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BACKGROUND & AIMS: Exocrine pancreatic insufficiency (EPI) contributes to malnutrition, marked by muscle loss during chemotherapy for advanced pancreatic cancer (aPC). Pancreatic enzyme replacement therapy (PERT) is recommended for patients with EPI; however, it's efficacy for attenuating muscle loss has not been demonstrated. We aimed to delineate the impact of PERT dose on muscle loss using a 7-year population-based cohort with aPC who were provided PERT at the discretion of their oncologist or dietitian according to clinical indications of EPI. METHODS: All patients treated with chemotherapy for aPC from 2013 to 2019 in Alberta, Canada (population â¼4.3 million) were included if they had computed tomography (CT) scans both prior to and 12 ± 4 weeks after chemotherapy initiation. Change in muscle area (cm2) was measured at 3rd lumbar level on repeated CT scans. Muscle loss was defined by measurement error (loss >2.3 cm2). Clinical and pharmaceutical data were retrieved from provincial registries. For patients who were dispensed PERT -8 to +6 weeks from chemo start (PERT users), estimated dose consumed per day was calculated as: (total dose dispensed) / (days, first to last dispensation). PERT users were categorized as high dose or low dose users according to the median estimated dose consumed. Non-users were classified as No PERT. Association between PERT use and muscle loss was analyzed with multivariable logistic regression. RESULTS: Among 210 patients, 81 (39%) were PERT users. Median estimated dose consumed per day of 75 000 USP lipase units defined the cutoff between low dose and high dose uses. There were no significant differences in baseline characteristics between high dose and low dose groups. Muscle loss was more prevalent among low dose compared to both high dose and No PERT groups (88% vs. 58% and 67%, p < 0.05). In the multivariable model predicting muscle loss, low dose PERT was independently associated with greater odds of muscle loss (OR 5.4, p = 0.004) vs. high dose, independent of tumour response, disease stage, and chemotherapy regimen. CONCLUSION: In patients with clinical indications of EPI during chemotherapy for aPC, low doses of PERT were insufficient to prevent muscle loss. Patients with EPI consuming higher doses of PERT had similar odds of muscle maintenance to patients without clinical indications of EPI. Provider education for optimal PERT dosing in patients with EPI should be prioritized, and resources must be allocated to support dose titration.
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Terapia de Reposição de Enzimas , Insuficiência Pancreática Exócrina , Neoplasias Pancreáticas , Humanos , Terapia de Reposição de Enzimas/métodos , Masculino , Feminino , Insuficiência Pancreática Exócrina/tratamento farmacológico , Insuficiência Pancreática Exócrina/etiologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Sarcopenia/tratamento farmacológico , Sarcopenia/etiologia , Alberta , Músculo Esquelético/efeitos dos fármacos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Tomografia Computadorizada por Raios X , Relação Dose-Resposta a DrogaRESUMO
Muscle and adipose wasting during chemotherapy for advanced pancreatic cancer (aPC) are associated with poor outcomes. We aimed to quantify the contributions of chemotherapy regimen and tumour progression to muscle and adipose wasting and evaluate the prognostic value of each tissue loss. Of all patients treated for aPC from 2013-2019 in Alberta, Canada (n = 504), computed-tomography (CT)-defined muscle and adipose tissue index changes (∆SMI, ∆ATI, cm2/m2) were measured for patients with CT images available both prior to and 12 ± 4 weeks after chemotherapy initiation (n = 210). Contributions of regimen and tumour response to tissue change were assessed with multivariable linear regression. Survival impacts were assessed with multivariable Cox's proportional hazards models. Tissue changes varied widely (∆SMI: -17.8 to +7.3 cm2/m2, ∆ATI: -106.1 to +37.7 cm2/m2) over 116 (27) days. Tumour progression contributed to both muscle and adipose loss (-3.2 cm2/m2, p < 0.001; -12.4 cm2/m2, p = 0.001). FOLFIRINOX was associated with greater muscle loss (-1.6 cm2/m2, p = 0.013) and GEM/NAB with greater adipose loss (-11.2 cm2/m2, p = 0.002). The greatest muscle and adipose losses were independently associated with reduced survival (muscle: HR 1.72, p = 0.007; adipose: HR 1.73, p = 0.012; tertile 1 versus tertile 3). Muscle and adipose losses are adverse effects of chemotherapy and may require regimen-specific management strategies.
