Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number

Abstract

Purpose: To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response and outcome.

Patients and methods: Sixty-six patients (51 male; 15 female) with stage III to IV squamous cell carcinoma of the oropharynx (SCCOP) were treated with one cycle of cisplatin (100 mg/m(2)) or carboplatin (AUC 6) and with fluorouracil (1,000 mg/m(2)/d for 5 days) to select candidates for CRT. Those achieving a greater than 50% response at the primary tumor received CRT (70 Gy; 35 fractions with concurrent cisplatin 100 mg/m(2) or carboplatin (AUC 6) every 21 days for three cycles). Adjuvant paclitaxel was given to patients who were complete histologic responders. Patients with a response of 50% or less underwent definitive surgery and postoperative radiation. Pretreatment biopsies from 42 patients were tested for high-risk HPV.

Results: Fifty-four of 66 patients (81%) had a greater than 50% response after IC. Of these, 53 (98%) received CRT, and 49 (92%) obtained complete histologic response with a 73.4% (47 of 64) rate of organ preservation. The 4-year overall survival (OS) was 70.4%, and the disease-specific survival (DSS) was 75.8% (median follow-up, 64.1 months). HPV16, found in 27 of 42 (64.3%) biopsies, was associated with younger age (median, 55 v 63 years; P = .016), sex (22 of 30 males [73.3%] and five of 12 females [41.7%]; P = .08), and nonsmoking status (P = .037). HPV titer was significantly associated with IC response (P = .001), CRT response (P = .005), OS (P = .007), and DSS (P = .008).

Conclusion: Although the numbers in this study are small, IC followed by CRT is an effective treatment for SCCOP, especially in patients with HPV-positive tumors; however, for patients who do not respond to treatment, alternative treatments must be developed.

Fig 1

UMCC 9921 study schema. CDDP, cisplatin; FU, fluorouracil; CR, complete response; PR, partial response; XRT, radiation therapy. (^*) If the original neck node was > 3 cm, selective neck dissection was performed. (^**) If a positive biopsy was obtained, primary site resection with or without neck dissection was performed.

Fig 2

Schema showing the response of patients according to treatment. Endoscopy*, endoscopy with biopsy. DoD, died of disease; Sec, second; DM, distant metastases; CRT, concurrent chemotherapy/radiation therapy; XRT, radiation therapy; LR, local/regional unresectable; CR/PR, complete response/partial response (> 50% response to induction chemotherapy); < PR, stable disease or progressive disease (≤ 50% response to induction chemotherapy); DPD, dihydropyrimidine dehydrogenase deficiency; DoC, died of other causes.

Fig 3

(A) Overall survival and (B) disease-specific survival plots of patients (n = 66). (C) Disease-specific survival based on sex. (D) Disease-specific survival based on smoking status. (E) Response to induction chemotherapy based on mean human papilloma virus (HPV) titers; blue box, interquartile range (25th to 75th percentile), not including outliers; horizontal black line, median; range bars, range of minimum to maximum observations, not including outliers; red dot, mean; blue dot, outlier. (F) Disease-specific survival according to HPV16 titers. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.