Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR).

BACKGROUND: Perioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen is considered as the new standard chemotherapy regimen for perioperative strategy, despite associated with a 5-year overall survival rate (OS) amounting 45% following radical surgery. Immunotherapy with antibodies that inhibit PD-1/ PD-L1 interaction has recently emerged as a new treatment option with promising and encouraging early trial results for patients with advanced or metastatic gastric or GEJ adenocarcinoma. Currently, no trials have investigated the impact of perioperative immunotherapy in combination with chemotherapy for resectable gastric or GEJ adenocarcinoma. METHODS: GASPAR trial is a multicenter open-label, nonrandomized, phase II trial to evaluate the efficacy and safety of Spartalizumab in combination with the FLOT regimen as perioperative treatment for resectable gastric or GEJ adenocarcinoma. The main endpoint is the proportion of patients with pathological complete regression (pCR) in the primary tumour after preoperative treatment. Systemic treatment will include a pre-operative neoadjuvant and a post-operative adjuvant treatment, during which FLOT regimen will be administered every two weeks for 4 cycles and Spartalizumab every four weeks for 2 cycles. For patients with confirmed tumor resectability on imaging assessment, surgery will be realized within 4-6 weeks after the last dose of preoperative chemotherapy. Post-operative systemic treatment will then be initiated within 4-10 weeks after surgery. Using a Simon's two-stage design, up to 67 patients will be enrolled, including 23 in the first stage. DISCUSSION: Currently, no trials have investigated the impact of immunotherapy in combination with FLOT chemotherapy as perioperative treatment for resectable gastric or GEJ adenocarcinoma. Some studies have suggested a change in the tumor immune micro-environment following neoadjuvant chemotherapy in this setting, reinforcing the relevance to propose a phase II trial evaluating efficacy and safety of Spartalizumab in combination with perioperative chemotherapy, with the aim of improving treatment efficacy and survival outcomes. TRIAL REGISTRATION: NCT04736485, registered February, 3, 2021.

[Composite lymphoma: Case report of a coexisting follicular and mantle cell lymphoma in situ in a cervical node]. / Lymphome composite : Case report d'un ganglion cervical siège d'un lymphome folliculaire et d'un lymphome à cellules du manteau in situ.

Composite lymphoma represents 1-4% of lymphomas. Only 8 case reports concerned coexisting follicular lymphoma and mantle cell lymphoma. Here, we report the case of an 81 years old man who has been diagnosed with a composite follicular and in situ mantle cell lymphoma. The use of a large panel of immunohistochemical stains associated with the flow cytometry results have allowed us to make this particular diagnosis. We highlight here a common clonal origin of the composite lymphoma's two entities, as described in previous publications.

Thyroid 18F-fluorocholine uptake in patients with chronic autoimmune thyroiditis.

Objective: 18F-Fluorocholine (18FCH) PET/CT has high sensitivity for parathyroid adenoma detection and can reliably exclude malignancy in thyroid nodules with indeterminate cytology. Data regarding 18FCH uptake in chronic autoimmune thyroiditis (CAT) are scarce. We aimed to assess thyroid 18FCH uptake in CAT with biological and histological correlation. Methods: This is an ancillary study from the Chocolate trial (NCT02784223) that prospectively enrolled 107 patients planned for thyroid surgery. 18FCH PET/CT acquisitions were performed 20 and 60 min after injection. 18FCH uptake in the thyroid gland was assessed by measuring maximum (SUVmax) and mean (SUVmean) standardized uptake values. Thyrotropin, free thyroxine (FT4), thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies were collected. The intensity of thyroiditis and the degree of fibrosis were assessed on pathology. Results: CAT was evidenced in 19/107 (18%) patients. Of these, 13 (68%) displayed an increased and diffuse 18FCH thyroid uptake. This uptake pattern was not observed in patients without CAT. SUVmax and SUVmean were higher in patients with CAT than in those without (P < 0.001). At both acquisition times, SUVmax showed a monotonic relationship with the intensity of thyroiditis (Spearman ρ = 0.44 and 0.51, respectively, P < 0.001) and with the degree of fibrosis (Spearman ρ = 0.55 and 0.62, respectively, P < 0.001). SUVmax showed a linear relationship with TPOAb titers at 20 min (Pearson r = 0.54, P < 0.05; Spearman ρ = 0.59, P = 0.03). Conclusions: More than two-thirds of the patients with CAT present high and diffuse thyroid 18FCH uptake. This uptake pattern is highly specific to CAT and is correlated with pathology and TPOAb titers.

