Lean Body Mass and Endocrine Status But Not Age Are Determinants of Resting Energy Expenditure in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: Cancer and aging are both frequently associated with malnutrition, a factor of poor prognosis. In adult cancer patients, this may be related in part to impaired energy metabolism, with higher than predicted resting energy expenditure (REE) in about 50% of patients. We hypothesized that frequently impaired energy metabolism in elderly patients could potentiate cancer-associated hypermetabolism, further promoting risk of malnutrition. OBJECTIVE: To study the hypermetabolic response to cancer in a predominantly aged population and the potential underlying determinants. METHODS: This was a cross-sectional exploratory study in patients with non-small-cell lung cancer. REE was measured by indirect calorimetry. Body composition was determined from a single CT scan imaging at L3 level. Endocrine, inflammatory, nutritional and metabolic status were evaluated. RESULTS: Twenty-seven patients, of median age 68 years (range 32-81) completed the study. In this population, mean measured REE was 7.5% higher than calculated REE. Sex and weight accounted for about 51% of REE variations, whereas age accounted only for 4%. However, these parameters did not explain the REE-to-lean body mass (LBM) ratio variations, suggesting that they influenced REE only through their effect on LBM. Among the other parameters evaluated, only the thyroid-stimulating hormone and interleukin-6 plasma levels appeared to have an influence on REE. The study of the consequences of this increase in REE-to-LBM ratio showed a growing inability of patients to meet their energy needs but showed no effect on nutritional markers such as transthyretin. CONCLUSIONS: The results of this pilot study suggest that in our population, age was not an important factor of REE. The elevated energy metabolism was associated with patients' failure to increase their energy intakes sufficiently, which can contribute to the development of cachexia. CLINICAL TRIAL: This trial is registered at clinicaltrials.gov under NCT0314.

Nutritional status is superior to the ECOG performance status in predicting the dose-intensity of the GEMOX chemotherapy regimen in patients with advanced cancer.

The increasing number of unfit patients calls for better risk assessment prior to initiating anti-tumor treatment. This is a major concern in the prevention and reduction of treatment-related complications. The aim of our study was to evaluate the nutritional status for the risk assessment of patients qualifying to receive the gemcitabine and oxaliplatin (GEMOX) regimen. This single-center, retrospective study examined baseline clinical and biological characteristics in a cohort of 165 unselected, consecutive cancer patients receiving GEMOX. Malnutrition was defined as either body mass index (BMI) <18.5 kg/m(2), body weight loss >10% over 3 mo, or albuminemia <35 g/L. A total of 165 patients (median age 61 yr, PS 0-1: 71%) were studied. Malnutrition was seen in 43% of PS 0-1 patients, vs. 60% of PS 2 and 66% of PS 3 patients (P > 0.05). Median relative dose-intensity was 0.90 (0.17-1.04). GEMOX dose-intensity correlated negatively with loss of baseline weight (r = -0.24, P < 0.02). In patients who did not complete more than 2 cycles of chemotherapy, median PS (P < 0.01), mean C-reactive protein (CRP; P < 0.01), and mean albuminemia (P < 0.05) were, respectively, significantly higher, higher, and lower. Malnutrition is associated with a high risk of early discontinuance of treatment. Systematic basal evaluation of the nutritional status, including albuminemia and BMI, is recommended.

Safety of bevacizumab 7.5 mg/kg infusion over 10 minutes in NSCLC patients.

