Addition of Chemotherapy Is Associated With Decreased Survival in Early-Stage (T1-2N0M0) Glottic Squamous Cell Carcinoma Treated With Definitive Radiotherapy.

PURPOSE: The role of chemoradiation (CRT) in treating patients with early-stage glottic squamous cell carcinoma (SCC), especially for T2N0M0 glottic SCC with impaired vocal cord mobility, remains unexplored. We sought to evaluate the impact of CRT on survival in early-stage glottic SCC by using the SEER database. PATIENTS AND METHODS: We included patients with localized (T1-4N0M0) glottic SCC (N = 4,743) diagnosed between 2004 and 2014 and treated with definitive radiotherapy (RT) alone, CRT, or laryngectomy alone in the SEER database. Disease-specific mortality (DSM) was evaluated via multivariable regression using a competing risk model that accounts for other-cause mortality as a competing risk event for DSM. One-to-one propensity score matching between CRT and RT cohorts was also performed to facilitate comparison of cumulative DSM and other-cause mortality incidences stratified by T stage. RESULTS: After stratification by T stage, CRT was associated with increased DSM in T1-2N0M0 glottic SCC (adjusted hazard ratios [AHRs], 4.222 and 2.260 for T1 and T2 disease, respectively; P < .001 for both). For T2N0M0 glottic SCC with and without impaired vocal cord mobility, CRT resulted in significantly increased DSM compared with RT alone in both cohorts (AHR, 2.084; P = .046 and AHR, 2.412; P < .001, respectively). After propensity score matching, cumulative incidence plots demonstrated a statistically significant increase in DSM associated with CRT compared with RT alone for both T1 and T2 glottic SCC (P < .001 and P = .003, respectively). CONCLUSION: CRT for T1-2N0M0 glottic SCC was associated with increased DSM compared with RT alone. This pattern persisted upon further stratification on the basis of vocal cord mobility status for T2N0M0 glottic SCC. This finding warrants careful consideration of chemotherapy in early-stage glottic SCC.

Prognostic significance of HPV status in the re-irradiation of recurrent and second primary cancers of the head and neck.

PURPOSE: To evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field. METHODS AND MATERIALS: The medical records of 54 consecutive patients who underwent re-irradiation for squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of recurrent disease that had previously been treated with doses of radiation therapy of at least 60 Gy were included. Determination of HPV status at the time of recurrence was performed by p16 immunohistochemistry. The median age at re-irradiation was 58.5 years (range, 27.9 to 81.5 years). Thirty patients (55.5%) were lifelong never-smokers. The Kaplan Meier method was used to calculate overall survival, progression-free survival, and local-regional control, and distant metastasis-free survival with comparisons between groups performed using the log-rank test. RESULTS: HPV status among tumors that were re-irradiated was as follows: 16 positive (29.7%); 7 negative (12.9%); 31 unknown (57.4%). The median overall survival in the entire cohort was 11.7 months (range, 8 to 27 months), with the 1-year and 2-year estimates of overall survival being 47.2% and 38.4%, respectively. A statistical trend was identified favoring patients with HPV-positive cancers with respect to the endpoints of overall survival (p = 0.06) and progression-free survival (p = 0.08) after re-irradiation when compared to the HPV-negative/unknown population. There was no significant difference in distant control between the two cohorts (p = 0.40). CONCLUSIONS: The favorable prognostic significance of HPV seemingly extends to patients treated by re-irradiation suggesting that this biomarker may be useful in risk stratification in this setting.

Inadequate target volume delineation and local-regional recurrence after intensity-modulated radiotherapy for human papillomavirus-positive oropharynx cancer.

