RESUMEN
PURPOSE: Numerous randomized controlled trials (RCTs) have shown beneficial exercise effects on fatigue, anxiety and depression and health-related quality of life (HRQoL) in breast cancer (BC) patients during and shortly after treatment. Here, we investigated the long-term effects of exercise during chemotherapy for BC on these outcomes. METHODS: We invited participants of two highly comparable RCTs that investigated the effects of exercise (EX) (versus usual care (UC)) during chemotherapy in patients with non-metastatic BC (N = 357) to participate in an 8-year follow-up. In both trials, fatigue, anxiety and depression and HRQoL were assessed using the same questionnaires, at multiple timepoints. Linear mixed-effect models were used to compare study arms over time. RESULTS: In total, 156 participants (EX = 82; UC = 74) completed the follow-up questionnaires. EX reported comparable general (between-group difference 0.73, 95% confidence interval (- 0.35; 1.80), ES = 0.18) and physical fatigue (0.55 (- 0.55; 1.65), ES = 0.13), small but statistically significantly higher levels of anxiety (1.24 (0.47 to 2.00), ES = 0.39) and depression (1.10 (0.34; 1.85), ES = 0.38), significantly lower global HRQoL (- 5.99 (- 10.65; - 1.32), ES = 0.34) and comparable summary HRQoL (- 1.90 (- 4.70; 0.89), ES = 0.16) compared to UC. CONCLUSION: No long-term beneficial effects of exercise during chemotherapy on BC patients' fatigue, anxiety, depression or HRQoL were observed. The less favourable outcomes for mood and HRQoL that were observed 8 years after participation in an exercise intervention may be explained by selective loss-to-follow-up. IMPLICATIONS FOR CANCER SURVIVORS: The results highlight the need to incorporate strategies that promote physical activity maintenance after participation in an exercise programme to also counteract long-term detrimental side effects of cancer treatment.
RESUMEN
AIM: The aim of this study was to longitudinally investigate dietary and lifestyle inflammation scores and their interaction in relation to risk of colorectal cancer (CRC) recurrence and all-cause mortality. METHODS: Data of two prospective cohort studies among CRC survivors was used. Information about diet and/or lifestyle was available for 2739 individuals for at least one of the following time points: at diagnosis, six months after diagnosis and two years after diagnosis. The dietary and lifestyle inflammation scores (DIS and LIS) were used to evaluate the inflammatory potential of diet and lifestyle. Joint modelling, combining mixed models and Cox proportional hazards regression, were used to assess associations between DIS and LIS over time and CRC recurrence and all-cause mortality. Interactions between DIS and LIS were assessed using time-dependent Cox proportional hazard regression. RESULTS: The median follow-up time was 4.8 (IQR 2.9-6.9) years for recurrence and 5.7 (IQR 3.5-8.5) years for all-cause mortality, with 363 and 453 events, respectively. A higher DIS as well as LIS was associated with a higher risk of all-cause mortality (HRDIScontinuous 1.09 95%CI 1.02; 1.15; HRLIScontinuous 1.24 95%CI 1.05; 1.46). Individuals who were in the upper tertile of both DIS and LIS had the highest all-cause mortality risk (HR 1.62 95%CI 1.16; 2.28), compared to the individuals in the lowest tertile of both DIS and LIS. No consistent associations with recurrence were observed. CONCLUSION: A more pro-inflammatory diet and lifestyle was associated with a higher risk of all-cause mortality, but not recurrence, in CRC survivors.
RESUMEN
PURPOSE: Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials. METHODS: A post hoc analysis was performed on individual patient data from the anti-programmed cell death-1 (anti-PD-1) + anti-cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex. RESULTS: Of the 1,959 patients who received anti-PD-1 + anti-CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HRadj), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HRadj, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HRadj, 1.21 (95% CI, 1.06 to 1.39) and HRadj, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HRadj of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS. CONCLUSION: Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.