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Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta-analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative-intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta-analysis. Studies that measured computed tomography-defined SM and/or AT change in adult patients during palliative-intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6 weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm2 /m2 , cm2 or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex-specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta-analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care.
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Neoplasias , Adulto , Feminino , Humanos , Masculino , Tecido Adiposo/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Obesidade , Padrões de Referência , Tomografia Computadorizada por Raios X , Metanálise como AssuntoRESUMO
PURPOSE OF REVIEW: Systemic cancer therapy-associated skeletal muscle wasting is emerging as a powerful impetus to the overall loss of skeletal muscle experienced by patients with cancer. This review explores the clinical magnitude and biological mechanisms of muscle wasting during systemic cancer therapy to illuminate this adverse effect. Emerging strategies for mitigation are also discussed. RECENT FINDINGS: Clinical findings include precise, specific measures of muscle loss over the course of chemotherapy, targeted therapy and immunotherapy. All these therapeutic classes associate with quantitatively important muscle loss, independent of tumor response. Parallel experimental studies provide understanding of the specific molecular basis of wasting, which can include inhibition of protein synthesis, proliferation and differentiation, and activation of inflammation, reactive oxygen species, autophagy, mitophagy, apoptosis, protein catabolism, fibrosis and steatosis in muscle. Strategies to mitigate these muscle-specific adverse effects of cancer therapy remain in the earliest stages of development. SUMMARY: The adverse side effect of cancer therapy on skeletal muscle has been largely ignored in the development of cancer therapeutics. Given the extent to which loss of muscle mass and function can bear on patients' function and quality of life, protection/mitigation of these side effects is a research priority.
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Miotoxicidade , Neoplasias , Humanos , Miotoxicidade/metabolismo , Miotoxicidade/patologia , Qualidade de Vida , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Neoplasias/metabolismoRESUMO
Fortified snacks can increase nutrient intake among patients with cancer. The aim of this study was to identify snack foods preferred as potential vehicles for fortification and how experienced symptoms influence preferences.A study-specific survey among 150 patients identified snack foods for fortification, influence of symptom presence, desired nutrients and characteristics of a fortified snack, and perception of oral nutritional supplements.Patients had mainly breast, gastrointestinal, lung, and colorectal tumors. Soup, yogurt, cheese, fruit juice, egg products, and protein bars were identified as suitable fortified snacks by >60% of subjects. Desired characteristics for snacks included nutritious, flavorful, convenient, ready to eat, easy to chew, and easy to swallow. Vitamins, minerals, and protein were the nutrients of interest. Three clusters of symptoms were identified that predicted patients' desired characteristics of fortified snacks and satisfaction with food-related life. Patients in High and Moderate symptom clusters were more likely to have reduced food intake and higher consumption of oral nutritional supplements.Preferences for fortified snacks and their characteristics are influenced by symptom presence. The results of this study provide insight to guide the development of fortified snacks for patients with cancer.
