Patient-reported treatment toxicity and adverse events in Black and White women receiving chemotherapy for early breast cancer.

PURPOSE: It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I-III) receiving current chemotherapy regimens and, in turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization. METHODS: Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher's exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes RESULTS: In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White, p = .04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (p = .05) and diabetes (p = .05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White, p = .01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen. CONCLUSION: Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients.

Identifying clinically meaningful severity categories for PROMIS pediatric measures of anxiety, mobility, fatigue, and depressive symptoms in juvenile idiopathic arthritis and childhood-onset systemic lupus erythematosus.

PURPOSE: A key limitation to widespread adoption of patient-reported outcome (PRO) measures is the lack of interpretability of scores. We aim to identify clinical severity thresholds to distinguish categories of no problems, mild, moderate, and severe along the PROMIS® Pediatric T-score metric for measures of anxiety, mobility, fatigue, and depressive symptoms for use in populations with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematosus (cSLE). METHODS: We used a modified standard setting methodology from educational testing to identify clinical severity thresholds (clinical cut scores). Using item response theory-based parameters from PROMIS item banks, we developed a series of clinical vignettes that represented different severity or ability levels along the PROMIS Pediatric T-score metric. In stakeholder workshops, participants worked individually and together to reach consensus on clinical cut scores. Median cut-score placements were taken when consensus was not reached. Focus groups were recorded and qualitative analysis was conducted to identify decision-making processes. RESULTS: Nine adolescents (age 13-17 years) with JIA (33% female) and their caregivers, five adolescents (age 14-16 years) with cSLE (100% female) and their caregivers, and 12 pediatric rheumatologists (75% female) participated in bookmarking workshops. Placement of thresholds for bookmarks was highly similar across stakeholder groups (differences from 0 to 5 points on the PROMIS t-score metric) for all but one bookmark placement. CONCLUSION: This study resulted in clinical thresholds for severity categories for PROMIS Pediatric measures of anxiety, mobility, fatigue, and depressive symptoms, providing greater interpretability of scores in JIA and cSLE populations.

Incorporating the patient perspective in the study of rare bone disease: insights from the osteogenesis imperfecta community.

There is limited research which examines health concerns of individuals with osteogenesis imperfecta (OI). Discussion groups with leaders of the adult OI community identified a broad range of medical priorities beyond fractures and brittle bones. Our work underscores the need to include patient-reported outcomes in rare bone disease research. INTRODUCTION: Osteogenesis imperfecta (OI) is a rare genetic disorder affecting collagen protein leading to brittle bones and a number of other medical complications. To date, there is limited research which examines the life-long process of aging with this rare disease, much less the perspective of individuals with OI. METHODS: In order to explore and prioritize health concerns that adults with OI feel have been inadequately addressed in health care and research, investigators held discussions with leaders from the global adult OI community. The meetings were held in August 2017 at the 13th International Conference on OI in Oslo, Norway as part of the preconference seminar "Patient Participation in OI Research". Investigators were part of the Brittle Bone Disease Consortium (BBDC), a multicenter research program devoted to the study of OI, and their focus was on patient-reported outcomes (PRO). RESULTS: Participants noted that while fractures and brittle bones are the most common feature of OI, a number of body systems are under-studied in this disorder. They particularly emphasized breathing, hearing, and the effects of aging as primary concerns that researchers and physicians may not fully understand or address. Other areas included pain, gastrointestinal problems, mental health, nutrition, menopause/pregnancy, and basilar invagination. Participants also emphasized that they must be informed of study results. They underscored that outcome measures incorporated into future drug trials must look beyond fractures and consider the whole patient. CONCLUSIONS: This work will help guide the incorporation of PROs into the next phase of the BBDC Natural History Study of OI and underscores the importance of including PROs in the study of rare diseases.

Psychometric properties of the PROMIS short form measures in a U.S. cohort of 961 patients with chronic hepatitis C prescribed direct acting antiviral therapy.

