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Fatigue is the most prevalent symptom of cancer and its treatments. Changes in the intestinal microbiome have been identified in chronic fatigue syndrome and other neuropsychiatric disorders, and cancer patients. However, the association between intestinal microbiome and fatigue in patients with advanced cancers has not been evaluated. Understanding the connection between intestinal microbiome and fatigue will provide interventional and therapeutic opportunities to manipulate the microbiome to improve fatigue and other patients’ reported outcomes. In this project, we aimed to identify associations between microbiome composition and fatigue in advanced cancer patients. In this cross-sectional observational study at a tertiary cancer care center, we included 88 patients with advanced, metastatic, unresectable cancers who were in a washout period from chemotherapy. We measured fatigue using the MD Anderson Symptom Inventory—Immunotherapy fatigue score, and used 16srRNA to analyze intestinal microbiome. Using correlation analysis we found that Eubacterium hallii was negatively associated with fatigue severity scores (r = − 0.30, p = 0.005), whereas Cosenzaea was positively associated with fatigue scores (r = 0.33, p = 0.0002). We identified microbial species that exhibit distinct composition between high-fatigued and low-fatigued cancer patients. Further studies are warranted to investigate whether modulating the microbiome reduces cancer patients’ fatigue severity and improves their quality of life.

Purpose Acute radiation-induced esophagitis (ARIE) leads to treatment delays, decreased quality of life (QOL), and secondary adverse events such as weight loss. Grade 3 ARIE occurs in 15%–30% of patients undergoing radiotherapy to the esophagus, leading to disruption or discontinuation of treatment. The purpose of this study was to assess the effects of glutamine, a common nutritional supplement, on ARIE in patients with thoracic malignancies. Patients and methods This double-blind, placebo-controlled trial enrolled patients with advanced thoracic malignancies receiving concurrent chemotherapy/radiotherapy or radiotherapy alone, with radiation doses to the esophagus ≥45 Gy. Patients were randomized (1:1) to receive 4 g of glutamine or glycine placebo twice daily. The primary objective was to determine whether glutamine decreases the severity of ARIE in these patients. Secondary objectives included assessment of the effects of glutamine on other measures of ARIE, weight, symptom burden measure assessed by the MD Anderson Symptom Inventory (MDASI-HN) questionnaire and the toxicity profile of glutamine. Results At the time of interim analysis, 53 patients were enrolled: 27 in the glutamine arm and 26 in the placebo arm. There was no difference in the incidence of esophagitis in the first 6 weeks of radiotherapy between the glutamine and placebo arms (74% versus 68%; P = 1.00). There were no significant differences between the two arms for time to onset of esophagitis. The duration of ARIE was shorter (6.3 versus 7.1 weeks; P = 0.54) and median weight loss was lower (0.9 kg versus 2.8 kg; p = 0.83) in the glutamine arm versus the placebo arm. The groups differ significantly in core symptom severity (2.1 vs 1.5, p

Objective The MD Anderson Symptom Inventory for Brain Tumor (MDASI-BT) module is a widely used instrument for measuring symptom burden and interference of daily activities in brain tumor patients. This study aims to develop and validate its Japanese version (MDASI-BT-Japanese). Methods Following forward and backward translation of the original MDASI-BT into Japanese, understandability and feasibility were assessed by cognitive debriefing. Subsequently, patients with brain tumors were asked to fill out MDASI-BT-Japanese and European Quality of Life-5 Dimensions (EQ-5D). Feasibility, reliability and validity of MDASI-BT-Japanese were assessed. Results Cognitive debriefing confirmed overall ease of completion and good understandability. The study population composed of 140 patients with brain tumors (most commonly gliomas). The mean symptom severity score and mean interference score were 1.9 ± 1.7 and 2.8 ± 2.7, respectively. The top items included distress and drowsiness for symptom severity and general activity and work for interference. The median time required was 4 minutes (range, 0.5–30), and missing values were seen in 1%. Internal consistency was proven by excellent Cronbach’s coefficient alpha (0.94 for symptom severity, 0.92 for interference). Test–retest reliability was assessed with acceptable intra-class correlation coefficient (mean, 0.76). Correlation efficient ranged between 0.7 and 0.9 for convergent validity. Known-group validity was confirmed by significantly different mean symptom severity score and mean interference score among patients with different performance status. As evidence of concurrent validity, MDASI-BT-Japanese correlated with EQ-5D in the hypothesized magnitude and direction. Conclusions The newly developed MDASI-BT-Japanese has demonstrated feasibility, reliability and validity in evaluation of clinical benefit in Japanese-speaking brain tumor patients.

Purpose Body image (BI) is an important issue for cancer patients, as patients with BI concerns are susceptible to depression, anxiety, difficulty coping, and poor quality of life (QoL). While this concern has been documented in patients with other malignancies, no data exists of this QoL issue in patients with primary brain tumors (PBT). Methods A cross-sectional survey of 100 PBT patients was conducted on an IRB approved prospective protocol using structured questionnaires. Participants completed the body image scale (BIS), Appearance Scheme Inventory Revised (ASI-R), MD Anderson Symptom Inventory Brain Tumor (MDASI-BT), and Patient-Reported Outcomes Measurement Information System (PROMIS) Depression, Anxiety, and Psychosocial Impact Positive measures. Results The prevalence of clinically significant body image dissatisfaction (BIS ≥ 10) was 28% (95% CI 19–37%), median BIS score was 5 (range 0–27). The median ASI-R composite score was 2.9 (range 1.5–4.7). BIS was significantly correlated with the ASI-R (r = 0.53, 95% CI 0.37 to 0.65). The mean PROMIS Depression score was 48.4 (SD = 8.9), PROMIS Anxiety score was 49.4 (SD = 9.9), and PROMIS Psychosocial Illness Impact Positive score was 48.9 (SD = 9.7). BIS was significantly correlated with age, and trended with BMI and sex. The PROMIS Psychosocial Illness Impact Positive and PROMIS Anxiety scores were the most strongly related to BIS. Conclusions This study, the first to explore altered body image in PBT patients, revealed clinically significant body image dissatisfaction in nearly 1/3 of patients, similar to other malignancies. These findings underscore the potential contribution of disease and treatment-related body image concerns on psychosocial wellbeing in patients with PBT.

Background Cancer pain, one of the most common symptoms for patients with advanced cancer, is often refractory to maximal medical therapy. A controlled clinical trial is needed to provide definitive evidence to support the use of ablative procedures such as cordotomy for patients with medically refractory cancer pain. Objective To assess the efficacy of cordotomy for patients with unilateral advanced cancer pain using a controlled clinical trial study design. The secondary objectives are to define the patient experience of cordotomy for medically refractory cancer pain as well as to determine the utility of magnetic resonance imaging as a non-invasive biomarker for successful cordotomy. Methods We will undertake a single-institution, double-blind, sham-controlled clinical trial of cordotomy in patients with refractory cancer pain. Patients in the cordotomy arm will undergo a percutaneous computed tomography-guided cordotomy at C1-C2, while patients in the control arm will undergo a similar procedure where the needle will not penetrate the thecal sac. The primary endpoint will be the reduction in pain intensity, as measured by the Edmonton Symptoms Assessment Scale. Expected outcomes We expect that patients randomized to cordotomy will have a significantly greater reduction in pain intensity than those patients randomized to the control surgical intervention. Discussion This randomized clinical trial comparing cordotomy with a control intervention will provide the level of evidence necessary to determine whether cordotomy should be the standard of care intervention for patients with advanced cancer pain.

Purpose In patients with non-small cell lung cancer (NSCLC), concurrent chemoradiation therapy (CRT) exacerbates a cluster of difficult-to-manage symptoms, especially cancer-related fatigue. Minocycline is a readily available, low-cost antibiotic with antiinflammatory properties. We conducted a phase 2 randomized, double-blinded, placebo-controlled trial to investigate the effect of minocycline in reducing CRT-symptom burden in NSCLC. Methods and Materials Patients with NSCLC scheduled to receive CRT provided consent and were randomized to receive either minocycline (100 mg twice daily) or a matching placebo during 6 to 7 weeks of CRT. Patient-reported fatigue and other symptoms were assessed on MD Anderson Symptom Inventory weekly from the start of CRT for 12 weeks. The primary outcome was 12-week (±2 days) area under the curve for symptom burden, which was compared between treatment groups. Results Forty of 49 enrolled patients (80%) were evaluable (19 on minocycline and 21 on placebo). There were no grade 3 + adverse events related to the study medication. Fatigue was significantly reduced in the minocycline group compared with placebo group during the 12-week trial period (area under the curve = 31.2 ± 14.2 vs 45.0 ± 20.9, P = .011), with a large effect size (Cohen’s d = 0.77). Pain (Cohen’s d = 0.54) and shortness of breath (Cohen’s d = 0.55) were also significantly reduced in the minocycline group (all P Conclusions Minocycline during CRT for NSCLC was feasible, had a low toxicity profile, and yielded a clinically and statistically significant positive signal in reducing symptom burden related to NSCLC and CRT. This study is a proof of concept so a larger trial in CRT patients is warranted.

