Cancer Institute's Patient-Reported Outcomes Research Articles

Patient-Reported Outcomes in Chinese Patients with Locally Advanced or Recurrent Colorectal Cancer After Pelvic Exenteration.

Pelvic exenteration (PE) is often the only curative treatment option for selected locally advanced and locally recurrent colorectal cancer associated with significant morbidity. Open and laparoscopic approaches were accepted for this procedure. This study aimed to examine the Chinese patient-reported outcomes (PROs) and health-related quality of life (HRQoL) after PE. A total of 122 enrolled participants were asked to complete PROs at baseline and 1, 3, 6, 9 and 12 months after PE. PROs included seven symptoms from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The HRQoL was assessed using the Functional Assessment of Cancer Therapy-Colorectal (FACT-C). The overall postoperative complication rate was 41.0%. Patients experienced lower physical and functional well-being and FACT-C 1month after surgery, then gradually recovered. The FACT-C score returned to baseline 9 months after surgery. Social and emotional well-being did not show signs of recovery until 6 months after the surgical procedure, and did not fully return to baseline until 12 months post-surgery. Symptom rates of insomnia, anxiety, discouragement, and sadness (composite score >0) did not improve significantly from baseline until 12 months after surgery. PE is a feasible treatment choice for locally advanced primary and recurrent colorectal cancer. Social, psychological, and emotional recovery in the Chinese population after PE tends to be slower compared with the physical condition.

Patient-Reported Outcome Measures Associated with Overall Survival and Acute Care Use in Patients with Newly Diagnosed Myelodysplastic Syndrome, Acute Myelogenous Leukemia, or Acute Lymphoblastic Leukemia

Background: There is limited data on the real-world application of patient-reported outcomes (PROs) and their clinical utility in patients with acute leukemias or myelodysplastic syndrome (MDS). While the associations of PROs with clinical outcomes, such as overall survival (OS) and acute care utilization have been established in patients with solid tumors (Basch E et al. JAMA, 2017.318(2):197-198), these same associations are not well known in patients with hematologic malignancies. Objectives: We assessed the characteristics of baseline PRO measurements in patients with newly diagnosed acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS) and examined their associations with OS as well as time to acute care use (TAC). Methods: This retrospective cohort study was conducted on patients with newly diagnosed AML, ALL or MDS between 11/2018-02/2022 who were receiving care at our institution and completed a baseline PRO survey within 30 days of therapy initiation. The PRO survey consisted of a 14-question assessment from the National Cancer Institute's PRO Version of The Common Terminology Criteria for Adverse Events. Each of the symptom domains of the survey are measured on a 1-5 Likert scale. OS was defined as time from therapy initiation to the time of death. TAC was defined as time from therapy initiation to first unplanned acute care visit (emergency room visit or unplanned admission). OS curves were estimated using the Kaplan-Meier method and compared using log-rank tests. Cox proportional-hazards regression modeling was used to compare the hazards of death and acute care use between groups. Results: 56 patients were included with a median age of 63 years (range 26-79). The cohort consisted of more males, non-Hispanic Whites, and patients that received intensive initial therapy (Table 1). Fatigue was the most frequently reported symptom (n=49, 87.5%, mean score of 2.90/5 (SD 1.30), with a majority reporting mild or no symptoms (score < 4, n=33, 58.9%) and 28.6% (n=16) reporting more severe symptoms (scores > or = 4). Similarly, most patients in this cohort reported mild or no symptoms in terms of anorexia, anxiety, or sadness (Table 1). In terms of OS, univariate models for the presence of fatigue, anorexia, anxiety, or sadness was not associated with significantly higher hazard of death. On multivariate analyses adjusting for age, sex, and treatment intensity, every point increase in reported fatigue severity was associated with a 41% increased hazard of death (HR 1.41,95% CI: 1.03-1.93). When stratified by fatigue severity (> or = 4 severe vs < or = 3 mild/no symptoms), patients reported severe fatigue had an 145% increased hazard of death compared to those reported mild/no fatigue (HR 2.45 (95% CI: 1.07-5.61) (Figure 1). Multivariate analyses for anorexia, anxiety, and sadness were not associated with significant differences after adjusting for the above covariates, respectively. Fourteen (25.0%) and 24 (42.9%) patients in this cohort had at least one unplanned acute care visit within 30 and 90 days from initiation of therapy, respectively. The median TAC for this cohort was 4.15 months (range 0.60-27.20 months). Univariate regression modeling revealed no differences for any of the PROs examined in this study. Similarly, no differences were observed in multivariate analyses for each of the PROs after adjusting for age, sex, and therapy intensity. Conclusions: Fatigue was the most severe and frequently reported baseline symptom among patients with newly diagnosed acute leukemia or MDS. Patients reporting increased fatigue were found to have a higher hazard of death compared to those who did not after adjusting for age, sex, and treatment intensity. The characteristics and PROs examined in this study were not associated with TAC or predictive of acute care use at different time points from therapy initiation. Future work is needed to understand how PRO data can be used to identify higher-risk patients prior to treatment initiation.