RESUMEN
PURPOSE: Patient outcomes may differ from randomized trial averages. We aimed to predict benefit from FOLFOXIRI versus infusional fluorouracil, leucovorin, and oxaliplatin/fluorouracil, leucovorin, and irinotecan (FOLFOX/FOLFIRI), both plus bevacizumab, in patients with metastatic colorectal cancer (mCRC). METHODS: A Cox model with prespecified clinical, molecular, and laboratory variables was developed in 639 patients from the TRIBE2 trial for predicting 2-year mortality. Data from the CHARTA (n = 232), TRIBE1 (n = 504), and CAIRO5 (liver-only mCRC, n = 287) trials were used for external validation and heterogeneity of treatment effects (HTE) analysis. This involves categorizing patients into risk groups and assessing treatment effects across these groups. Performance was assessed by the C-index and calibration plots. The C-for-benefit was calculated to assess evidence for HTE. The c-for-benefit is specifically designed for HTE analysis. Like the commonly known c-statistic, it summarizes the discrimination of a model. Values over 0.5 indicate evidence for HTE. RESULTS: In TRIBE2, the overoptimism-corrected C-index was 0.66 (95% CI, 0.63 to 0.69). At external validation, the C-index was 0.69 (95% CI, 0.64 to 0.75), 0.68 (95% CI, 0.64 to 0.72), and 0.65 (95% CI, 0.65 to 0.66), in CHARTA, TRIBE1, and CAIRO5, respectively. Calibration plots indicated slight underestimation of mortality. The c-for-benefit indicated evidence for HTE in CHARTA (0.56, 95% CI, 0.48 to 0.65), but not in TRIBE1 (0.49, 95% CI, 0.44 to 0.55) and CAIRO5 (0.40, 95% CI, 0.32 to 0.48). CONCLUSION: Although 2-year mortality could be reasonably estimated, the HTE analysis showed that clinically available variables did not reliably identify which patients with mCRC benefit from FOLFOXIRI versus FOLFOX/FOLFIRI, both plus bevacizumab, across the three studies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Camptotecina , Neoplasias Colorrectales , Fluorouracilo , Leucovorina , Compuestos Organoplatinos , Humanos , Bevacizumab/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Leucovorina/administración & dosificación , Leucovorina/uso terapéutico , Fluorouracilo/administración & dosificación , Masculino , Femenino , Camptotecina/análogos & derivados , Camptotecina/administración & dosificación , Camptotecina/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Persona de Mediana Edad , Anciano , Metástasis de la Neoplasia , Resultado del Tratamiento , Pronóstico , Modelos de Riesgos Proporcionales , AdultoRESUMEN
AIM: Adjuvant chemotherapy has been advised for high-risk stage II and III colon cancer since 2004. After the IDEA study showed no clinically relevant difference in outcome, reduction of adjuvant CAPOX duration from 6 to 3 months was rapidly adopted in the Dutch treatment guideline in 2017. This study investigates the real-world impact of the guideline change on overall survival (OS) and patient-reported outcomes (PROs). METHODS: Patients with high-risk stage II (pT4 +) and III (pN+) colon cancer were selected from the Netherlands Cancer Registry, based on surgical resection and adjuvant CAPOX before (2015-2016) versus after (2018-2019) the guideline change. Both groups were compared on OS, using multivariable Cox regression, and on PROs. RESULTS: Patients treated before (n = 2330) and after (n = 2108) the guideline change showed similar OS (HR 1.02; 95 %CI [0.89-1.16]), also in high-risk stage III (pT4/N2, HR 1.06 [0.89-1.26]). After the guideline change, 90 % of patients were treated for 3 months with no inferior OS to those still receiving 6 months (HR 0.89 [0.66-1.20]). PROs 2 years after CAPOX completion, available for a subset of patients, suggest a lower neuropathy (n = 366; 26.2 [21.3-31.1] to 16.5 [14.4-18.6]) and better quality of life (n = 396; 80.9 [78.6-83.2] to 83.9 [82.8-84.9]), but no significant difference in workability (n = 120; 31.5 [27.9-35.1]) to 35.3 [33.8-36.7]), with reduction from 6 to 3 months of CAPOX. CONCLUSION: This real-world study confirmed that shorter adjuvant CAPOX did not compromise OS and may improve PROs, complementing the IDEA study and supporting 3 months of adjuvant CAPOX in daily clinical practice.
