We hypothesized that patients with oropharyngeal cancer treated with intensity modulated proton therapy (IMPT) would have lower symptom burdens, as measured by patient-reported outcome (PRO) surveys, ...than patients treated with intensity modulated photon therapy (IMRT).
Patients were treated for oropharyngeal cancer from 2006 to 2015 through prospective registries with concurrent chemotherapy and IMPT or chemotherapy and IMRT and completed the MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) module at various times before treatment (baseline), during treatment (acute phase), within the first 3 months after treatment (subacute phase), and afterward (chronic phase). Individual symptoms and the top 5 and top 11 most severe symptoms were summarized and compared between the radiation therapy modalities.
PRO data were collected and analyzed from 35 patients treated with chemotherapy and IMPT and from 46 treated with chemotherapy and IMRT. The baseline symptom burdens were similar between both groups. The overall top 5 symptoms were food taste problems (mean score 4.91 on a 0-10 scale), dry mouth (4.49), swallowing/chewing difficulties (4.26), lack of appetite (4.08), and fatigue (4.00). Among the top 11 symptoms, changes in taste and appetite during the subacute and chronic phases favored IMPT (all P<.048). No differences in symptom burden were detected between modalities during the acute and chronic phases by top-11 symptom scoring. During the subacute phase, the mean (±standard deviation) top 5 MDASI scores were 5.15 ± 2.66 for IMPT versus 6.58 ± 1.98 for IMRT (P=.013).
According to the MDASI-HN, symptom burden was lower among the IMPT patients than among the IMRT patients during the subacute recovery phase after treatment. A prospective randomized clinical trial is underway to define the value of IMPT for the management of head and neck tumors.
Background:
The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library designed for eliciting patient-reported adverse events in oncology. For each ...adverse event, up to three individual items are scored for frequency, severity, and interference with daily activities. To align the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events with other standardized tools for adverse event assessment including the Common Terminology Criteria for Adverse Events, an algorithm for mapping individual items for any given adverse event to a single composite numerical grade was developed and tested.
Methods:
A five-step process was used: (1) All 179 possible Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events score combinations were presented to 20 clinical investigators to subjectively map combinations to single numerical grades ranging from 0 to 3. (2) Combinations with <75% agreement were presented to investigator committees at a National Clinical Trials Network cooperative group meeting to gain majority consensus via anonymous voting. (3) The resulting algorithm was refined via graphical and tabular approaches to assure directional consistency. (4) Validity, reliability, and sensitivity were assessed in a national study dataset. (5) Accuracy for delineating adverse events between study arms was measured in two Phase III clinical trials (NCT02066181 and NCT01522443).
Results:
In Step 1, 12/179 score combinations had <75% initial agreement. In Step 2, majority consensus was reached for all combinations. In Step 3, five grades were adjusted to assure directional consistency. In Steps 4 and 5, composite grades performed well and comparably to individual item scores on validity, reliability, sensitivity, and between-arm delineation.
Conclusion:
A composite grading algorithm has been developed and yields single numerical grades for adverse events assessed via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, and can be useful in analyses and reporting.
Pain is prevalent among patients with cancer, yet pain management patterns in outpatient oncology are poorly understood.
A total of 3,123 ambulatory patients with invasive cancer of the breast, ...prostate, colon/rectum, or lung were enrolled onto this prospective study regardless of phase of care or stage of disease. At initial assessment and 4 to 5 weeks later, patients completed a 25-item measure of pain, functional interference, and other symptoms. Providers recorded analgesic prescribing. The pain management index was calculated to assess treatment adequacy.
Of the 3,023 patients we identified to be at risk for pain, 2,026 (67%) reported having pain or requiring analgesics at initial assessment; of these 2,026 patients, 670 (33%) were receiving inadequate analgesic prescribing. We found no difference in treatment adequacy between the initial and follow-up visits. Multivariable analysis revealed that the odds of a non-Hispanic white patient having inadequate pain treatment were approximately half those of a minority patient after adjusting for other explanatory variables (odds ratio, 0.51; 95% CI, 0.37 to 0.70; P = .002). Other significant predictors of inadequate pain treatment were having a good performance status, being treated at a minority treatment site, and having nonadvanced disease without concurrent treatment.