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Neoplasias , Lanches , Ingestão de Alimentos , Preferências Alimentares , Alimentos Fortificados , Humanos , VitaminasRESUMO
Oat-based beverages are a nutritious product with the potential to support increased nutrient intake of patients with cancer. The aim of this research was to evaluate the sensory acceptance of oat-based beverages and perceptions of oats among patients with cancer as future vehicles for nutrient delivery. In study 1, three flavors of oat-beverages were well accepted without significant difference in liking among flavors or serving temperature, or between patients with cancer and healthy participants. Patients with cancer more frequently rated the beverages as too sweet compared to healthy participants; flavor intensity was just about right for all participants. In the second study, one of two formulations fortified with protein and fish oil was not different in liking compared to the unfortified chocolate product. Patients associated oat food products with specific oat-based food products and oat health benefits in a free-word association task in the third study. Together, sensory acceptance and the perceived health benefits of oats indicate the potential for oats to be incorporated in fortified and unfortified products tailored for patients with cancer. PRACTICAL APPLICATION: The three studies presented here to assess the sensory acceptance of oat-based beverages and perceptions of oats among patients with cancer demonstrate that oats can be incorporated in fortified and unfortified products tailored for patients with cancer. Inadequate nutrition is highly prevalent among oncology patients and there is a lack of available products targeted to improve their nutritional intake. These findings can support product developers and sensory scientists in the development and evaluation of food products acceptable to this population.
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Avena/química , Bebidas/análise , Ingestão de Energia , Desnutrição/dietoterapia , Neoplasias/complicações , Paladar/fisiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Aromatizantes/análise , Humanos , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Adulto JovemRESUMO
Pre-operative nutrition screening is recommended to identify cancer patients at risk of malnutrition, which is associated with poor outcomes. Low muscle mass (sarcopenia) and lipid infiltration to muscle cells (myosteatosis) are similarly associated with poor outcomes but are not routinely screened for. We investigated the prevalence of sarcopenia and myosteatosis across the nutrition screening triage categories of the Patient-Generated Subjective Global Assessment Short Form (PG-SGASF) in a pre-operative colorectal cancer (CRC) cohort. Data were prospectively collected from patients scheduled for surgery at two sites in Edmonton, Canada. PG-SGASF scores ≥ 4 identified patients at risk for malnutrition; sarcopenia and myosteatosis were identified using computed-tomography (CT) analysis. Patients (n = 176) with a mean age of 63.8 ± 12.0 years, 52.3% male, 90.3% with stage I-III disease were included. Overall, 25.2% had PG-SGASF score ≥ 4. Sarcopenia alone, myosteatosis alone or both were identified in 14.0%, 27.3%, and 6.4% of patients, respectively. Sarcopenia and/or myosteatosis were identified in 43.4% of those with PG-SGASF score < 4 and in 58.5% of those with score ≥ 4. Overall, 32.9% of the cohort had sarcopenia and/or myosteatosis with PG-SGASF score < 4. CT-defined sarcopenia and myosteatosis are prevalent in pre-operative CRC patients, regardless of the presence of traditional nutrition risk factors (weight loss, problems eating); therefore, CT image analysis effectively adds value to nutrition screening by identifying patients with other risk factors for poor outcomes.
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Composição Corporal , Neoplasias do Colo/complicações , Neoplasias Colorretais/complicações , Recuperação Pós-Cirúrgica Melhorada , Estado Nutricional , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Tomografia Computadorizada por Raios X/métodos , Idoso , Canadá , Estudos de Coortes , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Desnutrição/diagnóstico por imagem , Programas de Rastreamento , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Fatores de Risco , Sarcopenia/patologiaRESUMO
PURPOSE: Many patients with cancer are interested in complementary therapies, including strategies such as reduced carbohydrate diets. Guidelines regarding the use of these diets during cancer treatment are lacking; therefore, we aimed to explore the perceptions and practices of medical oncologists in Canada regarding low-sugar and ketogenic diets. METHOD: A cross-sectional, online multiple-choice survey was distributed to 206 Canadian medical oncologists. Questions explored frequency of patient interactions, oncologist perceptions of efficacy, advice given to patients, and concerns about side effects related to reduced carbohydrate diets. RESULTS: Responses were received from 57 medical oncologists in seven of thirteen provinces and territories, with an overall response rate of 28%. Forty-nine percent of respondents were asked at least weekly about a low-sugar diet, and 9% about the ketogenic diet. Eighty-five percent supported the use of a low-added sugar diet in patients with diabetes or hyperglycemia, while conversely 87% did not support the use of a ketogenic diet for any of their patients undergoing active cancer treatment. Respondents felt either that a ketogenic diet was not effective (31%) or that the effect on cancer outcomes was unknown (69%). Ninety-six percent of respondents had concerns about a ketogenic diet for patients receiving active cancer treatment. CONCLUSION: The role of reduced carbohydrate diets during cancer treatment is topical. Canadian oncologists are particularly reluctant to support a ketogenic diet for patients on active cancer treatment, with concerns about side effects and unknown efficacy. There may be a role for continuing medical education and institutional guidelines to inform these discussions with patients.
