The prevalence of CT-defined low skeletal muscle mass in patients with metastatic cancer: a cross-sectional multicenter French study (the SCAN study).

BACKGROUND: Cachexia, characterized by involuntary muscle mass loss, negatively impacts survival outcomes, treatment tolerability, and functionality in cancer patients. However, there is a limited appreciation of the true prevalence of low muscle mass due to inconsistent diagnostic methods and limited oncologist awareness. METHODS: Twenty-nine French healthcare establishments participated in this cross-sectional study, recruiting patients with those metastatic cancers most frequently encountered in routine practice (colon, breast, kidney, lung, prostate). The primary outcome was low skeletal muscle mass prevalence, as diagnosed by estimating the skeletal mass index (SMI) in the middle of the third-lumbar vertebrae (L3) level via computed tomography (CT). Other objectives included an evaluation of nutritional management, physical activity, and toxicities related to ongoing treatment. RESULTS: Seven hundred sixty-six patients (49.9% males) were enrolled with a mean age of 65.0 years. Low muscle mass prevalence was 69.1%. Only one-third of patients with low skeletal muscle mass were receiving nutritional counselling and only 28.4% were under nutritional management (oral supplements, enteral or parenteral nutrition). Physicians highly underdiagnosed those patients identified with low skeletal muscle mass, as defined by the primary objective, by 74.3% and 44.9% in obese and non-obese patients, respectively. Multivariate analyses revealed a lower risk of low skeletal muscle mass for females (OR: 0.22, P < 0.01) and those without brain metastasis (OR: 0.34, P < 0.01). Low skeletal muscle mass patients were more likely to have delayed treatment administration due to toxicity (11.9% versus 6.8%, P = 0.04). CONCLUSIONS: There is a critical need to raise awareness of low skeletal muscle mass diagnosis among oncologists, and for improvements in nutritional management and physical therapies of cancer patients to curb potential cachexia. This calls for cross-disciplinary collaborations among oncologists, nutritionists, physiotherapists, and radiologists.

Impact on Health-Related Quality of Life of Parenteral Nutrition for Patients with Advanced Cancer Cachexia: Results from a Randomized Controlled Trial.

BACKGROUND: Malnutrition worsens health-related quality of life (HRQoL) and the prognosis of patients with advanced cancer. This study aimed to assess the clinical benefits of parenteral nutrition (PN) over oral feeding (OF) for patients with advanced cancer cachexia and without intestinal impairment. MATERIAL AND METHODS: In this prospective multicentric randomized controlled study, patients with advanced cancer and malnutrition were randomly assigned to optimized nutritional care with or without supplemental PN. Zelen's method was used for randomization to facilitate inclusions. Nutritional and performance status and HRQoL using the European Organization for Research and Treatment of Cancer QLQ-C15-PAL questionnaire were evaluated at baseline and monthly until death. Primary endpoint was HRQoL deterioration-free survival (DFS) defined as a definitive deterioration of ≥10 points compared with baseline, or death. RESULTS: Among the 148 randomized patients, 48 patients were in the experimental arm with PN, 63 patients were in the control arm with OF only, and 37 patients were not included because of early withdrawal or refused consent. In an intent to treat analysis, there was no difference in HRQoL DFS between the PN arm or OF arm for the three targeted dimensions: global health (hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.88-1.94; p = .18), physical functioning (HR, 1.58; 95% CI, 1.06-2.35; p = .024), and fatigue (HR, 1.19; 95% CI, 0.80-1.77; p = .40); there was a negative trend for overall survival among patients in the PN arm. In as treated analysis, serious adverse events (mainly infectious) were more frequent in the PN arm than in the OF arm (p = .01). CONCLUSION: PN improved neither HRQoL nor survival and induced more serious adverse events than OF among patients with advanced cancer and malnutrition. Clinical trial identification number. NCT02151214 IMPLICATIONS FOR PRACTICE: This clinical trial showed that parenteral nutrition improved neither quality of life nor survival and generated more serious adverse events than oral feeding only among patients with advanced cancer cachexia and no intestinal impairment. Parenteral nutrition should not be prescribed for patients with advanced cancer, cachexia, and no intestinal failure when life expectancy is shorter than 3 months. Further studies are needed to assess the useful period with a potential benefit of artificial nutrition for patients with advanced cancer.

