OncoSNIPE® Study Protocol, a study of molecular profiles associated with development of resistance in solid cancer patients.

BACKGROUND: Nowadays, evaluation of the efficacy and the duration of treatment, in context of monitoring patients with solid tumors, is based on the RECIST methodology. With these criteria, resistance and/or insensitivity are defined as tumor non-response which does not allow a good understanding of the diversity of the underlying mechanisms. The main objective of the OncoSNIPE® collaborative clinical research program is to identify early and late markers of resistance to treatment. METHODS: Multicentric, interventional study with the primary objective to identify early and / or late markers of resistance to treatment, in 600 adult patients with locally advanced or metastatic triple negative or Luminal B breast cancer, non-small-cell lung cancer or pancreatic ductal adenocarcinoma. Patients targeted in this study have all rapid progression of their pathology, making it possible to obtain models for evaluating markers of early and / or late responses over the 2-year period of follow-up, and thus provide the information necessary to understand resistance mechanisms. To explore the phenomena of resistance, during therapeutic response and / or progression of the pathology, we will use a multidisciplinary approach including high-throughput sequencing (Exome-seq and RNAseq), clinical data, medical images and immunological profile by ELISA. Patients will have long-term follow-up with different biological samples, at baseline (blood and biopsy) and at each tumoral evaluation or tumoral progression evaluated by medical imaging. Clinical data will be collected through a dedicated Case Report Form (CRF) and enriched by semantic extraction based on the French ConSoRe (Continuum Soins Recherche) initiative, a dedicated Semantic Clinical Data Warehouse (SCDW) to cancer. The study is sponsored by Oncodesign (Dijon, France) and is currently ongoing. DISCUSSION: The great diversity of intrinsic or acquired molecular mechanisms involved in resistance to treatment constitutes a real therapeutic issue. Improving understanding of mechanisms of resistance of cancer cells to anti-tumor treatments is therefore a major challenge. The OncoSNIPE cohort will lead to a better understanding of the mechanisms of resistance and will allow to explore new mechanisms of actions and to discover new therapeutic targets or strategies making it possible to circumvent the escape in different types of cancer. TRIAL REGISTRATION: Clinicaltrial.gov. Registered 16 September 2020, https://clinicaltrials.gov/ct2/show/NCT04548960?term=oncosnipe&draw=2&rank=1 and ANSM ID RCB 2017-A02018-45.

Seroprevalence of SARS-CoV-2 among the staff and patients of a French cancer centre after first lockdown: The canSEROcov study.

BACKGROUND: In view of the potential gravity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection for patients with cancer, epidemiological data are vital to assess virus circulation among patients and staff of cancer centres. We performed a prospective study to investigate seroprevalence of SARS-CoV-2 antibodies among staff and patients with cancer at a large cancer centre, at the end of the period of first national lockdown in France and to determine factors associated with the risk of SARS-CoV-2 infection. METHODS: After the first lockdown, all medical and non-medical staff, as well as all patients attending the medical oncology department were invited to undergo serological testing for SARS-CoV-2 between 11 May and 30 June 2020. All participants were also invited to complete a questionnaire collecting data about their living and working conditions, and for patients, medical management during lockdown. FINDINGS: A total of 1,674 subjects (663 staff members, 1011 patients) were included. Seroprevalence was low in both staff (1.8%) and patients (1.7%), despite more features of high risk for severe forms among patients. None of the risk factors tested in our analysis (working or living conditions, comorbidities, management characteristics during lockdown) was found to be statistically associated with seroprevalence in either staff or patients. There was no significant difference in the proportion of symptomatic and asymptomatic subjects between staff and patients. Only fever, loss of smell, and loss of taste were significantly more frequent among seropositive patients, in both staff and patients. INTERPRETATION: We report very low seroprevalence of antibodies against SARS-CoV-2 in the staff (caregiving and non-caregiving) and patients of a large cancer care centre in which strict hygiene, personal protection, and social distancing measures were implemented.

5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer.