Patients with rare solid tumors treated on early phase trials experience toxicities from their tumors and treatments. However, limited data exist to describe the detailed symptom burden suffered by these patients, particularly those with rare solid tumors treated with immunotherapy. We performed a prospective longitudinal study to capture patient-reported symptom burden. Patients completed the validated MD Anderson Symptom Inventory (MDASI)—Immunotherapy with 20 symptoms including 7 immunotherapy-specific items and 6 interference items at baseline and weekly thereafter for up to 9 weeks. Symptoms and interference were rated on 0–10 scales (0 = none or no interference, 10 = worst imaginable or complete interference). Group-based trajectory modelling determined higher and lower symptom groups. A total of 336 MDASI questionnaires were completed by 53 patients (mean age 55.4y, 53% male) with advanced rare cancers receiving pembrolizumab in a Phase II clinical trial. Symptoms reported as most severe over the course of the treatment over 9 weeks were fatigue [mean (M) = 3.8, SD = 2.3], pain (M = 3.7, SD = 2.9), disturbed sleep (M = 2.7, SD = 2.3), drowsiness (M = 2.6, SD = 2.0) and lack of appetite (M = 2.5, SD = 2.1). Pain in the abdomen (M = 2.2, SD = 2.4), rash (M = 1.1, SD = 1.8) and diarrhea (M = 0.9, SD = 1.5) were less severe. Interference with walking was rated the highest (M = 3.4, SD = 2.8) and relations with others was rated the lowest (M = 2.1, SD = 2.6). Using a composite score based on the five most severe symptoms (fatigue, pain, lack of appetite, feeling drowsy and sleep disturbance), 43% were classified into the high symptom burden group. Using a score based on immunotherapy-specific symptoms (e.g., rash, diarrhea) 33% of patients were included in the high symptom group. Symptom burden stayed relatively stable in the high- and low-symptom burden patient groups from baseline through 9 weeks. Some patients with rare malignancies experienced high symptom burden even at baseline. In patients with rare cancers, symptom trajectories stayed relatively stable over nine weeks of treatment with pembrolizumab.Trial registration: ClinicalTrials.gov identifier: NCT02721732.

CONTEXT: Increasing numbers of oncology therapies are being approved based on early-phase single-arm studies. Yet, little is known regarding the use of patient-reported outcomes in single-arm oncology trials testing novel therapies. OBJECTIVES: We examined patient-reported symptom severity and symptom interference with activity- (WAW: work, general activity, walking) and mood-(REM: relations with others, enjoyment of life, mood) related functioning, and their association with factors known to influence symptom severity reporting in early-phase clinical trials clinic patients. METHODS: Patients completed the validated MD Anderson Symptom Inventory, containing 13 severity items and six interference items, each rated on a 0–10 scale (higher scores=worse symptom severity/interference). Performance status (ECOG-PS) and age were ascertained. Multiple linear regression was performed. RESULTS: In 248 phase I patients (51% female, 90% ECOG 0–1, and 74% ≤65 years), 67% of patients had ≥seven concurrent symptoms of any severity level, and 51% of patients described ≥three concurrent symptoms as moderate-to-severe (severity rating≥5). Composite symptom severity, WAW and REM were worse in patients with ECOG-PS≥2 vs. 0–1, and worse in patients with ECOG-PS=1 than in patients with ECOG-PS=0. Compared with patients over 65y, adolescent and young adult (AYA) patients (18y-39y) and patients aged 40y to 65y had worse composite symptom severity. As expected, being employed full-time/retired was associated with better symptom profiles in phaseI patients. CONCLUSION: The variation of symptom burden by performance status and age suggest that these factors need to be considered in the design of early-phase trials, particularly if patient-reported symptoms are used as primary/secondary/exploratory endpoints.

Fatigue is the most reported and most distressing symptom among patients with cancer. However, no questionnaire that measures fatigue and fatigue interference with life has been translated into Arabic.This study aimed to translate and validate the Arabic version of the Brief Fatigue Inventory (BFI-A).The BFI was translated into Arabic using the forward-backward translation technique. This cross-sectional study collected data from cancer patients through a self-administered questionnaire that included the BFI-A, Insomnia Severity Index (ISI), Zung Depression Scale (ZDS), MD Anderson Symptom Inventory total score (MDASI), and Medical Outcome Study Short Form 36 (SF-36) Vitality Subscale. Descriptive and inferential statistics were used including mean, standard deviation, internal consistency, and correlation coefficient using Pearson's correlation.A total of 79 patients were recruited in Amman, Jordan, in 2015. Mean of the total BFI-A was 4.01 (2.4), showing that 83.5% had nonsevere fatigue. Cronbach's α coefficient of the BFI-A was 0.93. The correlations between total BFI-A scores and BFI-A items were significant (P0.05) and ranged from 0.75 to 0.86. BFI-A showed a significant correlation (P0.05) with the following tools: ISI = 0.70, ZDS = 0.69, MDASI = 0.75, and SF-36 Vitality Subscale = -0.57.This study suggests that the BFI-A is a reliable and valid tool to assess fatigue among Arab cancer patients.دراسة للتحقق من النسخة العربية لمقياس التعب الوجيز (BFI–A).خالد سليمان، محمود الكلالدة، لؤي أبو شحرور، برنيس ييتس، آن بيرجر، تيتو مندوزا، ملكة ملك، أيمن بني سلامة، شارلز كليلاند، أحمد المنشاوي.يُعدّ التعب أكثر الأعراض التي يشكو منها مرضى السرطان وأكثرها تكديراً لهم. ومع ذلك، لم يُترجَم إلى اللغة العربية أي استبيان يقيس التعب ومدى إعاقته لحياة المريض.كانت هذه الدراسة تهدف إلى ترجمة "مقياس التعب الوجيز" (BFI-A) والتحقق من نسخته العربية.تُرجم المقياس إلى اللغة العربية بطريقة الترجمة المباشرة والعكسية. وجمعت هذه الدراسة المقطعية بيانات من مرضى السرطان من خلال استبيان ملأه المرضى بأنفسهم وتضمَّن "مقياس التعب الوجيز" (BFI-A)، و"مؤشر شدة الأرق" (ISI)، و"مقياس زونج للاكتئاب" (ZDS)، ومجموع درجات "قائمة أعراض" (MDASI)، و"المقياس الفرعي للحيوية في دراسة النتائج الطبية المختصرة المكونة من 36 بنداً" (SF-36). واستُخدمت إحصاءات وصفية واستنتاجية، منها المتوسط، والانحراف المعياري، والاتساق الداخلي، ومعامل الارتباط باستخدام ارتباط بيرسون.استعين اجمالا بتسعة وسبعين مريضا في مدينة عمان الاردنية عام 2015. وكان متوسط مجموع درجات « مقياس التعب الوجيز (BFI-A) هو 4.1)، مما يدل على ان 83.5٪ كانوا يعانون تعبا غير شديد. وكان معامل كرونباخ الفا لمقياس التعب الوجيز هو 0.93. وكانت علاقات الترابط بين مجموع درجات « مقياس التعب الوجيز » وبنود هذا المقياس علاقات وثيقة (0.05P)، وتراوحت من 0.75 الى 0.86. وتبين وجود ترابط وثيق (0.05P) بين « مقياس التعب الوجيز BFI-A)» والمقاييس التالية: مؤشر شدة الارق (0.70) (ISI)، ومقياس زونج للاكتئاب (0.69) (ZDS)، وقائمة الاعراض (0.75) (MDASI)، والمقياس الفرعي للحيوية في دراسة النتائج الطبية المختصره المكونه من 36 بندا (0.57-) (SF-36).تشير هذه الدراسة إلى أن (BFI-A) أداة موثوقة وصالحة لتقييم التعب لدى مرضى السرطان الناطقين بالعربية.Étude de validation de la version arabe du Brief Fatigue Inventory (BFI-A).La fatigue est le symptôme le plus fréquent et le plus éprouvant chez les patients atteints de cancer. Cependant, aucun questionnaire mesurant la fatigue et son interférence avec la vie quotidienne n’a été traduit en arabe.La présente étude visait à traduire et à valider la version arabe du Brief Fatigue Inventory (BFI-A).Le BFI a été traduit en arabe à l’aide de la technique de traduction/rétro-traduction. La présente étude transversale a permis de collecter des données de patients atteints de cancer en recourant à un auto-questionnaire comprenant le BFI-A, l’index de Sévérité de l’Insomnie (ISI), l’échelle d’auto-évaluation de la dépression de Zung (ZDS), l’inventaire des symptômes M.D. Anderson (MDASI) et la sous-échelle vitalité de la forme abrégée du questionnaire généraliste SF-36 (qualité de vie) du Medical Outcome Study. Des statistiques descriptives et inférentielles ont été utilisées, y compris la moyenne, l’écart type, la cohérence interne et le coefficient de corrélation de Pearson.79 patients au total ont été recrutés à Amman (Jordanie) en 2015. La moyenne totale du BFI-A était de 4,01 (2,4), indiquant que 83,5 % des patients présentaient un état de fatigue non sévère. Le coefficient alpha de Cronbach du BFI-A était de 0,93. Les corrélations entre les scores totaux et les rubriques du BFI-A étaient significatives (p0,05) et étaient comprises entre 0,75 et 0,86. Le BFI-A affichait une corrélation importante (p0,05) avec les instruments suivants : ISI = 0,70 ; ZDS = 0,69 ; MDASI = 0,75 et la sous-échelle vitalité du SF-36 (qualité de vie) = −0,57.La présente étude suggère que le BFI-A est un outil valable et fiable pour évaluer la fatigue chez les patients arabes atteints de cancer.