Clinician and Patient Reporting of Symptomatic Adverse Events in Cancer Clinical Trials: Using CTCAE and PRO-CTCAE® to Provide Two Distinct and Complementary Perspectives.

Inclusion of the patient perspective in the reporting of symptomatic adverse events provides different and complementary information to clinician reporting using the Common Terminology Criteria for Adverse Events (CTCAE). The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) is designed for patients to self-report their symptomatic adverse events in a manner that complements CTCAE reporting. Using CTCAE and PRO-CTCAE together offers the potential to refine our understanding of the prevalence and trajectory of lower grade AEs that can lead to elective discontinuation of therapy and diminished quality of life. This review addresses the development of PRO-CTCAE with an emphasis on the differences between PRO-CTCAE scores and CTCAE severity grades. This distinction is important when evaluating, grading and reporting toxicity and tolerability in cancer clinical trials.

Deep Learning for Cancer Symptoms Monitoring on the Basis of Electronic Health Record Unstructured Clinical Notes.

Symptoms are vital outcomes for cancer clinical trials, observational research, and population-level surveillance. Patient-reported outcomes (PROs) are valuable for monitoring symptoms, yet there are many challenges to collecting PROs at scale. We sought to develop, test, and externally validate a deep learning model to extract symptoms from unstructured clinical notes in the electronic health record. We randomly selected 1,225 outpatient progress notes from among patients treated at the Dana-Farber Cancer Institute between January 2016 and December 2019 and used 1,125 notes as our training/validation data set and 100 notes as our test data set. We evaluated the performance of 10 deep learning models for detecting 80 symptoms included in the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) framework. Model performance as compared with manual chart abstraction was assessed using standard metrics, and the highest performer was externally validated on a sample of 100 physician notes from a different clinical context. In our training and test data sets, 75 of the 80 candidate symptoms were identified. The ELECTRA-small model had the highest performance for symptom identification at the token level (ie, at the individual symptom level), with an F1 of 0.87 and a processing time of 3.95 seconds per note. For the 10 most common symptoms in the test data set, the F1 score ranged from 0.98 for anxious to 0.86 for fatigue. For external validation of the same symptoms, the note-level performance ranged from F1 = 0.97 for diarrhea and dizziness to F1 = 0.73 for swelling. Training a deep learning model to identify a wide range of electronic health record-documented symptoms relevant to cancer care is feasible. This approach could be used at the health system scale to complement to electronic PROs.

Normal Tissue Injury Induced by Photon and Proton Therapies: Gaps and Opportunities.

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RTwith passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

Congruence of patient- and clinician-reported toxicity in women receiving chemotherapy for early breast cancer.