Asunto(s)
Neoplasias del Colon , Estadificación de Neoplasias , Medición de Resultados Informados por el Paciente , Humanos , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Neoplasias del Colon/tratamiento farmacológico , Masculino , Femenino , Quimioterapia Adyuvante , Anciano , Persona de Mediana Edad , Países Bajos , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Capecitabina/administración & dosificación , Capecitabina/uso terapéutico , Factores de Tiempo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano de 80 o más Años , Sistema de RegistrosRESUMEN
BACKGROUND: Low muscle mass and skeletal muscle mass (SMM) loss are associated with adverse patient outcomes, but the time-consuming nature of manual SMM quantification prohibits implementation of this metric in clinical practice. Therefore, we assessed the feasibility of automated SMM quantification compared to manual quantification. We evaluated both diagnostic accuracy for low muscle mass and associations of SMM (change) with survival in colorectal cancer (CRC) patients. METHODS: Computed tomography (CT) images from CRC patients enrolled in two clinical studies were analyzed. We compared i) manual vs. automated segmentation of preselected slices at the third lumbar [L3] vertebra ("semi-automated"), and ii) manual L3-slice-selection + manual segmentation vs. automated L3-slice-selection + automated segmentation ("fully-automated"). Automated L3-selection and automated segmentation was performed with Quantib Body Composition v0.2.1. Bland-Altman analyses, within-subject coefficients of variation (WSCVs) and Intraclass Correlation Coefficients (ICCs) were used to evaluate the agreement between manual and automatic segmentation. Diagnostic accuracy for low muscle mass (defined by an established sarcopenia cut-off) was calculated with manual assessment as the "gold standard". Using either manual or automated assessment, Cox proportional hazard ratios (HRs) were used to study the association between changes in SMM (>5% decrease yes/no) during first-line metastatic CRC treatment and mortality adjusted for prognostic factors. SMM change was also assessed separately in weight-stable (<5%, i.e. occult SMM loss) patients. RESULTS: In total, 1580 CT scans were analyzed, while a subset of 307 scans were analyzed in the fully-automated comparison. Included patients (n = 553) had a mean age of 63 ± 9 years and 39% were female. The semi-automated comparison revealed a bias of -2.41 cm2, 95% limits of agreement [-9.02 to 4.20], a WSCV of 2.25%, and an ICC of 0.99 (95% confidence intervals (CI) 0.97 to 1.00). The fully-automated comparison method revealed a bias of -0.08 cm2 [-10.91 to 10.75], a WSCV of 2.85% and an ICC of 0.98 (95% CI 0.98 to 0.99). Sensitivity and specificity for low muscle mass were 0.99 and 0.89 for the semi-automated comparison and 0.96 and 0.90 for the fully-automated comparison. SMM decrease was associated with shorter survival in both manual and automated assessment (n = 78/280, HR 1.36 [95% CI 1.03 to 1.80] and n = 89/280, HR 1.38 [95% CI 1.05 to 1.81]). Occult SMM loss was associated with shorter survival in manual assessment, but not significantly in automated assessment (n = 44/263, HR 1.43 [95% CI 1.01 to 2.03] and n = 51/2639, HR 1.23 [95% CI 0.87 to 1.74]). CONCLUSION: Deep-learning based assessment of SMM at L3 shows reliable performance, enabling the use of CT measures to guide clinical decision making. Implementation in clinical practice helps to identify patients with low muscle mass or (occult) SMM loss who may benefit from lifestyle interventions.