Is Nutritional Screening of Patients with Lung Cancer Optimal? An Expert Opinion Survey of French Physicians and Surgeons.

Objectives: To assess how physicians and surgeons carried out malnutrition screening and follow-up for patients with lung cancer. Materials and methods: We carried out an expert opinion survey in France using an anonymous self-administered online questionnaire. Results: In 2017, 206 practitioners responded, of which 60.7% were pulmonologists, 17.4% thoracic surgeons, 11.2% oncologists, and 10.7% radiotherapists. At initial diagnosis, 79.3% of practitioners recorded patients' percentage of weight loss. During follow-up examinations, 67.5% recorded this data for patients at risk of malnutrition and 70.4 % for malnourished patients. Food intake was evaluated by 21.7% of practitioners at initial diagnosis. Surgeons assessed percentage of weight loss and food intake significantly less often than pulmonologists did, they were less likely to request serum albumin tests and waited for a greater percentage of weight loss before referring patients to a nutrition professional. All practitioners were well aware of the prevalence of malnutrition among lung cancer patients and its consequences. The main factors preventing optimal nutritional assessment reported by practitioners were a lack of time and limited specialized knowledge. Conclusion: Nutritional assessment remained suboptimal, especially for surgical patients. The importance granted to malnutrition needs to be increased for patients with lung cancer, especially in surgical departments. Highlights Physicians and thoracic surgeons are well aware of the prevalence and consequences in lung cancer patients. Thoracic surgeons seemed to be less sensitized to malnutrition screening than pulmonologists. Lack of time and limited specialized knowledge were reported as the main factors preventing optimal nutritional assessment.

Fasting and weight-loss restrictive diet practices among 2,700 cancer survivors: results from the NutriNet-Santé cohort.

Nutrition is often used by cancer survivors as a lever to take charge of their own health. However, some dietary behaviors are not currently recommended for patients without medical supervision. Our study aimed at evaluating weight-loss restrictive diets and fasting practices among cancer survivors of the NutriNet-Santé cohort, as well as related socio-demographic and lifestyle factors. In October 2016, 2,741 cancer survivors had completed a specific questionnaire about their practices. Fasting and non-fasting patients (respectively dieting and non-dieting) were compared using logistic regression models. Analyses were weighted according to the age, gender, and cancer location distribution of French cancer cases. 13.8% had already practiced weight-loss restrictive diet as their diagnosis. They were more likely to be women, professionally active, overweight/obese, to use dietary supplements and to have breast cancer (all p < 0.05). 6.0% had already fasted, 3.5% as their diagnosis. They were more likely to be younger, with higher educational level, higher incomes, professionally active, to have a healthy weight, and to use dietary supplements (all p < 0.05). Fasting was associated with the opinion that such practice could improve cancer prognosis (p < 0.0001). Patients who received nutritional information from health care professionals were less likely to practice fasting or weight-loss restrictive diet (0.42[0.27-0.66], p < 0.0001 and 0.49[0.38-0.64], p < 0.0001 respectively). Our study provided original results suggesting that weight-loss restrictive diets are widely practiced by cancer survivors. Fasting was less common in our study though non negligible. Sources of nutritional information received as cancer diagnosis seemed to be a key determinant of these practices.

Factors which modulate the rates of skeletal muscle mass loss in non-small cell lung cancer patients: a pilot study.