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Dieta com Restrição de Carboidratos , Dieta Cetogênica , Neoplasias/dietoterapia , Oncologistas , Percepção , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Canadá/epidemiologia , Terapias Complementares/métodos , Terapias Complementares/psicologia , Terapias Complementares/estatística & dados numéricos , Estudos Transversais , Dieta com Restrição de Carboidratos/efeitos adversos , Dieta com Restrição de Carboidratos/psicologia , Dieta com Restrição de Carboidratos/estatística & dados numéricos , Dieta Cetogênica/efeitos adversos , Dieta Cetogênica/psicologia , Dieta Cetogênica/estatística & dados numéricos , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Oncologistas/psicologia , Oncologistas/estatística & dados numéricos , Percepção/fisiologia , Inquéritos e QuestionáriosRESUMO
PURPOSE OF REVIEW: Recommendations for intakes of nâ-â3 fatty acids (FAs) in patients who are receiving chemotherapy for cancer are based on weak evidence. This review highlights themes within the emergent literature to suggest improvements in the design of studies that provide nâ-â3 FA supplements concurrent with cytotoxic agents. RECENT FINDINGS: Following earlier research in animal models and human pilot studies, recent human studies have evaluated the effect of providing nâ-â3 FAs during delivery of single agent and multiagent chemotherapy regimens for breast and gastro-intestinal cancers. Regimens were based on platinum compounds, fluoropyrimidines or both, and a variety of additional agents. Tumor location and stage, supplement dose and duration, and endpoints were dissimilar across studies. Overall, the recent research continues to support the safety and tolerability of nâ-â3 FA supplementation with chemotherapy and provides additional evidence, albeit weak, for enhanced tumor response, maintenance of weight and muscle, and reduction in inflammation and toxicities in the host across multiple cancer sites and chemotherapy regimens. SUMMARY: The barriers to implementation in practice remain small study sizes, variations in supplement dosage and methodology, and differences in primary endpoints. Randomized, blinded trials with a justifiable sample size, adequate doses, monitored compliance and measures of clinically important endpoints are required to move these findings to a higher level of evidence for implementation into clinical practice.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos Antineoplásicos/normas , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Neoplasias da Mama/tratamento farmacológico , Ensaios Clínicos como Assunto , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Masculino , Resultado do TratamentoRESUMO
Aims To explore and describe perceptions and experiences of living with type 1 Diabetes Mellitus among children/youths in Tajikistan. Methods Qualitative methods were employed. Participants were recruited through purposive and snowball samplings. Data were collected using a semi-structured interview guide with children/youths having diabetes, their parents as well as health professionals. Data were analyzed according to Malterud's systematic text condensation. Results Children/youths with diabetes (n = 18), their parents (n = 19) and endocrinologists (n = 4) were interviewed. Families described unique stories in which "emotional stress" and a spiritual "evil eye" were perceived as possible causes of diabetes. Life-threatening complications and maltreatment preceding diagnosis of diabetes were frequent. From manifestation of diabetes onwards, families struggled with systemic and cultural obstacles, causing stigma, discrimination, high school-drop-out rates, diabetic coma, chronic complications or death of the child/youth with diabetes. Conclusions Results of this qualitative study highlight the severity and complexity of challenges families living with a child/youth having diabetes in this low-income country face. Efforts to improve life expectancy and life quality are strongly needed and require addressing both systemic and cultural factors in order to accomplish sustainable impact.