PSMA Expression in Differentiated Thyroid Cancer: Association With Radioiodine, 18FDG Uptake, and Patient Outcome.

CONTEXT: Little is known about prostate-specific membrane antigen (PSMA) expression in patients with cervical involvement of differentiated thyroid cancer (DTC). OBJECTIVE: We investigated PSMA expression in neck persistent/recurrent disease (PRD) using immunohistochemistry and the association with radioiodine (RAI) or 18-fluorodeoxyglucose (18FDG) uptake, and patient outcome. DESIGN, SETTING, AND PATIENTS: Data from 44 consecutive DTC patients who underwent neck reoperation from 2006 to 2018 in a comprehensive cancer center. MAIN OUTCOME MEASURE(S): Immunostaining was performed with vascular endothelial marker CD31 and PSMA. PSMA expression was quantified using the immunoreactive score (IRS). RAI and 18FDG uptake were assessed before surgery using posttherapeutic RAI scintigraphy and 18FDG positron emission tomography with computed tomography. Mean follow-up after reintervention was 6.5 ±â€…3.7 years. RESULTS: Thirty patients (68%) showed at least 1 PSMA-positive lesion (IRS ≥ 2) with similar proportions in RAI-positive and RAI-negative patients (75% vs 66%). In RAI-negative patients, however, the proportion of PSMA-positive disease (79% vs 25%, P < 0.01) and the mean IRS (4.0 vs 1.0, P = 0.01) were higher in 18FDG-positive than in 18FDG-negative patients. Furthermore, mean IRS was higher in patients ≥ 55 years, large primary tumors (>40 mm) or aggressive subtypes, and was correlated with structural disease at last follow-up. Strong PSMA expression (IRS ≥ 9) was associated with shorter progression-free survival (PFS). CONCLUSIONS: Our findings show that PSMA expression was present in two-thirds of patients with neck PRD, that it was related to poor prognostic factors and that very high expression was associated with poorer PFS. This preliminary study may offer new perspectives for the management of RAI-refractory DTC.

Contribution of the IdyllaTM System to Improving the Therapeutic Care of Patients with NSCLC through Early Screening of EGFR Mutations.

Epidermal growth factor receptor (EGFR) genotyping, a critical examen for the treatment decisions of patients with non-small cell lung cancer (NSCLC), is commonly assayed by next-generation sequencing (NGS), but this global approach takes time. To determine whether rapid EGFR genotyping tests by the IdyllaTM system guides earlier therapy decisions, EGFR mutations were assayed by both the IdyllaTM system and NGS in 223 patients with NSCLC in a bicentric prospective study. IdyllaTM demonstrated agreement with the NGS method in 187/194 cases (96.4%) and recovered 20 of the 26 (77%) EGFR mutations detected using NGS. Regarding the seven missed EGFR mutations, five were not detected by the IdyllaTM system, one was assayed in a sample with insufficient tumoral cells, and the last was in a sample not validated by the IdyllaTM system (a bone metastasis). IdyllaTM did not detect any false positives. The average time between EGFR genotyping results from IdyllaTM and the NGS method was 9.2 ± 2.2 working days (wd) (12.6 ± 4.0 calendar days (cd)). Subsequently, based on the IdyllaTM method, the timeframe from tumor sampling to the initiation of EGFR-TKI was 7.7 ± 1.2 wd (11.4 ± 3.1 cd), while it was 20.3 ± 6.7 wd (27.2 ± 8.3 cd) with the NGS method (p < 0.001). We thus demonstrated here that the IdyllaTM system contributes to improving the therapeutic care of patients with NSCLC by the early screening of EGFR mutations.