PURPOSE: Advanced non-small cell lung cancer (NSCLC) is associated with weight loss which may reflect skeletal muscle mass (SMM) and/or total adipose tissue (TAT) depletion. This study aimed to describe changes in body composition (BC) parameters and to identify the factors unrelated to the tumor which modulate them. METHODS: SMM, TAT, and the proportion of SMM to SMM + TAT were assessed with computed tomography. Estimates of each BC parameter at follow-up initiation and across time were derived from a mixed linear model of repeated measurements with a random intercept and a random slope. The same models were used to assess the independent effect of gender, age, body mass index (BMI), and initial values on changes in each BC parameter. RESULTS: Sixty-four patients with stage III or IV NSCLC were reviewed. The mean ± SD decreases in body weight and SMM were respectively 59 ± 3 g/week (P < 0.03) and 7 mm2/m2/week (P = 0.0003). During follow-up, no changes were identified in TAT nor in muscle density or in the proportion of SMM to SMM + TAT, estimated at 37 ± 2% at baseline. SMM loss was influenced by initial BMI (P < 0.0001) and SMM values (P = 0.0002): the higher the initial BMI or SMM values, the greater the loss observed. Weight loss was greater when the initial weight was heavier (P < 0.0001). CONCLUSION: Our results demonstrate that SMM wasting in NSCLC is lower when initial SMM and BMI values are low. These exploratory findings after our attempt to better understand the intrinsic factors associated with muscle mass depletion need to be confirmed in larger studies.

Sarcopenia is Associated with Chemotherapy Toxicity in Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Colorectal Cancer.

BACKGROUND: Despite the positive survival results of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), criticisms have been put forward regarding the safety of this treatment as a result of a high morbidity rate. Muscle depletion (sarcopenia) is associated with the occurrence of postoperative complications. The purpose of this study was to determine the association between sarcopenia and postoperative morbidity after CRS-HIPEC for peritoneal carcinomatosis from colorectal cancer by distinguishing the complications linked to CRS itself and those associated with chemotherapy (HIPEC) toxicities. METHODS: Data concerning 97 consecutive patients who had undergone CRS-HIPEC were recorded. We analyzed the events occurring within 30 days after surgery that were prospectively recorded in a database. Sarcopenia was assessed using the L3 muscle index on computed tomography performed during the 2 months preceding surgery. RESULTS: The sarcopenic patients experienced significantly more chemotherapy toxicities (57 vs. 26 %; p = 0.004) and especially neutropenia (36 vs. 17 %; p = 0.04) than their nonsarcopenic counterparts. There was no difference in complications linked to the CRS procedure between sarcopenic and nonsarcopenic patients. In the multivariate analysis, sarcopenia was the only parameter independently associated with the risk of chemotherapy toxicity (odds ratio 3.97; 95 % confidence interval 1.52-10.39; p = 0.005). CONCLUSIONS: Despite the local administration of chemotherapy, systemic toxicity was observed in sarcopenic patients after CRS-HIPEC. This relationship favors new treatment strategies with white blood cell growth factors or chemotherapy dosing based on muscle value.

[Nutritional management of patients during surgical prehabilitation and rehabilitation programs]. / Prise en charge nutritionnelle des patients pendant les programmes de préhabilitation et de réhabilitation en chirurgie.

Undernutrition (UD) increases perioperative morbidity and mortality. Its prevention and treatment are therefore essential in surgical prehabilitation and rehabilitation programs. Nutritional treatment is individualized according to the patient's nutritional status, ingesta and protein-energy requirements. Oral nutrition is optimized to increase intakes through personalized dietary advice and oral nutritional supplements. Artificial nutrition support is indicated in cases of UD or high risk of UD before major surgery. Enteral nutrition is preferred to parenteral nutrition when the digestive tract is functional.

Prevalence and survival implications of malnutrition and sarcopenia in metastatic breast cancer: A longitudinal analysis.