Advanced prostate cancer (PCa) patients with bone metastases are treated with androgen pathway directed therapy (APDT). However, this treatment invariably fails and the cancer becomes castration resistant. To elucidate resistance mechanisms and to provide a more predictive pre-clinical research platform reflecting tumor heterogeneity, we established organoids from a patient-derived xenograft (PDX) model of bone metastatic prostate cancer, PCSD1. APDT-resistant PDX-derived organoids (PDOs) emerged when cultured without androgen or with the anti-androgen, enzalutamide. Transcriptomics revealed up-regulation of neurogenic and steroidogenic genes and down-regulation of DNA repair, cell cycle, circadian pathways and the severe acute respiratory syndrome (SARS)-CoV-2 host viral entry factors, ACE2 and TMPRSS2. Time course analysis of the cell cycle in live cells revealed that enzalutamide induced a gradual transition into a reversible dormant state as shown here for the first time at the single cell level in the context of multi-cellular, 3D living organoids using the Fucci2BL fluorescent live cell cycle tracker system. We show here a new mechanism of castration resistance in which enzalutamide induced dormancy and novel basal-luminal-like cells in bone metastatic prostate cancer organoids. These PDX organoids can be used to develop therapies targeting dormant APDT-resistant cells and host factors required for SARS-CoV-2 viral entry.

Objectives This study sought to evaluate advanced psychometric properties of the 15-item Economic Strain and Resilience in Cancer (ENRICh) measure of financial toxicity for cancer patients. Methods We surveyed 515 cancer patients in the greater Houston metropolitan area using ENRICh from March 2019 to March 2020. We conducted a series of factor analyses alongside parametric and non-parametric item response theory (IRT) assessments using Mokken analysis and the graded response model (GRM). We utilized parameters derived from the GRM to run a simulated computerized adaptive test (CAT) assessment. Results Among participants, mean age was 58.49 years and 278 (54%) were female. The initial round factor analysis results suggested a one-factor scale structure. Negligible levels of differential item functioning (DIF) were evident between eight items. Three items were removed due to local interdependence (Q3>+0.4). The original 11-point numerical rating scale did not function well, and a new 3-point scoring system was implemented. The final 12-item ENRICh had acceptable fit to the GRM (p Conclusion These CAT and 4-item versions provide options for quick screening in clinical practice and low-burden assessment in research.

Background Professional organizations recommend the use of shared decision‐making (SDM) in supporting patients’ decisions about lung cancer screening (LCS). The objective of this study was to assess the impact of the SDM process on patient knowledge about LCS, decisional conflict, intentions to adhere to screening recommendations, and its role in how the patient made the final decision. Methods This study surveyed patients screened for lung cancer within 12 months of the survey, recruited from two academic tertiary care centers in the South Central Region of the U.S. (May to July 2018). Results Two hundred and sixty‐four patients completed the survey (87.9% White, 52% male, and mean age of 64.81). Higher SDM process scores (which indicates a better SDM process reported by patients) were significantly associated with greater knowledge of LCS (b = 0.17 p

Background: The indications for intracranial pressure (ICP) monitoring in patients with acute brain injury and the effects of ICP on patients’ outcomes are uncertain. The aims of this study were to describe current ICP monitoring practises for patients with acute brain injury at centres around the world and to assess variations in indications for ICP monitoring and interventions, and their association with long-term patient outcomes. Methods: We did a prospective, observational cohort study at 146 intensive care units (ICUs) in 42 countries. We assessed for eligibility all patients aged 18 years or older who were admitted to the ICU with either acute brain injury due to primary haemorrhagic stroke (including intracranial haemorrhage or subarachnoid haemorrhage) or traumatic brain injury. We included patients with altered levels of consciousness at ICU admission or within the first 48 h after the brain injury, as defined by the Glasgow Coma Scale (GCS) eye response score of 1 (no eye opening) and a GCS motor response score of at least 5 (not obeying commands). Patients not admitted to the ICU or with other forms of acute brain injury were excluded from the study. Between-centre differences in use of ICP monitoring were quantified by using the median odds ratio (MOR). We used the therapy intensity level (TIL) to quantify practice variations in ICP interventions. Primary endpoints were 6 month mortality and 6 month Glasgow Outcome Scale Extended (GOSE) score. A propensity score method with inverse probability of treatment weighting was used to estimate the association between use of ICP monitoring and these 6 month outcomes, independently of measured baseline covariates. This study is registered with ClinicalTrial.gov, NCT03257904. Findings: Between March 15, 2018, and April 30, 2019, 4776 patients were assessed for eligibility and 2395 patients were included in the study, including 1287 (54%) with traumatic brain injury, 587 (25%) with intracranial haemorrhage, and 521 (22%) with subarachnoid haemorrhage. The median age of patients was 55 years (IQR 39–69) and 1567 (65%) patients were male. Considerable variability was recorded in the use of ICP monitoring across centres (MOR 4·5, 95% CI 3·8–4·9 between two randomly selected centres for patients with similar covariates). 6 month mortality was lower in patients who had ICP monitoring (441/1318 [34%]) than in those who were not monitored (517/1049 [49%]; p

PURPOSE: Local/systemic symptoms during cancer therapy may be exacerbated by dysregulated inflammation and its downstream toxic effects. Minocycline can suppress proinflammatory cytokine release; therefore, we investigated its potential to reduce patient-reported symptom severity during radiotherapy (RT) for head and neck cancer (HNC). METHODS: Eligible patients for this blinded, placebo–controlled trial were adults with T0–3, N-any, and M0 HNC receiving single-modality RT. Participants were randomized 1:1 to either minocycline (200 mg/day) or placebo during RT. The primary endpoint was the area under the curve (AUC) of 5 prespecified symptoms (pain, fatigue, disturbed sleep, poor appetite, difficulty swallowing/chewing) during RT, assessed with the MD Anderson Symptom Inventory for HNC (MDASI-HN). RESULTS: We analyzed data from 20 evaluable patients per arm. Overall, 75% had oropharyngeal cancer and 78% were male. No grade 3+ adverse events potentially related to study medication were observed. Two minocycline patients required a feeding tube during RT vs 5 placebo patients (P = 0.21). The average daily AUC during RT for the 5 MDASI-HN symptoms was 3.1 (SD =1.0) for minocycline and 3.7 (SD = 1.7) for placebo (P = 0.16); the 0.37 effect size was less than our 0.70 target. AUC comparisons for several individual symptoms and symptom interference favored minocycline but were not statistically significant. The greatest numerical differences occurred for systemic symptoms, larger toward treatment end, and in early post-RT recovery. CONCLUSIONS: Minocycline was feasible, well tolerated, and achieved a positive signal toward reducing patient-reported symptom severity during RT for HNC, particularly for systemic symptoms. This justifies additional study and informs future trial design.

IntroductionImmunotherapies have revolutionized the treatment of various cancers, but little is known about their symptomatic toxicity. Assessing these symptoms is best accomplished by asking the patients themselves. However, such reports are subjective and may face challenges as bonafide scientific data. Demonstrating the validity of symptom assessment tools, mainly through the reduction of measurement errors, has the potential to improve patient care if these tools are widely adopted. To that end, we present herein the psychometric properties of the Immunotherapy for Early-Phase Trials module of the MD Anderson Symptom Inventory (MDASI-Immunotherapy EPT) in patients receiving various immunotherapies in early phase trials at a major cancer center.MethodsOne hundred forty-five patients completed the inventory at baseline, with 85 of them also doing so after 9 weeks of treatment. The mean (±SD) age of the patients was 57.0±12.9 years. Also, 56% of the patients were women, 79% identified as white, and 49% had at least some college education.ResultsThe internal consistency reliability of the MDASI-Immunotherapy EPT was excellent, as the Cronbach’s alphas for all of its subscales were at least 0.88 (range 0.88–0.95). Known-group validity based on Eastern Cooperative Oncology Group performance status groupings was excellent at 9 weeks after the start of an immunotherapy trial for the MDASI-Immunotherapy EPT severity (effect size, 0.96) and interference (effect size, 0.82) subscales. We found substantial changes in the symptom items difficulty remembering (effect size, −0.85), fever and/or chills (effect size, −0.63), disturbed sleep (effect size, −0.52), diarrhea (effect size, −0.42), and swelling of hands, legs, or feet (effect size, −0.39).ConclusionsIn conclusion, the MDASI-Immunotherapy EPT is a valid, reliable, and sensitive tool for measuring symptomatic toxicity.

