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). 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. 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). 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. NCT02797197 June 13, 2016 retrospectively registered.

Small-intestinal neuroendocrine tumors (SI-NETs) are the most prevalent small bowel neoplasms with an increasing frequency. In the multimodal management of SI-NETs, surgery plays a key role, either in curative intent, even if R0 resection is feasible in only 20% of patients due to advanced stage at diagnosis, or palliative intent. Surgeons must be informed about the specific surgical management of SI-NETs according to their hormonal secretion, their usual dissemination at the time of diagnosis and the need for bowel-preserving surgery to avoid short bowel syndrome. The aim of this paper is to review the surgical indications and techniques, and perioperative and postoperative management of SI-NETs.

PURPOSE: Alkylating agents (ALKY) are the main chemotherapies used for advanced neuroendocrine tumors (NETs). O ⁶ -Methylguanine-DNA methyltransferase (MGMT) status, as proficient (p) or deficient (d), may predict the response to ALKY. PATIENTS AND METHODS: MGMT-NET (ClinicalTrials.gov identifier: NCT03217097 ) was a phase II trial randomly assigning 1:1 for pMGMT or 2:1 for dMGMT-NETs to either ALKY or oxaliplatin (Ox). Inclusion criteria were a confirmed advanced pancreatic, thoracic, or unknown primary NETs with an indication for chemotherapy and tissue available. The primary aim was to detect a difference of 35% between the 3-month objective response rate (ORR) in pMGMT-NETs versus in dMGMT-NETs when treated with ALKY. A biomarker-stratified design was performed to compare ALKY and Ox in the dMGMT and pMGMT strata for the secondary end points. dMGMT was defined using pyrosequencing (PSQ; methylated MGMT ≥9%) and using immunochemistry ( H -score of MGMT <50) when PSQ was not interpretable. RESULTS: From October 2018 to October 2021, 105 patients (55 pancreas, 38 thorax, 12 unknown) started either ALKY (n = 62) or Ox (n = 43). The median age was 63 years (range, 30-84), and 59% were males. NETs were G1 (19%), G2 (69%), or G3 (10%). Among patients with interpretable MGMT status, 56.9% (58 of 102) had a dMGMT-NET. The primary end point was not reached; the 3-month ORR was 10 (29.4%) versus 2 (8%), and the odds ratio was 3.5 (0.58-21.16), P = .172. However, best ORR (18 [52.9%] v 3 [11.5%]) and median progression-free survival (14.6 [95% CI, 7.2 to 22.1] v 11.3 [9.4 to 13.2] months) were higher for dMGMT-NETs versus pMGMT-NETs. MGMT status does not seem to affect the Ox efficacy. CONCLUSION: Despite the fact that the primary end point was not reached, ALKY has clinical activity in patients with dMGMT-NETs.

Neuroendocrine tumors (NETs) are highly vascularized neoplasms. While FOLFOX chemotherapy has shown efficacy in patients with advanced NETs, its combination with antiangiogenics has been scarcely described. Here, we report the efficacy and tolerance of FOLFOX‐bevacizumab in this setting. We retrospectively studied all consecutive patients with metastatic NET treated by FOLFOX‐bevacizumab in two expert centers from 2013 to 2020. We assessed time to treatment failure (TTF), objective response rate (ORR) and toxicity. We explored factors associated with TTF and ORR using multivariate analyses. We included 57 patients (35.1% female, median age 61.7 years), with pancreatic (66.7%), small‐intestine (14%) or lung (7%) NETs. Most patients (57.9%) had extra‐hepatic metastases and G3 NETs accounted for 40.3% of cases. Patients received a median of 17 cycles of treatment, including a median of seven cycles of bevacizumab and/or 5‐fluorouracile maintenance. Median TTF was 15.5 months (95% CI: 9.8–21.2) and was shorter in patients age > 60 years (HR 2.56, 95% CI: 1.16–5.64), p = .020) and >1 previous systemic treatment line (HR 4.15, 95% CI: 1.96–8.78), p < .001). The ORR was 42.9% and was higher in cases of performance status at 0 (OR 5.25, 95% CI: 1.13–24.35), p = .034) and G3 NET (OR 5.39, 95% CI: 1.23–23.52), p = .025). The FOLFOX‐bevacizumab combination has promising efficacy in patients with progressive metastatic NETs and notably for G3 NETs, for which optimal treatment as yet remains ill‐defined. Hence, it could be a relevant alternative to alkylating‐based chemotherapy in this setting and should be further explored prospectively.

Objectives Acute bronchiolitis is a major public health issue with high number of infants hospitalised worldwide each year. In France, hospitalisations mostly occur between October and March and peak in December. A reduction of emergency visits for bronchiolitis has been observed at onset of the COVID-19 outbreak. We aimed to assess the pandemic effects on the hospitalisations for bronchiolitis during the 2020–2021 winter (COVID-19 period) compared with three previous winters (pre-COVID-19). Design Retrospective, observational and cross-sectional study. Setting Tertiary university paediatric hospital in Paris (France). Participants All infants aged under 12 months who were hospitalised for acute bronchiolitis during the autumn/winter seasons (1 October to 31 March) from 2017 to 2021 were included. Clinical and laboratory data were collected using standardised forms. Results During the COVID-19 period was observed, a 54.3% reduction in hospitalisations for bronchiolitis associated with a delayed peak (February instead of November–December). Clinical characteristics and hospitalisation courses were substantially similar. The differences during the COVID-19 period were: smaller proportion of infants with comorbidities (8% vs 14% p=0.02), lower need for oxygen (45% vs 55%, p=0.01), higher proportions of metapneumovirus, parainfluenzae 3, bocavirus, coronavirus NL63 and OC43 (all p≤0.01) and no influenza. The three infants positive for SARS-CoV-2 were also positive for respiratory syncytial virus, suggesting that SARS-CoV-2 alone does not cause bronchiolitis, despite previous assumptions. Conclusion The dramatic reduction in infants’ hospitalisations for acute bronchiolitis is an opportunity to change our future habits such as advising the population to wear masks and apply additional hygiene measures in case of respiratory tract infections. This may change the worldwide bronchiolitis burden and improve children respiratory outcomes.

In the FIGHTDIGO study, digestive cancer patients with dynapenia experienced more chemotherapy-induced neurotoxicities. FIGHTDIGOTOX aimed to evaluate the relationship between pre-therapeutic handgrip strength (HGS) and chemotherapy-induced dose-limiting toxicity (DLT) or all-grade toxicity in digestive cancer patients. HGS measurement was performed with a Jamar dynamometer. Dynapenia was defined according to EWGSOP2 criteria (<27 kg (men); <16 kg (women)). DLT was defined as any toxicity leading to dose reduction, treatment delay, or permanent discontinuation. We also performed an exploratory analysis in patients below the included population’s median HGS. A total of 244 patients were included. According to EWGSOP2 criteria, 23 patients had pre-therapeutic dynapenia (9.4%). With our exploratory median-based threshold (34 kg for men; 22 kg for women), 107 patients were dynapenic (43.8%). For each threshold, dynapenia was not an independent predictive factor of overall DLT and neurotoxicity. Dynapenic patients according to EWGSOP2 definition experienced more hand-foot syndrome (p = 0.007). Low HGS according to our exploratory threshold was associated with more all-grade asthenia (p = 0.014), anemia (p = 0.006), and asthenia with DLT (p = 0.029). Pre-therapeutic dynapenia was not a predictive factor for overall DLT and neurotoxicity in digestive cancer patients but could be a predictive factor of chemotherapy-induced anemia and asthenia. There is a need to better define the threshold of dynapenia in cancer patients.