BACKGROUND: Malnutrition and sarcopenia are challenges for patients with metastatic breast cancer and have been proposed as independent prognostic factors. Very few studies have addressed the temporal evolution of these parameters and, notably, the separate and combined analysis of sarcopenia and malnutrition. This study aimed to i) determine the prevalence of malnutrition and sarcopenia, individually and combined, and their evolution over time, ii) identify risk factors for each condition, and iii) explore their impact on overall survival (OS). METHODS: This retrospective study was conducted on 111 patients treated for at least a third-line metastatic breast cancer at the Institut Curie between January 1st and March 31st, 2018. Solitary malnutrition was defined from weight loss and body mass index values while solitary sarcopenia was defined solely based on low muscle mass. We analyzed solitary malnutrition, solitary sarcopenia, and then malnutrition with or without sarcopenia, at three key stages (T1: diagnosis of metastasis, T2: initiation of third-line treatment, and T3: 3-month re-evaluation). Univariate and multivariate logistic regression analyses were conducted to investigate the risk factors. We performed Cox proportional hazards analyses for each variable. RESULTS: At T1, the prevalence of solitary malnutrition, solitary sarcopenia and malnutrition with or without sarcopenia was 18.6%, 36.1% and 48.9% respectively, increasing to 27.7%, 45.5% and 56.6% at T2. At T2, in multivariate logistic regression analyses, patients aged over 60 years were at an elevated risk of experiencing solitary malnutrition as well as malnutrition with or without sarcopenia, but not solitary sarcopenia. In multivariate analyses, solitary malnutrition was significantly associated with poorer OS (HR 2.2 [95% CI 1.1-4.1], p = 0.02), while solitary sarcopenia and malnutrition with or without sarcopenia showed no association. CONCLUSION: Solitary malnutrition and sarcopenia were highly prevalent in patients with metastatic breast cancer, affecting around a quarter and half of patients respectively at third-line treatment initiation. Notably, solitary malnutrition emerged as a prognostic factor for overall survival, whereas no significant association was observed for solitary sarcopenia or malnutrition with or without sarcopenia. This highlights the critical need for early identification of patients at risk of malnutrition and the importance of timely intervention.

Psoas muscle index is not representative of skeletal muscle index for evaluating cancer sarcopenia.

BACKGROUND: A common method for diagnosing sarcopenia involves estimating the muscle mass by computed tomography (CT) via measurements of the cross-sectional muscle area (CSMA) of all muscles at the third lumbar vertebra (L3) level. Recently, single-muscle measurements of the psoas major muscle at L3 have emerged as a surrogate for sarcopenia detection, but its reliability and accuracy remain to be demonstrated. METHODS: This prospective cross-sectional study involved 29 healthcare establishments and recruited patients with metastatic cancers. The correlation between skeletal muscle index (SMI = CSMA of all muscles at L3/height2 , cm2 /m2 ) and psoas muscle index (PMI = CSMA of psoas at L3/height2 , cm2 /m2 ) was determined (Pearson's r). ROC curves were prepared based on SMI data from a development population (n = 488) to estimate suitable PMI thresholds. International low SMI cut-offs according to gender were studied for males (<55cm2 /m2 ) and for females (<39 cm2 /m2 ). Youden's index (J) and Cohen's kappa (κ) were calculated to estimate the test's accuracy and reliability. PMI cut-offs were validated in a validation population (n = 243) by estimating the percentage concordance of sarcopenia diagnoses with the SMI thresholds. RESULTS: Seven hundred and sixty-six patients were analysed (mean age 65.0 ± 11.8 years, 50.1% female). Low SMI prevalence was 69.1%. Correlation between the SMI and PMI for the entire population was 0.69 (n = 731, P < 0.01). PMI cut-offs for sarcopenia were estimated in the development population at <6.6cm2 /m2 in males and at <4.8 cm2 /m2 for females. The J and κ coefficients for PMI diagnostic tests were weak. The PMI cut-offs were tested in the validation population where 33.3% of the PMI measurements were dichotomously discordant. CONCLUSIONS: A diagnostic test employing single-muscle measurements of the psoas major muscle as a surrogate for sarcopenia detection was evaluated but found to be unreliable. The CSMA of all muscles must be considered for evaluating cancer sarcopenia at L3.

Delivering adapted physical activity by videoconference to patients with fatigue under immune checkpoint inhibitors: Lessons learned from the PACTIMe-FEAS feasibility study.

