Outcomes of patients with initially locally advanced pancreatic adenocarcinoma who did not benefit from resection: a prospective cohort study.

BACKGROUND: The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings. METHODS: Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan-Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method. RESULTS: FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR) = 1.2, 95% confidence interval: 0.86-1.6, P = .03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0-1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR = 1.38, 95% confidence interval: 1-1.9, P < .01) and limited short-term treatment-related toxicity. CONCLUSIONS: The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.

Development of a disease-specific graded prognostic assessment index for the management of sarcoma patients with brain metastases (Sarcoma-GPA).

BACKGROUND: Brain metastases from sarcomatous lesions pose a management challenge owing to their rarity and the histopathological heterogeneity. Prognostic indices such as the Graded Prognostic Assessment (GPA) index have been developed for several primary tumour types presenting with brain metastases (e.g. lung, breast, melanoma), tailored to the specifics of different primary histologies and molecular profiles. Thus far, a prognostic index to direct treatment decisions is lacking for adult sarcoma patients with brain metastases. METHODS: We performed a multicentre analysis of a national group of expert sarcoma tertiary centres (French Sarcoma Group, GSF-GETO) with the participation of one Canadian and one Swiss centre. The study cohort included adult patients with a diagnosis of a bone or soft tissue sarcoma presenting parenchymal or meningeal brain metastases, managed between January 1992 and March 2012. We assessed the validity of the original GPA index in this patient population and developed a disease-specific Sarcoma-GPA index. RESULTS: The original GPA index is not prognostic for sarcoma brain metastasis patients. We have developed a dedicated Sarcoma-GPA index that identifies a sub-group of patients with particularly favourable prognosis based on histology, number of brain lesions and performance status. CONCLUSIONS: The Sarcoma-GPA index provides a novel tool for sarcoma oncologists to guide clinical decision-making and outcomes research.

NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial.

BACKGROUND: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma. METHODS: Act.In.Sarc is a phase 2-3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0-2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3 g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete. FINDINGS: Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3-4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3-4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3-4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3-4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred. INTERPRETATION: This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. FUNDING: Nanobiotix SA.

Effect of clinical status on survival in patients with borderline or locally advanced pancreatic adenocarcinoma.

OBJECTIVE: To determine the effect of clinical status (weight variation and performance status [PS]) at diagnosis and during induction treatment on resectability and overall survival (OS) rates in patients with borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC). METHODS: From 2005 to 2017, 454 consecutive patients were diagnosed with LAPC or BRPC. We evaluated the PS (0-1 or 2-3), body mass index at diagnosis, and weight loss (WL) > 5% at initial staging and after induction treatment and separated continuous weight loss (CWL) from weight stabilization. RESULTS: A total of 294 patients (64.8%) presented with WL, and 57 patients (12.6%) presented with a PS of 2-3. At restaging, 60 patients (13.2%) presented with CWL. Independent factors that poorly influenced the OS were a PS of 2-3 at diagnosis (P < .01), CWL at restaging (P < .01), and absence of resection (P < .01). Factors independently impeding resection were LAPC (P < .01), PS > 1 at diagnosis (P < .01), and CWL (P = .01). In total, 142 patients (31.3%) underwent pancreatectomy. Independent factors that poorly influenced the OS in the resected group were PS > 0 at diagnosis (P = .01) and obesity (P < .01). For the 312 unresected cancer patients (68.7%), CWL (P < .01) was identified as an independent factor that poorly influenced the OS. CONCLUSION: Clinical parameters that are easy to measure and monitor are independent factors of poor prognosis. The variation of weight during the induction treatment, more than WL at diagnosis, significantly precluded resection and was an independent factor of shorter OS in unresected patients.

Brain Metastases from Adult Sarcoma: Prognostic Factors and Impact of Treatment. A Retrospective Analysis from the French Sarcoma Group (GSF/GETO).

