NESC Multicenter Phase II Trial in the Preoperative Treatment of Gastric Adenocarcinoma with Chemotherapy (Docetaxel-Cisplatin-5FU+Lenograstim) Followed by Chemoradiation Based 5FU and Oxaliplatin and Surgery.

PURPOSE: Preoperative chemoradiation (CRT) is expected to increase the rate of curative resection and complete histological response. In this trial, we investigated the efficacy of a neoadjuvant CRT regimen in gastric adenocarcinoma (NCT01565109 trial). MATERIALS AND METHODS: Patients with stage IB to IIIC gastric adenocarcinoma, endoscopy ultrasound and computed tomography-scan diagnosed, were eligible for this phase II trial. Neoadjuvant treatment consisted of 2 cycles of chemotherapy with DCF (docetaxel, cisplatin, and 5-fluorouracil [5FU]) followed by preoperative CRT with oxaliplatin, continuous 5FU and radiotherapy (45 Gy in 25 fractions of 1.8 Gy, 5 fractions per week for 5 weeks) administered before surgery. R0-resection rate, pathological complete response (pathCR) rate, and survival (progression-free survival [PFS] and overall survival [OS]) were evaluated as primary endpoints. RESULTS: Among 33 patients included, 32 patients (97%) received CRT and 26 (78.8%) were resected (R0 resection for all patients resected). Among resected patients, we report pathCR in 23,1% and pathologic major response (tumor regression grade 2 according to Mandard's classification) in 26,9%. With a median follow-up duration of 5.82 years (range, 0.4 to 9.24 years), the estimated median OS for all 33 patients was not reached; 1-, 3-, and 5-year OS rates were 85%, 61%, and 52%, respectively. Among resected patients, those whose histological response was tumor grade regression (TRG) 1-2 had significantly better OS and PFS rates than those with a TRG 3-4-5 response (p=0.019 and p=0.016, respectively). CONCLUSION: Promising results from trials involving preoperative chemoradiation followed by surgery in gastric cancer need to be further evaluated in a phase III trial.

Capecitabine/Mitomycin versus 5-Fluorouracil/Mitomycin in Combination with Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy for Anal Cancer.

Since EXTRA, a non-randomized phase II trial with 31 patients, explored the use of capecitabine, mitomycin and radiation therapy (RT) in the treatment of localized squamous cell carcinoma of the anal canal (SCCAC), this treatment has been considered as an acceptable alternative to infusional 5-FU. However, the differences in efficacy between capecitabine and 5-FU in chemoradiation therapy (CRT) with simultaneous integrated boost (SIB) radiation therapy (SIB-IMRT) for local SCCAC are not well documented. Patients included in this prospective monocentric cohort study were treated with SIB-RapidArc (a unique RT method treatment for all patients: identical technique, volume and constraints for at-risk organs), mitomycin C and 5-FU each day of RT for 7 weeks (group 1) or capecitabine each day of RT (group 2). Patients treated between July 2009 and August 2017 (group 1) and between November 2012 and April 2018 (group 2) for local SCCAC T2-4 classified as N, M0 or T, N1-3, M0 were included. Primary endpoints were progression-free survival (PFS) and acute toxicities. Results: One hundred forty-seven patients were included, 91 in group 1 and 56 in group 2. The two groups were statistically comparable in terms of sex, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and TNM. With a median duration of follow-up of 53.5 months, the PFS rate at 3 years was 80% for group 1 and 75% for group 2 (p = 0.32). The 3-year colostomy-free survival rate was 92% for group 1 and 85% for group 2 (p = 0.11). The rate of patients with at least one grade 3 or higher acute toxicity was 35.5% in group 1 and 21.4% in group 2 (p = 0.10), with a trend of fewer acute toxicities with capecitabine. Conclusion: Capecitabine/mitomycin in combination with SIB RapidArc radiation therapy for anal cancer seems as effective as 5-FU-based chemotherapy and is well tolerated with minimal toxicity.

Stereotactic radiotherapy for brain metastases: predictive factors of radionecrosis.