BACKGROUND: To better understand symptoms experienced by patients infected with chronic hepatitis C virus (HCV), valid and reliable patient-reported outcome (PRO) measures are needed. AIM: To assess the reliability and validity of 10 patient-reported outcomes measurement information system (PROMIS) measures and the Headache Impact Test-6 (HIT-6) in a large national sample of patients with HCV. METHODS: Pre-treatment data from 961 patients with HCV starting direct acting antiviral therapy at 11 U.S. liver centers were analyzed. Internal reliability was evaluated using Cronbach's alpha coefficient; frequency distributions were examined for floor and ceiling effects; structural validity was investigated via item-response-theory models; convergent validity was evaluated using correlations with theoretically-similar items from the HCV-PRO and memorial symptom assessment scale (MSAS); and known-groups validity was investigated by observing PRO differences by liver disease status and number of comorbidities. RESULTS: The HIT-6 and the majority of the PROMIS measures yielded excellent reliability (alphas ≥ 0.87). Ceiling effects were infrequent ( < 4%), while 30%-59% of patients reported no symptoms (floor effects). The data supported structural validity of the HIT-6 and most PROMIS measures. The PROMIS measures showed moderate to strong correlations with theoretically-similar items from the HCV-PRO and MSAS (0.39-0.77). Trends were observed between worse PRO scores and advanced cirrhosis and greater number of comorbidities, lending support for known-groups validity. CONCLUSIONS: The psychometric properties of the HIT-6 and PROMIS measures performed satisfactorily in this large cohort of patients with HCV starting direct acting antiviral therapy. Opportunities exist for further refinement of these PROs. Evaluation of performance over time and in under-represented subgroups is needed.

Determinants of longitudinal health-related quality-of-life change in children with asthma from low-income families: a report from the PROMIS® Pediatric Asthma Study.

BACKGROUND: How the longitudinal asthma control status and other socio-demographic factors influence the changes of health-related quality of life (HRQOL) among asthmatic children, especially from low-income families, has not been fully investigated. OBJECTIVES: This study aimed to describe the trajectories of asthma-specific HRQOL over 15 months and examine the effect of asthma control status on HRQOL by taking socio-demographic factors into consideration. METHODS: A total of 229 dyads of asthmatic children and their parents enroled in public insurance programs were recruited for assessing asthma control status and HRQOL over four time points of assessment. Asthma control status was measured using the Asthma Control and Communication Instrument, and asthma-specific HRQOL was assessed using the Patient-Reported Outcomes Measurement Information System's Pediatric Asthma Impact Scale. Latent growth models (LGMs) were applied to examine the trajectory of HRQOL and the factors contributing to the changes of HRQOL. RESULTS: Unconditional LGM revealed that HRQOL was improved over time. Conditional LGM suggested that accounting for asthma control and participants' socio-demographic factors, the variation in the initial level of HRQOL was significant, yet the rate of change was not. Conditional LGM also revealed that poorly controlled asthma status was associated with poor HRQOL at each time point (P's < 0.05). Lower parental education was associated with lower baseline HRQOL (P < 0.05). Hispanic children had a larger increase in HRQOL over time (P < 0.01) than non-Hispanic White children. CONCLUSIONS: Vulnerable socio-demographic characteristics and poorly controlled asthma status affect HRQOL in children. This finding encourages interventions to improve asthma control status and HRQOL in minority children.

Personalized home-based interval exercise training may improve cardiorespiratory fitness in cancer patients preparing to undergo hematopoietic cell transplantation.

Impaired cardiorespiratory fitness is associated with inferior survival in patients preparing to undergo hematopoietic cell transplantation (HCT). Exercise training based on short, higher intensity intervals has the potential to efficiently improve cardiorespiratory fitness. We studied home-based interval exercise training (IET) in 40 patients before autologous (N=20) or allogeneic (N=20) HCT. Each session consisted of five, 3 min intervals of walking, jogging or cycling at 65-95% maximal heart rate (MHR) with 3 min of low-intensity exercise (<65% MHR) between intervals. Participants were asked to perform sessions at least three times weekly. The duration of the intervention was at least 6 weeks, depending on each patient's scheduled transplantation date. Cardiorespiratory fitness was assessed from a peak oxygen consumption test (VO2peak) and a 6 min walk (6MWD) before and after the intervention period. For the autologous HCT cohort, improvements in VO2peak (P=0.12) and 6MWD (P=0.19) were not statistically significant. For the allogeneic cohort, the median VO2peak improvement was 3.7 ml/kg min (P=0.005) and the median 6MWD improvement was 34 m (P=0.006). Home-based IET can be performed before HCT and has the potential to improve cardiorespiratory fitness.

Does change in health-related quality of life score predict survival? Analysis of EORTC 08975 lung cancer trial.

