Recently, immune checkpoint blockade has become a new avenue of immunotherapy; the strategy being to reduce inhibitory signaling and restore the patient's natural tumor-specific T-cellmediated immune responses [Ascierto et al. Nivolumab in renal cell carcinoma: latest evidence and clinical potential Camille Mazza, Bernard Escudier and Laurence Albiges Abstract: Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed deathligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses. The strategy of immune checkpoint blockade is to reduce inhibitory signaling and restore the patient's natural tumor-specific T-cell-mediated immune responses. Nivolumab is the first PD-1 inhibitor to have gained approval for the treatment of patients with metastatic melanoma, squamous and nonsquamous non-small cell lung cancer (NSCLC), Hodgkin disease and recently RCC. In this review, we discuss results from studies of nivolumab in RCC, clinical experience with this agent, and its future development.
Background
FIGHTDIGO study has shown the feasibility of handgrip strength (HGS) measurements in 201 consecutive digestive cancer patients undergoing chemotherapy.
Objective
This study focuses on a secondary aim of FIGHTDIGO study: the relationship between muscle mass and HGS.
Design
Two consecutive bilateral measures of HGS were performed using a Jamar dynamometer before the start of each chemotherapy. The highest value was chosen for final evaluation. Dynapenia (loss of muscle strength) was defined as HGS < 30 kg (men) and < 20 kg (women). Muscle mass was measured at lumbar level (L3) on Computed Tomography (CT) scans performed less than 3 weeks before or after the measurement of HGS. Muscle mass loss was defined by skeletal muscle index (SMI) < 53 cm
2
/m
2
(in men with a body mass index (BMI)> 25 kg/m
2
), < 43 cm
2
/m
2
(in men with a BMI < 25 kg/m
2
), and < 41 cm
2
/m
2
(in women regardless of BMI). Sarcopenia was defined by the association of a dynapenia and a loss of muscle mass.
Results
A total of 150 patients were included in this analysis (mean age: 65.6 ± 10.9 years, 87 males (58%), colorectal cancer (47.3%), metastatic stage (76.7%)). A total of 348 CT scans were evaluated. For the 348 measurements, mean SMI and HGS were 41.8 ± 8.7 cm
2
/m
2
and 32.1 ± 11.0 kg, respectively. Muscle mass loss, dynapenia, or sarcopenia were reported at least once, in 120 (80%), 45 (30%), and 30 (20%) patients, respectively. SMI was significantly correlated with HGS (Pearson coefficient = 0.53,
P
< 0.0001). At concordance analysis, 188 dyad SMI/HGS (54%) were in agreement (Kappa = 0.14 [95% CI, 0.07‐0.21]).
Conclusion
Correlation between the measurements of HGS and SMI is strong but the concordance between dynapenia and muscle mass loss is poor. Further studies should be performed to confirm the diagnostic thresholds, and to study the chronology of dynapenia and loss of muscle mass.
BackgroundFIGHTDIGO study showed the feasibility and acceptability of handgrip strength (HGS) measure in routine in 201 consecutive patients with digestive cancer treated with ambulatory chemotherapy. The present study focuses on the second aim of FIGHTDIGO study: the relationships between pre-therapeutic dynapenia and chemotherapy-induced Dose-Limiting Toxicities (DLT).MethodsIn this ancillary prospective study, DLT were analyzed in a sub-group of 45 chemotherapy-naive patients. Two bilateral consecutive measures of HGS were performed with a Jamar dynamometer before the first cycle of chemotherapy. Dynapenia was defined as HGS < 30 kg (men) and < 20 kg (women). DLT and/or Dose-Limiting Neurotoxicity (DLN) were defined as any toxicity leading to dose reduction, treatment delays or permanent treatment discontinuation.ResultsTwo-thirds of chemotherapies were potentially neurotoxic (n = 31 [68.7%]) and 22 patients (48.9%) received FOLFOX (5FU, leucovorin plus oxaliplatin) regimen chemotherapy. Eleven patients (24.4%) had pre-therapeutic dynapenia. The median number of chemotherapy cycles was 10 with a median follow-up of 167 days. Twenty-two patients experienced DLT (48.9%). There was no significant association between pre-therapeutic dynapenia and DLT (p = 0.62). Nineteen patients (42.2%) experienced DLN. In multivariate analysis, dynapenia and tumoral location (stomach, biliary tract or small intestine) were independent risk factors for DLN (HR = 3.5 [1.3; 9.8]; p = 0.02 and HR = 3.6 [1.3; 10.0]; p = 0.01, respectively).ConclusionsDigestive cancer patients with pre-therapeutic dynapenia seemed to experience more DLN. HGS routine measurement may be a way to screen patients with frailty marker (dynapenia) who would require chemotherapy dose adjustment and adapted physical activity programs.Trial registrationNCT02797197 June 13, 2016 retrospectively registered.
The purpose of this study was to evaluate whether a particular genotype of the dopamine D2 receptor (DRD2) gene would affect the clinical features of migraine. In a group of 118 migraineurs (55 migraine with aura and 63 migraine without aura patients), we tested the association of the biallelic C/T NcoI DRD2 polymorphism with several characteristics of the disease. Genotype and allele frequencies resulted similarly distributed in migraine with aura and migraine without aura patients (chi2 = 1.58, P = 0.45 and chi2 = 0.09, P = 0.77, respectively). The different DRD2 genotypes (C/C, C/T and T/T) had no significant effects on age at onset of migraine, presence of premonitory phenomena, frequency of headache attacks, associated symptoms, psychological features and quality of life of our migraine patients. The results of our study do not support a role for the DRD2 gene in modifying the clinical features of migraine.
Objective: To compare the effects of Pilates ® , a 30 s static stretching protocol and elastic bands resistance training on lower and hand-grip strength, rachis morphology, flexibility and body balance among RRMS patients.Methods: Twenty-two subjects affected by relapsing-remitting multiple sclerosis (RRMS, EDSS ≤ 6) were randomly divided into 3 groups whose members each performed 16 weeks of training. Stabilometry, rachis morphology, sit and reach, handgrip and sit to stand tests were performed three times: T0, after a month of learning training protocols; T1, after eight weeks of training; and T2, after sixteen weeks of training.
Results
Conclusion:Static stretching, Pilates and resistance training are useful to increase the autonomy in the daily life of people with MS thanks to the adoption of these three different training methods.
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