PURPOSE: Stereotactic radiotherapy (SRT) is a highly effective approach and represents the current standard of treatment for patients with limited number of brain metastasis (BM). SRT is generally well tolerated but can sometimes lead to radionecrosis (RN). The aim of this study was to identify predictive factors of radionecrosis related to SRT for brain metastasis. METHODS: This retrospective observational cohort study included patients who underwent SRT in the Institut Sainte Catherine between January 1st, 2017 and December 31st, 2020 for the treatment of brain metastasis from any cancer. Individual data and particularly signs of radionecrosis (clinical, imaging, anatomopathological) were collected from electronic medical records. Radionecrosis was defined as the occurrence on MRI of contrast-enhancing necrotic lesions, surrounded by edema, occurring at least 6 months after SRT and localized within fields of irradiation. RESULTS: 123 patients were included; median age was 66 years. 17 patients (11.8%) developed radionecrosis after a median follow up of 418.5 days [63;1498]. Predictive factors of radionecrosis in multivariate analysis were age under 66 years with a sensitivity of 77% and a specificity of 56%. No other factor as the presence of comorbidities, the number of irradiated metastases, the PTV volume or the volume of irradiated healthy brain were predictive of radionecrosis. CONCLUSION: Age at treatment initiation and tumor location seems to be correlated with radionecrosis in patients with brain metastasis treated with SRT. These elements could be useful to adapted radiation therapy.

[Needs assessment for the establishment of an Oral Therapy Unit]. / Évaluation des besoins pour la mise en place d'une Unité de Thérapie Orale.

INTRODUCTION: Oncological at home-treatment improves patient quality of life and autonomy but requires close watchfulness of adverse events and compliance to treatment. For nearly ten years, pharmaceutical consultations for home-based anticancer oral therapies patients are proposed on medical request in Avignon-Provence Cancer Institute (ICAP). Organizational changes led us to modify this management by integrating dedicated nurses to create an Oral Therapy Unit (OTU). MATERIALS ET METHODS: Needs and expectations assessment questionnaires were proposed to healthcare professionals and patients treated by oral therapies. The analysis of these questionnaires allows to set up an OTU, integrating a dedicated nurse, adapted to the expectations of patients and healthcare professionals. About 8 months later, a new evaluation was carried out to assess the impact of this new support for patient care and health professionals' organization. RESULTS: The results of the studies carried out before OTU implementation highlight the importance of multi-professional support for patients from the start of treatment and during the follow-up. With the new OTU pathway, professionals expect a patient course improvement (94%), a better compliance (88%), a therapeutic accidents reduction (81%) and an improvement in the patient-caregiver relationship (69%). Regarding the organization, 56% of them are expecting to save medical and pharmaceutical time. CONCLUSION: The OTU creation in our institution and these new multi-professionals' teams' management of patients has obtained a favourable opinion from healthcare professionals and patient satisfaction.

Non-compliance with end-of-life parenteral nutrition prescription recommendations: retrospective study of 1,260 cancer patients.

BACKGROUND: Cancer patients near end of life (EOL) often suffer malnourishment and cachexia. In these patients, the prescription of parenteral nutrition (PN) remains highly controversial. Guidelines state that nutritional support does not improve quality of life in dying patients. We aimed to assess the compliance with international recommendations about PN prescription in advanced cancer, identify factors associated with PN at EOL and to evaluate the risk of blood stream infections (BSI). METHODS: Retrospective analysis of data from medical records of patients who died in 2013, 2015, 2017 and 2019 in a cancer center. RESULTS: One thousand two hundred and sixty patients with advanced cancer were included. PN was prescribed in 574 (45.6%) patients, the mean duration of PN was 10±9.7 days. Patients with a severe malnutrition [odds ratio (OR) =2.36; 95% confidence interval (CI): 1.42-4.02], a malignant bowel obstruction (MBO) (OR =2.25; 95% CI: 1.44-3.56), a length of hospitalization >12 days (OR =2.21; 95% CI: 1.67-2.94), a body mass index (BMI) <22.14 kg/m2 (OR =2.02; 95% CI: 1.52-2.67), an antitumor treatment (OR =1.58; 95% CI: 1.14-2.20) were more frequently prescribed a PN. BSI was diagnosed in 113 patients (9%) and was more frequent in patients receiving a PN (13% vs. 6%; OR =2.01; 95% CI: 1.18-3.54). CONCLUSIONS: International guidelines on PN in EOL cancer patients are poorly applied in the studied settings. Factors associated with the use of PN were low BMI, severe malnutrition, antitumor treatment, increased length of hospitalization. These findings argue for the use of a survival estimation tool and a multidisciplinary integrative care intervention when considering PN.

