Impact of cisplatin dose and smoking pack-years in human papillomavirus-positive oropharyngeal squamous cell carcinoma treated with chemoradiotherapy

Abstract

Background: To evaluate the impact of cisplatin cumulative dose (CDDP-D) and smoking pack-years (PYs) on cause-specific survival (CSS) and overall survival (OS) in human papillomavirus-positive (HPV+) oropharyngeal carcinoma (OPSCC) using the eighth edition tumour-node-metastasis (TNM) staging classification (TNM8).

Patients and methods: We reviewed patients with HPV+ OPSCC treated with high-dose CDDP and intensity-modulated radiotherapy between 2005 and 2015 at Princess Margaret Cancer Centre. CSS and OS were compared according to CDDP-D <200/=200/>200 mg/m² stratified by TNM8.

Results: A total of 482 consecutive patients were evaluated (stage I/II/III: N = 189/174/119; CDDP-D <200/=200/>200 mg/m²: N = 112/220/150). Median follow-up duration was 5.1 years (range: 0.6-12.8). Five-year CSS and OS differed by stages I/II/III: 96%/85%/88% (p=0.005) and 93%/84%/78% (p = 0.001), respectively. Five-year CSS by CDDP-D <200/=200/>200 mg/m² was similar in stage I (98%/95%/95%, p = 0.74) and stage II (88%/84%/84%, p = 0.86) but different in stage III (76%/98%/84%, p = 0.02). Five-year OS by CDDP-D <200/=200/>200 mg/m² did not differ significantly among stages. In the multivariable analysis, CDDP-D <200 mg/m² did not influence CSS in the whole cohort versus = 200/>200 mg/m² (p=0.53/0.79, respectively) but was associated with reduced CSS in stage III subgroup versus =200 mg/m² (=200 mg/m² versus < 200 mg/m² hazard ratio [HR] = 0.08; 95% confidence interval [CI]: 0.01-0.67; p = 0.02). Higher smoking PYs had no effect on CSS (p = 0.34) but reduced OS in the whole cohort (HR = 1.14 [95% CI: 1.02-1.27], p=0.01).

Conclusion: CDDP-D correlated with neither survival nor disease-specific outcomes in this large and homogeneous HPV+ cohort, although reduced CSS was observed in stageIII HPV+ OPSCC receiving CDDP-D <200 mg/m². Smoking PYs were negatively associated with OS but not with CSS.

Keywords: Chemoradiotherapy; Cisplatin dose; Human papillomavirus; Oropharyngeal squamous cell carcinoma; Outcome; Smoking pack-years.