BACKGROUND: Bevacizumab is a humanized IgG1 monoclonal antibody against VEGF. Because infusion-related hypersensitivity reactions (HSRs) are a concern with monoclonal antibodies, initial phase 1 trials used a 90-, 60-, then 30-min initial infusion sequence. We evaluated the impact of a shortened bevacizumab infusion (10 min) on toxicity in nonsmall cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Consecutive patients with stage IV NSCLC eligible for anti-VEGF therapy received a platinum doublet plus bevacizumab 7.5 mg/kg infused over 10 min, every 3 weeks, in the outpatient setting. Blood pressure was monitored at home twice daily, and other toxicities (HSRs and proteinuria) were monitored at each treatment administration. RESULTS: Bevacizumab was given as a 10 min infusion in 55 patients (group A), and using the standard sequence in another 36 patients (group B). Hypertension (grade ≥ 2) was observed in 18/55 (32.7%) patients in group A and 13/36 (38.9%) patients in group B (p = 0.77). Similarly, no difference was seen regarding the incidence of grade ≥ 2 proteinuria (12.7% vs. 19.4%, p = 0.39), arterial thrombo-embolic events (0 in each group) or venous thromboembolic events (1.8% vs. 8.3%, p = 0.29). CONCLUSIONS: Our data suggest that bevacizumab 7.5 mg/kg can be safely infused over 10 min in unselected NSCLC patients despite their cardio-vascular and respiratory comorbidities, saving time for both patients and caregivers.

Feasibility of oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX-4) in cirrhotic or liver transplant patients: experience in a cohort of advanced hepatocellular carcinoma patients.

PURPOSE: The only drug that improves survival in hepatocellular carcinoma is sorafenib. FOLFOX-4 regimen is safe and widely used in patients with colorectal cancer, yielding interesting results with little toxicity. We conducted a retrospective study to evaluate the safety and the effectiveness of FOLFOX-4 in cirrhotic or liver transplanted patients with hepatocellular carcinoma ineligible for sorafenib. METHODS: Thirty seven patients were enrolled in the study. The medical record of either cirrhotic patients or liver transplanted patients with advanced hepatocellular carcinoma receiving FOLFOX-4 regimen between November 1999 and March 2006 were retrospectively analyzed. Patients received oxaliplatin 85 mg/m(2) as a 2-hour infusion on day one, and leucovorin 200 mg/m(2) as a 2-hour infusion followed by bolus 5-fluorouracil 400 mg/m(2) and a 48-hours infusion of 5-fluorouracil 2400 mg/m(2). Treatment was repeated every 2 weeks until disease progression or unacceptable adverse effects occurred. RESULTS: Patients had a Child-Pugh class A (n = 16), class B cirrhosis (n = 10) or a liver transplant (n = 11) and received 2 to 37 cycles of chemotherapy (total of 310 cycles). Two (5.4%) cirrhotic patients developed neutropenic sepsis and one (2.7%) toxic death occurred. At first assessment, five patients from Child-Pugh class A (33%) and two from Child-Pugh class B group (20%) achieved a radiological response and/or alpha foeto-protein decrease, and no patient achieved a complete response. CONCLUSIONS: In conclusion, with a manageable toxicity profile in cirrhotic Child-Pugh class A-B or liver transplanted patients, the FOLFOX-4 regimen appears to be a feasible treatment option for patients with advanced hepatocellular carcinoma unfit for sorafenib. These data need to be confirmed in a prospective study.

Feasibility of gemcitabine and oxaliplatin in patients with advanced biliary tract carcinoma and a performance status of 2.

The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age: 63 years, range 41-83) received a total of 175 cycles (median per patient: 6, range 2-12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2-4: n=4, 14.3%), peripheral neuropathy (grades 2-3: n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients [95% confidence interval (CI): 0-22.2] and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI: 2.5-6.3) and 7.5 (95% CI: 5.2-9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia: 7.0 months (95% CI: 4.4-8.0) vs. 2.2 months (95% CI: 2.0-2.5), P less than 0.01, and 10.4 months (95% CI: 7.5-11.6) vs. 4.9 months (95% CI: 3.7-5.2), P less than 0.01, respectively. In our experience, gemcitabine-oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings.

Validation of the Cochin Risk Index Score (CRIS) for life expectancy prediction in terminally ill cancer patients.