BACKGROUND: Brain metastases (BM) from adult soft tissue or bone sarcomas are rare, and sparse data exist on their prognostic factors and management. SUBJECTS, MATERIALS AND METHODS: A retrospective study was conducted in 15 centers of the French Sarcoma Group, plus one Canadian and one Swiss center, to report on clinical, histological, and treatment characteristics and to identify predictive factors of outcome. RESULTS: Between 1992 and 2012, 246 patients with a median age of 50 years (range: 16-86) were managed for BM. BM included 221 cerebral and cerebellar metastases and 40 cases of meningeal sarcomatosis. The most frequent histopathological subtype was leiomyosarcoma (18.7%). Histological grade was high in 118 (48%) cases. Surgery of BM was carried out for 38 (15.5%) patients. Radiotherapy and chemotherapy were administered in 168 (68.3%) and 91 (37.0%) patients, respectively. Irrespective of treatment modality, BM were controlled in 113 patients (45.9%), including 31 partial responses (12.6%) and 18 complete responses (7.3%). The median overall survival from diagnosis of brain metastasis was 2.7 months (range: 0-133). In the multivariate analysis, the following parameters influenced overall survival: chemotherapy (hazard ratio [HR] = 0.38; 95% confidence interval [CI]: 0.26-0.48), surgery (HR = 0.40; 95% CI: 0.22-0.72), stereotactic radiotherapy (HR = 0.41; 95% CI: 0.19-0.90), whole-brain radiotherapy (HR = 0.51; 95% CI: 0.35-0.76), and grade (HR = 0.65; 95% CI: 0.43-0.98). CONCLUSION: BM of sarcomas are rare and associated with a dismal outcome. Multidisciplinary management with chemotherapy, radiation therapy, and surgery is associated with a better survival. IMPLICATIONS FOR PRACTICE: The incidence of brain and meningeal metastasis in bone and soft tissue sarcomas is estimated between 1% and 8%. Published data are derived from small retrospective case series, often in the pediatric population. A prognostic index is important to guide both clinical decision-making and outcomes research, but one such is lacking for adult sarcoma patients with brain metastases. The current study describes brain metastasis in a large cohort of sarcoma patients. This study, conducted within the French Sarcoma Group, describes the natural history of sarcoma brain metastasis and enables the proposal of strategic recommendations for subsequent clinical trials and for the management of such patients.

Safety and benefit of using a virtual bolus during treatment planning for breast cancer treated with arc therapy.

PURPOSE: This study evaluates the benefit of a virtual bolus method for volumetric modulated arc therapy (VMAT) plan optimization to compensate breast modifications that may occur during breast treatment. METHODS: Ten files were replanned with VMAT giving 50 Gy to the breast and 47 Gy to the nodes within 25 fractions. The planning process used a virtual bolus for the first optimization, then the monitors units were reoptimized without bolus, after fixing the segments shapes. Structures and treatment planning were exported on a second scanner (CT) performed during treatment as a consequence to modifications in patient's anatomy. The comparative end-point was clinical target volume's coverage. The first analysis compared the VMAT plans made using the virtual bolus method (VB-VMAT) to the plans without using it (NoVB-VMAT) on the first simulation CT. Then, the same analysis was performed on the second CT. Finally, the level of degradation of target volume coverage between the two CT using VB-VMAT was compared to results using a standard technique of forward-planned multisegment technique (Tan-IMRT). RESULTS: Using a virtual bolus for VMAT does not degrade dosimetric results on the first CT. No significant result in favor of the NoVB-VMAT plans was noted. The VB-VMAT method led to significant better dose distribution on a second CT with modified anatomies compared to NoVB-VMAT. The clinical target volume's coverage by 95% (V95%) of the prescribed dose was 98.9% [96.1-99.6] on the second CT for VB-VMAT compared to 92.6% [85.2-97.7] for NoVB-VMAT (P = 0.0002). The degradation of the target volume coverage for VB-VMAT is not worse than for Tan-IMRT: the median differential of V95% between the two CT was 0.9% for VMAT and 0.7% for Tan-IMRT (P = 1). CONCLUSION: This study confirms the safety and benefit of using a virtual bolus during the VMAT planning process to compensate potential breast shape modifications.

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.

Impact of radiotherapy in the management of locally advanced extrahepatic cholangiocarcinoma.

