Better than RECIST and Faster than iRECIST: Defining the Immunotherapy Progression Decision Score to Better Manage Progressive Tumors on Immunotherapy.

PURPOSE: The objective of the study is to propose the immunotherapy progression decision (iPD) score, a practical tool based on patient features that are available at the first evaluation of immunotherapy treatment, to help oncologists decide whether to continue the treatment or switch rapidly to another therapeutic line when facing a progressive disease patient at the first evaluation. EXPERIMENTAL DESIGN: This retrospective study included 107 patients with progressive disease at first evaluation according to RECIST 1.1. Clinical, radiological, and biological data at baseline and first evaluation were analyzed. An external validation set consisting of 31 patients with similar baseline characteristics was used for the validation of the score. RESULTS: Variables were analyzed in a univariate study. The iPD score was constructed using only independent variables, each considered as a worsening factor for the survival of patients. The patients were stratified in three groups: good prognosis (GP), poor prognosis (PP), and critical prognosis (CP). Each group showed significantly different survivals (GP: 11.4, PP: 4.4, CP: 2.3 months median overall survival, P < 0.001, log-rank test). Moreover, the iPD score was able to detect the pseudoprogressors better than other scores. On the validation set, CP patients had significantly worse survival than PP and GP patients (P < 0.05, log-rank test). CONCLUSIONS: The iPD score provides oncologists with a new evaluation, computable at first progression, to decide whether treatment should be continued (for the GP group), or immediately changed for the PP and CP groups. Further validation on larger cohorts is needed to prove its efficacy in clinical practice.

Feasibility and Impact of Adapted Physical Activity (APA) in Cancer Outpatients Beginning Medical Anti-Tumoral Treatment: The UMA-CHAPA Study.

Adapted physical activity (APA) improves quality of life and cancer outcomes. The aim of this study was to assess the feasibility of an APA program in outpatients beginning medical anticancer treatment. The secondary objective was to assess the impact of APA on fatigue, anxiety, depression, and handgrip strength (HGS). This prospective study was conducted between January and July 2017. Among 226 patients beginning treatment in the unit for a digestive, lung, hematological, or dermatological cancer, 163 were included. Adherence to the APA program was defined as more than or equal to one one-hour session per week for 3 months. The first evaluation was conducted at 3 months (M3), and the second evaluation at 6 months (M6). A total of 163 patients were included (mean age 62.5 ± 14.3); 139 (85.3%) agreed to follow the APA program. At M3, 106 of them were evaluated, of which 86 (81.1%) declared that they had followed the program. Improvement in anxiety was observed at M3 (-1.0 ± 3.2; p = 0.002) but there was no significant change in fatigue or depression. HGS decreased significantly (-1.2 ± 5.5; p = 0.04). The APA program was feasible in cancer outpatients beginning medical anticancer treatment. APA should be part of standard support care.

Dynapenia in digestive cancer outpatients: association with markers of functional and nutritional status (the FIGHTDIGO study).

BACKGROUND: The FIGHTDIGO study determined the feasibility and acceptability of handgrip strength (HGS) measurement in digestive cancer outpatients. PURPOSE: To assess the relationship between muscle strength and markers of functional and nutritional status in this population. DESIGN: In this prospective study, a total of 201 patients were followed during 6 months and were asked to perform HGS measurement at each hospitalization. Anthropometric measurements, laboratory tests, and performance status (PS) evaluation were collected. The modified Glasgow Prognostic Score (mGPS) was calculated using CRP and albumin levels. Severe malnutrition was defined as body mass index (BMI) < 18 kg/m2 in patients > 70 years old, and BMI < 16 kg/m2 in those < 70 years old. Dynapenia was defined as HGS < 30 kg (men) and < 20 kg (women). Mixed logistic regressions and mixed linear regressions were performed to study factors associated with dynapenia and HGS value, respectively. RESULTS: A total of 879 HGS measurements were analyzed. Dynapenia occurred in 177 measurements (20.1%). BMI and HGS were significantly associated in univariate analysis (p = 0.001). In multivariate analysis, mGPS score (ß = - 0.54 ± 0.31; p = 0.06) and severe malnutrition (ß = - 2.8 ± 1.4; p = 0.08) tended to be associated with HGS. Dynapenia was only associated with functional status impairment in univariate analysis (n = 140/803, 17.4% in ECOG 0 and 1 versus n = 37/76, 58.7% in ECOG 2 and 3; p = 0.002). CONCLUSIONS: Identification of dynapenia using HGS measurement may be useful to predict nutritional vulnerability in digestive cancer outpatients undergoing chemotherapy. Patients could then benefit from nutritional support, adapted physical activity programs, and early therapeutic adjustments. Trial registration ClinicalTrials.gov, NCT02797197.

Identification of Neoadjuvant Chemotherapy Response in Muscle-Invasive Bladder Cancer by Fourier-Transform Infrared Micro-Imaging.