AIMS: 5-FU is used as the main backbone of chemotherapy regimens for patients with colorectal and other gastrointestinal cancers. Despite development of new strategies that allowed enhancing clinical effectiveness and tolerability of 5-FU, 10-30% of patients treated with 5-FU-based regimens experience severe treatment-related toxicity. In our study, we evaluated the 5-FU exposure-toxicity relationship and investigated the efficacy of PK-guided dosing in increasing tolerability of 5-FU-based chemotherapy. RESULTS: 50.7% of patients required dose adjustments after cycle 1. Percentage of patients within 5-FU AUC range was 49.3%, 66.9%, 61.0% at cycle 1, 2 and 3 respectively (p = 0.002 cycle 1 vs cycle 2). At all 3 cycles, lower incidences of grade I/II toxicities were observed for patients below or within range compared with those above range (19.4% vs 41.3%, p < 0.001 respectively). CONCLUSIONS: Our analysis confirms that the use of BSA-guided dosing results in highly variable 5-FU exposure and strongly suggests that PK-guided dosing can improve tolerability of 5-FU based chemotherapy in patients with gastrointestinal cancers, thus supporting 5-FU therapeutic drug monitoring. METHODS: 155 patients with gastrointestinal cancers, who were to receive 5-FU-based regimens were included in our study. At cycle 1, the 5-FU dose was calculated using patient's Body Surface Area (BSA) method. A blood sample was drawn on Day 2 to measure 5-FU concentration. At cycle 2, the 5-FU dose was adjusted using a PK-guided dosing strategy targeting a plasma AUC range of 18-28 mg·h/L, based on cycle 1 concentration. Assessments of toxicity was performed at the beginning of every cycle.

Assessment of the interest of the geriatric oncology consultation among French general practitioners.

OBJECTIVE: We assessed the interest of the geriatric oncology (GO) consultation (GOC) among general practitioners (GPs). MATERIALS AND METHODS: We conducted a survey among GPs whose patients had had a GOC in 2012. A questionnaire was sent to GPs. The 1st part collected GPs' characteristics including medical education in geriatrics and GO, and knowledge of GOC. The following parts concerned the GOC and included the cancer type, GOC report and care plan. RESULTS: One-hundred twenty-six questionnaires corresponding to 94 GPs were collected. Concerning the GPs' characteristics, age range 50-59 (44.7%), men (62.8%) and urban practice (79.8%) were the most represented, 80.8% had no expertise in geriatrics, 60.6% knew of the existence of GOCs, and 14.9% had received medical education in GO. The most frequent cancer location was gynecological (40.7%) (82.6% were breast cancers). Of the GPs, 69.8% had received a GOC report and 92% were (very) satisfied with the delivery time. A care plan was proposed after the GOC in 83% of cases. It was satisfactory in 96.4% of cases, and applied by 74.7% of GPs. Sixteen percent of GPs were called by the GO team. The less the GP was satisfied with the GOC, the more he or she wanted phone contact (p=0.02); 94% of GPs considered the GOC (very) satisfactory. Sixty-seven percent of GPs wanted to be trained in GO. CONCLUSION: Very few GPs had been trained in geriatrics and/or GO. They were mostly satisfied with GOC and expressed a wish to be trained in GO.

Mapping of failures after radiochemotherapy in patients with non-metastatic esophageal cancer: A posteriori analysis of the dose distribution in the sites of loco-regional relapse.

BACKGROUND AND PURPOSE: We aimed to evaluate the patterns of loco-regional failure (LRF) after exclusive chemoradiotherapy (eCRT) for esophageal cancer with respect to planned dose and/or the incidental (unplanned) dose outside target volumes. MATERIALS AND METHODS: Co-image registration of CT or (18)F-FDG PET-CT at the time of failure (tf) and at the time of CRT (t0) was performed in 34 patients with LRF. Dosimetric parameters with regard to local failure (LF), nodal failure (NF) and involved nodal stations (NS) were derived. RESULTS: Twenty-two patients (64.7%) had LF, the majority of which (95.5%) were located at the epicenter of the GTV of the primary tumor. The mean doses recalculated to the NS at tf were more likely to be lower than the planned dose delivered to the PTV at t0: Dmean=33.9 ± 20.8 Gy vs 52.2 ± 8.5 Gy (p=0.0009), D95%=27.5 ± 21 Gy vs 46.1 ± 4.8 Gy (p=0.004). Among the 12 patients with NF outside the elective nodal irradiation (ENI) volume, Dmean of NS outside the ENI was significantly lower (19.4 ± 21.4 Gy) than the Dmean of NS with failure within the ENI (45.1 ± 6.1 Gy, p=0.01). CONCLUSION: Loco-regional failure after exclusive chemoradiotherapy for esophageal cancer may be due to an inadequately low dose.

Pattern of occult nodal relapse diagnosed with (18)F-fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy.