Objective: To estimate the prevalence of depression and abuse and identify the associated factors in medical interns in Peruvian hospitals. Methods: We conducted a multicentre, cross-sectional and analytical study during the months of March to May 2016. We included medical interns from 18 Peruvian hospitals, in Lima and provinces. We used a survey that included sociodemographic data and a scale to measure the perception of abuse (psychological, physical and sexual). In addition, we used the Spanish version of the PHQ-9 to evaluate depression. We used Poisson regression with robust variances to calculate prevalence ratios (PRs). Results: A total of 402 medical interns participated in the study, the median age was 25 [IQR: 21-33], and 52.7% were male. Moreover, 25.4% of them suffered from depression. In the adjusted model, the variables associated with depression were age (PRa = 1.15), the number of hours they sleep per day (PRa = 1.23), being a woman (PRa = 3.33), performing the internship in a province (PRa = 0.25), studying at a public university (PRa = 0.64), living with parents (PRa = 0.65) or alone (PRa = 0.33), and having perceived some type of abuse (PRa = 1.07). Conclusions: A quarter of surveyed medical interns had depression. Early screening is necessary to identify perceived abuse and other triggering depression factors that may adversely affect work performance and overall mental health during medical internships. RESUMEN Objetivo: Estimar la prevalencia de depresión y maltrato e identificar sus factores asociados en los internos de Medicina de los hospitales peruanos. Métodos: Estudio multicéntrico, transversal y analítico, llevado a cabo durante los meses de marzo a mayo de 2016. Conformaron la población los internos de Medicina en 18 sedes hospitalarias de Lima y provincias. Se aplicó una encuesta que incluía características sociodemográficas y una escala para medir la percepción de maltrato (psicológico, físico y sexual). Asimismo, para evaluar la depresión, se usó el cuestionario PHQ-9 en su versión en español. Se usó regresión de Poisson con varianzas robustas para calcular las razones de prevalencia (RP). Resultados: Participaron 402 internos de Medicina; la mediana de edad fue 25 [intervalo intercuartílico, 21-33] años y el 52,7% eran varones. Además, el 25,4% padecía depresión. En el modelo ajustado, las variables asociadas con padecer depresión son edad (RPa = 1,15), cuántas horas duermen durante el día (RPa = 1,23), ser mujer (RPa = 3,33), realizar el internado en provincia (RPa = 0,25), estudiar en una universidad pública (RPa = 0,64), vivir con sus padres (RPa = 0,65) o solo (RPa = 0,33) y percibir algún tipo de maltrato (RPa = 1,07). Conclusiones: La cuarta parte de los internos encuestados tenían depresión. Es necesario realizar un cribado temprano para identificar posibles maltratos percibidos y otros factores desencadenantes de depresión, y así evitar repercusiones negativas en el desempeño laboral y la salud mental general durante el internado médico.

PURPOSE: Symptom monitoring has demonstrated improved outcomes in patients with cancer, including quality of life, resource utilization, ability to continue treatment, and survival. The use of disease-specific patient-reported outcome (PRO) measures facilitates symptom monitoring. While the MD Anderson Symptom Inventory–Lung Cancer (MDASI-LC), a PRO measure of symptom burden in lung cancer, is psychometrically validated for use in patients with NSCLC, its content validity has not been verified through direct patient input. Our purpose is to describe the symptom experience of patients with NSCLC and to confirm that the MDASI-LC contains the key symptoms specific to NSCLC from the patient perspective. METHODS: Patients with NSCLC described their symptom experience in single qualitative interviews. Content analysis was used to define the content domain for a PRO measure of NSCLC symptom burden. RESULTS: Participants (N = 40) had a mean age of 66.1 years (standard deviation, 10.9 years); 60.0% were male, 77.5% were White, and 56.4% had stage IV disease. Thirty-two symptoms were described, with 6 reported by ≥ 20% of participants. Symptom variations were noted by treatment modality but not by stage of disease. Patients with NSCLC commonly reported shortness of breath, cough, distress, fatigue, pain, and constipation. In patients receiving chemotherapy, treatment-related symptoms, including neuropathy and sore mouth, were commonly noted. The presence of these symptoms resulted in interference with daily activities, relationships, life plans, treatment adherence, and mood. CONCLUSION: The symptoms included in the MDASI-LC are important components of the content domain of an NSCLC symptom burden measure. The presence of these symptoms affect daily life and, therefore, is of clinical consequence.

Treatment-induced peripheral neuropathy (TIPN) is a difficult problem experienced by patients with cancer that can interfere with their ability to receive optimal therapy. The Treatment-Induced Peripheral Neuropathy Scale (TNAS) is a patient-reported outcome (PRO) measure developed to assess TIPN symptom burden. However, PRO validation is an ongoing process. The aim of this qualitative study was to define the conceptual model, establish content domain validity, and refine items for the TNAS based on patient input. Patients who received bortezomib, oxaliplatin, or platinum–taxane combination therapy reported their experience of TIPN in single qualitative audiotaped interviews. Themes of the TIPN experience were identified by descriptive analysis of the transcribed interviews. Three groups of 10 patients each who had received bortezomib, oxaliplatin, or platinum–taxane combination therapy, for a total of 30 patients, reported their experiences. Two themes reported by patients were TIPN sensations and functional interference. Five sensations (numbness, tingling, pain, heat or burning, and coldness) and five functional impacts (using hands, walking, maintaining balance or falling, wearing shoes, and sleeping) were reported by at least 20% of patients and were selected for inclusion in the TNAS v3.0 for additional psychometric testing. The assessment of TIPN must be convenient, reliable, and practical for patients, who are the most reliable source of information about symptoms. The TNAS, developed with direct patient input, provides an easily administered and conceptually valid method of patient report of TIPN burden for use in research and practice.

PURPOSE: For treatment of choroidal melanoma, Palladium-103 ((103)Pd) and Ruthenium-106 ((106)Ru) plaque brachytherapy demonstrates reduced toxicity compared to the historical standard Iodine-125 ((125)I). No report has directly compared clinical outcomes between (103)Pd and (106)Ru, and reasons for selection of one over the other remain purely theoretical. MATERIALS/METHODS: Patients with choroidal melanoma with apical tumor height ≤ 5 mm were included. Patients from Emory University were treated with (103)Pd between 1993 and 2012. Patients from Cleveland Clinic were treated with (106)Ru between 2005 and 2010. Medical records were retrospectively reviewed. We compared post-treatment visual acuity (VA), toxicity, and oncologic outcomes. RESULTS: (103)Pd patients (n = 124) and (106)Ru patients (n = 42) had median follow up of 4.2 and 5.0 years, respectively. Radiation retinopathy-free survival was similar for both radioisotopes but (106)Ru had lower grades of retinopathy (p=0.006). (103)Pd was associated with worse VA preservation (≥20/40) by year 3 (OR 3.8, 95% CI 1.01–14.31, p=0.048). (103)Pd was associated with higher distant metastases-free survival (DMFS) in multivariate analysis (MVA) (HR 0.10, 95% CI 0.02–0.38, p

To identify a clinically meaningful cut-point for the single item dry mouth question of the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN).Head and neck cancer survivors who had received radiation therapy (RT) completed the MDASI-HN, the University of Michigan Hospital Xerostomia Questionnaire (XQ), and the health visual analog scale (VAS) of the EuroQol Five Dimension Questionnaire (EQ-5D). The Bayesian information criteria (BIC) were used to test the prediction power of each tool for EQ-5D VAS. The modified Breiman recursive partitioning analysis (RPA) was used to identify a cut point of the MDASI-HN dry mouth score (MDASI-HN-DM) with EQ-5D VAS, using a ROC-based approach; regression analysis was used to confirm the threshold effect size.Two-hundred seven respondents formed the cohort. Median follow-up from the end of RT to questionnaire completion was 88 months. The single item MDASI-HN-DM score showed a linear relationship with the XQ composite score (ρ = 0.80, p 0.001). The MDASI-HN-DM displayed improved model performance for association with EQ-5D VAS as compared to XQ (BIC of 1803.7 vs. 2016.9, respectively). RPA showed that an MDASI-HN-DM score of ≥6 correlated with EQ-5D VAS decline (LogWorth 5.5).The single item MDASI-HN-DM correlated with the multi-item XQ and performed favorably in the prediction of QOL. A MDASI-HN-DM cut point of ≥6 correlated with decline in QOL.

