Clinical Investigation
Long-Term Quality of Life After Swallowing and Salivary-Sparing Chemo–Intensity Modulated Radiation Therapy in Survivors of Human Papillomavirus–Related Oropharyngeal Cancer

Presented in part at the 56th Annual Meeting of the American Society for Radiation Oncology (ASTRO), September 14-16, 2014, San Francisco, CA; and at Best of ASTRO 2014, October 16-17, 2014, Miami Beach, FL.
https://doi.org/10.1016/j.ijrobp.2014.12.045Get rights and content

Purpose

To evaluate long-term health-related quality of life (HRQOL) in 2 prospective studies of chemo–intensity modulated radiation therapy (chemo-IMRT) for oropharyngeal cancer (OPC).

Methods and Materials

Of 93 patients with stage III/IV OPC treated on prospective studies of swallowing and salivary organ-sparing chemo-IMRT, 69 were eligible for long-term HRQOL assessment. Three validated patient-reported instruments, the Head and Neck QOL (HNQOL) questionnaire, the University of Washington quality of life (UWQOL) questionnaire, and the Xerostomia Questionnaire (XQ), previously administered from baseline through 2 years in the parent studies, were readministered at long-term follow-up, along with the Short-Form 36. Long-term changes in HRQOL from before treatment and 2 years were evaluated.

Results

Forty patients (58%) with a median follow-up of 6.5 years participated, 39 of whom (97.5%) had confirmed human papillomavirus–positive OPC. Long term, no clinically significant worsening was detected in mean HRQOL scores compared with 2 years, with stable or improved HRQOL from before treatment in nearly all domains. “Moderate” or greater severity problems were uncommon, reported by 5% of patients for eating, 5% for swallowing, and 2.5% and 5% by HNQOL and UWQOL summary scores, respectively. Freedom from percutaneous endoscopic gastrostomy tube dependence and stricture dilation beyond 2 years was 97.5% and 95%, respectively. Eleven percent and 14% of patients reported “moderate” or “severe” long-term worsening in HNQOL Pain and Overall Bother domains, respectively, which were associated with mean dose to the cervical esophagus, larynx, and pharyngeal constrictors.

Conclusions

At more than 6 years' median follow-up, OPC patients treated with swallowing and salivary organ-sparing chemo-IMRT reported stable or improved HRQOL in nearly all domains compared with both before treatment and 2-year follow-up. New late toxicity after 2 years was uncommon. Further emphasis on sparing the swallowing organs may yield additional HRQOL gains for long-term OPC survivors.

Introduction

Concomitant chemo-radiation therapy (CRT) is considered standard-of-care treatment for organ preservation in patients with locally advanced head and neck cancer (HNC). Traditionally, CRT using conventional radiation therapy was associated with significant morbidity. Xerostomia and dysphagia in particular have been identified as the primary determinants of health-related quality of life (HRQOL) in long-term survivors of HNC 1, 2. Advances in radiation therapy planning with intensity modulated radiation therapy (IMRT) in recent years have enabled selective sparing of structures critical for salivary production and swallowing 3, 4, which have translated into improvements in xerostomia, dysphagia, and global HRQOL 5, 6, 7, 8.

We previously reported 2-year results of a prospective study of IMRT designed to spare the swallowing structures in patients with locally advanced oropharyngeal cancer (OPC) receiving CRT, which demonstrated very low rates of patient- and observer-rated dysphagia and percutaneous endoscopic gastrostomy (PEG) tube dependence while maintaining high rates of locoregional control and overall survival (8). Although the 2-year outcomes are encouraging, long-term HRQOL after IMRT remains scarcely reported, and concerns remain regarding radiation therapy–related complications that may manifest several years after CRT and thereby compromise HRQOL in long-term survivors 9, 10. Herein we report long-term HRQOL outcomes in patients with locally advanced OPC treated with definitive CRT using IMRT specifically aimed to spare the salivary and swallowing structures.

Section snippets

Patients and treatment

Between May 2003 and January 2011, 93 patients were enrolled on 2 consecutive prospective institutional review board–approved studies of swallowing and salivary organ-sparing chemo-IMRT for locally advanced OPC. Patient eligibility and treatment in both protocols were as previously detailed 8, 11. Patients with newly diagnosed, nonmetastatic stage III or IV OPC without posterior pharyngeal wall involvement or distant metastases were eligible for the original parent studies. Patients who

Patient characteristics

Sixty-nine patients who were alive and without recurrence/second primary cancer met eligibility for the present study. Forty (58%) responded to the mailed questionnaires. Of the nonrespondents, 12 were unable to be reached and 17 elected to not participate. A comparison of T and N stages of patients in the parent studies, those eligible for the present study, and those who participated in the present study is provided in Table e1 (available online at www.redjournal.com). Possible attrition bias

Discussion

The present study demonstrates that chemo-IMRT intended to spare the swallowing and salivary structures in patients with locally advanced OPC can achieve highly encouraging long-term patient-reported HRQOL, with overall and most HN-specific symptoms showing stability or continued improvement after 2 years. Compared with before treatment, the overall cohort experienced clinically meaningful improvement in HNQOL Emotion and Overall Bother domain scores at long-term follow-up, stable HNQOL summary

References (36)

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J.M.V. and D.H.M. contributed equally to this work.

J.M.V.'s present address is Emory University School of Medicine, Winship Cancer Institute, Department of Radiation Oncology, Atlanta, GA.

This study was supported in part by National Institutes of Health grant PO1 CA59827 and the Newman Family Foundation.

Conflict of interest: none.

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