INTRODUCTION: The purpose of this study was to describe the pattern of nodal relapse with (18)F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy. MATERIALS AND METHODS: Eighty-three patients had a FCH PET/CT at time of biochemical failure. Of 65 patients with positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy with or without a prior radical prostatectomy. Each FCH positive node was assigned to a lymph node station with respect to the CTV defined by the RTOG guidelines (CTVRTOG). 3D mapping was performed after each node was manually placed in a reference planning CT scan after automatic co-registration of the two scans based on bone anatomy. Eighteen patients (58%) underwent focal salvage FCH PET-guided stereotactic radiotherapy with no hormones. RESULTS: Fourteen patients (45.2%) had a relapse outside the CTVRTOG. Of the 17 patients with a positive node inside the CTVRTOG, 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTVRTOG had ⩾2 positive nodes on FCH PET/CT (OR=8.75, [95% CI: 1.38-54.80], p=0.020). Relapses that occurred outside the CTVRTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2-L3. CONCLUSION: 3D mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2-L3 safely to cover 95% of nodal stations at risk of an occult relapse.

Stereotactic Body radiation therapy for liver tumors with or without rotational intensity modulated radiation therapy.

BACKGROUND: To evaluate the feasibility and efficacy of Stereotactic body radiation therapy (SBRT) for primary liver lesions and liver metastases treated with linear accelerators with or without rotational Intensity Modulated RadioTherapy (IMRT). METHODS: Patients with either hepatocellular carcinoma, cholangiocarcinoma or metastatic liver lesions who had one to three lesions treated with SBRT in a single institution were retrospectively reviewed. Tumor response was evaluated according to EASL criteria 3 months after SBRT completion using MRI and/or abdominal CT scan. Responses were categorised as: Stable Disease (SD), Partial Response (PR), Complete Response (CR), Local Progression or Distant Progression in cases of new intra-hepatic lesions out-of-field or extra-hepatic metastases. Local Control (LC), Progression Free Survival (PFS), Overall Survival (OS) and treatment-related toxicities are reported. RESULTS: Between 2007 and 2012, 20 patients with a total of 24 lesions were treated with SBRT. Fourteen patients presented hepatocellular carcinoma (HCC), the others had either metastatic lesions from colorectal cancer (CRC) or cholangiocarcinoma. The median diameter of the lesions was 23 mm (5-98).The dose per fraction ranged from 6 to 20 Gy with a median total dose of 60 Gy (range: 36-60 Gy). The dose was prescribed to the 80% isodose line covering the PTV.The median follow-up was 24 months (15.7-29.7).The actuarial LC rate was 78% for patients with HCC and 83% for those with adenocarcinoma and cholangiocarcinoma. Median OS was 37 months and OS rates were 83% at 12 and 24 months for HCC and 100% for adenocarcinoma. PFS was 54% for HCC and 50% for other types of tumors at 24 months.Acute grade 3-4 toxicities occurred in 2 patients; a small proportion of the other patients experienced grade 1 or 2 toxicities. CONCLUSIONS: SBRT provides excellent local control with minimal side effects in selected patients.

Impact on overall survival of radioactive iodine in low-risk differentiated thyroid cancer patients.

CONTEXT: American Thyroid Association and European Thyroid Association guidelines cannot recommend for or against radioactive iodine (RAI) ablation after surgery in low-risk differentiated thyroid cancer (DTC) patients. OBJECTIVES: The objective of the study was to assess the survival benefit of RAI for these patients. DESIGN: We identified 1298 DTC patients at low risk treated between 1975 and 2005. Logistic regressions were used to identify variables associated to RAI and to calculate the propensity score to receive RAI after surgery. We compared overall survival (OS) and disease-free survival (DFS) according to RAI with the log-rank tests and univariate and multivariate Cox analyses. Analyses stratified on propensity score were also performed. RESULTS: Median follow-up was 10.3 yr. Nine hundred eleven patients received RAI after surgery vs. 387 patients without RAI after surgery. Using univariate analysis, 10-yr OS was found to be 95.8% in patients without RAI after surgery vs. 94.6% in RAI after surgery (P = 0.006), and 10-yr DFS was found to be 93.1% vs. 88.7% (P = 0.001). All clinical factors except sex were significantly associated with RAI. Using multivariate Cox analyses, RAI was neither significantly nor independently associated with OS (P = 0.243) and DFS (P = 0.2659). After stratification on propensity score, Cox univariate analyses showed that OS did not differ according to RAI (P = 0.3524), with a hazard ratio for RAI of 0.75 (95% confidence interval 0.40-1.38). Similarly, DFS did not differ (P = 0.48) with a stratified univariate hazard ratio of 1.11 (95% confidence interval 0.73-1.70). CONCLUSION: With a long-term follow-up of 10.3 yr, we failed to prove any survival benefit of RAI after surgery in a large cohort of low-risk DTC patients.