Clinical Investigation
Quality of Life for Patients With Favorable-Risk HPV-Associated Oropharyngeal Cancer After De-intensified Chemoradiotherapy

https://doi.org/10.1016/j.ijrobp.2018.10.033Get rights and content

Purpose

Oropharynx cancers associated with human papillomavirus (HPV) have a favorable prognosis, but current treatment approaches carry significant long-term morbidity. Strategies to de-intensify treatment in this population are under investigation, but the impact of these approaches on quality of life (QOL) is not well understood. We present patient-reported outcomes from 2 prospective studies examining de-intensified chemoradiotherapy.

Methods and Materials

This study included patients enrolled in 2 prospective phase 2 trials of de-intensified chemoradiotherapy in patients with HPV-associated oropharynx cancer who had at least 1 year of follow-up. Treatment included concurrent radiation therapy (60 Gy) and chemotherapy (weekly cisplatin, 30 mg/m2). Patients reported QOL and symptoms using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module-35, and the Eating Assessment Tool-10 instruments before treatment and at regular intervals thereafter. Changes in QOL and individual symptoms were examined over time, and multivariate analysis was used to identify clinical factors associated with recovery to baseline symptom levels.

Results

Of the 154 patients enrolled, 126 patients had at least 1 year of follow-up and were included in this study (median follow-up, 25 months). Global QOL, functional indices, and most individual symptoms returned to baseline 3 to 6 months after treatment. Swallowing (Eating Assessment Tool-10 score) returned to baseline function by 2 years, but dry mouth, sticky saliva, and taste/senses did not return to baseline levels. However, from 1 to 2 years, continued improvement occurred in dry mouth score (55 vs 48), sticky saliva score (35 vs 27), and senses score (24 vs 20). On multivariate analysis, unilateral radiation therapy was associated with returning to baseline level of swallowing and sticky saliva.

Conclusions

The use of de-intensified chemoradiotherapy in HPV-associated oropharynx cancer led to favorable patient-reported outcomes, with early recovery of QOL and continued improvement of xerostomia and dysphagia beyond 1-year posttreatment.

Introduction

The role of the human papillomavirus (HPV) in the pathogenesis and increasing incidence of oropharyngeal cancer has been well documented.1, 2, 3 Fortunately, individuals with HPV-associated oropharynx cancers have a better response to traditional treatments as well as a better prognosis compared with those with non-HPV related cancer.4, 5 The standard approach for locally advanced disease is concurrent chemoradiotherapy with a cumulative radiation therapy (RT) dose of 70 gray (Gy) and high-dose cisplatin (300 mg/m2). However, this treatment results in long-term morbidity that can affect quality of life (QOL),6, 7, 8 which is a significant issue given the excellent prognosis for these patients. As a result, there is a great interest in de-intensifying treatment of this population of patients, with the goal of preserving cancer control while reducing treatment-related morbidity.

In 2011, we began a program of de-intensified chemoradiotherapy using a substantial reduction in RT and chemotherapy dose, which has subsequently been explored in a series of prospective trials. The de-intensified regimen consists of 60 Gy intensity modulated radiation therapy (IMRT), a 10 Gy1 dose reduction from standard treatment, and concurrent weekly cisplatin with a cumulative dose of 180 mg/m2, a reduction from the standard cumulative dose of 300 mg/m2. We have previously shown excellent cancer control (pathologic complete response rate, 86%; 3-year local control, 100%) and favorable early QOL with this approach.9, 10 We present a pooled analysis of patient-reported outcomes for patients prospectively treated with our de-intensified chemoradiotherapy regimen.

Section snippets

Study design and eligibility

Data were pooled from 2 multi-institutional phase 2 studies: LCCC1120 (NCT01530997 2012-2014) and LCCC1413 (NCT02281955 2015-2017). Both trials were designed to examine the efficacy of a de-intensified chemoradiotherapy regimen for individuals with favorable-risk, HPV-associated oropharynx cancer.

Inclusion criteria for both studies included previously untreated HPV-negative or p16-positive squamous cell carcinoma of the oropharynx/unknown primary; T0-3, N0-N2c, M0; age ≥18 years; ≤10 pack-years

Patient characteristics

Of the 154 patients enrolled in the 2 studies, 126 completed 1-year surveys and were included in the analysis. Eighty-seven of these patients completed the 2-year survey, and the median follow-up for the entire analytical cohort was 25 months (10.3-66.8 months). Fifty-three percent were older than age 60, and 87% were male (Table 1). Eighty-seven percent received concurrent systemic therapy (83% received cisplatin; 4% received cetuximab), and 16% received unilateral RT. Characteristics of those

Discussion

Patients with HPV-associated oropharynx cancer are known to have an excellent prognosis, but standard treatment approaches carry a high risk of long-term morbidity.5, 6, 7, 8 This patient population tends to be younger and healthier, with a very good baseline QOL, compared with individuals with other types of head and neck cancer. As has been noted in previous studies16, 17 and in the current study, these individuals are less likely to return to baseline function compared with those with worse

Conclusions

We present the largest QOL study of patients receiving de-intensified chemoradiotherapy for HPV-associated oropharynx cancer. We observed the following favorable QOL outcomes: (1) rapid recovery to baseline of many QOL indices/items and (2) continued improvement in dry mouth, taste, and swallowing beyond 1 year. These findings suggest that de-intensified chemoradiotherapy of 60 Gy IMRT with concurrent weekly cisplatin 30 mg/m2 can preserve QOL and reduce long-term morbidity for patients with

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    Conflict of interest: none.

    Funding was provided by the University of North Carolina School of Medicine, Department of Radiation Oncology and the University of Florida School of Medicine, Department of Radiation Oncology.

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