INTRODUCTION: Fatigue is one of the most frequent symptoms in anti-cancer immune therapy. Physical activity has been proven effective in reducing fatigue, but unmet needs remain regarding the provision and access to adapted programmes, which efficiently addresses the main barriers to PA. METHODS: The PACTIMe-FEAS study primarily aimed at primarily to evaluate the feasibility and the acceptability of a videoconference-based 6-month programme promoting physical activity, and secondarily to assess its potential post-immediate and short-term effectiveness in reducing fatigue in cancer patients under immune therapy. Numeric self-reported questionnaires (Visual Analogue Scale-fatigue, Multidimensional Fatigue Inventory, International Physical Activity Questionnaire, Échelle de Motivation envers l'Activité Physique en contexte de Santé, Medical Outcomes Study 36-Item Short Form Health Survey, Hospital Anxiety and Depression Scale and Insomnia Severity Index) were completed by participants through an online secure platform at three time points: just before (T1), and after (T2) the programme, and 3 months later (T3). RESULTS: Sixteen participants (50% male, 50% female, mean age 54 years, 69% melanoma, 31% overweight), with moderate-to-severe fatigue, entered the internet-delivered intervention; 14 completed it, with an average completion rate of physical activity supervised sessions of 75%. Satisfaction was high, confirming a demand for group format, personalised approach, professional guidance and home-based device, to support the practice of regular physical activity. A decrease in fatigue was observed at the end of the programme. DISCUSSION: The recruitment process did prove to be challenging, with a relatively small eligible population, and will need to be reconsidered to envision a larger scale trial. But here and now, this feasibility study provides the first promising foundations to develop further research on the effectiveness of an original remote programme.

Implementing a PROACTive Care Pathway to Empower and Support Survivors of Breast Cancer.

PURPOSE: Optimal comprehensive survivorship care is insufficiently delivered. To increase patient empowerment and maximize the uptake of multidisciplinary supportive care strategies to serve all survivorship needs, we implemented a proactive survivorship care pathway for patients with early breast cancer at the end of primary treatment phase. METHODS: Pathway components included (1) a personalized survivorship care plan (SCP), (2) face-to-face survivorship education seminars and personalized consultation for supportive care referrals (Transition Day), (3) a mobile app delivering personalized education and self-management advice, and (4) decision aids for physicians focused on supportive care needs. A mixed-methods process evaluation was performed according to the Reach, Effectiveness, Adoption, Implementation and Maintenance framework including administrative data review, pathway experience survey (patient, physician, and organization), and focus group. The primary objective was patient-perceived satisfaction with the pathway (predefined progression criteria for pathway continuation ≥70%). RESULTS: Over 6 months, 321 patients were eligible for the pathway and received a SCP and 98 (30%) attended the Transition Day. Among 126 patients surveyed, 77 (66.1%) responded. 70.1% received the SCP, 51.9% attended the Transition Day, and 59.7% accessed the mobile app. 96.1% of patients were very or completely satisfied with the overall pathway, whereas perceived usefulness was 64.8% for the SCP, 90% for the Transition Day, and 65.2% for the mobile app. Pathway implementation seemed to be positively experienced by physicians and the organization. CONCLUSION: Patients were satisfied with a proactive survivorship care pathway, and the majority reported that its components were useful in supporting their needs. This study can inform the implementation of survivorship care pathways in other centers.

Hyperthermic pelvic perfusion with tumor necrosis factor-α for locally advanced cancers: encouraging results of a phase II study.