BACKGROUND: Oncologists often overestimate survival of advanced cancer patients. This study aimed to validate a score for survival prediction in terminally ill cancer patients. METHODS: Between 2004 and 2008, a prospective study was performed in 500 consecutive advanced cancer patients referred to a palliative care unit. Evaluation at admission included physical examination and routine blood tests. On a randomly selected training set, independent factors assessable at inclusion predicting 2-week survival by a multiple logistic regression were assigned integer-rounded weights to develop a risk index score, which was tested on a validation set. RESULTS: On the training set (334 patients), predictive factors were: urea >12 mmol/L (weight = 5, odds ratio (OR) = 3.72, 95% confidence interval (95%CI) = [1.59; 8.71], p = 0.002), Karnofsky Performance Status ≤30% (weight = 4, OR = 3.28, 95%CI = [1.80; 6.01], p < 0.001), leucocytes >15 g/L (weight = 3, OR = 2.49, 95%CI = [1.18; 5.25], p = 0.017), transthyretin ≤0.05 g/L (weight = 3, OR = 2.42, 95%CI = [1.16; 5.04], p = 0.019) and male gender (weight = 2, OR = 2.25, 95%CI = [1.28; 3.97], p = 0.005). On the validation set (166 patients), the Cochin Risk Index Score (CRIS) ≥ 7 identified high-risk patients, with a positive predictive value of 78%. CONCLUSION: We validated the CRIS for survival prediction in terminally ill cancer patients.

Interaction between serotonin reuptake inhibitors, 5-HT3 antagonists, and NK1 antagonists in cancer patients receiving highly emetogenic chemotherapy: a case-control study.

BACKGROUND: Previous reports suggested that selective serotonin reuptake inhibitors (SSRI) could decrease the activity of 5-hydroxytryptamine type 3 (5-HT3) antagonists against acute chemotherapy-induced nausea and vomiting (CINV), possibly through serotonin accumulation for 5-HT3 receptors. PATIENTS AND METHODS: Chemonaive cancer patients receiving SSRI and antiemetic agents, including the 5-HT3 antagonist ondansetron and the neurokinin 1 (NK1) antagonist aprepitant for highly emetogenic chemotherapy (etoposide-platinum), were matched to control patients for the following variables: age, gender, primary tumor, past history of gestational emesis, chronic intake of benzodiazepines and/or corticosteroids, chronic alcohol intake, and aprepitant use. The primary evaluation criterion was the occurrence of acute vomiting during the first two cycles of treatment. RESULTS: Forty-four patients were eligible for this analysis. The proportion of patients, who experienced at least one episode of grade ≥ 1 acute vomiting in patients receiving SSRI, compared to patients who did not, was significantly higher (59.1 vs. 22.7%, respectively, p = 0.03, odds ratio 4.72, 95% confidence interval 1.13-22.88). Grade ≥ 2 acute vomiting was also significantly more frequent in patients receiving SSRI, even after the implementation of aprepitant to antiemetic prophylaxis (41.2 vs. 5.9%, p = 0.04). CONCLUSIONS: Our findings reinforce the hypothesis that SSRI decrease the antiemetic activity of the 5-HT3 serotonin antagonist ondansetron, resulting in higher rates of acute vomiting in cancer patients despite adequate antiemetic prophylaxis. Adding the NK1 antagonist aprepitant do not counterbalance the deleterious effect of SSRI, probably due to the synergistic effects of SSRI and NK1 antagonists on serotonin transmission.

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.

Energy expenditure profiles and the risk of early limiting toxicity in older patients with cancer: The ELCAPA-25 prospective cohort survey.