BACKGROUND: Optimal therapy for patients with unresectable locally advanced extrahepatic cholangiocarcinoma (ULAC) remains controversial. We analysed the role of radiotherapy in the management of such tumors. METHODS: We retrospectively reviewed the charts of patients treated in our institution with conformal-3D external-beam-radiotherapy (EBRT) with or without concurrent chemotherapy. RESULTS: Thirty patients were included: 24 with a primary tumor (group 1) and 6 with a local relapse (group 2). Toxicity was low. Among 25 patients assessable for EBRT response, we observed 9 complete responses, 4 partial responses, 10 stabilisations, and 2 progressions. The median follow-up was 12 months. Twenty out of 30 patients (66%) experienced a relapse, which was metastatic in 75% of cases in the whole series, 87% in group 1, 60% in group 2 (p = 0.25). Twenty-eight patients (93%) died of relapse or disease complications. Median overall survivals in the whole group and in group 1 or 2 were respectively 12, 11 and 21 months (p = 0.11). The 1-year and 3-year progression-free survivals were respectively 38% and 16% in the whole series; 31% and 11% in group 1, 67% and 33% in group 2 (p = 0.35). CONCLUSION: EBRT seems efficient to treat ULAC, with acceptable toxicity. For primary disease, the high rate of metastatic relapse suggests to limit EBRT to non-progressive patients after induction chemotherapy.

The impact of brachytherapy boost for anal canal cancers in the era of de-escalation treatments.

PURPOSE: To analyze clinical outcomes of high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) for the treatment of anal canal cancers (ACC). METHODS AND MATERIALS: A total of 78 patients with ACC were treated at our institution by ISBT. Local Control (LC), disease-free survival (DFS), overall survival (OS), colostomy-free survival (CFS) and toxicity rates were analyzed. RESULTS: With a median followup (FU) of 59.8 months (95% CI [55.8-64.2]), six (7.7%) local recurrences with 2 patients (2.6%) having persistent disease at 3 months were observed. The 5-year rate of LC for the entire population was 92% [83-96%]. The 5-year DFS rate was 86% [76-93%]. The 5-year OS was 96% [88-99%]. In the univariate analysis, chemotherapy was significantly associated with morbidity grade ≥2. Late digestive toxicity grade ≥3 was reported in 8.9% patients, 1 patient underwent colostomy due to toxicity. The 5-year CFS rate was 88% [79-94%]. CONCLUSIONS: HDR interstitial brachytherapy boost provide excellent rates of tumor control and colostomy-free survival with a favorable profile of GI toxicity. Continence in anal cancer survivors is a challenge and the boost technique must be discussed in a multidisciplinary approach as part of de-escalation treatments.

Repeated Multimodality Ablative Therapies for Oligorecurrent Pulmonary Metastatic Disease.

Stereotactic body radiotherapy (SBRT) and percutaneous thermal ablation (TA) are alternatives to surgery for the management of pulmonary oligometastases. In this collaborative work, we retrospectively analyzed patients who had undergone iterative focal ablative treatments of pulmonary oligometastases. We hypothesized that repeated ablative therapies could benefit patients with consecutive oligometastatic relapses. Patients treated with SBRT and/or TA for pulmonary oligometastases in two French academic centers between October 2011 and November 2016 were included. A total of 102 patients with 198 lesions were included; 45 patients (44.1%) received repeated focal treatments at the pulmonary site for an oligorecurrent disease (the "multiple courses" group). Median follow-up was 22.5 months. The 3-year overall survival rates of patients who had a single treatment sequence (the "single course" group) versus the "multiple courses" were 73.9% and 78.8%, respectively, which was not a statistically significant difference (p = 0.860). The 3-year systemic therapy-free survival tended to be longer in the "multiple courses" group (50.4%) than in the "single course" group (44.7%) (p = 0.081). Tolerance of repeated treatments was excellent with only one grade 4 toxicity. Thereby, multimodality repeated ablative therapy is effective in patients with pulmonary oligorecurrent metastases. This strategy may delay the use of more toxic systemic therapy.

Impact of fiducial markers placement on the delineation of target volumes in radiation therapy for oesophageal cancer: FIDUCOR study.