RESUMEN
Physical exercise both during and after curative cancer treatment has been shown to reduce side effects. Evidence in the metastatic cancer setting is scarce, and interventions that improve health-related quality of life (HRQOL) are much needed for patients with metastatic breast cancer (MBC). The multinational randomized controlled PREFERABLE-EFFECT trial assessed the effects of exercise on fatigue and HRQOL in patients with MBC. In total, 357 patients with MBC and a life expectancy of ≥6 months but without unstable bone metastases were recruited at eight study centers across five European countries and Australia. Participants were randomly assigned (1:1) to usual care (control group, n = 179) or a 9-month supervised exercise program (exercise group, n = 178). Intervention effects on physical fatigue (European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-FA12 scale) and HRQOL (EORTC QLQ-C30 summary score) were determined by comparing the change from baseline to 3, 6 (primary timepoint) and 9 months between groups using mixed models for repeated measures, adjusted for baseline values of the outcome, line of treatment (first or second versus third or higher) and study center. Exercise resulted in significant positive effects on both primary outcomes. Physical fatigue was significantly lower (-5.3 (95% confidence interval (CI), -10.0 to -0.6), Bonferroni-Holm-adjusted P = 0.027; Cohen's effect size, 0.22) and HRQOL significantly higher (4.8 (95% CI, 2.2-7.4), Bonferroni-Holm-adjusted P = 0.0003; effect size, 0.33) in the exercise group than in the control group at 6 months. Two serious adverse events occurred (that is, fractures), but both were not related to bone metastases. These results demonstrate that supervised exercise has positive effects on physical fatigue and HRQOL in patients with MBC and should be recommended as part of supportive care.ClinicalTrials.gov Identifier: NCT04120298 .
RESUMEN
Objective: To improve sustainability of a patient decision aid for systemic treatment of metastatic colorectal cancer, we evaluated real-world experiences and identified ways to optimize decision aid content and future implementation. Methods: Semi-structured interviews with patients and medical oncologists addressed two main subjects: user experience and decision aid content. Content analysis was applied. Fifteen experts discussed the results and devised improvements based on experience and literature review. Results: Thirteen users were interviewed. They confirmed the relevance of the decision aid for shared decision making. Areas for improvement of content concerned; 1) outdated and missing information, 2) an imbalance in presentation of treatment benefits and harms, and 3) medical oncologists' expressed preference for a more center-specific or patient individualized decision aid, presenting a selection of the guideline recommended treatment options. Key points for improvement of implementation were better alignment within the care pathway, and clear instruction to users. Conclusion: We identified relevant opportunities for improvement of an existing decision aid and developed an updated version and accompanying implementation strategy accordingly. Innovation: This paper outlines an approach for continued decision aid and implementation strategy development which will add to sustainability. Implementation success of the improved decision aid is currently being studied in a multi-center mixed-methods implementation study.
RESUMEN
BACKGROUND: Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus far, we assessed the association of immunosuppressant type and dose with survival in melanoma patients with irAEs. METHODS: Patients with advanced melanoma who received immunosuppressants for irAEs induced by first-line anti-PD-1 ± anti-CTLA-4 were included from 18 hospitals worldwide. Associations of cumulative and peak dose corticosteroids and use of second-line immunosuppression with survival from start of immunosuppression were assessed using multivariable Cox proportional hazard regression. RESULTS: Among 606 patients, 404 had anti-PD-1 + anti-CTLA-4-related irAEs and 202 had anti-PD-1-related irAEs. 425 patients (70 %) received corticosteroids only; 181 patients (30 %) additionally received second-line immunosuppressants. Median PFS and OS from starting immunosuppression were 4.5 (95 %CI 3.4-8.1) and 31 (95 %CI 15-not reached) months in patients who received second-line immunosuppressants, and 11 (95 %CI 9.4-14) and 55 (95 %CI 41-not reached) months in patients who did not. High corticosteroid peak dose was associated with worse PFS and OS (HRadj 1.14; 95 %CI 1.01-1.29; HRadj 1.29; 95 %CI 1.12-1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HRadj 1.32; 95 %CI 1.02-1.72) and OS (HRadj 1.34; 95 %CI 0.99-1.82) compared with corticosteroids alone. CONCLUSIONS: High corticosteroid peak dose and second-line immunosuppressants to treat irAEs are both associated with impaired survival. While immunosuppression is indispensable for treatment of severe irAEs, clinicians should weigh possible detrimental effects on survival against potential disadvantages of undertreatment.
