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.

Implantation of tissue expander prior to irradiation in the era of intensity modulated radiotherapy: impact on the management of patients with pelvic digestive cancers.

PURPOSE: Before the introduction of intensity-modulated radiation therapy (IMRT), few teams used to implant a pelvic tissue expander to keep the bowel away from the radiation field, so as to reduce the risk of acute and late enteritis. However, this unexpected surgery could impact patient's overall treatment and may be no more necessary in the era of modern radiotherapy. MATERIAL AND METHODS: This is a retrospective cross-sectional study including 13 patients who underwent tissue expander implantation before radiotherapy or chemoradiotherapy for rectal or anal carcinoma between November 2008 and March 2019. First, we aim to show that IMRT could sometimes be insufficient to respect dosimetric constraints, and then we aim to report the impact of tissue expander implantation on the global strategy of care of patients with anal and rectal cancers. RESULTS: Seventy-seven percent of the included patients were treated for anal neoplasms, while the remaining 23% had locally advanced rectal cancer. The median follow-up since implantation of the expander was 51 months [3.7-115]. Three patients recurred. One patient developed grade III toxicity related to the implantation of a tissue expander. The delay between diagnosis and the start of irradiation was significantly prolonged (median of 3 months), requiring unusual induction chemotherapy. CONCLUSION: Implantation of tissue expander prior to chemoradiotherapy should be considered, even in the era of IMRT, when irradiated peritoneal cavity volume (V15Gy-V45Gy) far exceeds usual dose constraints. However, it impacts the global strategy of care by delaying the start of irradiation, by introducing induction chemotherapy, and rarely by causing post-operative complications.

A supportive care dedicated hospitalization ward in comprehensive cancer center.

INTRODUCTION: Supportive care development has created new needs in patients' care pathway. In order to anticipate, evaluate, and take care of patients' needs, a supportive care dedicated hospitalization ward was created in late 2016 in our comprehensive cancer center, including 15 beds (11 for week care and 4 for day care). We aimed to assess the activity of this supportive care ward in 2018. METHODS: Data were extracted from weekly activity reports of supportive care ward and retrospectively analyzed. Those reports are automatically generated from hospitalization scheduling software. RESULTS: In week care ward, 627 stays were recorded. Occupancy rate was 88%. Mean stay duration was 3.01 days. Main indications for week stay were pain evaluation and management (47.4%) and nutritional management (31.7%). In day care ward, 1191 stays were registered. Turnover rate was 1.18 patients/bed/day. Main indications for day stay were pain management (41.6%) and comprehensive geriatric assessment in oncology (22.8%). CONCLUSION: The 2018 supportive care ward evaluation showed its viability in comprehensive cancer center. The main activity was based on pain and nutritional management.

Avelumab vs Standard Second-Line Chemotherapy in Patients With Metastatic Colorectal Cancer and Microsatellite Instability: A Randomized Clinical Trial.