Purpose: This prospective monocentric phase II study (FIDUCOR-study, NCT02526134) aimed to assess the impact of fiducial markers (FMs) implantation on conformal chemo-radiation therapy (CRT) planning in oesophageal carcinoma (EC) patients. Methods/materials: Fifteen EC patients were enrolled in the study. Each patient underwent two simulation CT-scans before (CT1) and after (CT2) FMs implantation, in the same position. FMs (3 mm length gold markers, preloaded in a 22G needle) were implanted after sedation, under endoscopic ultrasound (EUS) and X-Ray guidance, and were placed at the tumor's extremities, and in the visible lymph nodes. Target delineation and treatment plan were both performed first on CT1 with the assistance of diagnosis CT, gastroscopy and EUS details, and second on CT2 using FMs and CT-data. The value of FMs implantation was assessed by the difference of growth-tumor-volume (GTV) and clinical-target-volume (CTV) between CT1-based and CT2-based delineation. A significant difference was defined as a ≥5 mm-difference on axial(x) or coronal(y) slices, a ≥10mm-difference on sagittal slices, or a ≥20%-difference in GTV. The impact on dose distribution in organs at risk (OAR) (lung, heart, liver) was also studied. Results: Between 09/2014 and 12/2015, 15 patients could achieve fiducial procedures, without any complication. One FM migration occurred. We observed a significant modification of the GTV-dimension in 100% of the cases (15/15, 95%CI: [78.2;100.0]), mainly due to a difference in sagittal dimension with a mean variation of 11.2 mm and a difference> 10 mm for 8/15 patients (53.3%). One patient had a significant isocenter displacement as high as 20 mm. The oesophagus tumor was not seen on the CT-scan in one patient due to its small size. One patient had a distant lymph node metastasis not visible on CT-scan. We observed no significant impact on OAR distribution. Conclusion: In our study, FMs-implantation under EUS had a positive impact on accurate volume definition in EC-patients (modification of GTV in 15/15 patients). Close cooperation between gastroenterologist and radiation oncologist has the potential to improve local treatment of oesophageal carcinoma.

Primary leiomyosarcoma of the seminal vesicle: case report and review of the literature.

BACKGROUND: Primary leiomyosarcoma of the seminal vesicle is exceedingly rare. CASE PRESENTATION: We report a case of a 59-year-old man with tumour detected by rectal symptoms and ultrasonography. Computed tomography and magnetic resonance imaging suggested an origin in the right seminal vesicle. Transperineal biopsy of the tumour revealed leiomyosarcoma. A radical vesiculo-prostactectomy with bilateral pelvic lymphadenectomy was performed. Pathological examination showed a grade 2 leiomyosarcoma of the seminal vesicle. The patient received adjuvant radiotherapy. He developed distant metastases 29 months after diagnosis, and received chemotherapy. Metastatic disease was controlled by second-line gemcitabine-docetaxel combination. Fifty-one months after diagnosis of the primary tumour, and 22 months after the first metastases, the patient is alive with excellent performance status, and multiple asymptomatic stable lung and liver lesions. CONCLUSIONS: We report the eighth case of primary leiomyosarcoma of the seminal vesicle and the first one with a so long follow-up.

Efficacy of epidermal growth factor receptor targeting in advanced chordoma: case report and literature review.

BACKGROUND: Chordomas are very rare low-grade malignant bone tumors that arise from the embryonic rests of the notochord. They are characterized by slow growth and long history with frequent local relapses, and sometimes metastases. While chemotherapy is not efficient, imatinib has shown antitumor activity. CASE PRESENTATION: We report on a 76-year-old patient with EGFR-overexpressing advanced chordoma that progressed on imatinib and subsequently responded to erlotinib during 12 months. CONCLUSIONS: We report the fourth case of advanced chordoma treated with an EGFR inhibitor. We also review the literature concerning the rationale and potential of EGFR targeting in chordoma.

Systematic Early Urinary Catheter Removal Integrated in the Full Enhanced Recovery After Surgery (ERAS) Protocol After Laparoscopic Mid to Lower Rectal Cancer Excision: A Feasibility Study.