BACKGROUND & AIMS: Predicting the risk of early limiting toxicity (ELT) is major challenge for the clinician seeking an effective, safe treatment for older patients with cancer. The Cancer and Aging Research Group (CARG) and CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) toxicity scores were designed to predict chemotherapy-related toxicity. Elevated resting energy expenditure (REE) may predispose to cachexia and increase ELT and mortality in older patients with cancer. The primary objective was to assess the association between elevated REE and ELT in older patients with cancer. The secondary objectives were to assess the discriminant ability of a predictive model including REE (relative to the CARG and CRASH scores) and the prognostic value of elevated REE. METHODS: We assessed patients aged 70 or over included in the prospective ELCAPA cohort between 2014 and 2018. The inclusion criteria were a solid tumour, a measurement of REE at baseline (mREE, by indirect calorimetry), and a geriatric assessment prior to cancer treatment in a teaching hospital (Paris, France). The mREE was compared with the predicted REE (pREE), as defined by the Harris-Benedict equation. Depending on the mREE/pREE ratio, study participants were classified as hypermetabolic, hypometabolic or normometabolic. The primary endpoint was 3-month ELT, defined as any unplanned hospitalization or any event leading to dose reduction, a treatment delay of more than 7 days, or treatment discontinuation within 3 months of initiation. The secondary endpoint was the 3-month mortality rate. RESULTS: A total of 179 patients were included. The median age was 80 [interquartile range: 76-84] years, 37% of the patients were female, 81.8% had metastatic disease, 67.6% received chemotherapy, 20.7% received hormone therapy, and 11.7% received targeted therapies. According to the mREE/pREE ratio, 85 patients (47%) were hypermetabolic, 63 (35%) were normometabolic, and 31 (18%) were hypometabolic. Sixty patients (33.5%; 95% confidence interval (CI): 26.7-40.9) experienced ELT. The discriminant ability (as assessed by the C-index) of a multivariate model including REE and adjustment factors was 0.82 [95%CI: 0.73-0.91]. In comparison, the discriminant ability of the CARG and CRASH models was 0.57 [0.45-0.68] and 0.51 [0.40-0.62], respectively. In our model, hypermetabolism was an independent risk factor for ELT (adjusted odds ratio = 2.44; 95%CI: 1.02-5.80). Other risk factors were the cancer type and stage, the treatment protocol, a clinical diagnosis of depression, the presence of grade 3 or 4 comorbidities, and the serum lactate dehydrogenase level. CONCLUSION: Hypermetabolism status is an independent predictor of ELT in older patients with cancer, relative to normometabolic status. Baseline REE measurement might improve the ELT risk assessment and decision-making process.

Association of Energy Expenditure and Efficacy in Metastatic Renal Cell Carcinoma Patients Treated with Nivolumab.

Background: Nivolumab improved patients' survival in metastatic renal cell carcinoma (mRCC). We aimed to evaluate resting energy expenditure (REE) (i.e., patients' basal metabolism) to predict efficacy. Methods: We conducted a monocentric, observational study of mRCC patients receiving nivolumab between October 2015 and May 2020. REE was measured prior to initiating immunotherapy using indirect calorimetry to determine hypo, normo and hypermetabolism. Primary endpoint was 6-month, progression-free survival (PFS), and secondary endpoints were response rate, PFS and overall survival (OS). Results: Of the 51 consecutive patients, 15 (29%) were hypermetabolic, 24 (47%) normometabolic, and 12 (24%) hypometabolic. The 6-month PFS was 15% for hypermetabolic patients and 65% for non-hypermetabolic patients (p < 0.01). In the multivariate analysis, hypermetabolism was the only baseline factor predicting 6-month PFS (OR 9.91, 95%CI [1.62−60.55], p = 0.01). Disease progression was noted as the best response in 73% of hypermetabolic patients and 26% of non-hypermetabolic patients (p = 0.02). Median PFS was 2.8 and 8.7 months (p < 0.01), and median OS was 20.2 and 35.1 months (p = 0.13) in the hypermetabolic and non-hypermetabolic groups, respectively. Conclusions: Our study identifies an association between mRCC patients' energy expenditure and nivolumab efficacy. The measurement of REE by indirect calorimetry in routine practice could help identify patients at risk of nivolumab failure.

An observational study of bevacizumab-induced hypertension as a clinical biomarker of antitumor activity.

