Chen AM, Daly ME, Farwell DG, Vazquez E, Courquin J, Lau DH, Purdy JA. Quality of Life Among Long-Term Survivors of Head and Neck Cancer Treated by Intensity-Modulated Radiotherapy. JAMA Otolaryngol Head Neck Surg. 2014;140(2):129-133. doi:10.1001/jamaoto.2013.5988
Radiation therapy to the head and neck has traditionally been associated with adverse effects that can affect oral health and physical functioning. Although intensity-modulated radiotherapy (IMRT) has been widely adopted as a means of decreasing toxic effects, limited clinical data exist on its potential effect on long-term quality of life.
To analyze quality of life among long-term survivors of head and neck cancer treated with IMRT.
Design, Setting, and Participants
This cross-sectional analysis studied 50 consecutive long-term survivors of head and neck cancer from a comprehensive cancer center who had previously undergone IMRT that required bilateral neck irradiation for locally advanced disease. All patients were clinically without evidence of recurrent disease and had at least 5 years of follow-up.
Main Outcomes and Measures
The University of Washington Quality of Life (UW-QOL) scores were reviewed for all study participants. The UW-QOL questionnaire consists of 12 domains that pertain to the degree of quality of life in the categories of pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder function, taste, saliva, mood, and anxiety.
Five years after completion of IMRT, 42 patients (84%) reported that their health-related quality of life was “much better” or “somewhat better” than at the time of cancer diagnosis. With respect to recent health-related quality of life during the preceding 7 days at the time of completing the UW-QOL questionnaire, 40 patients (80%) treated with IMRT reported “outstanding” or “very good” levels of functioning. Five years after completion of treatment, 41 (82%) rated their overall quality of life as “outstanding” or “very good.” The lowest domain score on the UW-QOL questionnaire at 5 years pertained to salivary dysfunction. However, 42 patients (84%) reported saliva “of normal consistency” or “less saliva than normal but enough” compared with 8 (16%) reporting “too little saliva.” No patient reported having “no saliva.”
Conclusions and Relevance
Our findings add to the body of literature that supports the acceptance of IMRT as standard treatment for head and neck cancer. The fact that most 5-year survivors were satisfied with their quality of lives points to the ability of IMRT to preserve long-term functioning.
During the last decade, intensity-modulated radiotherapy (IMRT) has become widely adopted in the treatment of head and neck cancer. However, limited clinical data exist on its potential effect on long-term quality of life. This issue is particularly relevant because an increasing number of patients with head and neck cancer are surviving for prolonged periods after treatment and have been presumed cured. Moreover, because radiation therapy has traditionally been associated with profoundly detrimental effects on oral and physical health, the influence of more recently applied advanced technologies, such as IMRT, on long-term quality of life is of considerable interest.1- 3 Although radiation therapy to the head and neck negatively affects short-term quality of life because of such adverse effects as skin irritation, xerostomia, dysgeusia, esophagitis, and mucositis, among others, few studies have analyzed the quality of life beyond 3 years after completion of treatment. The purpose of this study was therefore to evaluate quality of life with respect to both overall wellness and specific functional domains related to treatment, including swallowing, chewing, and salivation, among long-term survivors of head and neck cancer treated with IMRT.
This study was approved by the institutional review board at the University of California–Davis School of Medicine. A waiver for informed consent was obtained for this retrospective research. The University of Washington Quality of Life (UW-QOL) questionnaire is a brief, previously validated, self-administered questionnaire that patients returning for follow-up after completion of radiation therapy for head and neck cancer have routinely completed at our institution since 2007.4 A review of institutional databases identified 50 patients previously treated with IMRT for squamous cell carcinomas of the oropharynx, oral cavity, larynx, hypopharynx, and nasopharynx and of unknown primary origin who required bilateral neck irradiation for locally advanced disease. The UW-QOL scores were retrospectively reviewed for these patients, all of whom were clinically without evidence of recurrent disease and had at least 5 years of follow-up. Patients who had undergone total laryngectomy and/or tracheostomy at any time were specifically excluded. Patients had a Karnofsky performance score of at least 70 at the time of initial treatment. Thirty-one patients (62%) were male, and 19 (38%) were female. The median age at diagnosis was 56 years (range, 38-77 years). Thirty-three patients (66%) were treated by definitive radiation therapy and 17 patients (34%) were treated postoperatively. Concurrent chemotherapy was administered with radiation therapy, for 20 patients (40%). Patient and disease characteristics are listed in Table 1.
