24 Dec Breast Cancer Patients Report More Treatment Side Effects Than Their Physicians Recognize
MedicalResearch.com Interview with:
Filippo Montemurro, M.D.
Director, Investigative Clinical Oncology (INCO)
Fondazione del Piemonte per l’Oncologia
Candiolo Cancer Institute (IRCCS)
Medical Research: What is the background for this study?
Dr. Montemurro: The evaluation of treatment-related side effects is a critical step in cancer patient management. It is important in the clinical practice, where the decision to modify doses, omit administrations or establish supportive care measures is based on treatment tolerance and side effects severity and duration. It is also important in the context of clinical trials. In the latter setting, the mere information of the antitumor activity of a new drug or regimen under investigation is worth little if it not accompanied by an accurate reporting of the side effect profile. For this reason, over the years reference protocols to standardize the process of toxicity reporting in clinical trials have been established. The most recent and widespread is the Common Terminology Criteria for Adverse Events (CTCAE), that is issued and constantly updated by the National Cancer Institute. The CTCAE allows the description of the incidence and on the grade of severity on a scale ranging from 0 (no toxicity) to 5 (death due to that toxicity). Normally, the medical or nursing staff data collects information to fill in the CTCAE reports either by interviewing patients or extracting data from the clinical notes taken by physicians. The “indirectness” of this process has consequences that are becoming acknowledged for their potential implications. The incidence and severity of toxicities results often underestimated by doctors when their reports are compared with corresponding reports provided directly by patients without intermediaries (so called Patient reported outcomes-PRO). If this phenomenon is described in the context of clinical trials, it might occur to a greater extent also in the clinical practice, where the process of toxicity reporting is not mandated by a protocol and no reference standard is recommended.
Based on these premises, we designed a study to pursue two aims;
- the first was to assess whether a 10-item questionnaire derived by the CTCAE could be used by breast cancer patients receiving adjuvant chemotherapy after surgery in the daily clinical practice;
- the second was to compare doctors and patients reports of toxicities at corresponding time-points.
Medical Research: What are the main findings?
Dr. Montemurro: We administered the 10-item questionnaire after the first and third cycle of adjuvant chemotherapy to 601 women who had undergone surgery for breast cancer. To develop this questionnaire, CTCAE definitions of severity for each item (nausea, vomiting, constipation, anorexia, dysgeusia, diarrhea, fatigue, pain, paresthesia, and dyspnea) were translated into Italian and rephrased into statements. Patients were asked to choose the statement that best represented the worst experience with that side effect after the reference cycle of chemotherapy. At the same time-points, research nurses extracted information from the medical charts and reported them in paired doctor questionnaires. A total of 99% and 97% of the patient returned filled in questionnaires. Pairwise comparisons showed that doctors systematically underestimated both incidence and severity for all the side effects. Interestingly, comparison of the two patient questionnaires revealed temporal changes that were possibly related to the effect of prophylactic measures taken after the first cycle (i.e. reduction in vomiting, diarrhea and pain) or to cumulative toxicties (i.e. worsening dysgeusia and dyspnea). No such changes except for worsening dyspnea were observed comparing the two doctors questionnaires. Finally, we found a direct relationship between number of patients and magnitude of discrepancy in side effects reporting was observed, suggesting that the workload could be a factor influencing this phenomenon.
Medical Research: What should clinicians and patients take away from your report?
Dr. Montemurro: First of all, physician must be aware that, regardless of the setting (adjuvant or metastatic disease), the type of cancer, and the environment (experimental clinical trial or current clinical practice), there is a discrepancy in their perception and reporting of treatment-related side effects compared with that of the patient. This discrepancy goes systematically into the direction of underestimation. When the patients are given “voice” on side effects, without intermediaries, their perceived incidence and severity of side effects depicts a higher burden that should be accounted for.
Second, patients are able (and in our experience are strongly willing) to provide information that is compliant with widely accepted standardized reporting tools like the CTCAE.
Third, high patient workload should be dealt with adopting methodological and organizational solutions that consider the high risk of underreporting. We believe that the further development and adoption of questionnaires like the one that we tested in this study, together the possibility to develop an electronic version that could be integrated in the medical chart, could be a successful strategy to reinforce the doctor-patient relationship and improve management.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Montemurro: Currently, how and to what extent underreporting of side effects really affects cancer outcomes is not clear. For sure, a patient that directly participates in the description of treatment-related side effects has better copying with treatment and improved quality of life. Therefore, although further research will identify and quantify potential the harms of underreporting, we believe that integration of PROs in the current clinical trials would be an achievement by itself. In this direction, a PRO version of the CTCAE system (PRO-CTCAE) is being financed, supported and disseminated worldwide by the National Cancer Institute. For each of the selected 78 toxicities the PRO-CTCAE, which has been prospectively validated, contains up to three patient questions that define severity. The English version of PRO-CTCAE is currently being translated into different languages, including Italian, and we strongly encourage testing of this tool not only for clinical trials, but also for its potential use in the clinical practice.
Montemurro F, Mittica G, Cagnazzo C, et al. Self-Evaluation of Adjuvant Chemotherapy-Related Adverse Effects by Patients With Breast Cancer. JAMA Oncol. Published online December 23, 2015. doi:10.1001/jamaoncol.2015.4720.
Filippo Montemurro, M.D. (2015). Breast Cancer Patients Report More Treatment Side Effects Their Physicians Recognize