PURPOSE: To assess the efficacy of isolated pelvic perfusion (IPP) with tumor necrosis factor (TNF)-α and melphalan in patients with locally advanced cancers in the pelvic and groin area requiring mutilating surgery. METHODS: A total of 27 patients were enrolled (carcinoma, n = 17; sarcoma/melanoma, n = 4; and endocrine tumor, n = 6). They were candidates for exarticulation (n = 3) or exenteration (n = 11) or were judged unresectable (n = 13). In installing IPP, tourniquets were positioned around both thighs, and an inflated pressure suit was placed at a subthoracic position. Tumor necrosis factor-α (300 µg) was injected in the perfusate, followed 5 minutes later by melphalan at 1.5 mg/kg. After 30 minutes, the remaining drugs were washed out. Leakage was assessed with technetium Tc 99m radiolabeled human serum albumin, and a pharmacokinetic study was performed. Efficacy was based on the complete response rate observed on magnetic resonance imaging. RESULTS: Pelvic/systemic ratios of melphalan/TNF/technetium Tc 99m were 14.2/7/3.6. Responses on magnetic resonance imaging were as follows: 30% complete, 30% partial, 19% no change, and 15% progression. Two patients were not evaluable because they did not receive the treatment. Pre-IPP/post-IPP median percentage of necrosis on magnetic resonance imaging was 10%/70%. Median follow-up was 43 months. Median overall survival was 17 months. Twelve-month survival rate, disease-free survival, and local and metastatic recurrence rates were 67%, 30%, 57%, and 26%, respectively. CONCLUSIONS: Isolated pelvic perfusion with TNF-α compares favorably with historical data, as it was observed in limb perfusion and could provide a chance to translate its successful combination with chemotherapy into treatment of locally advanced pelvic cancers.

[Nutrition and physical activity (PA) during and after cancer treatment: Therapeutic benefits, pathophysiology, recommendations, clinical management]. / Nutrition et activité physique adaptée (APA) pendant et après les traitements du cancer : bénéfices thérapeutiques, physiopathologie, recommandations, prise en charge clinique.

Lifestyle behaviors, such as diet and physical activity, are factors that influence risk of numerous cancers. They are also decisive during and after cancer for the course of oncological treatment, but also in the immediate and long-term prognosis, and quality of life during and after treatment. Separately, physical activity and nutritional support can reduce the risk of sarcopenia and its consequences, and improve quality of life during treatment. Whan introduced early, such a combination, increases the prognostic benefits. In remission, particularly in overweight patients, the APA-diet combination reduces the risk of cancer relapse and improves cardiovascular performance. These programs require a precise assessment of capacities and habits of each patient, and interventions of trained professionals (certified exercise instructor, dietician trained in oncology). The funding conditions for these programs exist for cancer survivors and should be considered for oncological treatment period.

Association between Nutritional Status and Treatment Response and Survival in Patients Treated with Immunotherapy for Lung Cancer: A Retrospective French Study.

Malnutrition is associated with a greater risk of morbidity and mortality and lower tolerance to chemotherapy. Our purpose was to study the association between nutritional status and the efficiency and tolerance of immunotherapy in non-small cell lung cancer (NSCLC). Nutritional and oncological data were reported at 2 months (M2) and 4 months (M4) after the initiation of immunotherapy (M0). The influence of nutritional status at M0 was estimated with the efficacy and toxicity of immunotherapy at M2 to M4. In total, 127 patients were included in the study, and nutritional status was estimated at M0 for 120 patients: 67% were not malnourished, 20% presented with moderate malnutrition, and 13% presented with severe malnutrition. There was no significant link between the nutritional status at M0 and the toxicity of immunotherapy at M2 and M4. However, severe malnutrition was significantly associated with treatment efficacy at M2 (p = 0.04) and with a lower survival rate with an HR (Hazard Ratio) = 2.32-95% C.I: 1.13-4.75 (p = 0.02). Furthermore, a monthly decrease of 1% of the weight had an HR = 1.17-95% C.I: 1.13-1.21 (p = 0.0001). Severe malnutrition and weight loss are independent factors associated with lower survival. Studies integrating the systemic detection of sarcopenia with a closer nutritional follow-up could highlight an improvement in survival.

Relationship between the creatinine/cystatin C ratio and muscle mass measured by CT-scan in cancer patients.