The IMRT was administered with a simultaneous-integrated boost technique and inclusion of the low neck in an extended field. For patients treated definitively, the gross tumor volume was specified as the gross extent of tumor as demonstrated by imaging and physical examination. The high-risk clinical target volume (CTV1) was the gross tumor volume plus a margin up to 2 cm to account for microscopic disease spread. For patients treated with IMRT postoperatively, the CTV1 was defined as the surgical nodal bed, including all areas of extracapsular extension. Most of the ipsilateral neck was also included in the CTV1. The low-risk clinical target volume (CTV2) included the prophylactically treated contralateral neck. In selected patients, a CTV3 was created to designate an area at lowest risk within the prophylactically treated neck. The planning target volume (PTV) contained an automated 0.3- to 0.5-cm expansion of the CTV to account for patient setup error to create PTV1, PTV2, and PTV3, if necessary.
The median radiation doses for those treated postoperatively and definitively were 60 Gy (range, 54-66 Gy) and 70 Gy (range, 66-74 Gy), respectively. Treatment plans were generated to ensure that 95% of the PTV1 received the prescription dose. In general, the IMRT plan was designed to limit the maximum dose to 54 Gy for the brainstem, 45 Gy for the spinal cord, 60 Gy for the temporal lobes, and 30 Gy to 50% of the contralateral parotid gland. Dysphagia-sparing IMRT (ie, contouring the pharyngeal constrictor muscles) was not performed. Daily image-guided radiotherapy (IGRT) images were acquired volumetrically for patients receiving IMRT using either kilovoltage cone beam or megavoltage fan beam before each fraction to assist patient setup and positioning. Our guidelines for IMRT planning and IGRT use have previously been documented.5
Patients were typically seen 2 to 4 weeks after radiation therapy and then every 2 to 3 months thereafter for the first year, every 4 to 6 months for the second and third years, and then annually. The UW-QOL questionnaire (version 4) was administered at each follow-up visit and completed by the patient with the assistance of nursing and/or physician staff. The UW-QOL questionnaire consists of 12 domains that pertain to the degree of quality of life in the categories of pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder function, taste, saliva, mood, and anxiety. A score of 0 indicates very poor or no functional capacity with regard to that domain, whereas a score of 100 indicates no disability in that domain. In the final part of the UW-QOL questionnaire, patients are asked 3 general questions comparing (1) current health-related quality of life to 1 month before developing cancer, (2) health-related quality of life during the past 7 days, and (3) global quality of life during the past 7 days. This segment is scored with 0 indicating very poor quality of life and 100 indicating outstanding, with a range of scores in between.
Mean scores for each of the functional domains and quality of life were tabulated. On univariate analysis, global quality-of-life scores were compared between patients according to various clinical and treatment-related characteristics using the Wilcoxon signed-rank test. All tests were 2-tailed, and differences were considered statistically significant at P < .05.
Mean scores for each of the functional domains at 3 and 5 years after completion of IMRT are listed in Table 2. No significant changes were found in any of these scores from 3 to 5 years. The lowest domain scores on the UW-QOL questionnaire at 5 years pertained to salivary function and mood, with mean values of 72.8 and 79.0, respectively. At 5 years, 42 patients (84%) reported saliva “of normal consistency” or “less saliva than normal but enough” compared with 8 (16%) reporting “too little saliva.” No patient reported having “no saliva.” Although 36 patients (72%) reported mood as “excellent” or “generally good,” 3 patients (6%) reported being “somewhat depressed” or “extremely depressed” about their cancer at the 5-year follow-up.
With respect to long-term swallowing and chewing function, the mean scores at 5 years were 87.4 and 89.0, respectively. A total of 14 patients (28%) reported that they “cannot swallow certain solid foods” at 5 years. An additional 2 patients (4%) reported being able to “only swallow liquid food” (1 patient) or could not swallow because “it goes down the wrong way” (1 patient), both of whom were gastrostomy tube dependent. Among all patients, 34 patients (68%) reported that they could “swallow as well as ever.” Forty patients (80%) reported being able to “chew as well as ever” at 5 years. The number of patients who reported that they could “taste food normally” or “taste most foods normally” was 44 (88%) and 46 (92%), respectively, at 3 and 5 years after IMRT.