PURPOSE: Enhanced Recovery After Surgery (ERAS) programs advocate early urinary catheter removal after rectal cancer surgery; however, the optimal duration remains unclear. This study assessed the feasibility of the early urinary catheter removal protocol after rectal cancer surgery within an ERAS pathway and identified predictive factors for failure of this strategy. METHODS: Between March 2017 and October 2018, all unselected and consecutive patients who underwent rectal cancer resection and benefited from our ERAS program were included. Urinary complications (infection and retention) were prospectively recorded. Success was defined as catheter removal on postoperative day (POD) 3 without urinary complications. RESULTS: Of 135 patients (male, 63.7%; neoadjuvant chemoradiation, 57.0%; urology history, 17.8%), 120 had early urinary catheter removal with no complications (success rate, 88.9%), 8 did not have urinary catheter removal on POD 3 due to clinical judgment or prescription error, 5 experienced a urinary tract infection, and 2 had acute urinary retention. Obesity (odds ratio [OR], 0.16; P = 0.003), American Society of Anesthesiologists physical status classification > II (OR, 0.28; P = 0.048), antiaggregant platelet medication (OR, 0.12; P < 0.001), absence of anastomosis (OR, 0.1; P = 0.003), and prolonged operative time (OR, 0.21; P = 0.020) were predictive factors for failure. Conversely, optimal compliance with the ERAS program (OR, 7.68; P < 0.001), postoperative nonsteroidal anti-inflammatory drug use (OR, 21.71; P < 0.001), and balanced intravenous fluid therapy (OR, 7.87; P = 0.001) were associated with increased strategy success. CONCLUSION: Withdrawal of the urinary catheter on POD 3 was successfully achieved after laparoscopic rectal resection and can be safely implemented in the ERAS program.

[Start of activity with the MRIdian® system: The first 200 patients treated at the Institut Paoli-Calmettes]. / Retour d'expérience clinique à propos des 200 premiers patients traités au MRIdian® à l'Institut Paoli-Calmettes.

INTRODUCTION: Several centers have recently been equipped with MRI-guided radiotherapy systems, including the Paoli-Calmettes Institute which was the first French center to start this activity. We report in this article our early experience. METHODS: Data related to patients treated on the MRIdian® (Viewray®) were prospectively collected. Procedures concerning the implementation of the system and internal organizational issues were summarized. RESULTS: Between February 2019 and March 2020, 201 patients were treated: 40% of treatments were normofractionated (n=70) and 60% used hypofractionation (n=105). The reported monthly occupancy rate at one, six and twelve months was 30%, 62%, and 90%. The distribution of normofractionated treatments was dominated by prostatic (29%) and pancreatic (26%) cancers, followed by abdomino-pelvic irradiations for gynecological cancers (12%) or lymph node diseases (12%) and boosts for rectal or vaginal cancers (11%). Regarding treatments with moderate hypofractionation (dose by fraction between 3 and 5Gy), they corresponded mainly to integrated boost for abdomino-pelvic lymph nodes (38%), while the stereotaxic treatments primarily concerned hepatic lesions (15%), bones (30%). DISCUSSION: The MRIdian® was initially used widely in our service corresponding to a learning curve for MRI guidance. This new tool for image-guided radiotherapy helped us to secure our practice providing solutions for both inter and intra-fraction movements making it possible to reduce the additional margin in order to better protect the organs at risk. The main technical difference with conventional accelerators is the possibility of performing adaptive radiotherapy in real time, the start of which was more gradual.

Locoregional relapses in the ACCORD 12/0405-PRODIGE 02 study: Dosimetric study and risk factors.

PURPOSE: The aim of this study is to correlate locoregional relapse with radiation therapy volumes in patients with rectal cancer treated with neoadjuvant chemoradiation in the ACCORD 12/0405-PRODIGE 02 trial. PATIENTS AND METHODS: We identified patients who had a locoregional relapse included in ACCORD 12's database. We studied their clinical, radiological, and dosimetric data to analyze the dose received by the area of relapse. RESULTS: 39 patients (6.5%) presented 54 locoregional relapses. Most of the relapses were in-field (n = 21, 39%) or marginal (n = 13, 24%) with only six out-of-field (11%), 14 could not be evaluated. Most of them happened in the anastomosis, the perirectal space, and the usual lymphatic drainage areas (presacral and posterior lateral lymph nodes). Only patients treated for a lower rectum adenocarcinoma had a relapse outside of the treated volume. 2 patients with T4 tumors extending into anterior pelvic organs had relapses in anterior lateral and external iliac lymph nodes. CONCLUSIONS: Lowering the upper limit of the treatment field for low rectal tumors increased the risk of out of the field recurrence. For very low tumors, including the inguinal lymph nodes in the treated volume should be considered. Recording locoregional involvement, treated volumes, and relapse areas in future prospective trials would be of paramount interest to refine delineation guidelines.