BACKGROUND: Sarcopenia is observed in about 50% of cancer patients. Cancer-related sarcopenia negatively affects survival and is a predictive factor of anticancer drug toxicity. Sarcopenia diagnosis is challenging in routine care. We investigated whether plasma creatinine and cystatin C predict sarcopenia diagnosis in the specific population of cancer patients. METHODS: Two common diagnostic criteria of cancer-related sarcopenia based on skeletal muscle mass ± handgrip strength were separately applied as the "gold standard" sarcopenia definition. Four sarcopenia indexes based on creatinine and cystatin C values were evaluated: Creatinine/Cystatin C, Glomerular Filter rate (GFR) Cockroft-Gault/GFR CKD-EPI, GFR Cockroft-Gault/GFR Grubb and GFR Cockroft-Gault/GFR simple. The receiver operating characteristic (ROC) curves and the area under the ROC curves were applied to evaluate the sarcopenia diagnostic accuracy of the four different sarcopenia indexes. RESULTS: A total of 99 patients were included. Among them, 47.5% were overweight or obese. The ratio creatinine/cystatin C (ratio value at 0.8) more accurately predicts the diagnosis of sarcopenia in the entire population based on low skeletal muscle mass and low handgrip strength (sensitivity, specificity, accuracy and Youden index at 0.77, 0.57, 0.90, 0.34 respectively). The other evaluated ratios predict sarcopenia with a lower specificity in all conditions. In the overweight/obese group, the results are similar. The ratio creatinine/cystatin C (ratio value at 1) accurately predicts sarcopenia with a sensitivity, a specificity, an accuracy and a Youden index at 0.50, 0.86, 0.95, 0.36 respectively in overweight/obese population. CONCLUSIONS: The creatinine/cystatin C ratio is a useful and simple biomarker to predict sarcopenia in cancer patients. Moreover, this sarcopenia index also seems to be a strong sarcopenia diagnosis biomarker in overweight and obese cancer patients. Our results must be confirmed in a larger cohort.

Is sarcopenia a missed factor in the management of patients with metastatic breast cancer?

BACKGROUND: Sarcopenia has emerged as an important parameter to predict outcomes and treatment toxicity. However, limited data are available to assess sarcopenia prevalence in metastatic breast cancer and to evaluate its management. METHODS: The SCAN study was a cross-sectional multicenter French study that aimed to estimate sarcopenia prevalence in a real-life sample of metastatic cancer patients. Sarcopenia was identified by low muscle mass (estimated from the skeletal muscle index at the third lumbar, via computed tomography) and low muscle strength (defined by handgrip strength). Three populations were distinguished based on EWGSOP criteria: a sarcopenic group with low muscle mass AND strength, a pre-sarcopenic group with low muscle mass OR strength and a normal group with high muscle mass AND strength. RESULTS: Among 766 included patients, 139 patients with breast cancer and median age of 61.2 years (29.9-97.8 years) were evaluable; 29.5% were sarcopenic and 41.0% were pre-sarcopenic. Sarcopenic patients were older (P < 0.01), had a worse PS-score (P < 0.05), and a higher number of metastatic sites (P < 0.01), the majority being hepatic and bone. A moderate agreement between the oncologist's diagnosis and sarcopenia evaluation by muscle mass and strength was recognized (Cohen's kappa = 0.45). No associations were found between sarcopenia and adverse event occurrence in the 12 patients for whom these were reported. Sarcopenic patients were underdiagnosed and nutritional care and physical activity were less proposed. CONCLUSION: It is necessary to evaluate sarcopenia due to its impact on patient prognosis, and its utility in guiding patient management in metastatic breast cancer.

Weight and skeletal muscle loss with cabozantinib in metastatic renal cell carcinoma.