Thirty-five patients (70%) reported that their level of activity was as high as it had ever been, with an additional 12 patients (24%) reporting “there are times when I can’t keep up my old pace, but not often.” Only 3 patients (6%) reported feeling “often tired.” With respect to recreation, 46 patients (92%) reported that there were “no limitations to recreation at home or away from home” or “few things I can’t do” compared with only 4 patients (8%) who reported that “there were many times when I wish I could get out more but am not up to it.”
At 5 years after completion of IMRT, 42 patients (84%) reported that their health-related quality of life was “much better” or “somewhat better” than at the time of cancer diagnosis. With respect to recent health-related quality of life during the preceding 7 days at the time of completing the UW-QOL questionnaire, 40 patients (80%) treated with IMRT reported “outstanding” or “very good” levels of functioning. At 5 years after completion of treatment, 41 (82%) reported their overall quality of life as “outstanding” or “very good.” No patients rated their global quality of life as “poor” or “very poor.” The mean global quality-of-life scores at 3 and 5 years for patients treated by IMRT were 77.0 and 81.5, respectively. These scores did not differ based on primary site, T stage, treatment modality (primary surgery vs primary radiation), ethnicity, or whether chemotherapy or neck dissection was used.
The results of the present study, representing one of the few series to date that has reported on quality of life beyond 3 years for patients treated with IMRT for head and neck cancer, are noteworthy because they demonstrate that most long-term survivors are seemingly satisfied with their levels of physical functioning and emotional wellness. In view of the well-established toxic effects of IMRT in the acute care setting, these findings offer powerful assurances to patients that the long-term adverse effects of IMRT are tolerable and worth the risks of aggressive treatment.6
It must be noted that our results were derived from an observational study limited to a highly selected sample of patients. Although the data were prospectively collected, they were retrospectively analyzed and hence subject to inherent biases. Because these patients have all lived a relatively long duration, it is reasonable that they had time to adjust to any functional deficiencies and may have undergone rehabilitation to optimize their quality of life. For instance, all patients with any subjective dysphagia after radiation therapy were routinely referred for swallow studies, endoscopic examination, and/or consideration of esophageal dilation. The contribution of survivorship bias cannot be discounted either. Given that all of the included patients were presumably cured of cancer, they may have had a favorable outlook on life and were therefore more likely to report a more positive picture of their function than otherwise.
We also acknowledge that quality of life is somewhat of an abstract concept without a single, universally accepted definition. The World Health Organization definition, for example, focuses on the subjective perspective, accounting for both positive and negative aspects of life defined by patient experiences, states, and perceptions.7 Other constructs are broader and include objective indicators of health, finances, housing, and other material circumstances.8 These indicators suggest that subjective and objective information contributes to the multidimensional concept known as quality of life. Thus, measuring quality of life is difficult and complicated by a variety of factors, including socioeconomic status, cultural and spiritual influences, medical comorbidities, and variabilities of treatment. This is exemplified by the high number of instruments in use to screen for quality of life.9 The multifactorial nature of quality of life is particularly germane for patients with head and neck cancer given the relatively high incidence of tobacco use, substance addiction, alcoholism, and psychological disorders in this population.
The present study is nonetheless notable given that all patients had at least 5 years of follow-up, and the study was optimally designed to detect late improvements and recovery of functional impairments. It is becoming increasingly recognized that late toxic effects can develop and/or persist many years after completion of treatment. Machtay et al10 found that rates of late toxic effects due to laryngopharyngeal dysfunction were staggeringly high among 230 patients treated in Radiation Therapy Oncology Group trials and did not appear to plateau until nearly 3 years after completion of treatment. With the use of IMRT, studies are confirming that recovery of function (eg, salivation) can be a gradual, drawn-out process that occurs in the span of many years.11
The existing literature reporting on quality of life after IMRT for head and neck cancer is not only limited by relatively short follow-up but also hampered by such factors as heterogeneous patient populations, variability in treatment techniques, and differing screening instruments across studies. Because IMRT is a heavily user-dependent process, discrepancies with respect to planning and delivery invariably exist from one center to another. How the use of daily IGRT, for instance, in conjunction with IMRT may have influenced quality of life in the present series is uncertain. In our opinion, however, IGRT offers an additional degree of precision and provides assurance that what is being targeted at the time of treatment planning is actually being treated on a day-by-day basis. In addition, IGRT enables the shrinking of PTV margins, which reduces the amount of irradiation to normal tissue, theoretically improving the adverse effect profile.
