Velikova, Galina

AbstractThe adiposity influence on colorectal cancer prognosis remains poorly characterised. We performed a systematic review and meta‐analysis on post‐diagnosis adiposity measures (body mass index [BMI], waist circumference, waist‐to‐hip ratio, weight) or their changes and colorectal cancer outcomes. PubMed and Embase were searched through 28 February 2022. Random‐effects meta‐analyses were conducted when at least three studies had sufficient information. The quality of evidence was interpreted and graded by the Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel. We reviewed 124 observational studies (85 publications). Meta‐analyses were possible for BMI and all‐cause mortality, colorectal cancer‐specific mortality, and cancer recurrence/disease‐free survival. Non‐linear meta‐analysis indicated a reverse J‐shaped association between BMI and colorectal cancer outcomes (nadir at BMI 28 kg/m2). The highest risk, relative to the nadir, was observed at both ends of the BMI distribution (18 and 38 kg/m2), namely 60% and 23% higher risk for all‐cause mortality; 95% and 26% for colorectal cancer‐specific mortality; and 37% and 24% for cancer recurrence/disease‐free survival, respectively. The higher risk with low BMI was attenuated in secondary analyses of RCTs (compared to cohort studies), among studies with longer follow‐up, and in women suggesting potential methodological limitations and/or altered physiological state. Descriptively synthesised studies on other adiposity‐outcome associations of interest were limited in number and methodological quality. All the associations were graded as limited (likelihood of causality: no conclusion) due to potential methodological limitations (reverse causation, confounding, selection bias). Additional well‐designed observational studies and interventional trials are needed to provide further clarification.

AbstractLow physical activity and high sedentary behaviour have been clearly linked with colorectal cancer development, yet data on their potential role in colorectal cancer survival is limited. Better characterisation of these relationships is needed for the development of post‐diagnosis physical activity and sedentary behaviour guidance for colorectal cancer survivors. We searched PubMed and Embase through 28 February 2022 for studies assessing post‐diagnosis physical activity, and/or sedentary behaviour in relation to all‐cause and cause‐specific mortality and recurrence after colorectal cancer diagnosis. Total and recreational physical activity were assessed overall and by frequency, duration, intensity, and volume using categorical, linear, and non‐linear dose–response random‐effects meta‐analyses. The Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel interpreted and graded the likelihood of causality. We identified 16 observational studies on 82,220 non‐overlapping patients from six countries. Physical activity was consistently inversely associated with colorectal cancer morbidity and mortality outcomes, with 13%–60% estimated reductions in risk. Sedentary behaviour was positively associated with all‐cause mortality. The evidence had methodological limitations including potential confounding, selection bias and reverse causation, coupled with a limited number of studies for most associations. The CUP Global Expert panel concluded limited‐suggestive evidence for recreational physical activity with all‐cause mortality and cancer recurrence. Total physical activity and its specific domains and dimensions, and sedentary behaviour were all graded as limited‐no conclusion for all outcomes. Future research should focus on randomised trials, while observational studies should obtain objective and repeated physical activity measures and better adjustment for confounders.

AbstractBased on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta‐analyses to investigate the association of post‐diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non‐linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J‐shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited‐no conclusion). The evidence on recreational physical activity and lower risk of all‐cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62–0.77) and recurrence/disease‐free survival (RR: 0.80, 95% CI: 0.70–0.92) was graded as limited‐suggestive. There was limited‐suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant‐based foods), intake of whole grains and coffee with lower risk of all‐cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all‐cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited‐no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well‐designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients.

Abstract The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post‐diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random‐effects dose–response meta‐analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all‐cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease‐free events). Meta‐analyses, including 3–10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega‐3 polyunsaturated fatty acids, supplemental calcium, circulating 25‐hydroxyvitamin D (25[OH]D) and all‐cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer‐specific mortality; and for circulating 25(OH)D and recurrence/disease‐free survival. The overall evidence was graded as ‘limited’. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant‐based foods), whole grains, total, caffeinated, or decaffeinated coffee and all‐cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all‐cause mortality provided ‘limited—suggestive’ evidence. All other exposure‐outcome associations provided ‘limited—no conclusion’ evidence. Additional, well‐conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.