BACKGROUND: Cabozantinib, a standard of care metastatic renal cell carcinoma (mRCC), may be associated with weight and muscle loss. These effects of new generation VEGFR tyrosine kinase inhibitor on muscle mass loss are poorly described. METHODS: All cabozantinib-treated mRCC patients from January 2014 to February 2019 in our institution were included. Clinical data including weight were collected during therapy. Computed tomography images were centrally reviewed for response assessment, and axial sections at the third lumbar vertebrae were used to measure the total muscle area. Toxicities and cabozantinib outcomes were evaluated. Co-primary endpoints included skeletal muscle loss and weight loss (WL), longitudinally evaluated during treatment. WL has been classified according to CTCAEv5.0: Grade 1 (loss of 5 to <10% of baseline body weight), Grade 2 (loss of 10% to <20% of baseline body weight), and Grades 3-4 (loss >20% of baseline body weight). RESULTS: Patients were mostly men (70.3%), median age was 59.2 (range: 22.0-78.0) years, and median baseline body mass index was 25.0 (range: 16.4-49.3) kg/cm2 . Prognosis according to International Metastatic RCC Database Consortium score was good, intermediate, and poor for 13 (13.0%), 63 (63.0%), and 24 (24.0%) patients, respectively. Out of a total of 120 patients, 101 patients with a median follow-up of 22.3 months (range: 4.5-62.2) were eligible for analysis; 85 experienced muscle loss and muscle loss >10% increased during cabozantinib exposition, especially after 6 months of treatment. At cabozantinib baseline, 71 patients (70.3%) had sarcopenia, and 16/30 (53.3%) non-sarcopenic patients developed sarcopenia during treatment. Baseline sarcopenia was associated with lower response rates (P = 0.031) and higher grades 3-4 toxicities (P = 0.001). Out of 92 patients included in the WL analysis, 44 (47.8%) and 12 (13.0%) experienced grades 2 and 3 WL, respectively. CONCLUSIONS: We report a high incidence of grades 3-4 WL, fourth times higher than reported in prior pivotal trials, and half of the patients developed sarcopenia while on cabozantinib treatment. Weight and muscle mass loss with cabozantinib are underreported and may require further investigations and early management.

A phase III randomized trial of weight loss to reduce cancer-related fatigue among overweight and obese breast cancer patients: MEDEA Study design.

BACKGROUND: Elevated body mass index (BMI) represents a risk factor for cancer-related fatigue (CRF). Weight loss interventions are feasible and safe in cancer survivors, leading to improved cardio-metabolic and quality of life (QOL) outcomes and modulating inflammatory biomarkers. Randomized data are lacking showing that a lifestyle intervention aimed at weight loss, combining improved diet, exercise, and motivational counseling, reduces CRF. Motivating to Exercise and Diet, and Educating to healthy behaviors After breast cancer (MEDEA) is a multi-center, randomized controlled trial evaluating the impact of weight loss on CRF in overweight or obese survivors of breast cancer. Herein, we described the MEDEA methodology. METHODS: Patients (N = 220) with stage I-III breast cancer and BMI ≥ 25 kg/m2, within 12 months of primary treatment, and able to walk ≥ 400 m are eligible to enroll. Participants are randomized 1:1 to health education alone vs. a personalized telephone-based weight loss intervention plus health education. Both arms receive a health education program focusing on healthy living. Patients in the intervention arm are paired with an individual lifestyle coach, who delivers the intervention through 24 semi-structured telephone calls over 1 year. Intervention goals include weight loss ≥ 10% of baseline, caloric restriction of 500-1000 Kcal/day, and increased physical activity (PA) to 150 (initial phase) and 225-300 min/week (maintenance phase). The intervention is based on the social cognitive theory and is adapted from the Breast Cancer Weight Loss trial (BWEL, A011401). The primary endpoint is the difference in self-reported CRF (EORTC QLQ-C30) between arms. Secondary endpoints include the following: QOL (EORTC QLQ-C30, -BR45, -FA12), anxiety, and depression (HADS); weight and BMI, dietary habits and quality, PA, and sleep; health care costs (hospital-admissions, all-drug consumption, sick leaves) and cost-effectiveness (cost per quality-adjusted life-year); and patient motivation and satisfaction. The primary analysis of MEDEA will compare self-reported CRF at 12 months post-randomization between arms, with 80.0% power (two-sided α = 0.05) to detect a standardized effect size of 0.40. DISCUSSION: MEDEA will test the impact of a weight loss intervention on CRF among overweight or obese BC survivors, potentially providing additional management strategies and contributing to establish weight loss support as a new standard of clinical care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04304924.