BACKGROUND: Hypertension is a common toxicity of bevacizumab, but the frequency of assessment of blood pressure and standardized grading remain to be defined. This study aimed to describe the incidence of bevacizumab-induced hypertension and factors associated with its development, then to retrospectively assess its relation with activity. PATIENTS AND METHODS: One hundred nineteen patients with advanced or metastatic non-small cell lung cancer, colorectal cancer, or ovarian cancer receiving bevacizumab (2.5 mg/kg per week) and chemotherapy were eligible for this analysis. Blood pressure was measured at home twice daily according to international guidelines, and graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC), version 3.0, and the European Society of Hypertension (ESH) criteria. RESULTS: Home-based measurements detected significantly more cases of hypertension than in-clinic measurements did, according to the ESH criteria (54.6% versus 24.4%; p < .001) or the NCI-CTC (42.9% versus 22.7%; p = .0015). Very early hypertension (within 42 days, according to the ESH criteria) but not hypertension (occurring at any time during treatment period) was predictive of response (p = .0011 and p = .26, respectively). CONCLUSIONS: Our preliminary results indicate that home-based measurement and grading according to the ESH criteria represents a reliable method to detect bevacizumab-induced hypertension. Whether hypertension is a biomarker of bevacizumab activity remains to be determined in a prospective study.

Functional and clinical evidence of the influence of sorafenib binding to albumin on sorafenib disposition in adult cancer patients.

PURPOSE: Sorafenib, an oral multitargeted tyrosine kinase inhibitor, is highly bound to plasma proteins (>99.5%). Little is known about the influence of variations in sorafenib protein binding on its disposition. The aims of this study were to characterize in vitro sorafenib binding properties to albumin using the quenching fluorescence method and investigate the influence of albuminemia and bilirubinemia on sorafenib disposition in 54 adult cancer patients. RESULTS: In vitro estimate of sorafenib dissociation constant (Kd) for albumin was 0.22 µM [CI95 0.20-0.23]. In physiological conditions, sorafenib unbound fraction would increase 1.7-fold as albuminemia decreased from 45 g/L (680 µM) to 30 g/L (453 µM). In presence of bilirubin, apparent Kd of sorafenib was ~1.5-fold greater for bilirubin/albumin molar ratio of 1:4. In clinical settings, median sorafenib clearance (CL) was 1.42 L/h (0.75-2.13 L/h). In univariate analysis, sex, body mass index, and albuminemia were associated with CL (p = 0.04, 0.048, and 0.008, respectively). In multivariate analysis, albuminemia (p = 0.0036) was the single parameter independently associated with CL. CONCLUSION: These findings highlight the major influence of albuminemia on sorafenib clearance and its disposition in cancer patients.

Creatinine-to-cystatin C ratio and bioelectrical impedance analysis for the assessement of low lean body mass in cancer patients: Comparison to L3-computed tomography scan.

OBJECTIVES: Lean body mass (LBM) is an important prognostic factor in patients with cancer. Although the L3-computed tomography (CT) scan is considered a reference method for assessment, a convenient and easily available method for longitudinal follow-up is required. Although bioelectrical impedance analysis (BIA) is widely used, its accuracy is questioned; plasma creatinine-to-cystatin C (CC) ratio could be an attractive alternative. The aim of this study was to evaluate the ability of the CC ratio and BIA to detect myopenia in patients with cancer compared with the use of the CT scan as a standard. METHODS: Patients with any kind of cancer had body composition evaluation by CT scan, BIA, and CC. Statistical analysis included correlation test, Bland-Altman, and receiver operating characteristic curve analysis. RESULTS: Forty-four patients (14 women) were included. Of the participants, 59% had myopenia on CT scan. Both BIA LBM and CC ratio were well correlated with CT scan LBM (r = 0.763 and 0.648, respectively) but concordance analysis revealed a 3-kg constant bias toward BIA compared with CT scan. In terms of ability to detect myopenia, areas under the curve (AUC) for BIA were 0.675 and 0.388 for men and women, respectively. For CC ratio, AUCs were 0.813 and 0.673. CONCLUSION: This study demonstrated that LBM assessed by the CC ratio or BIA is well correlated with that determined by L3-CT scan. The ability of the CC ratio to detect myopenia was better than that of BIA. Findings from the present study demonstrated that CC ratio can be conveniently used in patients with cancer as a reliable biomarker of muscularity.

