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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.

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.

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.

Recently, the combination of complete cytoreductive surgery followed immediately by intraperitoneal chemotherapy achieved cure in some patients suffering from peritoneal carcinomatosis (PC). It is now well established that the prognostic impact of the completeness of cytoreduction is high. However, two different modes of intraperitoneal chemotherapy are proposed: early postoperative intraperitoneal chemotherapy (EPIC), which lasts for 5 days and is normothermic, and peroperative intraperitoneal chemohyperthermia (IPCH). To date, the results of these procedures have never been compared. To compare the complications and therapeutic results of EPIC and IPCH after complete cytoreductive surgery of colorectal PC. Twenty-three consecutive patients with colorectal PC were selected based on the completeness of cytoreductive surgery and sufficient follow-up. They received IPCH with oxaliplatin (460 mg/m(2)) in 2 l/m(2) of dextrose, for 30 min at an intraperitoneal temperature of 43 degrees C, using the coliseum technique. We retrospectively carefully selected another 23 patients, for comparison purposes, suffering from the same disease, with characteristics as similar as possible, but treated earlier with EPIC (mitomycin C 10 mg/m(2) at day 0 and 5-FU 650 mg/m(2) from days 1 to 4), in 1 l/m(2) of ringer lactate. Data concerning these two groups were verified prospectively, but this study was a comparative historical analysis. The two groups were statistically comparable, except for the duration of surgery which was 68 min longer for the IPCH group. Mortality and morbidity were not significantly different, even if two deaths occurred in the EPIC group, and none in the IPCH group. However, the rate of digestive fistulas was higher (P = 0.02) in the EPIC group (26%) than in the IPCH group (0%). Overall survival (OS) was higher in the IPCH group, (54% at 5 years vs. 28% for EPIC), but not significantly (P = 0.22). Peritoneal carcinomatosis recurred much (P = 0.03) more frequently in the EPIC group (57%) than in the IPCH-group (26%). This study provides strong arguments indicating that IPCH with oxaliplatin is better tolerated than EPIC with mitomycin C and 5-FU, and is twice as efficient in curing residual peritoneal carcinomatosis measuring less than 1 mm.

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/m 2 , 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

Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0-R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43 degrees C. A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m2) combined with irinotecan (360 mg/m2) in 2 L/m2 of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43 degrees C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously, resulting in tritherapy. Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001). This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.

A method of diagnosing catheter-related infection (CRI) without removing the catheter would be useful. An earlier positivity of central compared with peripheral venous-blood cultures may be associated with catheter-related bacteraemia. We evaluated prospectively the differential time to positivity (DTP) of paired blood cultures drawn simultaneously via the catheter hub and from a peripheral venous site. Over a 14-month period in an intensive-care unit of a cancer referral centre, simultaneous hub-blood and peripheral-blood cultures (a mean of two per patient) were obtained from patients with a suspected CRI. According to clinical criteria and quantitative culture of the catheter tip, cases were classified as CRI or sepsis of other origin. At least one pair of hub-blood and peripheral-blood cultures was obtained within 48 h before catheter removal, and we recorded the DTP between hub-blood and peripheral-blood cultures with an automatic device for detection of blood culture positivity. We analysed 93 catheters removed because of suspicion of CRI. In 28 episodes, the same micro-organisms were found in both hub-blood and peripheral-blood cultures. A diagnosis of definite bacteraemic CRI was made in 16 of the 17 patients in whom a positive hub-blood culture was detected at least 2 hours earlier than peripheral-blood culture. About half (9/17) of these episodes occurred in long-term (>30 days) devices. CRI was excluded in ten of the 11 patients with a DTP lower than 2 h. The DTP of paired blood cultures was significantly greater in patients with CRI than in others (p<10 −4). A cut-off DTP value of 120 min had 91% specificity and 94% sensitivity for the diagnosis of CRI. Three of 17 episodes with only hub-blood culture positive were associated with CRI. This prospective study suggests that measurement of the differential time to positivity between hub-blood and peripheral-blood cultures is a simple and reliable tool for in-situ diagnosis of catheter-related sepsis in cancer patients. Further studies are needed to confirm these data for short-term catheters.

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.

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.

Cancer cachexia occurs in patients with far advanced disease. It is known to be a prognostic factor for poor survival and is almost impossible to reverse. Therefore, early detection and prevention are essential. Sarcopenia, usually based in oncology on skeletal muscle mass loss, is a component of cachexia and an independent prognostic factor for the efficacy and toxicity of cancer therapies and a negative predictor for survival. Using CT to measure the muscular surface area at the third lumbar, vertebra (L3) section is of great interest in low skeletal muscle mass (LSMM) detection.