Abstract Background: Approximately 1% of all new cases of breast cancer (BC) occur in men. Care of male BC is largely based on extrapolation from treatment strategies and management of symptoms in women. The impact of BC diagnosis and therapy on Quality of Life (QoL) in women with BC is well documented. Comprehensive, prospective data about QoL in men treated for BC are sparse. Due to the lack of a validated male BC QoL questionnaire, we previously evaluated the QoL of the male BC using the original EORTC QLQ-C30 and breast module QLQ BR23 with “female” items replaced by male-specific items from the EORTC QoL prostate module (EORTC QLQ-PR25). The development of a validated worldwide questionnaire for male BC is sponsored by EORTC QoL Group and will be completed in cooperation with EORTC Breast Group and the International Male BC Program (a cooperation between EORTC-BCG, TBCRC, within the BIG and NABCG networks) Trial design: The evaluation of the QoL issues relevant for male BC, as well as the translation of issues into items to build the tool for QoL assessment in male BC will be carried out through four phases: 1. A systematic Literature review 2. Interviews with patients 3. Interviews with Health Care Professionals (HCP) 4. Consultation of experts in Oncology and QoL Inclusion criteria: • Histologically proven early BC or metastatic BC in male patients • Age ≥ 18 years • Ability to understand and fill out questionnaires • Written informed consent Exclusion criteria: • Other cancer in the past 5 years except non-melanotic skin cancer • Patients participating in interventional clinical studies with QoL as primary endpoint • Any condition potentially hampering compliance with the study protocol Aims: The study proposes to carry out an evaluation of the QoL issues relevant for male patients with BC, and translating the issues into questions to build the tool for an adequate QoL assessment in these patients. The specific aims are: 1) To carry out an evaluation of the existing EORTC QLQ-BR 45 (adapting for male BC) and for suitability of use in male BC patients 2) To carry out an evaluation of the EORTC QLQ-PR25 (adapting for male BC) for suitability of use in male BC patients 3) To provide recommendations to the EORTC on a suitable assessment approach to assess QOL in male BC Statistical methods: A systematic literature review to assess what factors are unique to male BC patients in influencing their QoL and what QoL measures exist for them will be performed. This will be conducted by reviewing all studies with male BC participants and including investigator brochures describing side effects in male BC patients, as well as by evaluating issues captured by other existing EORTC modules. The final list of potential QoL issues relevant to the male BC will be tested for relevance and importance in semi-structured qualitative interviews with patients and HCP. A total of 2-5 patients per year will be recruited from collaborating hospitals/countries. At least 40 in total will be interviewed before, during, or after treatment for male BC. At least 2 experts/country from the all collaborating centres will be included in the interview to discuss and consider the potential issues. Finally, the issue list will be translated into questions to build the tool for a QoL assessment in male BC patients. Present accrual and target accrual This study started in October 2019. A systematic literature review has been completed. Seventeen centres from worldwide are participating in the study. New centers may still join. Contact information for people with a specific interest in the trial Vesna Bjelic-Radisic E-Mail: Vesna.Bjelic-Radisic@helios-gesundheit.de Fatima Cardoso e-mail: fatimacardoso@fundacaochampalimaud.pt Citation Format: Vesna Bjelic-Radisic, Fatima Cardoso, Joachim Weis, Eveline Bleiker, David Cameron, Galina Velikova, Karatzyna Pogoda, Samantha Serpentini, Kevin Punie, Rinat Yerushalmi, Erika Matos, Birgit Carly, Ivana Bozovic-Spasojevic, Markus Fleisch, Zoe Luisa Probst, Sina Maria Schafer, Nicola Russell, Sofie Tombeur, Joanna Vermeij, Heidi Roelstraete, Kathryn Ruddy, Juan I Arraras, Andrew Bottomley. Adaption of the EORTC quality of life breast cancer module for male breast cancer - phase I [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-14-01.

1055^ Background: Key properties of QoL instruments in a clinical trial setting are reliability, the ability to detect a change, and content validity. Using data from the Study 301 phase III breast cancer trial, we report here content validity and ability to detect a change for the EORTC QLQ-C30 and breast cancer-specific QLQ-BR23 questionnaires. Methods: Patients with locally advanced or metastatic breast cancer were randomized to 21-day cycles of either eribulin mesylate 1.4 mg/m2 given on Days 1 and 8, or capecitabine 1.25 g/m2BID orally on Days 1-14. QoL questionnaires were completed at baseline and at 6 weeks, 3, 6, 12, 18, and 24 months. Objective tumor response was evaluated (complete response [CR]; partial response [PR]; stable disease [SD]; progressive disease [PD]). Univariate and multivariate longitudinal analyses using weighted generalized estimating equations were employed to assess the responsiveness of the QoL scales to objective tumor response. Results: 1,102 patients were randomized (554 eribulin, 548 capecitabine). Global health status (GHS)/QoL scores were low at baseline (55). GHS/QoL scores were highest for patients with CR (70.8), followed by those patients with PR (63.5), SD (60.5), and PD (58.1). Physical functioning followed the same pattern: CR (98.3); PR (79.1); SD (72.8); PD (71.0). Role and social functioning scores were also responsive. Pain increased, while fatigue and body image worsened, with poorer tumor responses. Using the weighted generalized estimating equations, there were improvements in physical (34.78; p<0.01), cognitive (27.29; p<0.01), and social (22.04; p<0.01) functioning, and future perspective 11.47 (p<0.01), in patients who responded (CR and PR) to treatment compared with non-responders. Pain decreased significantly by 28.62 (p<0.01) on a 0-100 scale. Patients who responded also gained appetite and had fewer breast symptoms. Conclusions: These results suggest content validity of the EORTC QLQ-30 and QLQ-BR23 questionnaires as they correlate with changes in objective tumor assessments. Clinical trial information: NCT00337103.

