Patient-Reported Toxic Effects-The Dawn of a New Era.

The article by Falchook et al1 in this issue of JAMA Otolaryngology–Head & Neck Surgery demonstrates the importance of fully assessing the toxic effects experienced by patients during and after def in it ive chemoradiotherapy for locally advanced head and neck cancers. With a focus on patient outcomes, such as response and survival, toxicity data may be underestimated in many clinical trials, which poses a concern for patients in the era of human papilloma virus (HPV)–related head and neck cancers. Because the long-term survival rates for HPV-positive disease are exceptional in most patients receiving definitive chemoradiotherapy, efforts are under way to reduce acute and long-standing adverse effects, while maintaining prolonged control of disease. As documented by Falchook et al,1 the inclusion of patient-reported toxic effects may enhance symptom management and improve data quality. The most notable difference between the practitioner and patient reports in this study is the higher number of lower grade toxic effects reported by the practitioners, begging the question of why. Perhaps this difference may be related to the practitioner’s interpretation of patient symptoms as recorded in the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Moreover, toxicity grading is based on the practitioner’s perception of the patient’s reported symptoms, but is this what the patient is truly experiencing? The grading for the CTCAE criteria lists words or phrases to capture a particular adverse event, sometimes making it difficult to determine the level of toxicity and therefore underestimating the severity of the event. Hence, the practitioner relies on the patient’s subjective report to define the grade of the toxic effect. This is particularly important in the recording of events that are subjective, such as depression, fatigue, and anxiety. As Falchook and colleagues1 observed, patients reported symptoms of anxiety and depression that developed earlier and were more severe compared with those reported by their practitioners. In general, anxiety and depression are greater at baseline in patients with HPV-positive disease since many are younger at the time of diagnosis and their disease is often related to sexual behavior vs the conventional risk factors of tobacco and alcohol exposure.2 Hence, early intervention is critical and may have a greater effect on overall tolerance to therapy and improvements in quality of life. The overall survival rates for patients with HPV-positive head and neck cancers range from 80% to 85%,3 and because most patients experience long-term survival, there is a movement to use deintensified treatments by decreasing the total dosage of radiation, similar to the clinical trial reported by Falchook and colleagues.1 Data presented at the American Society of Clinical Oncology Annual Meeting in 2014 suggest that reduced dosages of intense modulated radiotherapy in chemoresponsive, HPV-positive patients produce high disease control rates with fewer late-term toxic effects.4 Because such preliminary data appear to be promising, it will be important with the design of larger comparative phase 3 trials to know how much deintensified strategies reduce toxic effects compared with standard chemoradiotherapy regimens. In particular, obtaining such data on toxic reactions will be imperative at the end of therapy since practitioner underreporting is significant at this time per Falchook and colleagues.1 The incorporation of patientreported toxic effects will further enhance our understanding of how best to manage those undergoing chemoradiotherapy. The idea of strengthening the ability to capture data on toxic effects is appealing, and in the modern era of computer technology, it is readily feasible. The use of internet and mobile devices allows patients to report their symptoms in a timely manner, which may allow for real-time assessments. In the present study, investigators administered online questionnaires via a tablet computer to patients during weekly visits with an adherence rate of 97%, noting the ease with which data can be accessed. One recently published study5 noted that the Unites States National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) data can be collected equivalently using paper, interactive voice response systems, or touchscreen tablets. The authors noted that each mode was equally acceptable by most respondents and comparable to test-retest reliability, suggesting that the ability to collect patient-reported data readily will promote the improvement of patient care for early and late complications of therapy. Further data note that electronic web-based technology can improve quality of life data collection across multiple academic institutions.6 Since head and neck cancers rank among orphan tumors, the reliance on obtaining meaningful data lies within the setting of cooperative groups. Although the CTCAE and PRO-CTCAE instruments cannot be compared directly, they should be used to complement one another. As health care professionals, we should strive to improve not only survival outcomes, but also outcomes related to the well-being of patients. Too often our focus is on extending life rather than quality of life. We now live in an era in which the collection of symptomatic data are less difficult. Falchook and colleagues1 must be congratulated on their efforts to pioneer improvements in symptom-related patient outcomes. The medical community now has the responsibility to follow their lead in developing studies with more in-depth assessments of toxic effects. Related article page 517 Research Original Investigation Patientvs Practitioner-Reported Toxic Effects of Chemoradiotherapy