Importance: Only 1 randomized clinical trial has shown the superiority of immune checkpoint inhibitors in patients with deficient mismatch repair and/or microsatellite instability (dMMR/MSI) metastatic colorectal cancer (mCRC) in the first-line setting. Objectives: To determine whether avelumab (an anti-programmed cell death ligand 1 antibody) improves progression-free survival (PFS) compared with standard second-line chemotherapy in patients with dMMR/MSI mCRC. Design, Setting, and Participants: The SAMCO-PRODIGE 54 trial is a national open-label phase 2 randomized clinical trial that was conducted from April 24, 2018, to April 29, 2021, at 49 French sites. Patients with dMMR/MSI mCRC who experienced progression while receiving standard first-line therapy were included in the analysis. Interventions: Patients were randomized to receive standard second-line therapy or avelumab every 2 weeks until progression, unacceptable toxic effects, or patient refusal. Main Outcome and Measures: The primary end point was PFS according to RECIST (Response Evaluation Criteria in Solid Tumours), version 1.1, evaluated by investigators in patients with mCRC and confirmed dMMR and MSI status who received at least 1 dose of treatment (modified intention-to-treat [mITT] population). Results: A total of 122 patients were enrolled in the mITT population. Median age was 66 (IQR, 56-76) years, 65 patients (53.3%) were women, 100 (82.0%) had a right-sided tumor, and 52 (42.6%) had BRAF V600E-mutated tumors. There was no difference in patients and tumor characteristics between treatment groups. No new safety concerns in either group were detected, with fewer treatment-related adverse events of at least grade 3 in the avelumab group than in the chemotherapy group (20 [31.7%] vs 34 [53.1%]; P = .02). After a median follow-up of 33.3 (95% CI, 28.3-34.8) months, avelumab was superior to chemotherapy with or without targeted agents with respect to PFS (15 [24.6%] vs 5 [8.2%] among patients without progression; P = .03). Rates of PFS rates at 12 months were 31.2% (95% CI, 20.1%-42.9%) and 19.4% (95% CI, 10.6%-30.2%) in the avelumab and control groups, respectively, and 27.4% (95% CI, 16.8%-39.0%) and 9.1% (95% CI, 3.2%-18.8%) at 18 months. Objective response rates were similar in both groups (18 [29.5%] vs 16 [26.2%]; P = .45). Among patients with disease control, 18 (75.7%) in the avelumab group compared with 9 (19.1%) in the control group had ongoing disease control at 18 months. Conclusions: The SAMCO-PRODIGE 54 phase 2 randomized clinical trial showed, in patients with dMMR/MSI mCRC, better PFS and disease control duration with avelumab over standard second-line treatment, with a favorable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT03186326.

Treatment of hepatocellular carcinoma (HCC) with systemic chemotherapy combining epirubicin, cisplatinum and infusional 5-fluorouracil (ECF regimen).

PURPOSE: We tested the efficacy of a systemic chemotherapy regimen combining epirubicin, cisplatinum and infusional 5-fluorouracil (ECF) in a cohort of patients with hepatocellular carcinoma (HCC) who could not be given surgical, intraarterial or percutaneous treatment. PATIENTS AND METHODS: Between January 1998 and June 2000, 21 patients with metastatic and/or locally advanced HCC complicating a fibrous liver or a well-compensated (Child A) cirrhosis were given systemic chemotherapy with the ECF regimen. Tumor responses as assessed on CT scan and in terms of survival were studied. RESULTS: Patients completed a median of five chemotherapy courses. Overall tolerance was good but eight patients developed grade 3-4 toxicity, mainly hematological, and one patient experienced a grade 4 renal toxicity. Median survival was 10 months. Actuarial survivals (+/-SD) at 6 months, 1 year and 2 years were 90.2+/-9%, 70.3+/-10% and 24.6+/-19%, respectively. Of the 21 patients, 13 died, 12 from their tumor and 1 from treatment-related renal failure. There were only three objective responses (14.5%; CI95 1-28%) but one of these corresponded to a pathological complete response. The delay to tumor progression was 5.9+/-4.7 months. CONCLUSIONS: Systemic chemotherapy using the ECF regimen gave a poor response and low survival rates. It would appear reasonable to pursue the search for potentially efficacious chemotherapy protocols using other drug combinations.

Prospective evaluation of a new rapid urease test (Pronto Dry) for the diagnosis of Helicobacter pylori infection.