Development and validation of a host-dependent, PDL1-independent, biomarker to predict 6-month progression-free survival in metastatic non-small cell lung cancer (mNSCLC) patients treated with anti-PD1 immune checkpoint inhibitors (ICI) in the CERTIM Cohort: The ELY study.

BACKGROUND: Immune checkpoint inhibitors (ICI) are dramatically active in a minority of non-small cell lung cancer (NSCLC) patients. We studied here the relationship between patients's metabolism and outcome under ICI. METHODS: Metastatic NSCLC patients underwent a nutritional assessment prior to initiating immunotherapy. Resting energy expenditure (REE) was measured (mREE) using ambulatory indirect calorimetry and compared with the theoretical value (tREE) provided by the Harris and Benedict formula. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and disease control rate (DCR) based on investigator review per RECIST v1.1. and overall survival (OS). The association of patient's metabolism with 6-month PFS was first explored in a single-center training cohort to estimate the effect size. The relationship between patient's metabolism and 6-month PFS was then tested in an independent non interventional observational prospective cohort (ELY) of 100 patients recruited in two tertiary university centers. FINDINGS: In the entire cohort, the ORR was 14% for the hypermetabolic group (n = 10/74) vs 38% for the normometabolic group (n = 26/68), respectively (estimated difference 25%, 95CI 9-40%, p = 0.001). The DCR was 28% for the hypermetabolic group (n = 21/74) vs 53% for the normometabolic group (n = 36/68), respectively (estimated difference 25%, 95CI 7-42%, p = 0.005). In the validation cohort (100 patients, 2 centers), normometabolic patients (defined as mREE/tREE < 110%) had increased 6-month PFS (57% versus 22%; odds ratio: 4.76; IC95 [1.87 - 12.89]; p<0.001) and improved overall survival (HR 2.20; IC95: 1.41-3.44; p<0.001). The positive and negative predictive values of normometabolism to identify non-progressive patients at 6 months, were 57% and 78% respectively, sensitivity was 72% and specificity was 66%. In multivariate analysis including PD-L1 tumor status, basal metabolism was an independent predictive factor for 6-month PFS. INTERPRETATION: Normometabolism is a new independent parameter to identify mNSCLC patients who will benefit from ICI, with both improved tumor response, 6-month PFS, and survival. FUNDING: This work was supported by Baxter (04012016).

Hypermetabolism is an independent prognostic factor of survival in metastatic non-small cell lung cancer patients.

BACKGROUND & AIMS: Metastatic non-small cell lung cancer (NSCLC) is the first cause of cancer death worldwide. Increased resting energy expenditure (REE) is frequent among cancer patients and may contribute to cancer cachexia. The aim of this study was to examine the prognostic value of increased REE in metastatic NSCLC patients. METHODS: This observational study was conducted between June 2012 and November 2017 in the outpatient unit of the oncology department of Cochin hospital, Paris. Consecutive patients with newly diagnosed stage IV NSCLC underwent measurement of REE by indirect calorimetry before treatment initiation. Uni- and multivariate analysis of overall survival (OS, Cox models) included age, sex, smoking habit, histological subtype, performance status, body mass index, weight loss, albumin and CRP levels and the ratio of measured REE to the REE predicted by the Harris Benedict formula (mREE/pREE). RESULTS: 144 patients were enrolled: mean age 64 years, 63% male, 90% non-squamous carcinoma, including 17% with ALK/EGFR alteration. In univariate analysis, tobacco consumption (p = 0.007), histo-molecular subtype (p < 10-3), performance status (p = 0.04), weight loss (p < 10-4), albumin (p < 10-4), CRP (p = 0.001) and mREE/pREE ratio (>vs ≤ 120%: HR = 2.16, p < 10-3) were significant prognostic factors of OS. Median OS were 6.1 and 17.3 months in patients with mREE/pREE ratio > and ≤120%, respectively. In multivariate analysis, histo-molecular subtype (non-squamous ALK/EGFR mutated vs squamous carcinoma: HR = 0.25, p = 0.006), weight loss (>vs ≤ 5%: HR = 1.98, p = 0.004), albumin (≥vs < 35 g/L: HR = 0.56, p = 0.02) and mREE/pREE ratio (> vs ≤120%: HR = 1.90, p = 0.004) were identified as independent prognostic factors. CONCLUSIONS: Elevated resting energy expenditure emerges as an independent prognostic factor in metastatic NSCLC.