Asunto(s)
Corticoesteroides , Inhibidores de Puntos de Control Inmunológico , Inmunosupresores , Melanoma , Humanos , Masculino , Femenino , Melanoma/tratamiento farmacológico , Melanoma/inmunología , Melanoma/mortalidad , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Persona de Mediana Edad , Anciano , Corticoesteroides/uso terapéutico , Corticoesteroides/efectos adversos , Adulto , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Anciano de 80 o más AñosRESUMEN
Ventilator-associated respiratory tract infections (VARTI) are among the most common indications for hospitalization among children with chronic respiratory failure requiring at-home ventilation. This review aims to provide an overview of the key clinical features, diagnostic approaches, and management strategies for home VARTIs while highlighting the challenges in diagnosis and management.
Asunto(s)
Servicios de Atención de Salud a Domicilio , Respiración Artificial , Humanos , Niño , Neumonía Asociada al Ventilador , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/etiologíaRESUMEN
We previously demonstrated that intake of low-fat dairy, but not high-fat dairy, was associated with a decreased colorectal cancer (CRC) recurrence risk. These risks, however, may differ by sex, primary tumour location, and disease stage. Combining data from two similar prospective cohort studies of people with stage I-III CRC enabled these subgroup analyses. Participants completed a food frequency questionnaire at diagnosis (n = 2283). We examined associations between low- and high-fat dairy intake and recurrence risk using multivariable Cox proportional hazard models, stratified by sex, and primary tumour location (colon and rectum), and disease stage (I/II and III). Upper quartiles were compared to lower quartiles of intake, and recurrence was defined as a locoregional recurrence and/or metastasis. During a median follow-up of 5.0 years, 331 recurrences were detected. A higher intake of low-fat dairy was associated with a reduced risk of recurrence (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.43-0.83), which seemed more pronounced in men (HR: 0.51, 95% CI: 0.34-0.77) than in women (HR: 0.84, 95% CI: 0.47-1.49). A higher intake of high-fat dairy was associated with an increased risk of recurrence in participants with colon cancer (HR: 1.60, 95% CI: 1.03-2.50), but not rectal cancer (HR: 0.88, 95% CI: 0.54-1.45). No differences in associations were observed between strata of disease stage. Concluding, our findings imply that dietary advice regarding low-fat dairy intake may be especially important for men with CRC, and that dietary advice regarding high-fat dairy intake may be specifically important in people with colon cancer.
Asunto(s)
Neoplasias Colorrectales , Productos Lácteos , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Humanos , Masculino , Femenino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/epidemiología , Persona de Mediana Edad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/epidemiología , Anciano , Estudios Prospectivos , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/efectos adversos , Factores Sexuales , Factores de Riesgo , Modelos de Riesgos Proporcionales , Dieta Alta en Grasa/efectos adversosRESUMEN
Based 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.
Asunto(s)
Adiposidad , Neoplasias Colorrectales , Dieta , Ejercicio Físico , Conducta Sedentaria , Humanos , Pronóstico , Suplementos Dietéticos , Factores de RiesgoRESUMEN
Low 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.
Asunto(s)
Neoplasias Colorrectales , Ejercicio Físico , Conducta Sedentaria , Humanos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/diagnóstico , Pronóstico , Estudios Observacionales como AsuntoRESUMEN
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.
Asunto(s)
Neoplasias Colorrectales , Suplementos Dietéticos , Humanos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/epidemiología , Pronóstico , Dieta , Vitamina D/administración & dosificación , Vitamina D/análogos & derivados , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Observacionales como AsuntoRESUMEN
The 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.