Our findings are particularly notable given the increasing recognition that the generation of steep gradients between target and nontarget tissues that use IMRT may come at the expense of a higher dose to nondelineated extratarget organs, including the uninvolved oropharyngeal mucosa, larynx, and brain, leading to a greater integral dose. Although the effect of nontarget beam-path toxic effects associated with IMRT has been described by others, the fact that most patients’ functional capacities seemingly returned to near baseline 5 years after completion of treatment is encouraging.3 Although the rates of gastrostomy tube dependence during radiation therapy for head and neck cancer has been reported to be as high as 81%, only 2 patients in the present series were dependent on enteral feeds at 5 years.12 This is particularly important given that Terrell et al13 found that gastrostomy tube dependence was the most important factor that affected quality of life in the late setting. Because specific patient dosimetry was not analyzed in the present study, it is difficult to establish what specific IMRT planning variables may have contributed most to the therapeutic gain observed with this technique. Recently published data from Bhayani et al12 found that patients who continued to eat regularly during radiotherapy and adhered to swallowing exercises experienced significantly lower rates of dysphagia that required enteral feeding and had shorter duration of gastrostomy tube dependence.
Several published studies14- 17 have screened for subjective quality of life using a variety of instruments among patients treated for head and neck cancer with radiation therapy. van Rij et al15 sent questionnaires to 163 patients previously treated with IMRT or conventional radiation therapy at a median follow-up of 2.6 years. Patients treated with IMRT reported significantly improved quality of life, yet many still reported difficulty swallowing and requiring frequent water for xerostomia during the day, the night, and at meal times. These findings were consistent with results from a multi-institutional phase 3 trial of parotid-sparing IMRT vs conventional radiotherapy that indicated that, although IMRT improved xerostomia, the prevalence of grade 2 or greater xerostomia was still 29% at 2 years.18 The contribution of mood on quality of life after treatment for head and neck cancer has also been reported by others. Pourel et al16 screened 113 long-term survivors of oropharyngeal cancer using the European Organization for Research and Treatment of Cancer questionnaire at a median time of 62 months after completion of radiation therapy and found that negative emotional and social functioning were the domains that most impaired quality of life.
Because the literature to date on long-term quality of life after head and neck cancer is marked by considerable heterogeneity with respect to clinical and disease characteristics and treatment strategy, comparisons across series can be problematic. Nonetheless, our findings demonstrating reasonable quality-of-life outcomes among long-term survivors after IMRT compare favorably with historical controls treated by older techniques that used radiation therapy and/or surgery.19- 21
In conclusion, our long-term data add to the body of literature supporting the acceptance of IMRT as standard treatment for head and neck cancer. The fact that most 5-year survivors were satisfied with their quality of life points to the ability of IMRT to preserve long-term functioning. Continued long-term evaluation is imperative to confirm that the therapeutic gains associated with IMRT, especially as techniques are further refined, are maintained in the future.
Submitted for Publication: May 6, 2013; final revision received September 28, 2013; accepted October 14, 2013.
Corresponding Author: Allen M. Chen, MD, Department of Radiation Oncology, David Geffen School of Medicine at UCLA, 200 Medical Plaza, Ste B265, Los Angeles, CA 90095 (firstname.lastname@example.org).
Published Online: December 12, 2013. doi:10.1001/jamaoto.2013.5988.
Author Contributions: Dr Chen had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Chen, Purdy.
Acquisition of data: Chen, Vazquez, Courquin.
Analysis and interpretation of data: Chen, Daly, Farwell, Lau.
Drafting of the manuscript: Chen, Vazquez.
Critical revision of the manuscript for important intellectual content: Chen, Daly, Farwell, Courquin, Lau, Purdy.
Statistical analysis: Chen.
Administrative, technical, and material support: Chen, Vazquez, Courquin, Lau, Purdy.
Study supervision: Chen, Vazquez.
Conflict of Interest Disclosures: None reported.