Outcomes of patients with oropharyngeal squamous cell carcinoma treated with induction chemotherapy followed by concurrent chemoradiation compared with those treated with concurrent chemoradiation

Abstract

BACKGROUND: Induction chemotherapy (IC) has been associated with a decreased risk of distant metastasis in locally advanced head and neck squamous cell carcinoma. However, its role in the treatment of oropharyngeal squamous cell carcinoma (OPSCC) is not well established. METHODS: The outcomes of patients with OPSCC treated with IC followed by concurrent chemoradiation (CRT) were compared with the outcomes of those treated with CRT alone. The primary outcome was overall survival (OS), and the secondary end points were the times to locoregional and distant recurrence. RESULTS: In an existing database, 585 patients met the inclusion criteria: 137 received IC plus CRT, and 448 received CRT. Most patients were positive for human papillomavirus (HPV; 90.9%). Patients receiving IC were more likely to present with a higher T stage, a higher N stage, and low neck disease. The 3-year OS rate was significantly lower in patients receiving IC (75.7%) versus CRT alone (92.9%). In a multicovariate analysis, receipt of IC (adjusted hazard ratio [aHR], 3.4; P < .001), HPV tumor status (aHR, 0.36; P = .002), and receipt of concurrent cetuximab (aHR, 2.7; P = .002) were independently associated with OS. The risk of distant metastasis was also significantly higher in IC patients (aHR, 2.8; P = .001), whereas an HPV-positive tumor status (aHR, 0.44; P = .032) and completion of therapy (aHR, 0.51; P = .034) were associated with a lower risk of distant metastasis. In HPV-positive patients, IC remained associated with distant metastatic progression (aHR, 2.6; P = .004) but not OS. CONCLUSIONS: In contrast to prior studies, IC was independently associated with worse OS and a higher risk of distant metastasis in patients with OPSCC. Future studies are needed to validate these findings.

Response to induction chemotherapy predicts survival outcomes in oropharyngeal cancer

“…Sher et al 11 found no significant difference in OS between CCRT and IC plus CCRT. In another retrospective study, IC was predictive of even worse OS and DMFS in OPSCC, especially HPV‐positive OPSCC 12 . By contrast, Bhattasali et al 23 reported that IC remarkably improved PFS and DMFS in a selective high‐risk subgroup of p16‐positive OPSCC with low‐neck and/or N3 disease.…”

“…In another retrospective study, IC was predictive of even worse OS and DMFS in OPSCC, especially HPV‐positive OPSCC. 12 By contrast, Bhattasali et al 23 reported that IC remarkably improved PFS and DMFS in a selective high‐risk subgroup of p16‐positive OPSCC with low‐neck and/or N3 disease. In the present study, HPV‐positive and HPV‐negative subsets showed distinct survival rates, suggesting significant heterogeneity in OPSCC independent of HPV status.…”

“…In OPSCC, however, there is yet no consensus on the significance of IC due to the lack of solid evidence despite a category 3 recommendation in the National Comprehensive Cancer Network guidelines 5 . Previous data failed to support the routine use of IC prior to CCRT by showing insignificant and even worse OS either in HPV‐positive or HPV‐negative OPSCC 11,12 . This perplexity and controversy highlight the potential heterogeneity of treatment effects among patients that might counteract the eventual benefit of IC, and careful selection of the target population most likely to profit from IC is extremely important to elucidate its real impact on long‐term outcomes.…”

Moving from conventional to adaptive risk stratification for oropharyngeal cancer

“…Whereas positive margins and extra-nodal extension (ENE) were shown to be useful in assigning patients to treatment escalation with the addition of conventional chemotherapy in the adjuvant setting, their utility in the setting of HPV-associated disease may be more limited ( 47 ). For aggressive, advanced-stage disease, attempted escalation with induction chemotherapy failed to improve survival in the PARADIGM and DECIDE trials ( 51 , 52 ), and in a recent in-depth retrospective analysis appeared to be associated with reduced survival in OPC patients ( 53 ). As mentioned above, changing from cisplatin to cetuximab, a drug assumed to be more tolerable and thus better suited for the lower risk HPV-associated OPC population failed to maintain adequate survival in both RTOG1016 (which included intermediate-risk OPC) and De-ESCALaTE (which included exclusively low-risk OPC) trials ( 21 ).…”

Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

“…However, CDDP resistance, both intrinsic and acquired, is frequently encountered in clinical practice and has been linked to treatment failure and development of distant metastasis (DM; ref. 3 ). Therefore, it is critical to understand how tumor cells survive the stress of CDDP or evolve into therapy-resistant populations.…”