PURPOSE: To perform a spatial analysis of local-regional recurrences, in relation to quantitative dose distribution, among patients treated by intensity-modulated radiotherapy (IMRT) for human papillomavirus (HPV)-positive oropharyngeal cancer. METHODS AND MATERIALS: The records of 107 consecutive patients who presented for consideration of re-irradiation for local-regional recurrent disease occurring in a previously irradiated field were reviewed. The original IMRT plans were retrieved for those with HPV-positive disease originating from the oropharynx, and deformable image registration was used to fuse the magnetic resonance imaging (MRI) and positron emission tomography (PET) scans obtained at recurrence to the pre-treatment planning computed tomography (CT) dataset. The recurrent tumor volume (Vrecur) was subsequently identified on axial imaging, and the dose of radiation received by Vrecur was then calculated and analyzed using dose-volume histograms. RESULTS: A total of 83 recurrent lesions occurring in 50 oropharyngeal cancer patients were HPV-positive and met inclusion criteria. Using PET-defined Vrecur, thirty-three lesions were classified as in-field recurrences (40%), 35 were marginal misses (41%), and 15 were true misses (18%). Using the MRI-defined Vrecur, thirty-seven lesions were classified as in-field recurrences (45%), 32 were marginal misses (39%), and 14 were true misses (17%). CONCLUSION: A significant proportion of local-regional recurrences from HPV-positive oropharyngeal cancer represented geographical misses which possibly could have been prevented with more meticulous attention to IMRT planning. This finding has important implications with respect to ongoing attempts to de-escalate radiation dose for this disease. Our data highlight the importance of robust quality assurance with careful review of target volumes prior to the initiation of IMRT.

Re-irradiation for recurrent and second primary cancers of the head and neck.

PURPOSE: To evaluate a single-institutional experience with the use of re-irradiation for recurrent and new primary cancers of the head and neck. METHODS: The medical charts of 80 consecutive patients who underwent re-irradiation for local-regionally recurrent or second primary head and neck cancer between November 1998 and December 2015 were analyzed. Multivariate analysis was performed using Cox proportional hazard and logistic regression to determine predictors of clinical outcomes. RESULTS: Seventy-six of the 80 patients were evaluable. The median age was 57.5 (range 26.6-84.9); Intensity-modulated radiotherapy (IMRT) was used in 71 (93.4%) patients with a median dose of 60Gy. Thirty-one patients (40.8%) underwent salvage surgery before re-irradiation and 47 (61.8%) received concurrent systemic therapy. The median time interval between radiation courses was 25.3months (range 2-322months). The 2-year estimates of overall survival, progression free survival, locoregional control, and distant control were 51.0%, 31.3%, 36.8% and 68.3%, respectively. Patients who underwent salvage surgery prior to re-irradiation had significantly improved locoregional control, progression free survival, and overall survival (p<0.05, for all). On multivariate analysis, gross tumor volume (GTV) at re-irradiation and interval between radiation courses were associated with improved overall survival. Severe (grade⩾3) late complications were observed in 25 patients (32.8%). CONCLUSIONS: Re-irradiation for recurrent or second primary head and neck cancer is feasible and effective in select patients with head and neck cancer. The high observed rate of treatment-related morbidity highlights the continue challenges that accompany this approach.

Effect of daily fraction size on laryngoesophageal dysfunction after chemoradiation for squamous cell carcinomas of the larynx and hypopharynx.

BACKGROUND: The purpose of this study was to determine the effect of fraction size on laryngoesophageal dysfunction among patients treated by chemoradiotherapy for laryngeal and hypopharyngeal cancer. METHODS: Forty patients underwent chemoradiotherapy for stage III/IV squamous cell carcinomas of the larynx and hypopharynx. Median radiation dose was 70 Gy (range, 69.3-70.4 Gy) with daily fractionation ranging from 2 Gy to 2.2 Gy. RESULTS: When comparing 2 Gy versus >2 Gy daily fractionation, there was no difference in 2-year overall survival (71% vs 72%; p = .68), locoregional control (79% vs 77%; p = .43), or laryngectomy-free survival (60% vs 61%; p = .72). Use of 2 Gy versus >2 Gy fractionation improved laryngoesophageal dysfunction-free survival (2-year estimates, 49% vs 27%; p = .07). Patient-reported voice and swallowing were improved with the former. CONCLUSION: As the importance of a functional larynx becomes recognized as an endpoint for patients treated by voice preservation, the results of our study help refine treatment guidelines. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1322-1326, 2017.