[Cancers induced by occupational exposure: What progress has been made?] / Les cancers induits par les expositions professionnelles : les progrès.

INTRODUCTION: In 2019, only 1,790 occupational cancers were recognized, i.e., less than 1% of estimated occupational cancers. Our study aims to expand the methodology of a French cancer center to improve the detection and compensation of occupational bronchopulmonary cancers. PATIENTS AND METHODS: Between November 2014 and December 2020, all patients diagnosed with primary bronchopulmonary cancer (including mesothelioma) received a free questionnaire (Curriculum Laboris) aimed at retracing their professional career but also socio-demographic data. After an initial analysis of the questionnaire, a consultation can be scheduled if exposures are suspected. They will then be confirmed or not, during a consultation of around 1hour 30minutes during which the patient's precise career path is explored. RESULTS: Among the 498 patient questionnaires received, 261 patients (52%) benefited from a consultation. Of all the patients seen in consultation, 198 (or 76%) had a proposal to declare an occupational disease. Among the 151 declarations of which the fate is known, 107 (i.e., 54% of the proposed declarations or 21% of the questionnaires concerning primary lung cancer) received an agreement of recognition. CONCLUSION: The massive underreporting of occupational cancers at present in France is a real public health problem. The two major issues in the recognition of occupational diseases are, on the one hand, reparation for the damage suffered by victims or their beneficiaries and, on the other hand, the adaptation of national prevention programs considering past, present and emerging.

Paraneoplastic Cushing Syndrome in Gastrointestinal Neuroendocrine Tumour.

Ectopic production of adrenocorticotropic hormone (ACTH) by gastrointestinal neuroendocrine tumours (NETs) is relatively uncommon. We report a rare case of a liver metastatic G1 low-grade NET of the intestine that induced hypercortisolism after surgical resection. A 50-year-old man was admitted for an intestinal obstruction caused by a tumour of the intestine. Paraneoplastic Cushing syndrome was diagnosed more than a year later following the appearance of cushingoid symptoms, despite stable disease according to RECIST criteria but chromogranin A increase. Ketoconazole and sandostatin medical treatment and liver chemoembolization never managed to control the hypercortisolism unlike the bilateral adrenalectomy. The identification and effective management of this uncommon statement of ectopic ACTH secretion is important to improve the patient's prognosis and quality of life.

Pembrolizumab Treatment-Induced Liver Toxicity.

T cells play a critical role in immune responses against neoplasm. This finding contributed to the immunotherapy development, an effective treatment for many cancers nowadays. Programmed cell death protein 1 (PD1) is an inhibitory receptor on T cells which downregulate T-cell function per ligation with its ligands (PDL1 and PDL2). PD1 blockade is used to enhance antitumor immunity. Pembrolizumab is a humanized monoclonal anti-PD1 antibody currently used in the management of melanoma, non-small-cell lung cancer, and Hodgkin lymphoma. Most of the treatment toxicities are immune-related adverse events, but grade 3-4 toxicities occur in up to 5% of patients, mainly dermatologic. We present a case of grade 4 pembrolizumab-induced liver toxicity associated with an excellent treatment response in a Caucasian woman.

Venous thromboembolism associated with central venous catheters in patients with cancer: From pathophysiology to thromboprophylaxis, areas for future studies.

Symptomatic catheter related thrombosis (CRT) occurs in 4%-8% of cancer patients. The mean incidence of CRT, detected either by echography or Doppler ranges between 12 and 14% with a high negative predictive value of about 95%, allowing the subsequent occurrence of CRT (symptomatic and asymptomatic) to be safely excluded. Despite its frequency and its medico-economic consequences, no thromboprophylaxis has been validated to date. In most patients, CRT occurs immediately after catheter insertion, most often within the first week and almost all within the first month after insertion. Meta analyses show a reduction of asymptomatic and symptomatic CRT incidence by about 55%-60% using either vitamin K antagonists or low molecular weight heparins without an increased risk of major bleeding. This pharmacological prophylaxis is only effective when started before the central venous catheter insertion at prophylactic doses and thereafter continued at subtherapeutic doses. Since no population at high risk of CRT has been identified, this review focuses on pathophysiology, epidemiology and clinical supportive data that could lead to a new CRT prophylaxis strategy.