Vinorelbine and oxaliplatin in stage IV nonsmall cell lung cancer patients unfit for cisplatin: a single-center experience.

Many patients with stage IV nonsmall cell lung cancer (NSCLC) are unfit for cisplatin-based chemotherapy because of poor performance status, impaired renal function or severe comorbidity. We documented the feasibility of a combination of weekly vinorelbine and biweekly oxaliplatin in a population of stage IV NSCLC patients unable to receive cisplatin. Fifty-five chemo-naive patients (40 males, median age 60 years, range 43-84) were treated on an outpatient basis, and received every 2 weeks: vinorelbine 25 mg/m intravenously on day 1 and 60 mg/m orally on day 8, and oxaliplatin 85 mg/m intravenously on day 1. Patients were considered unfit for cisplatin because of performance status > or =2 (30 patients), impaired renal function (17 patients) or severe comorbidities (eight patients). Twenty-two patients (40%) had two or more metastatic sites, and 14 (25%) had central nervous system metastases. A total of 288 cycles were given (median per patient: 4, range 1-11). The planned dose intensity of vinorelbine was administered in 65% of patients. One complete and 13 partial responses were observed, providing an objective response rate of 26% (95% confidence interval: 14.4-37.6). The median progression-free survival and overall survival were 3.5 months and 9.5 months, respectively. The 1-year survival rate was 24% (95% confidence interval: 12.7-35.3). The main grade 3/4 toxicities were: neutropenia (15 patients, 27%), anaemia (12 patients, 22%) and peripheral neuropathy (eight patients, 15%). Three patients (5.5%) experienced febrile neutropenia. In a nonselected NSCLC patient population, the vinorelbine-oxaliplatin doublet had clinical activity in the same range as cisplatin-based combinations. This doublet allows combining a platinum derivative with a sustained dose intensity of vinorelbine in unfit patients.

Resting energy expenditure in the risk assessment of anticancer treatments.

BACKGROUND & AIMS: Alterations of nutritional and performance status (PS) are associated with higher risk of chemotherapy toxicity. Increased resting energy expenditure (REE) is frequent in cancer patients and may contribute to cachexia. We investigated whether abnormal energetic metabolism could predict early acute limiting toxicities (ELT) of anticancer treatments. METHODS: In this observational monocentric study, REE was measured by indirect calorimetry before treatment initiation. Based on the ratio of measured REE to REE predicted by the Harris-Benedict formula, patients were classified as hypometabolic (<90%), normometabolic (90-110%) or hypermetabolic (>110%). Body mass index, weight loss, PS, albumin, transthyretin, C-reactive protein (CRP) and muscle mass (CT-scan) were studied. Were defined as ELT any unplanned hospitalization or any adverse event leading to dose reduction or discontinuation during the first cycle of treatment. RESULTS: We enrolled 277 patients: 76% had metastatic disease; 89% received chemotherapy and 11% targeted therapy; 29% were normometabolic, 51% hypermetabolic and 20% hypometabolic. Fifty-nine patients (21%) experienced an ELT. Toxicity was associated with abnormal metabolism (vs normal: OR = 2.37 [1.13-4.94], p = 0.023), PS (2-3 vs 0-1: OR = 2.04 [1.12-3.74], p = 0.023), albumin (<35 vs ≥35 g/l: OR = 2.39 [1.03-5.54], p = 0.048), and inflammation (CRP ≥10 vs <10 mg/l: OR = 2.43 [1.35-4.38], p = 0.004). To predict toxicity, the most sensitive parameter was the REE (83%) followed by PINI (63%), GPS (59%), CRP (55%), PS (41%), NRI (37%), and albumin (16%). In multivariate analysis, elevated CRP was an independent predictor of toxicity (p = 0.047). CONCLUSION: Abnormal basal energy metabolism identifies patients at higher risk of treatment-related acute complications.