1050^ Background: In a phase III trial comparing eribulin (E) vs. capecitabine (C) in pts with locally advanced or MBC, a trend for improved OS was observed but a statistically significant superiority was not demonstrated with E vs. C for OS or PFS. The AE profiles were consistent with known side effects. We now report QoL results from this trial. Methods: Pts received eribulin mesylate 1.4 mg/m2 on Days 1 and 8, or C 1.25 g/m2 BID orally on Days 1-14, of a 21-day cycle. Eligible pts had received prior therapy including an anthracycline and taxane, and were receiving study drug as 1st-, 2nd-, or 3rd-line therapy for advanced disease. QoL, a secondary objective, was assessed using EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline, 6 weeks, 3, 6, 12, 18, and 24 months after starting treatment (or until progressive disease or treatment change), and at unscheduled visits. Longitudinal analyses were carried out using weighted generalized estimating equations adjusted for non-random attrition due to death within 12 months. Model covariates were time (visit), region, and baseline QoL. The primary endpoint was change from baseline for Global Health Status (GHS)/overall QoL; exploratory endpoints were change from baseline for each functional domain, and signs/symptoms. Results: 1,102 pts were randomized (E 554; C 548). GHS/QoL scores were low at baseline for E (56.3) and C (54.7) on a scale of 0 (worse) to 100 (best). GHS/QoL and cognitive functioning improved significantly more in pts receiving E vs. C, (6.5 [p=0.048] and 15.3 [p<0.001], respectively). Emotional functioning improved significantly for pts receiving C vs. E (3.3; p=0.033). Pain was comparable at baseline, and was lower at subsequent visits with both treatments. Patient-reported signs/symptoms in favor of E included nausea and vomiting (E1.9; p=0.043) and diarrhea (-3.7; p=0.001); systemic side effects (5.2; p<0.001) and upset by hair loss (9.3; p=0.023) favored C. Conclusions: GHS/QoL scores improved more in pts receiving E than C. E showed advantages in terms of gastrointestinal effects while C had advantages in relation to hair loss. Clinical trial information: NCT00337103.

Background There is currently a lack of consensus on how health-related quality of life and other patient-reported outcome measures in cancer randomized clinical trials are analyzed and interpreted. This makes it difficult to compare results across randomized controlled trials (RCTs) synthesize scientific research, and use that evidence to inform product labeling, clinical guidelines, and health policy. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data for Cancer Clinical Trials (SISAQOL) Consortium aims to develop guidelines and recommendations to standardize analyses of patient-reported outcome data in cancer RCTs. Methods and Results Members from the SISAQOL Consortium met in January 2017 to discuss relevant issues. Data from systematic reviews of the current state of published research in patient-reported outcomes in cancer RCTs indicated a lack of clear reporting of research hypothesis and analytic strategies, and inconsistency in definitions of terms, including “missing data,”“health-related quality of life,” and “patient-reported outcome.” Based on the meeting proceedings, the Consortium will focus on three key priorities in the coming year: developing a taxonomy of research objectives, identifying appropriate statistical methods to analyze patient-reported outcome data, and determining best practices to evaluate and deal with missing data. Conclusion The quality of the Consortium guidelines and recommendations are informed and enhanced by the broad Consortium membership which includes regulators, patients, clinicians, and academics.

Purpose This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer (MBC). Patients and Methods Women with MBC who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary end points were overall survival (OS) and progression-free survival (PFS). Results Median OS times for eribulin (n = 554) and capecitabine (n = 548) were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to 1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms. Both treatments had manageable safety profiles consistent with their known adverse effects; most adverse events were grade 1 or 2. Conclusion In this phase III study, eribulin was not shown to be superior to capecitabine with regard to OS or PFS.