BACKGROUND: Neoadjuvant chemotherapy (NAC) improves survival in responder patients. However, for non-responders, the treatment represents an ineffective exposure to chemotherapy and its potential adverse events. Predicting the response to treatment is a major issue in the therapeutic management of patients, particularly for patients with muscle-invasive bladder cancer. METHODS: Tissue samples of trans-urethral resection of bladder tumor collected at the diagnosis time, were analyzed by mid-infrared imaging. A sequence of spectral data processing was implemented for automatic recognition of informative pixels and scoring each pixel according to a continuous scale (from 0 to 10) associated with the response to NAC. The ground truth status of the responder or non-responder was based on histopathological examination of the samples. RESULTS: Although the TMA spots of tumors appeared histologically homogeneous, the infrared approach highlighted spectral heterogeneity. Both the quantification of this heterogeneity and the scoring of the NAC response at the pixel level were used to construct sensitivity and specificity maps from which decision criteria can be extracted to classify cancerous samples. CONCLUSIONS: This proof-of-concept appears as the first to evaluate the potential of the mid-infrared approach for the prediction of response to neoadjuvant chemotherapy in MIBC tissues.

Correlation between muscle mass and handgrip strength in digestive cancer patients undergoing chemotherapy.

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 cm2 /m2 (in men with a body mass index (BMI)> 25 kg/m2 ), < 43 cm2 /m2 (in men with a BMI < 25 kg/m2 ), and < 41 cm2 /m2 (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 cm2 /m2 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.

Oxaliplatin-desensitization procedure is safe and feasible in an outpatient cancer unit in France.

This study was undertaken to assess the previously unevaluated safety and feasibility of oxaliplatin-desensitization procedure add a French ambulatory cancer unit, which is a current topic in oncology. Our findings demonstrated that oxaliplatin-desensitization was safe and feasible in our ambulatory cancer unit. In routine practice, all these procedures are done on an inpatient basis starting at least the day before. Those results could change oncological practices in France and improve patients' quality of life and lower costs associated with inpatient administration.

Dynapenia could predict chemotherapy-induced dose-limiting neurotoxicity in digestive cancer patients.

BACKGROUND: FIGHTDIGO 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). METHODS: In 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. RESULTS: Two-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). CONCLUSIONS: Digestive 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 REGISTRATION: NCT02797197 June 13, 2016 retrospectively registered.

[Evaluation of the feasibility of a program of adapted physical activity in day hospital of digestive oncology: From the point of view of patients]. / Évaluation de la faisabilité d'un programme d'activité physique adaptée en hôpital de jour de cancérologie digestive : à partir du point de vue des patients.

INTRODUCTION: Adapted physical activity (APA) is recognized as an effective supportive care for asthenia and quality of life in oncology. Before an APA program was organized, the feasibility of such a program was evaluated among the patients. METHODS: Descriptive, prospective, semi-qualitative, single-center study over a 3-month period in patients treated with ambulatory chemotherapy for digestive cancer. A self-questionnaire was offered to all patients to evaluate their practice and knowledge about APA. In ten patients, fatigue, anxiety and depression were assessed, before and after 9 weeks of hospital-based APA. The scores were compared by matched Student test. RESULTS: Of the 123 patients treated, 80 questionnaires (65%) were exploitable. Before the diagnosis of cancer, 40 patients (50%) were physically active, 20% after (n=16). The reasons for not practicing were: lack of interest/not the idea (42%), lack of time (34%), do not believe in profit (9%), too expensive (8%). Fifty-three patients (66%) were interested in the program. In 10 patients, the APA program significantly reduced the depression score (P=0.024) and a non-significant improvement in anxiety and fatigue. DISCUSSION: This study shows that patients treated with chemotherapy are unaware of the usefulness of APA and that medical information can improve adherence to such a program. The establishment of an intra-hospital APA program proved to be possible and relevant.

Feasibility of systematic handgrip strength testing in digestive cancer patients treated with chemotherapy: The FIGHTDIGO study.

BACKGROUND: Handgrip strength (HGS) is a widely studied noninvasive test. Weak strength (dynapenia) seems to be associated with high morbidity and mortality in different populations, notably oncology populations. Despite this, HGS testing is not used in daily practice in oncology. The study was aimed at evaluating the feasibility and acceptability of HGS testing in patients with digestive cancer treated with ambulatory chemotherapy. METHODS: In this prospective, single-center study, enrolled patients were followed for 6 months. Two consecutive bilateral measures were performed with a Jamar dynamometer during each patient's appointments in the unit for intravenous treatment. A questionnaire was completed by patients and medical team members. RESULTS: There were 203 consecutive patients, and 201 were recruited. In all, 1704 of 1716 measurements (99.3%) were performed, and 201 patients (99.0%) performed at least 1 measure; 190 (94.5%) performed all expected measures. One hundred sixty-four of 171 participating patients (95.9%) found the test easy to perform, and 167 (97.7%) did not find the test restrictive. All of the 14 medical team members found the test easy to perform, unrestrictive, and undisruptive in their daily practice. CONCLUSIONS: HGS testing is routinely feasible, inexpensive, and well accepted by patients and medical teams in an ambulatory digestive cancer unit. Cancer 2018;124:1501-6. © 2017 American Cancer Society.

Peritoneal recurrence of thymoma treated by surgery and hyperthermic intraperitoneal chemotherapy.

Thymomas are rare (1,5 cases/million) and typically occur in adults with a median age of 50 years old. Thymomas are indolent with a 10-year overall survival for resected stage II thymomas of 70%. Late relapses occur in 20% of the cases, and distant metastasis from thymoma is rare. Peritoneal recurrence of thymoma treated with surgery associated with hyperthermic intraperitoneal chemotherapy (HIPEC) has not been described in the literature. This report manages peritoneal recurrence of thymoma with HIPEC, suggesting that aggressive therapies may decrease the risk of recurrence.

Nivolumab in renal cell carcinoma: latest evidence and clinical potential.

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 death-ligand-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.