AIM: Rapid urease tests are commonly used to establish the diagnosis of Helicobacter pylori infection during upper endoscopy. The aim of this study was to evaluate the performance of a new rapid urease test (Pronto Dry) compared with histology as the gold standard. METHODS: Six gastric biopsies (three in the antrum and three in the fundus) were performed in 113 consecutive patients. Eighteen patients were later excluded from analysis because they did not fulfil the inclusion criteria. Four biopsies were examined by two experienced pathologists blinded to the rapid urease tests. Two biopsies (one from antrum and one from the fundus) were pooled for the rapid urease test which was read by the endoscopist 5 and 30 minutes later using the color scale (yellow, pink, orange, dark pink, fuchsia) provided by the manufacturer. RESULTS: According to the histology findings 32 of the 95 patients retained for analysis (33.7%) were positive for Helicobacter pylori. Considering that a positive test was indicated by the dark pink or fuchsia colors, sensitivity and specificity of Pronto Dry were 62.5% and 98.4% at 5 minutes and 84.4% and 98.4% at 30 minutes respectively. Twenty-one of the 28 positive rapid urease tests (75%) were already positive at 5 minutes. CONCLUSION: Considering positive tests are indicated solely by the two darkest colors on the color scale, the performance of Pronto Dry is similar to that of other rapid urease tests. The rapid results provided by Pronto Dry in routine practice would seem to provide obvious advantages.

Adenocarcinoid of the appendix vermiformis: complete and persistent remission after chemotherapy (folfox) of a metastatic case.

A 58-year-old woman underwent surgery for a pelvic mass. Palliative resection was performed despite the presence of multiple retroperitoneal lymph nodes. All pathology specimens exhibited an adenocarcinomatous component associated with carcinoid proliferation related to an appendicular tumor leading to the diagnosis of appendicular adenocarcinoid with ovarian, peritoneal, and nodal metastases. The patient's general status worsened rapidly with widespread nodal metastasis. Chemotherapy (Folfox 4 regimen) was given, and the patient improved within six weeks. Complete response was achieved after three months. Presently, more than three years after the end of the treatment, the patient is still alive and in complete remission. Appendicular adenocarcinoid is exceptional. These tumors exhibit two cellular components. Ovarian metastasis is frequent. Prognosis is intermediate between adenocarcinoma and malignant carcinoid. When given to patients with colonic carcinoma, the Folfox regimen used effectively here, is associated with a 50% objective response but complete response is very exceptional.

Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection of hepatocellular carcinoma.

The high rate of recurrence after surgical resection of hepatocellular carcinoma (HCC) is a major therapeutic challenge. Postoperative injection of 131-iodine-labeled lipiodol (131I-Lip) into the hepatic artery has been proposed as adjuvant treatment (Lau et al.). We analyzed 2 retrospective series of matched patients treated in our unit before and after addition of 131I-Lip adjuvant therapy to our standard surgical strategy. Thirty-eight patients who had undergone surgical resection of HCC after January 1999 were given adjuvant intra-arterial injection of 131I-Lip after surgery. These patients were matched with 38 other patients who had undergone surgical resection only between January 1997 and January 1999. The frequency of recurrences, disease-free rates, and overall survival rates were compared. The 2 groups were similar for clinical, biologic, or histologic parameters studied and Cancer Liver Italian Program scores. There were 15 recurrences in the group without adjuvant treatment and 9 in the group with 131I-Lip adjuvant treatment. The 1-, 2-, and 3-year disease-free survival rates (+/-95% confidence interval) were different (P <.02): 94.7% +/- 3.6%, 83.7% +/- 6.1%, and 68.4% +/- 9.7%, respectively, in the 131I-Lip group versus 73.7% +/- 7.1%, 54.3% +/- 8.2%, and 41.5% +/- 10.5% in the surgery group. The 1-, 2-, and 3-year survival rates (+/-95% confidence interval) also were different (P <.02): 94.7% +/- 3.6%, 91.7% +/- 4.6%, and 91.7% +/- 4.6%, respectively, in the 131I-Lip group versus 94.7% +/- 3.6%, 71.3% +/- 7.8%, and 49.9% +/- 10% in the surgery group. In conclusion, this retrospective analysis supports the promising contribution of postoperative injection of 131I-Lip after resection of HCC. A randomized study including more patients would be necessary to confirm its contribution to therapeutic management.