Pituitary adenoma invasion into the orbit is a rare phenomenon with only 22 cases, including the present case, in the literature. Our case is a 31-year-old man who presented with biopsy-proven atypical pituitary adenoma invading the right orbit after a prior resection. We compare his clinical course with previous cases and discuss clinical features, radiological features, management considerations, histologic features, and prognosis. Cases are organized by specific pituitary tumor type to aid in determining appropriate management. Early surgical intervention is the key, especially in the setting of pathologic features indicating aggressive tumor behavior or worsening visual function but is generally not indicated in prolactin-secreting adenomas that may respond to medical therapy. The role of radiation therapy is not fully established; however, it should be strongly considered in conjunction with or after surgery, especially in cases where complete resection is not achieved or histological and molecular analyses indicate a high likelihood of recurrence. More uniform and comprehensive data about management and outcomes are needed to determine the optimal treatment approach for this rare entity.

Background We aimed to provide a simple, descriptive health-status profile for cancer patients with bone metastases, based on the EuroQol EQ-5D, a tool commonly used to measure health utility scores, and to evaluate its association with the Brief Pain Inventory (BPI), a legacy pain-assessment tool. Although pain is one of five health-status dimensions measured by the EQ-5D, our understanding of how pain relates to the other EQ-5D dimensions is limited. Methods We derived data from 5500 patients with bone metastases who completed the EQ-5D and BPI. Regression analyses examined how BPI severity and interference scores correlated with EQ-5D utility scores and how BPI items associated with EQ-5D items, for the entire sample and by disease-type subgroup. Results Regardless of cancer site, the percentage of patients reporting moderate/severe problems in each of the five EQ-5D dimensions were pain/discomfort, 78%; usual activities, 58%; mobility, 55%; anxiety/depression, 57%; and self-care, 26%. BPI pain interference explained more of the variability in the EQ-5D utility scores than did pain severity (R2 = 41% vs. 34%). BPI worst pain, average pain, pain now, interference with general activity, and interference with work significantly predicted EQ-5D pain/discomfort, with odds ratio estimates

We present the first reported work that explores the potential of radiomics to predict patients who are at risk for developing immunotherapy-induced pneumonitis. Despite promising results with immunotherapies, immune-related adverse events (irAEs) are challenging. Although less common, pneumonitis is a potentially fatal irAE. Thus, early detection is critical for improving treatment outcomes; an urgent need to identify biomarkers that predict patients at risk for pneumonitis exists. Radiomics, an emerging field, is the automated extraction of high fidelity, high-dimensional imaging features from standard medical images and allows for comprehensive visualization and characterization of the tissue of interest and corresponding microenvironment. In this pilot study, we sought to determine whether radiomics has the potential to predict development of pneumonitis. We performed radiomic analyses using baseline chest computed tomography images of patients who did (N = 2) and did not (N = 30) develop immunotherapy-induced pneumonitis. We extracted 1860 radiomic features in each patient. Maximum relevance and minimum redundancy feature selection method, anomaly detection algorithm, and leave-one-out cross-validation identified radiomic features that were significantly different and predicted subsequent immunotherapy-induced pneumonitis (accuracy, 100% [p = 0.0033]). This study suggests that radiomic features can classify and predict those patients at baseline who will subsequently develop immunotherapy-induced pneumonitis, further enabling risk-stratification that will ultimately lead to better treatment outcomes.

Background The Brief Pain Inventory (BPI) is both a questionnaire and an outcome measure that is used widely in clinical trials to assess pain associated with many conditions. The BPI Short Form has been extensively translated into foreign languages. The aim of this study was to assess the validity and reliability of a Turkish Brief Pain Inventory Short Form (BPI-TR) to evaluate musculoskeletal pain. Methods In total, 297 patients with musculoskeletal pain participated in the study. Demographic characteristics and brief medical histories were recorded. Pain intensity was assessed using a visual analogue scale (VAS) and quality-of-life was assessed using the Short Form 36 (SF-36). Pain was evaluated using the BPI-TR in all patients. Internal consistency and test-retest analysis were used to assess reliability. The internal consistency of the scale items was assessed by calculating Cronbach's α value, which was expected to be > 0.7. The criterion validity of the BPI-TR was assessed by correlation with VAS scores. Results Pain intensity, pain interference, and other components of the Turkish version were consistent with validity thereof. Cronbach's α was 0.84 for pain intensity and 0.89 for pain interference. The extent of BPI-TR and VAS correlation was statistically significant. Conclusions The BPI-TR may be used for assessment of musculoskeletal pain.

PURPOSE: To explore for fatigue-related regions of interest and the radiotherapy (RT) dose-fatigue relationship in nasopharyngeal cancer (NPC) survivors. METHODS: Eighty disease-free NPC survivors completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN) after RT. Fatigue was evaluated by the MDASI-HN fatigue item (MDASI-HN-F) and Common Terminology Criteria for Adverse Events v3.0 (CTC-AE), between 6 and 36 months after RT to determine the presence of chronic fatigue. Skull base MRIs and planning CT/RT dose were retrievable for 56 patients. Dosimetric data were extracted for 10 MRI-defined potential fatigue at-risk structures (FARS): brainstem (BS), pituitary gland (PG), hypothalamus (HT), basal ganglia, internal capsule, pineal gland, sub-thalamic nuclei, thalamus, substantia nigra, and hippocampus (HC). Recursive partitioning analysis (RPA) were used to identify dose-volume effects associated with chronic fatigue. RESULTS: 56 pts formed the cohort. Thirty patients (54%) reported any fatigue per MDASI-HN-F. Thirty-three pts (59%) had any fatigue by CTC-AE. The maximum point doses (Dmax) for PG, BS, HC, and HT were numerically higher in patients with fatigue. Dmax and Dmean of the PG were significantly higher in patients with chronic fatigue, p ≤ 0.01. A dose-volume threshold of PG V52Gy ≥16% (Logworth 2.4, AUC 0.7) was identified on RPA, and potential sensitivity to the PG doses was observed in younger patients (< 53 years-old). CONCLUSION: A dose-fatigue relationship was identified for the pituitary gland, both patient-reported and observer ratings. We recommend limiting the Dmax of PG to

The impact of supportive medications on patient-reported outcomes (PROs) has not been systematically evaluated. We describe the supportive medications used by treatment-naive lung cancer patients and assess their association with PROs from MD Anderson Symptom Inventory (MDASI). Treatment-naive lung cancer patients who completed PROs from MDASI at the initial visit to MD Anderson Cancer Center were included. Medications from the initial visit were abstracted from the electronic medical records system and categorized into therapeutic classes based on U.S. Pharmacopeia v7.0. A chi-square or Mann-Whitney U test was conducted as appropriate. Among 459 patients, ~ 50% took any analgesics and 25% were on opioids. One-third of patients with moderate-severe pain were not on any analgesics. Patients taking opioids had significantly worse median pain scores (6 vs. 0) compared with those not taking any analgesics (p

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.

Context The assessment of cancer-related symptoms requires culturally adapted and psychometrically validated symptom assessment tools. The M. D. Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) is a useful instrument for measuring symptom burden that was specifically developed for head and neck cancer patients. Objectives To validate the Spanish version of the MDASI-HN. Methods We evaluated the psychometric features of the MDASI-HN in patients with head and neck cancer. We evaluated the item-scale correlations and the internal consistency. We conducted principal axis factoring to identify the underlying dimensions as a measure of construct validity. The convergence/concurrent validity was assessed with the University of Washington Quality of Life Questionnaire for Head and Neck Patients, and known-group validity and test-retest reliability also were assessed. Results One hundred thirty patients were included. The mean ± SD age was 60.5 ± 13.6 years; 68% of patients were male, 42% had laryngeal tumors, and 45.9% had Stage III tumors. Forty-seven percent of the patients underwent surgery, 55% underwent radiotherapy, and 36% underwent chemotherapy. The global Cronbach alpha for the HN module was 0.81. The factor analysis identified two factors (Factor 1: speech, mucus, coughing, and constipation; Factor 2: teeth, taste, sores, swallowing, and skin). The correlation with the global score of the University of Washington Quality of Life was -0.68. The difference in the MDASI-HN scores according to Eastern Cooperative Oncology Group performance status was statistically significant (2.72 vs. 4.01, P = 0.006). The intraclass test-retest correlation was 0.62. Conclusion The Spanish version of the MDASI-HN is reliable and valid for evaluating cancer-related symptoms in head and neck cancer patients. © 2016 American Academy of Hospice and Palliative Medicine.

Autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma (MM) is associated with high symptom burden, particularly for older patients and those with amyloid light-chain (AL) amyloidosis. Symptom burden peaks during leukopenia. We hypothesized that higher doses of CD34(+) stem cells would be associated with an improved symptom outcome. Patients undergoing ASCT for MM who were ≥60 years old or had AL amyloidosis were randomized to receive either a standard (4 to 6 × 10(6) cells/kg) or high dose (10 to 15 × 10(6) cells/kg) of CD34(+) cells after melphalan 200 mg/m(2). Symptom burden was assessed via the MD Anderson Symptom Inventory MM module. Eighty patients were enrolled. Median CD34(+) cell doses were 5.1 × 10(6) cells/kg (standard dose) and 10.5 × 10(6) cells/kg (high dose). The most severe symptoms during the first week were fatigue, lack of appetite, drowsiness, disturbed sleep, and pain. The area under the curve for the mean composite severity score of these symptoms was similar between treatment arms (P = .819). Median times to neutrophil, lymphocyte, and platelet engraftment were also similar between groups. IL-6 increased similarly for both groups throughout the ASCT course. Infusion of higher autologous stem cell dose after high-dose chemotherapy does not yield a difference in symptom burden or engraftment time in the first few weeks after ASCT.

Objective: We examined the emergence of chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting toxicity of oxaliplatin, over the course of oxaliplatin-based chemotherapy for colorectal cancer (CRC). Predicting which patients will likely develop CIPN is an ongoing clinical challenge. Methods: Oxaliplatin-naïve patients with CRC underwent quantitative sensory testing (QST) before beginning oxaliplatin-based chemotherapy and then rated CIPN-related symptoms via the MD Anderson Symptom Inventory (MDASI) weekly for 26 weeks. Mixed modeling examined the value of QST for predicting higher CIPN (MDASI numbness/tingling) during treatment. Trajectory analysis identified a patient subgroup with consistently higher CIPN symptoms. Results: Numbness/tingling was the most frequent, most severe symptom, with 51% of patients clustering into a high CIPN subgroup. Touch sensation deficits (Bumps Detection test) significantly predicted the development of more severe numbness/tingling [estimate (est) = 0.106, p = 0.0003]. The high CIPN subgroup reported increased pain (est = 0.472, p < 0.0001) and interference with walking (est = 0.840, p < 0.0001). In the high CIPN subgroup, patient-reported numbness/tingling worsened rapidly in weeks 0-5 (est = 0.57, p < 0.0001) and then more gradually in weeks 6-26 (est = 0.07, p < 0.0001). Conclusion: Prechemotherapy screening with a simple, easily administered objective measure of touch sensation deficits (Bumps Detection test) and monitoring of patient-reported numbness/tingling during the first 2-3 chemotherapy cycles may support improved personalized care of CRC patients with oxaliplatin-induced CIPN.

Cytologic features such as the shape and size of tumor cells can predict metastatic death in uveal melanoma and other cancers but suffer from poor reproducibility. In this study, we investigate the interobserver concordance of digital morphometry, and correlate the results with BRCA associated protein-1 (BAP-1) expression and BAP-1 gene mutation status, monosomy 3, gene expression classifications and patient survival in uveal melanoma. The average number of cells analyzed in each of 107 tumors, was 1957 (SD 349). Mean time consumption was less than 2.5 minutes per tumor. Identical morphometric classification was obtained for ≥ 85 % of tumors in all twelve evaluated morphometric variables (κ 0.70–0.93). The mean nucleus area, nucleus perimeter, nucleus max caliper and nucleus to cell area ratio were significantly greater in tumors with low BAP-1 expression and gene expression class 2. Patients had significantly shorter survival if their tumors had low BAP-1 (Log-Rank p=0.002), gene expression class 2 (p=0.004), long nucleus perimeters (p=0.031), long nucleus max calipers (p=0.029) and high mean nucleus to cell area ratios (p=0.041) as defined in a training cohort and then tested in a validation cohort. In the validation cohort, long nucleus perimeters and long nucleus max calipers correlated with monosomy 3 (Pearson Chi-Square p=0.006 and p=0.009, respectively). Long nucleus perimeters also correlated with BAP-1 mutation (p=0.017). We conclude that digital morphometry can be fast and highly reproducible, that for the first time, morphometry parameters can be objectively quantitated in thousands of cells at a time in sub-μm resolutions, and that variables describing the shape and size tumor nuclei correlate to BAP-1 status, monosomy 3, gene expression class as well as patient survival.

Context: Following spinal cord injury (SCI), early prediction of future walking ability is difficult, due to factors such as spinal shock, sedation, impending surgery, and secondary long bone fracture. Accurate, objective biomarkers used in the acute stage of SCI would inform individualized patient management and enhance both patient/family expectations and treatment outcomes. Using magnetic resonance imaging (MRI) and specifically a midsagittal T2-weighted image, the amount of tissue bridging (measured as spared spinal cord tissue) shows potential to serve as such a biomarker. Ten participants with incomplete SCI received MRI of the spinal cord. Using the midsagittal T2-weighted image, anterior and posterior tissue bridges were calculated as the distance from cerebrospinal fluid to the damage. Then, the midsagittal tissue bridge ratio was calculated as the sum of anterior and posterior tissue bridges divided by the spinal cord diameter. Each participant also performed a 6-minute walk test, where the total distance walked was measured within six minutes. Findings: The midsagittal tissue bridge ratio measure demonstrated a high level of inter-rater reliability (ICC = 0.90). Midsagittal tissue bridge ratios were significantly related to distance walked in six minutes (R = 0.68, P = 0.03). Conclusion/clinical relevance: We uniquely demonstrated that midsagittal tissue bridge ratios were correlated walking ability. These preliminary findings suggest potential for this measure to be considered a prognostic biomarker of residual walking ability following SCI.

Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part owing to better prediction of high-risk disease and appropriate treatment stratification. High-risk histopathologic features and severe anaplasia both predict the need for more aggressive treatment; however, not all centers are able to assess tumor samples easily for the degree of anaplasia. Instead, identification of genetic signatures that are able to distinguish among anaplastic grades and thus predict high- versus low-risk retinoblastoma would facilitate appropriate risk stratification in a wider patient population. A better understanding of genes dysregulated in anaplasia also would yield valuable insights into pathways underlying the development of more severe retinoblastoma. Here, we present the histopathologic and gene expression analysis of 28 retinoblastoma cases using microarray analysis. Tumors of differing anaplastic grade show clear differential gene expression, with significant dysregulation of unique genes and pathways in severe anaplasia. Photoreceptor and nucleoporin expression in particular are identified as highly dysregulated in severe anaplasia and suggest particular cellular processes contributing to the development of increased retinoblastoma severity. A limited set of highly differentially expressed genes also are able to predict severe anaplasia accurately in our data set. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high-risk retinoblastoma.

Malignant pleural mesothelioma (MPM) is an aggressive cancer of the lung pleura. The MD Anderson Symptom Inventory (MDASI) is a patient-reported outcome (PRO) measure of symptom burden, the combined impact of disease-related and treatment-related symptoms on functioning. Validated PRO measures may require modification for use in specific study populations. We sought to modify the MDASI for patients with MPM and create a fit-for-purpose symptom-burden measure for use in a clinical trial, according to US Food and Drug Administration guidance on PRO utilization to support labeling claims. A literature review for MPM symptoms was conducted. Patients with MPM were qualitatively interviewed about experiences of disease and treatment. Descriptive analysis identified symptoms and interference with functioning to define MPM-related symptom burden. An expert panel rated the relevance of identified symptoms to patients with MPM. Patients who received the investigational drug in a previous Phase I study were interviewed for drug-specific symptoms. Literature review and interviews of 20 patients identified 31 MPM-related symptoms. A conceptual model of MPM-related symptom burden was developed. After expert-panel relevance review, five MPM-specific items and the 13 core MDASI symptoms met criteria for inclusion in a provisional MDASI-MPM for psychometric testing. Interviews with six patients identified six drug-specific symptoms; three were mentioned by multiple patients. Of these three, one was not in the core MDASI. The MDASI-MPM has established content validity and, with the addition of one symptom item, is ready for psychometric testing as fit-for-purpose for a clinical trial of an investigational agent.

Patients with newly diagnosed lung cancer who have not yet begun treatment may already be experiencing major symptoms produced by their disease. Understanding the symptomatic effects of cancer treatment requires knowledge of pretreatment symptoms (both severity and interference with daily activities). We assessed pretreatment symptom severity, interference, and quality of life (QOL) in treatment-naïve patients with lung cancer and report factors that correlated with symptom severity.This was a retrospective analysis of data collected at initial intake. Symptoms/interference were rated on the MD Anderson Symptom Inventory (MDASI) between 30 days prediagnosis and 45 days postdiagnosis. We examined symptom severity by disease stage and differences in severity by histology. Linear regression analyses identified significant predictors of severe pain and dyspnea.Of 460 eligible patients, 256 (62%) had adenocarcinoma, 30 (7%) had small cell carcinoma, and 100 (24%) had squamous cell carcinoma; 30% reported moderate-to-severe (rated ≥ 5, 0-10 scale) pretreatment symptoms. The most-severe were fatigue, disturbed sleep, distress, pain, dyspnea, sadness, and drowsiness. Symptoms affected work, enjoyment of life, and general activity (interference) and physical well-being (QOL) the most. Patients with advanced disease (n = 289, 63%) had more-severe symptoms. Cancer stage was associated with pain severity; both histology and cancer stage were associated with severe dyspnea.One third of lung cancer patients were symptomatic at initial presentation. Quantification of pretreatment symptom burden can inform patient-specific palliative therapy and differentiate disease-related symptoms from treatment-related toxicities. Poorly controlled symptoms could negatively affect treatment adherence and therapeutic outcomes.