Most outpatients with common solid tumors must confront issues related to pain and the use of analgesics. There is significant disparity in pain treatment adequacy, with the odds of undertreatment twice as high for minority patients. These findings persist over 1 month of follow-up, highlighting the complexity of these problems.
To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events ...(PRO-CTCAE).
To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items.
A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit.
Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30).
A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median range intraclass correlation coefficient, 0.76 0.53-.96). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were statistically significant for 27 prespecified items (median range r=0.43 0.10-.56; all P≤.006).
Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials.
The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute's (NCI's) Common Terminology ...Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research.
Radiation Therapy Oncology Group trial 0525 tested whether dose-intensifying temozolomide versus standard chemoradiotherapy improves overall survival (OS) or progression-free survival (PFS) in newly ...diagnosed glioblastoma. Tests of neurocognitive function (NCF) and symptoms (using the MD Anderson Symptom Inventory-Brain Tumor module; MDASI-BT) and of quality of life (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ -C30/BN20) examined the net clinical benefit (NCB) of therapy.
NCF tests (Hopkins Verbal Learning Test-Revised, Trail Making Test, and Controlled Oral Word Association), MDASI-BT, and EORTC QLQ-C30/BN20 were completed in a subset of patients. Multivariate Cox proportional hazard regression modeling determined the prognostic value of baseline and early change from baseline to cycle 1 for OS and PFS. Two-sample proportional test statistic was used to evaluate differences between treatments (dose-dense v standard-dose) on NCB measures from baseline to cycle 4 in stable patients.
Overall, 182 patients participated in the study. Baseline NCF tests and the physical functioning quality of life scale were associated with OS and PFS. Baseline to cycle 1 in all NCB components were associated with OS and PFS. There was greater deterioration in the dose-dense arm from baseline to cycle 4 in the Global Health and Motor Function subscales (EORTC QLQ-C30/BN20) as well as in overall symptom burden, overall symptom interference, and activity-related symptom interference subscales (MDASI-BT). There were no between-arm differences in NCF.
Longitudinal collection of NCB measures is feasible in cooperative group studies and provides an added dimension to standard outcome measures. Greater adverse symptom burden and functional interference, as well as decreased global health and motor function were observed in patients randomly assigned to the dose-dense arm. Baseline and early change in NCB measures were associated with decreased rates of survival.
Patients receiving cancer-related thoracotomy are highly symptomatic in the first weeks after surgery. This study examined whether at-home symptom monitoring plus feedback to clinicians about severe ...symptoms contributes to more effective postoperative symptom control.
We enrolled 100 patients receiving thoracotomy for lung cancer or lung metastasis in a two-arm randomized controlled trial; 79 patients completed the study. After hospital discharge, patients rated symptoms twice weekly for 4 weeks via automated telephone calls. For intervention group patients, an e-mail alert was forwarded to the patient's clinical team for response if any of a subset of symptoms (pain, disturbed sleep, distress, shortness of breath, or constipation) reached a predetermined severity threshold. No alerts were generated for controls. Group differences in symptom threshold events were examined by generalized estimating equation modeling.
The intervention group experienced greater reduction in symptom threshold events than did controls (19% v 8%, respectively) and a more rapid decline in symptom threshold events. The difference in average reduction in symptom interference between groups was -0.36 (SE, 0.078; P = .02). Clinicians responded to 84% of e-mail alerts. Both groups reported equally high satisfaction with the automated system and with postoperative symptom control.
Frequent symptom monitoring with alerts to clinicians when symptoms became moderate or severe reduced symptom severity during the 4 weeks after thoracic surgery. Methods of automated symptom monitoring and triage may improve symptom control after major cancer surgery. These results should be confirmed in a larger study.
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