BACKGROUND: Little is known about whether changes in health-related quality of life (HRQoL) scores from baseline during treatment also predict survival, which we aim to investigate in this study. METHODS: We analysed data from 391 advanced non-small-cell lung cancer (NSCLC) patients enrolled in the EORTC 08975 study, which compared palliative chemotherapy regimens. HRQoL was assessed at baseline and after each chemotherapy cycle using the EORTC QLQ-C30 and QLQ-LC13. The prognostic significance of HRQoL scores at baseline and their changes over time was assessed with Cox regression, after adjusting for clinical and socio-demographic variables. RESULTS: After controlling for covariates, every 10-point increase in baseline pain and dysphagia was associated with 11% and 12% increased risk of death with hazard ratios (HRs) of 1.11 and 1.12, respectively. Every 10-point improvement of physical function at baseline (HR=0.93) was associated with 7% lower risk of death. Every 10-point increase in pain (HR=1.08) was associated with 8% increased risk of death at cycle 1. Every 10-point increase in social function (HR=0.91) at cycle 2 was associated with 9% lower risk of death. CONCLUSIONS: Our findings suggest that changes in HRQoL scores from baseline during treatment, as measured on subscales of the EORTC QLQ-C30 and QLQ-LC13, are significant prognostic factors for survival.

Cardiopulmonary fitness in patients undergoing hematopoietic SCT: a pilot study.

Hematopoietic cell transplantation (HCT) is a life-saving treatment for patients with high-risk hematological malignancies. Prognostic measures to determine fitness for HCT are needed to inform decision-making and interventions. VO(2peak) is obtained by measuring gas exchange during cycle ergometry and has not been studied as a prognostic factor in HCT. Thirty-two autologous and allogeneic HCT patients underwent VO(2peak) and 6 Minute Walk (6MW) testing before HCT, and provided weekly symptom and health-related quality of life (HRQOL) assessments before HCT and concluding at Day 100. Twenty-nine patients completed pre-HCT testing. Pre-HCT VO(2peak) was positively correlated with pre-HCT 6MW (r=0.65, P<0.001) and negatively correlated with number of chemotherapy regimens and months of chemotherapy. Patients with lower VO(2peak) reported higher symptom burden and inferior HRQOL at baseline and during early post-HCT period. Patients with pre-HCT VO(2peak) <16 mL/kg/min had higher risk of mortality post HCT (entire cohort: hazard ratio (HR) 9.1 (1.75-47.0), P=0.01; allogeneic HCT patients only: HR 6.70 (1.29-34.75), P=0.02) and more hospitalized days before Day 100 (entire cohort: median 33 vs 19, P=0.003; allogeneic HCT patients only: median 33 vs 21, P=0.004). VO(2peak) pre-HCT is feasible and might predict symptom severity, HRQOL and mortality. Additional studies are warranted.

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients.

BACKGROUND: We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. MATERIALS AND METHODS: World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS: Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION: These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

US physicians' attitudes toward genetic testing for cancer susceptibility.

Genetic testing for an inherited susceptibility to cancer is an emerging technology in medical practice. Little information is currently available about physicians' attitudes toward these tests. To assess US physicians' opinions on unresolved issues surrounding genetic testing, a 15-min survey was administered to a stratified random sample of 1,251 physicians from 8 specialties, selected from a file of all licensed physicians in the US (response rate = 71.0%). Dependent measures included physicians' attitudes toward genetic counseling and testing qualifications, availability of guidelines, patient confidentiality and insurance discrimination issues, and clinical utility of genetic tests. More than 89% of physicians reported a need for physician guidelines, 81% thought that patients with positive genetic test results are at risk for insurance discrimination, and more than 53% thought that it was difficult to ensure the confidentiality of test results. Almost 25% indicated that genetic tests for cancer susceptibility have too many inaccurate or ambiguous results; nearly 75% thought that clear guidelines are not available for managing patients with positive test results. Only 29% of physicians reported feeling qualified to provide genetic counseling to their patients. More than 84% of oncologists considered themselves qualified to recommend genetic testing to their patients compared with 40% of primary care physicians (PCPs), and 57% of tertiary care physicians (TCPs). US physicians expressed great uncertainty about issues surrounding genetic testing for cancer susceptibility. Results of this national survey underscore the need to provide physicians with clear guidelines on the use of genetic cancer susceptibility tests and effective medical training on their appropriate implementation.