Background: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective: To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design: Nonprespecified subgroup analysis of a multicenter factorial trial. Computerized Internet randomization was done between 2010 and 2013. Patients, clinicians, data collectors, and outcome adjudicators were blinded to treatment assignment. (ClinicalTrials.gov: NCT01082874). Setting: 135 centers in 23 countries. Patients: Adults aged 45 years or older who had or were at risk for atherosclerotic disease and were having noncardiac surgery. Exclusions were placement of a bare-metal stent within 6 weeks, placement of a drug-eluting stent within 1 year, or receipt of nonstudy aspirin within 72 hours before surgery. Intervention: Aspirin therapy (overall trial, n = 4998; subgroup, n = 234) or placebo (overall trial, n = 5012; subgroup, n = 236) initiated within 4 hours before surgery and continued throughout the perioperative period. Of the 470 subgroup patients, 99.9% completed follow-up. Measurements: The 30-day primary outcome was death or nonfatal myocardial infarction; bleeding was a secondary outcome. Results: In patients with prior PCI, aspirin reduced the risk for the primary outcome (absolute risk reduction, 5.5% [95% CI, 0.4% to 10.5%]; hazard ratio [HR], 0.50 [CI, 0.26 to 0.95]; P for interaction = 0.036) and for myocardial infarction (absolute risk reduction, 5.9% [CI, 1.0% to 10.8%]; HR, 0.44 [CI, 0.22 to 0.87]; P for interaction = 0.021). The effect on the composite of major and life-threatening bleeding in patients with prior PCI was uncertain (absolute risk increase, 1.3% [CI, -2.6% to 5.2%]). In the overall population, aspirin increased the risk for major bleeding (absolute risk increase, 0.8% [CI, 0.1% to 1.6%]; HR, 1.22 [CI, 1.01 to 1.48]; P for interaction = 0.50). Limitation: Nonprespecified subgroup analysis with small sample. Conclusion: Perioperative aspirin may be more likely to benefit rather than harm patients with prior PCI.

Alopecia areata (AA) is an autoimmune disease that causes hair loss. Although persons with the disease can be physically described as having varying degrees of hair loss, the condition has significant ramifications on an individual's well-being. We previously reported the preliminary psychometric properties of the Alopecia Areata Symptom Impact Scale (AASIS), a disease-specific measure that asks participants about their AA symptoms and how these symptoms interfere with their daily functioning. The goals of this article are to provide a detailed description of the development of the AASIS items and to offer a psychometric update for the measure. Preliminary items for the AASIS were developed on the basis of responses from 1,649 participants to 125 health-related quality-of-life questions/items from the National Alopecia Areata Registry. Clinicians affiliated with the registry were asked to rate the relevance of these items for content validity. Cluster analysis and clinician ratings were used to reduce the number of items. The resulting 13-item AASIS was administered to 452 participants, who were also cognitively debriefed. Results showed that the AASIS is a valid and reliable measure of AA symptoms and their impact on functioning.

A questionnaire-based study was conducted to assess long-term patient reported outcomes (PROs) following definitive IMRT-based treatment for early stage carcinomas of the tonsillar fossa.Participants had received IMRT with or without systemic therapy for squamous carcinoma of the tonsillar fossa (T1-2 and N0-2b) with a minimum follow-up of 2years. Patients completed a validated head and neck cancer-specific PRO instrument, the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Symptoms were compared between treatment groups of interest and overall symptom burden was evaluated.Of 139 participants analyzed, 51% had received ipsilateral neck IMRT, and 62% single modality IMRT alone (no systemic therapy). There were no differences in mean severity ratings for the top-ranked individual symptoms or symptom interference for those treated with bilateral versus ipsilateral neck IMRT alone. However, 40% of those treated with bilateral versus 25% of those treated with ipsilateral neck RT alone reported moderate-to-severe levels of dry mouth (p=0.03). Fatigue, numbness/tingling, and constipation were rated more severe for those who had received systemic therapy (p0.05 for each), but absolute differences were small. Overall, 51% had no more than mild symptom ratings across all 22 symptoms assessed.The long-term patient reported symptom profile in this cohort of tonsil cancer survivors treated with definitive IMRT-based treatment showed a majority of patients with no more than mild symptoms, low symptom interference, and provides an opportunity for future comparison studies with other treatment approaches.

BACKGROUND: A set of common cancer and treatment-related symptoms has been proposed to enhance both quality of care and clinical research in patients with a variety of solid tumors. These symptoms include anorexia, anxiety, constipation, depression, diarrhea, dyspnea, fatigue, insomnia, nausea, pain, neuropathy, and vomiting. Using data from several prospective studies, this study evaluated the impact of tumor grade, disease stage and treatment in patients with primary brain tumors on the reporting of symptoms. METHODS: Aggregate symptom report data using the MD Anderson Symptom Instrument -Brain Tumor (MDASI-BT) from 617 patients enrolled in 8 clinical studies was used. Descriptive statistics were used to report the prevalence and severity of symptoms as they relate to tumor grade, treatment stage (newly diagnosed, on active treatment, on surveillance, at recurrence), and KPS. RESULTS: The sample was primarily white(83%) males(59%), with high grade gliomas(75%) with KPS ≥ 90(71%). Over 50% of patients reported at least 10 concurrent symptoms, and 40% of patients reporting at least 3 moderate-severe symptoms. Fatigue, drowsiness, difficulty remembering, difficulty with sleep, and distress were the most severe symptoms reported by all tumor grades. Patients with either grade 4 tumors or tumor recurrence reported weakness and difficulty speaking as severe. Newly diagnosed patients or on active treatment also reported irritability and problems concentrating as most severe. Functional interference of symptoms with ability to work, perform activities, walk, and enjoy life was reported by more than 25% of patients. Low KPS was associated with more severe symptoms and functional impact. CONCLUSIONS: These results support a core set of symptoms that are common across brain tumor patients that may impact clinical care, and assessment of treatment benefit. Although some symptoms overlap with those reported in patients with other solid tumors, the additional symptoms and functional limitations underscore the clinical complexity of patients with brain tumors.

Symptom burden and quality of life (QOL) are of particular importance in head-and-neck cancer treatment. The MD Anderson Symptom Inventory-Head-and-Neck (MDASI-HN) is a simple symptom assessment tool practicable for patient follow-up, but a validated Filipino translation was previously unavailable.The objectives of this study were to develop a valid Filipino translation of the MDASI-HN, to test the sensitivity of the validated MDASI core-F, and to report the prevalence and pattern of head-and-neck symptoms in our cohort.An MDASI-HN-Filipino (MDASI-HN-F) version was developed and examined for convergent validity, internal consistency, test-retest reliability, known-group validity and sensitivity to change. Eligible participants were aged 18-80 years, with histopathologically-proven head-and-neck (except thyroid) cancer, able to understand and read English and Filipino, and without cognitive impairment or other conditions precluding self-administration of the questionnaire.Participants (n=100) were aged 18-76 years; the majority were aged60, male, married, had college schooling, or were from a Tagalog-speaking region. The validity of the MDASI HN-F was demonstrated in all parameters. Age or educational attainment did not affect convergent validity or test-retest reliability. At baseline, 48% had multiple moderate/severe symptoms and 38% had at least one severe symptom.The MDASI-HN-F is valid, reliable and sensitive. The sensitivity of the MDASI core-F is demonstrated, and its validity and reliability reaffirmed. Moderate and severe head-and-neck symptoms are prevalent in early-stage and advanced-stage head-and-neck cancers, reflecting the utility of symptom screening for improvement of symptom management, QOL and compliance to treatment.

After autologous stem cell transplant (AuSCT), patients with multiple myeloma (MM) may receive lenalidomide maintenance therapy. This longitudinal study examined patient-reported symptom burden during the 3-9 months post-AuSCT and its association with maintenance therapy and circulating inflammatory markers. Fifty-one patients with MM rated symptom severity weekly using the MD Anderson Symptom Inventory MM module. When possible, blood for inflammatory marker assay was drawn at enrollment. Trajectory analysis identified clusters of patients who consistently reported higher or lower symptom severity. Although disease was relatively stable 3-9 months post-AuSCT, patients were not symptom-free: 35% were in the high-symptom group. Fatigue, pain, numbness/tingling, bone aches and muscle weakness were the most severe symptoms. Controlled for clinical variables, elevated baseline tumor necrosis factor-α (TNF-α) predicted high-symptom group membership (p = 0.014). Maintenance therapy and tumor response were not related to high symptom burden. Associations between inflammation and symptom burden in this exploratory study warrant further confirmatory study.