The National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, collected alongside the clinician-reported Common Terminology Criteria for Adverse Events, enables comparisons of patient and clinician reports on treatment toxicity. In a multisite study of women receiving chemotherapy for early-stage breast cancer, symptom reports were collected on the same day from patients and their clinicians for 17 symptoms; their data were not shared with each other. The proportions of moderate, severe, or very severe patient-reported symptom severity were compared with the proportions of clinician-rated grade 2, 3, or 4 toxicity. Patient-clinician agreement was assessed via κ statistics. Chi-square tests investigated whether patient characteristics were associated with patient-clinician agreement. Among 267 women, the median age was 58years (range, 24-83years), and 26% were nonwhite. There was moderate scoring agreement (κ=0.413-0.570) for 53% of symptoms, fair agreement for 41% (κ=0.220-0.378), and slight agreement for 6% (κ=0.188). For example, patient-reported and clinician-rated percentages were 22% and 8% for severe or very severe fatigue, 41% and 46% for moderate fatigue, 32% and 39% for mild fatigue, and 6% and 7% for none. Clinician severity scores were lower for nonwhite patients in comparison with white patients for peripheral neuropathy, nausea, arthralgia, and dyspnea. Although clinician reporting of symptoms is common practice in oncology, there is suboptimal agreement with the gold standard of patient self-reporting. These data provide further evidence supporting the integration of patient-reported outcomes into oncological clinical research and clinical practice to improve monitoring of symptoms as well as timely interventions for symptoms.

Reliability and Validity of the Korean Language Version of the U.S. National Cancer Institute's Patient-Reported Outcomes Common Terminology Criteria for Adverse Events

ContextTo improve precision and accuracy in the capture of symptomatic adverse events (AEs) by self-report, the U.S. National Cancer Institute has developed a library of 124 patient-reported outcome (PRO) items reflecting 78 symptomatic AEs drawn from the Common Terminology Criteria for Adverse Events (CTCAE). The PRO-CTCAE™ item library has been translated and linguistically validated in the Korean language. ObjectivesThe aim of this study was to examine the psychometric properties of PRO-CTCAE-Korean. MethodsPRO-CTCAE-Korean and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Core 30 (QLQ-C30) were administered to 1358 Korean-speaking individuals receiving treatment for cancer at two medical centers in Korea (mean age 55.1 years; SD ±11.9; 60% females; and 61% high school education or less). A subset of 82 study participants completed the same two measures on a second occasion approximately three days later. ResultsCorrelations between PRO-CTCAE-Korean and conceptually relevant QLQ-C30 items were all greater than r = 0.30 except for headache severity. Most PRO-CTCAE-Korean items correlated at least moderately with QLQ-C30 summary scores. Monotonically decreasing total QLQ-C30 scores were observed across worsening levels of symptom frequency, severity, and interference (all P < 0.01), indicating that PRO-CTCAE-Korean response choices are well comprehended, and that PRO-CTCAE-Korean discriminates respondents with different levels of symptom burden. PRO-CTCAE-Korean also demonstrated generally acceptable to good reliability (88% of items intraclass correlation coefficient >0.50). ConclusionPRO-CTCAE-Korean is a reliable and valid instrument to capture symptomatic AEs by self-report in patients on cancer clinical trials.

Patient free text reporting of symptomatic adverse events in cancer clinical research using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Patient free text reporting of symptomatic adverse events in cancer clinical research using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Electronic versus paper-pencil methods for assessing chemotherapy-induced peripheral neuropathy.

The aim of this study is to examine and compare with the validated, paper/pencil European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy Scale (QLQ-CIPN20), the psychometric properties of three electronically administered patient reported outcome (PRO) measures of chemotherapy-induced peripheral neuropathy (CIPN): (1) the two neuropathy items from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), (2) the QLQ-CIPN20, and (3) the 0-10 Neuropathy Screening Question (NSQ). We employed a descriptive, cross-sectional design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy at an academic hospital. Participants completed the paper/pencil QLQ-CIPN20 and electronic versions of the QLQ-CIPN20, PRO-CTCAE, and NSQ. Internal consistency reliability, intraclass correlation, and concurrent and discriminant validity analyses were conducted. The alpha coefficients for the electronic QLQ-CIPN20 sensory and motor subscales were 0.76 and 0.75. Comparison of the electronic and paper/pencil QLQ-CIPN20 subscales supported mode equivalence (intraclass correlation range >0.91). Participants who reported the presence of numbness/tingling via the single-item NSQ reported higher mean QLQ-CIPN20 sensory subscale scores (p<0.001). PRO-CTCAE neuropathy severity and interference items correlated well with the QLQ-CIPN20 electronic and paper/pencil sensory (r=0.76; r=0.70) and motor (r=0.55; r=0.62) subscales, and with the NSQ (r=0.72; r=0.44). These data support the validity of the electronically administered PRO-CTCAE neuropathy items, NSQ, and QLQ-CIPN20 for neuropathy screening in clinical practice. The electronic and paper/pencil versions of the QLQ-CIPN can be used interchangeably based on evidence of mode equivalence.

