemotherapy (ICT) in addition to concurrent chemoradiation (CCRT) in the definitive management of locally advanced oropharyngeal cancer is controversial. At our institution, certain patients with low-neck (level IV and/or Vb) or N3 lymphadenopathy are given ICT prior to CCRT at the discretion of the treating physicians with the objective of lowering the risk of distant failure. We compared the outcomes of these patients to their counterparts who received upfront CCRT alone. A retrospective review was conducted from June 2006 through June 2015. Out of 548 patients with locally advanced p16-positive oropharyngeal cancer, 88 were identified with low-neck and/or N3 disease. Among these patients, 44 received upfront CCRT, and 44 received ICT followed by CCRT. Upfront CCRT regimens included triweekly Cisplatin (43%), triweekly Carboplatin (32%), Cetuximab (14%), and weekly Cisplatin (11%). ICT regimens were Docetaxel and platinum based chemotherapy with (89%) or without 5-fluorouracil (11%) followed by CCRT using weekly Carboplatin (61%), triweekly Carboplatin (18%), weekly Cisplatin (11%), triweekly Cisplatin (7%), or Cetuximab (2%). All patients were planned for 70 Gy with intensity-modulated radiotherapy. Pathology review was performed of all cases with standardized p16 reporting. Median follow-up for surviving patients was 45 [13-115] months. Median age was lower in the ICT group compared to the CCRT group, 56 vs. 61, respectively (P = 0.02), with T stage, N stage, and rates of low-neck disease similar between the two groups. Compared to CCRT alone, ICT followed by CCRT was associated with a significant improvement in the rate of distant metastases (DM) (3-year: 18% vs. 37%; P = 0.01), progression-free survival (PFS) (3-year: 74% vs. 49%; P = 0.008), and overall survival (OS) (3-year: 82% vs. 67%; P = 0.05). No difference in locoregional failure was observed (3-year: 14% for both arms). Patients in the upfront CCRT group were more likely to require a feeding tube compared to the ICT group (27% vs. 57%; P = 0.005). Among ICT patients, 75% received 3 cycles of ICT with the remaining 25% receiving only 2 cycles either due to treatment-related toxicities, performance status, or suboptimal response to ICT. In this cohort of p16-positive oropharyngeal cancer patients with low-neck and/or N3 disease at high risk of distant failure, ICT followed by CCRT demonstrated a statistically significant reduction in DM which translated into an improvement in PFS and OS over upfront CCRT alone. Future randomized studies should concentrate on patients at the highest risk of developing distant metastases in order to assess the potential benefit of ICT in addition to CCRT in this population. Less intensive CCRT regimens employed in patients receiving ICT may have led to decreased rates of feeding tube placements compared to that observed in CCRT alone patients.