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.

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. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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.

97 Background: Degarelix, a GnRH antagonist, provides a very rapid and sustained testosterone suppression alongside with the VEGF pathway inhibition through the FSH receptors. This raises the question as to whether high risk localized prostate cancer (HRPCa) could respond differently to radiotherapy (RT) + Degarelix when compared with RT + GnRH agonist. Methods: 30 HRPCa patients were treated with exclusive RT combined with a GnRH agonist (n= 19) or Degarelix (n= 11). MRSI was performed before the start of hormones and 3 months after the end of RT. Choline (tumor metabolism) and citrate (healthy prostate metabolism) were quantified with MR spectroscopy and the slopes of gadolinium wash-in (SWI) and wash-out (SWO) were assessed in the peripheral zone (PZ), the central gland (CG) and the tumor with DCE-MRI. Results: At baseline, 14 patients had a T3 (46.7%) and 9 patients (30%) had a GS≥8. The median PSA values were 12.7 ng/mL [3.0-153.7] for agonists and 14.0 ng/mL [6.8-23.6] for Degarelix (p=ns). The mean prostate volumes (Pvol) were 32.0±15.5 mL for agonist and 33.0±10.0 mL for Degarelix (p=ns). The median dose of RT was 78Gy in each group, [72.0-80.0] with agonist and [70.2-80.0] with Degarelix. There were no significant differences in choline, citrate, SWI and SWO in the PZ, the CG and the tumor. At 3 months, Pvol were 20.8±8.0 mL for agonist and 21.4±6.2 mL for Degarelix (p=0.71) and the mean and median PSA values for agonist vs Degarelix were 0.5±0.8 ng/mL vs 0.1±0.1 ng/mL and 0.1 ng/mL [0.02-2.8] vs 0.1 ng/mL [0.005-0.3], respectively. Citrate was significantly decreased with Degarelix in the PZ (4.3±4.4 vs 1.1±0.8, p=0.0142), in the CG (4.0±4.0 vs 1.1±1.0, p=0.009) but not in the tumor (2.5±2.6 vs 1.7±1.9, p=0.23). Choline concentrations were similar between both groups in the PZ, the CG and the tumor. There was a trend towards a lower contrast uptake in the tumor with Degarelix (mean SWI and SWO: 134.6±56.2 s-1 vs 104.1±36.3 s-1, p=0.13 and 259.6±103.1 s-1 vs 306.1±70.4 s-1, p=0.15). Conclusions: Degarelix combined with RT offers a significant early, more profound metabolic atrophy in the prostate, but not in the tumor. There is a trend towards a lower tumor vascularization with Degarelix compared with GnRH agonists.

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.

IntroductionThe purpose of this study was to describe the pattern of nodal relapse with 18F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy.Materials and methodsEighty-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.ResultsFourteen 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.Conclusion3D 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.

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).