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66years; 47% female; 84% white). Median time for CRAs to learn the system was 60minutes (range, 30-240minutes), and median time for CRAs to teach a patient to self-report was 10minutes (range, 2-60minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.

Danish Translation and Linguistic Validation of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

ContextThe Common Terminology Criteria for Adverse Events (CTCAE) is the basis for standardized clinician-based grading and reporting of adverse events in cancer clinical trials. The U.S. National Cancer Institute has developed the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE) to incorporate patient self-reporting of symptomatic adverse events. ObjectivesThe aim of the study was to translate and linguistically validate a Danish language version of PRO-CTCAE. MethodsThe U.S. English language PRO-CTCAE was translated into Danish using forward and backward procedures with reconciliation. The linguistic validity of the PRO-CTCAE Danish was examined in two successive rounds of semistructured cognitive interviews in a sample of 56 patients equally distributed by gender and cancer type (prostate, head and neck, lung, breast, gynecological, gastrointestinal, and hematological cancer), and who were currently undergoing cancer treatment. ResultsIn the first round of linguistic validation (n = 42), the phrasing of five symptomatic toxicities was adjusted, and the refined phrasing was retested in a second round of interviews (n = 14). Agreement about phrasing that was both culturally acceptable and semantically comprehensible was achieved in the second round. Statements from participants describing the meaning of the PRO-CTCAE symptomatic toxicities support conceptual equivalence to the U.S. English language version. ConclusionAvailability of the NCI PRO-CTCAE in languages beyond English will support international congruence in self-reporting of side effects of cancer treatment. A rigorous methodology was used to develop the Danish language version of PRO-CTCAE. Results provide preliminary support for the use of PRO-CTCAE in cancer clinical trials that include Danish speakers.

Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Danish Translation and Linguistic Validation of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Danish Translation and Linguistic Validation of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE).

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.

Cognitive interviewing of the US National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library. Cognitive interviews were conducted among patients undergoing chemotherapy or radiation therapy at multiple sites to evaluate comprehension, memory retrieval, judgment, and response mapping related to AE terms (e.g., nausea), attribute terms (regarding frequency, severity, or interference), response options, and recall period. Three interview rounds were conducted with ≥20 patients completing each item per round. Items were modified and retested if ≥3 patients exhibited cognitive difficulties or if experienced by ≤25% patients. One hundred and twenty-seven patients participated (35% ≤high school, 28% non-white, and 59% female). Most AE terms (63/80) generated no cognitive difficulties. The remaining 17 were modified without further difficulties by Round 3. Terms were comprehended regardless of education level. Attribute terms and response options required no modifications. Patient adherence to recall period (7 days) was improved when the reference period was incorporated. This study provides evidence confirming comprehension of the US English language versions of items in the PRO-CTCAE library for measuring symptomatic AEs from the patient perspective within the context of cancer treatment. Several minor changes were made to the items to improve item clarity, comprehension, and ease of response judgment. This study helps to establish the content validity of PRO-CTCAE items for patient reporting of AEs during cancer treatment.

Supporting Quality and Patient Safety in Cancer Clinical Trials

Adverse event (AE) reporting is a critical component of all cancer clinical trials, and the National Cancer Institute's Common Terminology Criteria for Adverse Events™ (CTCAE) is the primary system used by clinicians to describe the severity of AEs. The National Cancer Institute's Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE) assesses patient self-reports of symptoms using a Web-based system that can be incorporated into all cancer clinical trials. Oncology clinical trial nurses are responsible for the protection and safety of patients enrolled in cancer trials and, therefore, should develop an understanding of PRO-CTCAE.