Background Immunotherapy is emerging as the cornerstone for treatment of patients with advanced cancer, but significant toxicity (immune-related adverse events [irAEs]) associated with unbridled T cell activity remains a concern. Patients and methods A retrospective review of the electronic medical records of 290 patients with advanced cancer treated on an immunotherapy-based clinical trial in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center between February 2010 and September 2015 was performed. Clinical and laboratory parameters were collected to determine the incidence of irAEs, risk factors, and their association with treatment outcomes. Results Ninety eight of 290 patients (34%) experienced any grade irAEs. Among the 15 (5.2%) patients with grade ≥ 3 irAEs, the most common irAEs were dermatitis and enterocolitis. Although 80% of the patients with grade ≥ 3 irAEs required systemic corticosteroids, all the 15 patients recovered from the irAEs. On re-challenge, 4 of the 5 patients who had received systemic corticosteroids for irAE continued to respond. There were no irAE-related deaths. Importantly, patients with grade ≥ 3 irAEs had improved overall response rate (25 vs. 6%; p = 0.039) and longer median time to progression (30 weeks vs. 10 weeks; p = 0.0040) when compared to those without grade ≥ 3 irAEs. Conclusion Incidence of irAEs with immunotherapeutic agents indicates an active immune status, suggestive of potential clinical benefit to the patient. Further validation of this association in a large prospective study is warranted.

Effective assessment and management of pain in patients with cancer is strengthened by the patient's report of how much pain interferes with daily functioning. This requires a clear delineation of different levels of pain interference. We derived optimal cutpoints for differentiating between mild, moderate, and severe pain interference assessed by the Brief Pain Inventory (BPI) and describe the prevalence and characteristics of pain-induced functional impairment in patients with cancer. Data were pooled across 3 Phase III pivotal trials. Patient-completed questionnaires included the EuroQol 5 dimensions questionnaire (EQ5D), Functional Assessment of Cancer Therapy-General Measure (FACT-G), and BPI. Optimal cutpoints for categorizing pain interference into 3 levels were derived using analysis of variance, with different cutpoint sets for BPI total interference (BPI-PITS, the average score of all 7 items), activity-related interference (BPI-WAW, the average score of work, general activity, and walking), and mood-related interference (BPI-REM, the average score of relations with others, enjoyment of life, and mood) as independent variables and EQ5D-visual analog scale and total FACT-G score as dependent variables. To validate the cutpoints, we assessed whether interference categories were in concordance with Eastern Cooperative Oncology Group performance status (ECOG-PS) levels. The optimal cutpoints were (2,5) for BPI-PITS, (2,6) for BPI-WAW, and (2,5) for BPI-REM. The mild (2), moderate (2-5 or 2-6), and severe (5 or6) pain interference groups were significantly concordant with ECOG-PS levels (P0.0001). We empirically derived patient-reported pain interference categories in relation to clinician-rated performance status. These cutpoints may facilitate the conduct and interpretation of clinical evaluation, symptom epidemiology, and clinical trials.

Purpose 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). Methods and Materials 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; 12 weeks 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. Results 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 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). 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.” Conclusions 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.

Aims: To explore whether the transfer of very poor quality (VPQ) embryos is associated with an increase in congenital malformations or perinatal problems. Methods: In this retrospective case-control study, 74 children conceived by in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) resulting exclusively from the transfer of VPQ embryos were compared with 1,507 children born after the transfer of top morphological quality (TQ) embryos over the same period of time in the same centers. Results: The prevalence of birth defects in children resulting from VPQ embryos was 1.35% (1/74), similar to the 1.72% (26/1,507) when only TQ embryos were transferred; the rate of chromosomal abnormalities detected was also similar (0.0 vs. 0.4%), as was perinatal mortality. After correcting for multiplicity (higher in the TQ group), the aforementioned parameters remained similar in the two groups. Conclusion: Congenital malformations and perinatal complications do not seem to be more common in children born after transfer of VPQ embryos in IVF/ICSI cycles. Given our preliminary data, which need to be confirmed in much larger studies, when only VPQ embryos are available for transfer in IVF/ICSI cycles, we do not believe that they should be discarded with the intention of avoiding birth defects or perinatal complications.

Radiation therapy (RT), with or without chemotherapy, can cause significant acute toxicity among patients treated for head and neck cancer (HNC), but predicting, before treatment, who will experience a particular toxicity or symptom is difficult. We created and evaluated 2 multivariate models and generated a nomogram to predict symptom severity during RT based on a patient-reported outcome (PRO) instrument, the MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN).This was a prospective, longitudinal, questionnaire-based study.Tertiary cancer care center.Subjects were 264 patients with HNC (mostly oropharyngeal) who had completed the MDASI-HN before and during therapy. Pretreatment variables were correlated with MDASI-HN symptom scores during therapy with multivariate modeling and then were correlated with the composite MDASI-HN score during week 5 of therapy.A multivariate model incorporating pretreatment PROs better predicted MDASI-HN symptom scores during treatment than did a model based on clinical variables and physician-rated patient performance status alone (Akaike information criterion = 1442.5 vs 1459.9). In the most parsimonious model, pretreatment MDASI-HN symptom severity (P.001), concurrent chemotherapy (P = .006), primary tumor site (P = .016), and receipt of definitive (rather than adjuvant) RT (P = .044) correlated with MDASI-HN symptom scores during week 5. That model was used to construct a nomogram.Our model demonstrates the value of incorporating baseline PROs, in addition to disease and treatment characteristics, to predict patient symptom burden during therapy. Although additional investigation and validation are required, PRO-inclusive prediction tools can be useful for improving symptom interventions and expectations for patients being treated for HNC.

Purpose: Increasing research suggests that inflammation mediates symptom development. In this longitudinal study, we examined inflammatory factors related to the development of high symptom burden during autologous hematopoietic stem cell transplant (AuSCT) for multiple myeloma. Experimental Design: Patients (n = 63) repeatedly reported symptom severity on the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM) and contributed blood samples periodically for up to 100 days after AuSCT for inflammatory marker assays. The temporal associations between serum inflammatory marker concentrations and symptom severity outcomes were examined by nonlinear mixed-effect modeling. Results: Fatigue, pain, disturbed sleep, lack of appetite, and drowsiness were consistently the most severe MDASI-MM symptoms during the study. Peak symptom severity occurred on day 8 after AuSCT, during white blood cell count nadir. Patterns of serum interleukin (IL)-6 (peak on day 9) and soluble IL-6 receptor (sIL-6R; nadir on day 8) expression paralleled symptom development over time (both P < 0.0001). By univariate analysis, serum IL-6, sIL-6R, IL-10, C-reactive protein, macrophage inflammatory protein (MIP)-1α, sIL-1R2, sIL-1RA, and soluble tumor necrosis factor receptor 1 were significantly related to the most severe symptoms during the first 30 days after AuSCT (all P < 0.05). By multivariate analysis, IL-6 (estimate = 0.170; P = 0.004) and MIP-1α (estimate = −0.172; P = 0.006) were temporally associated with the severity of the component symptom score. Conclusions: Systemic inflammatory response was associated with high symptom burden during the acute phase of AuSCT. Additional research is needed to understand how the inflammatory response is mechanistically associated with symptom expression and whether suppression of this response can reduce symptoms without compromising tumor control. Clin Cancer Res; 20(5); 1366–74. ©2014 AACR.

We developed a module of the MD Anderson Symptom Inventory (MDASI) for patients with chronic myeloid leukemia (CML). To develop the MDASI-CML, we identified CML-specific symptoms from qualitative interviews with 35 patients. A list of candidate symptoms was reduced by a panel of patients, caregivers, and clinicians to the 13 core MDASI symptom items and 6 CML-specific items; these items were subsequently administered to 30 patients. Cognitive debriefing confirmed that the items were clear, relevant, and easy to use. One additional CML-specific symptom item was added, for a total of 7. The refined MDASI-CML was administered to 152 patients once every 2 weeks for 1 year. The content, concurrent, known-group, and construct validity of the MDASI-CML were evaluated. The internal consistency and test-retest reliabilities of the module were adequate. Longitudinal analysis showed relatively stable symptom severity scores over time. The most severe symptoms were fatigue, drowsiness, disturbed sleep, muscle soreness and cramping, and trouble remembering things. Approximately one-third of the patients who completed the MDASI-CML reported persistent moderate-to-severe symptoms. The MDASI-CML is a valid and reliable symptom assessment instrument that can be used in clinical studies of symptom status in patients with CML.

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.