[Patients treated with palbociclib and endocrine therapy for metastatic breast cancer: Can we predict the occurrence of severe early hematological toxicity?] / Patients sous palbociclib et hormonothérapie pour un cancer du sein métastatique : peut-on prédire la survenue d'une hématotoxicité précoce et sévère ?

INTRODUCTION: The addition of palbociclib to endocrine therapy has been shown to improve progression free survival in hormone receptor positive metastatic breast cancer patients. This cyclin CDK4/6 inhibitor could expose patients to a grade 3-4 hematological toxicity, leading to treatment discontinuation or treatment interruption that is potentially associated with a lack of efficiency. The aim of this study was to identify predictive factors of severe early hematotoxicity (ESHT). METHODS: This retrospective cohort study included patients who started palbociclib in the Institut Sainte Catherine between December 1, 2016 and January 1, 2019 for the treatment of metastatic breast cancer. Individual data and hematological toxicity were collected from electronic medical records. ESHT was defined as the occurrence, during the first 3 cycles, of grade 4 or grade 3 hematological toxicity requiring palbociclib dose reduction. RESULTS: In total, 181 patients (180 females) were included; median age was 67 years. Forty-six patients (25.4%) experienced an ESHT. Predictive factors of ESHT in multivariate analysis were a performance status (PS) of 2 or more (P=0.024) and an history of radiotherapy of bone metastasis in the previous year (P=0.003). Before palbociclib initiation, a neutrophil count below 3.37g/L was predictive of ESHT with a sensibility of 76% and a specificity of 71%. CONCLUSIONS: ECOG PS, bone radiotherapy within the year and low baseline neutrophils count are associated with ESHT in palbociclib-treated metastatic breast cancer patients. These elements could be useful for a careful monitoring leading to adapted therapy.

Role of supportive care in improving the quality of life and reducing unscheduled hospital care in patients with metastatic breast cancer.

BACKGROUND: Metastatic breast cancer (MBC) patients experience long survival and report poorer quality of life than localized breast cancer patients. Comprehensive supportive care (CSC) has been shown to improve the quality of life (QoL) of MBC. The respective part of each support care has not been fully examined, and little is known about whether meeting patients' needs is accompanied by decreased unscheduled hospital care (UHC). METHODS: This prospective monocentric study included women who started a new treatment line for MBC between January 2018 and December 2018. The endpoints were factors associated with UHC and QoL (SF36) at month 12. RESULTS: 100 patients were offered CSC, 78 were included (21 refusals, 1 no MBC). CSC was provided to 60 patients: pain (43%), psychological (37%), kinesitherapy (30%), social assistance (22%), esthetic (18%), nutrition (18%), massage (13%), and none (10%). CSC rate was not statistically different among patients with (58%) and without UHD (49%). Factors associated with a decrease of UHC were age > 65 years (p = 0.01), no previous treatment for MBC (p = 0.0001) with a trend for the lack of CSC (p = 0.054). Among the 8 domains of the SF36 scale, only health change perception was improved (p = 0.01) and its predictive factors were treatment carried out as planned (p = 0.0004), pain care (p = 0.003), and lack of MBC progression (p = 0.0035). CONCLUSION: CSC can improve QoL in MBC. Painful patients might benefit more from CSC. UHC did not decrease for patients receiving CSC as expected possibly because of their important needs for clinical care.

Persistent response to vemurafenib in metastatic ameloblastoma with BRAF mutation: a case report.

BACKGROUND: Ameloblastomas are uncommon locally aggressive tumors of odontogenic epithelium that rarely metastasize. Currently, there is no standard of care for the metastatic forms. Several studies have shown that ameloblastomas frequently have a BRAF mutation. CASE PRESENTATION: We report a case of a 33-year-old Caucasian woman with ameloblastoma diagnosed 30 years ago who developed lung metastasis 19 years ago. Systemic oral treatment with vemurafenib, a BRAF inhibitor, was initiated 28 months ago within the AcSé French basket clinical trial of vemurafenib. CONCLUSIONS: The patient has shown a durable clinical, functional, and radiographic partial response with vemurafenib. These observations suggest the possibility of introducing neoadjuvant and/or adjuvant targeted therapy in locally advanced ameloblastoma to improve outcome. BRAF inhibition has proved to be an efficient strategy in patients with a BRAF-mutated ameloblastoma.