Institutional clinical trial accrual volume and survival of patients with head and neck cancer

Abstract

Purpose: National Comprehensive Cancer Network guidelines recommend patients with head and neck cancer (HNC) receive treatment at centers with expertise, but whether provider experience affects survival is unknown.

Patients and methods: The effect of institutional experience on overall survival (OS) in patients with stage III or IV HNC was investigated within a randomized trial of the Radiation Therapy Oncology Group (RTOG 0129), which compared cisplatin concurrent with standard versus accelerated fractionation radiotherapy. As a surrogate for experience, institutions were classified as historically low- (HLACs) or high-accruing centers (HHACs) based on accrual to 21 RTOG HNC trials (1997 to 2002). The effect of accrual volume on OS was estimated by Cox proportional hazards models.

Results: Median RTOG accrual (1997 to 2002) at HLACs was four versus 65 patients at HHACs. Analysis included 471 patients in RTOG 0129 (2002 to 2005) with known human papillomavirus and smoking status. Patients at HLACs versus HHACs had better performance status (0: 62% v 52%; P = .04) and lower T stage (T4: 26.5% v 35.3%; P = .002) but were otherwise similar. Radiotherapy protocol deviations were higher at HLACs versus HHACs (18% v 6%; P < .001). When compared with HHACs, patients at HLACs had worse OS (5 years: 51.0% v 69.1%; P = .002). Treatment at HLACs was associated with increased death risk of 91% (hazard ratio [HR], 1.91; 95% CI, 1.37 to 2.65) after adjustment for prognostic factors and 72% (HR, 1.72; 95% CI, 1.23 to 2.40) after radiotherapy compliance adjustment.

Conclusion: OS is worse for patients with HNC treated at HLACs versus HHACs to cooperative group trials after accounting for radiotherapy protocol deviations. Institutional experience substantially influences survival in locally advanced HNC.

Trial registration: ClinicalTrials.gov NCT00047008.

Fig 1.

CONSORT diagram. HPV, human papillomavirus; RTOG, Radiation Therapy Oncology Group.

Fig 2.

Kaplan-Meier estimates by (A, B) accrual volume and (C, D) radiotherapy (RT) compliance of (A, C) overall (OS) and (B, D) progression-free survival (PFS). Patients treated at historically low-accruing centers (HLACs) had significantly worse OS (P = .002) and PFS (P < .001) than patients treated at historically high-accruing centers (HHACs). (A) Five-year rates of OS were 51.0% (95% CI, 45.1 to 56.8) in HLAC group and 69.1% (95% CI, 61.6 to 76.7) in HHAC group. (B) Five-year rates of PFS were 42.7% (95% CI, 37.0 to 48.4) in HLAC group and 61.8% (95% CI, 53.8 to 69.7) in HHAC group. Patients with ≥ one RT compliance score of acceptable variation (AV) or with ≥ one RT compliance score of unacceptable deviation (UD) had significantly worse OS (P = .007 and P < .001) and PFS (P = .01 and P < .001) than patients treated per protocol (PP). (C) Five-year rates of OS were 63.0% (95% CI, 57.4 to 68.6) in PP group, 51.1% (95% CI, 40.1 to 62.3) in AV group, and 41.1% (95% CI, 26.6 to 55.6) in UD group. (D) Five-year rates of PFS were 55.6% (95% CI, 50.0 to 61.2) in PP group, 39.3% (95% CI, 28.0 to 50.7) in AV group, and 33.0% (95% CI, 19.2 to 46.8) in UD group.

Fig A1.

Kaplan-Meier estimates of overall survival for patients with complete data versus missing data.

Fig A2.

Kaplan-Meier estimates of progression-free survival for patients with complete data versus missing data.