Malnutrition in Patients With Cancer: Comparison of Perceptions by Patients, Relatives, and Physicians-Results of the NutriCancer2012 Study.

BACKGROUND: Malnutrition is a critical predictor of toxicity and outcome in patients with cancer and may be perceived differently by patients, relatives, and physicians. AIMS: To assess the prevalence of malnutrition in oncology departments and to compare it with the perceptions of nutrition status by patients themselves, their closest relatives, and attending physicians. MATERIALS AND METHODS: A 1-day multicentric cross-sectional survey on the prevalence of malnutrition was conducted in different oncology departments using patient-, relative-, and physician-specific questionnaires. Malnutrition was defined by a weight loss ≥5% within 1 month or ≥10% within 6 months, a body mass index ≤18.5 kg/m2 in patients aged <70 years or ≤21 kg/m2 in patients aged ≥70 years, and/or albuminemia <35 g/L. Questionnaires for assessing medical condition, knowledge of nutrition status, and perceptions of the impact of malnutrition on daily life were distributed to consenting patients, attending physicians, and closest relatives. RESULTS: A total of 2197 patients were included, and 2071 and 976 questionnaires were collected from patients and relatives, respectively. Prevalence of malnutrition was 39%. Physicians overestimated malnutrition (44%), whereas patients and relatives underestimated it (22% and 23%, respectively, P < .001). Conversely, malnutrition-associated symptoms were underestimated by physicians compared with patients and relatives. CONCLUSION: We found a prevalence of malnutrition of 39%: it was underestimated by patients and relatives and overestimated by physicians.

Relation between hypermetabolism, cachexia, and survival in cancer patients: a prospective study in 390 cancer patients before initiation of anticancer therapy.

Background: Cachexia is a major cause of death in cancer patients. The role of hypermetabolism in cancer cachexia remains unclear.Objective: We studied the relation between resting energy expenditure (REE), the estimated energy balance, clinical and biological markers of cachexia, and survival.Design: REE was measured with the use of indirect calorimetry in cancer patients before the initiation of anticancer therapies. Hypermetabolic, normometabolic, and hypometabolic patients were identified with the use of Boothby's standard. Weight loss, performance status (PS), C-reactive protein (CRP), albumin, the nutritional risk index, daily energy intake, energy balance (equal to daily energy intakes minus the REE), and survival were recorded.Results: Of 390 enrolled patients, 49% of subjects were hypermetabolic, 30% of subjects were normometabolic, and 21% of subjects were hypometabolic. Mean daily energy intakes did not differ significantly between the 3 groups. Hypermetabolic patients, compared with normometabolic patients, were more likely to have a negative energy balance [45% compared with 32%, respectively; OR: 1.74 (95% CI: 1.05, 2.91); P = 0.024], weight loss >5% [48% compared with 34%, respectively; OR: 1.83 (95% CI: 1.11, 3.04); P = 0.013], PS ≥2 [40% compared with 29%, respectively; OR: 1.70 (95% CI: 1.01, 2.88); P = 0.038], and CRP concentrations ≥10 mg/L [52% compared with 33%, respectively; OR: 2.2 (95% CI: 1.33, 3.66); P = 0.001]. In metastatic patients, compared with normometabolism, hypermetabolism was associated with a reduced median survival [14.6 compared with 21.4 mo, respectively; OR: 1.48 (95% CI: 1.01, 2.17); P = 0.044].Conclusions: Hypermetabolism is correlated with clinical and biological markers of cancer cachexia and is associated with a shorter survival in metastatic cancer patients. The development of therapeutic strategies that aim to blunt hypermetabolism appears warranted. This trial was registered at www.controlled-trials.com as ISRCTN46152275.