Asunto(s)
Adiposidad , Índice de Masa Corporal , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/diagnóstico , Pronóstico , Circunferencia de la Cintura , Relación Cintura-Cadera , Femenino , Obesidad/complicacionesRESUMEN
A State of the Art lecture titled "Cancer and Arterial Thrombosis: Therapeutic Options" was presented at the International Society on Thrombosis and Haemostasis Congress in 2023. This State of the Art review delves into the complex relationship between cancer and arterial thromboembolism (ATE), encompassing acute coronary syndrome, ischemic strokes, and peripheral arterial disease. The burden of cancer-associated ATE is not well defined, but studies indicate elevated risks, particularly in the 6 months after a cancer diagnosis. Incidence varies among cancer subtypes, with lung cancer displaying the highest rates. Additionally, the pathophysiology of cancer-associated ATE involves a multifaceted interplay of cancer-induced hypercoagulopathy, cancer therapy-related thrombosis, and personal risk factor contributors. ATEs are clinically heterogeneous and in the context of cancer have particular mechanistic differences compared with ATE patients without cancer. This requires modifications in approach and tailored management considerations. Specific etiologies contributing to ATE, such as coronary vasospasm and non-bacterial-thrombotic endocarditis, need to be considered. The diagnosis of cancer alone usually does not contraindicate patients to standard guideline-based therapies for the management of ATE, although nuances in treatment may need to be considered in light of the underlying cancer. Atrial fibrillation in cancer patients further complicates the thrombotic landscape. Cancer patients with atrial fibrillation are at a higher risk of ATE, necessitating careful consideration of anticoagulation therapy as clinical benefits and bleeding risks need to be weighed. ATE may also be a presenting sign of underlying malignancy, which requires increased awareness and focused clinical evaluation for cancer in selected cases. Finally, we summarize relevant new data on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress.
RESUMEN
The use of patient-reported outcomes (PROMs) of quality of life (QOL) is common in cachexia trials. Patients' self-report on health, functioning, wellbeing, and perceptions of care, represent important measures of efficacy. This review describes the frequency, variety, and reporting of QOL endpoints used in cancer cachexia clinical trials. Electronic literature searches were performed in Medline, Embase, and Cochrane (1990-2023). Seven thousand four hundred thirty-five papers were retained for evaluation. Eligibility criteria included QOL as a study endpoint using validated measures, controlled design, adults (>18 years), ≥40 participants randomized, and intervention exceeding 2 weeks. The Covidence software was used for review procedures and data extractions. Four independent authors screened all records for consensus. Papers were screened by titles and abstracts, prior to full-text reading. PRISMA guidance for systematic reviews was followed. The protocol was prospectively registered via PROSPERO (CRD42022276710). Fifty papers focused on QOL. Twenty-four (48%) were double-blind randomized controlled trials. Sample sizes varied considerably (n = 42 to 469). Thirty-nine trials (78%) included multiple cancer types. Twenty-seven trials (54%) featured multimodal interventions with various drugs and dietary supplements, 11 (22%) used nutritional interventions alone and 12 (24%) used a single pharmacological intervention only. The median duration of the interventions was 12 weeks (4-96). The most frequent QOL measure was the EORTC QLQ-C30 (60%), followed by different FACIT questionnaires (34%). QOL was a primary, secondary, or exploratory endpoint in 15, 31 and 4 trials respectively, being the single primary in six. Statistically significant results on one or more QOL items favouring the intervention group were found in 18 trials. Eleven of these used a complete multidimensional measure. Adjustments for multiple testing when using multicomponent QOL measures were not reported. Nine trials (18%) defined a statistically or clinically significant difference for QOL, five with QOL as a primary outcome, and four with QOL as a secondary outcome. Correlation statistics with other study outcomes were rarely performed. PROMs including QOL are important endpoints in cachexia trials. We recommend using well-validated QOL measures, including cachexia-specific items such as weight history, appetite loss, and nutritional intake. Appropriate statistical methods with definitions of clinical significance, adjustment for multiple testing and few co-primary endpoints are encouraged, as is an understanding of how interventions may relate to changes in QOL endpoints. A strategic and scientific-based approach to PROM research in cachexia trials is warranted, to improve the research base in this field and avoid the use of QOL as supplementary measures.
Asunto(s)
Caquexia , Neoplasias , Calidad de Vida , Humanos , Caquexia/etiología , Caquexia/terapia , Neoplasias/complicaciones , Neoplasias/psicología , Ensayos Clínicos como Asunto , Medición de Resultados Informados por el PacienteRESUMEN
INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.