Borderline or locally advanced pancreatic adenocarcinoma: A single center experience on the FOLFIRINOX induction regimen.

INTRODUCTION: This study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice. MATERIAL AND METHODS: From 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment. RESULTS: The 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3-16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P < 0.001). In resected patients, the ASA 3 score (P < 0.01), venous resection (P < 0.01), hemorrhage (P < 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P < 0.001). CONCLUSIONS: Neoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.

Phase II study of concomitant radiotherapy with atezolizumab in oligometastatic soft tissue sarcomas: STEREOSARC trial protocol.

INTRODUCTION: Up to 50% of soft tissue sarcoma (STS) patients develop metastases in the course of their disease. Cytotoxic therapy is a standard treatment in this setting but yields average tumour response rates of 25% at first line and ≤10% at later lines. In oligometastatic stage, stereotactic body radiation therapy (SBRT) allows reaching high control rates at treated sites (≥80%) and is potentially equally effective to surgery in term of overall survival. In order to shift the balance towards antitumour immunity by multisite irradiation, radiation could be combined with inhibitors of the immunosuppressive pathways. METHODS AND ANALYSIS: STEREOSARC is a prospective, multicentric, randomised phase II, designed to evaluate the efficacy of SBRT associated with immunotherapy versus SBRT only. Randomisation is performed with a 2:1 ratio within two arms. The primary objective is to evaluate the efficacy, in term of progression-free survival (PFS) rate at 6 months, of immunomodulated stereotactic multisite irradiation in oligometastatic sarcoma patients. The secondary objectives include PFS by immune response criteria, overall survival, quality-of-life evaluation and developing mathematical models of tumour growth and dissemination predictive of oligometastatic versus polymetastatic evolution. Patients will be randomised in two groups: SBRT with atezolizumab and SBRT alone. The total number of included patients should be 103. TRIAL REGISTRATION: The trial is registered on ClinicalTrials.gov (ID: NCT03548428). ETHICS AND DISSEMINATION: This study has been approved by Comité de Protection des Personnes du sud-ouest et outre-mer 4 on 18 October 2019 (Reference CPP2019-09-076-PP) and from National Agency for Medical and Health products Safety (Reference: MEDAECNAT-2019-08-00004_2017-004239-35) on 18 September 2019.The results will be disseminated to patients upon individual request or through media release from scientific meetings. The results will be communicated through scientific meetings and publications.

Bevacizumab-related surgical site complication despite primary tumor resection in colorectal cancer patients.

BACKGROUND: Combining conventional systemic chemotherapy with the angiogenesis inhibitor bevacizumab is now recommended as a first treatment for metastatic colorectal neoplasms. The risk for short-term postoperative complications related to bevacizumab has been assessed. Late postoperative complications related to bevacizumab have also been suggested by preliminary reports. METHODS: We reviewed a cohort of 142 patients with previous surgery for primary colonic or rectal tumor and without evidence of local recurrence, receiving bevacizumab for metastatic disease. RESULTS: Four patients experienced a late surgical site complication related to bevacizumab. Common features were rectal location, low anastomosis, and preoperative irradiation. Combining these three factors, the risk of a bevacizumab-related complication was 4 in 27 (14.8%); if previous history of postoperative leakage was reported, the risk was raised to 2 in 4. No complications occurred in colonic location or the non-irradiated patients. The mechanism of these complications could be ischemic lesion in post-irradiated tissues involving anastomoses. CONCLUSION: We conclude that angiogenesis inhibitors should be carefully considered for patients having low colorectal anastomosis and previous irradiation.

Neoadjuvant 5 fluorouracil-cisplatin chemoradiation effect on survival in patients with resectable pancreatic head adenocarcinoma: a ten-year single institution experience.

OBJECTIVES: It is the aim of this study to assess the outcome of patients who received neoadjuvant 5-fluorouracil-cisplatin chemoradiation (CRT) for stage I/III pancreatic adenocarcinoma. METHODS: Eligible patients (n = 101) received radiation therapy (45 Gy) associated with continuous infusion of 5-fluorouracil accompanied by a cisplatin bolus. RESULTS: Of the 102 patients enrolled in the study, 26 patients had progression of cancer during treatment and were deemed unresectable; 1 patient died during CRT of septic shock. Sixty-two of 75 remaining patients underwent pancreaticoduodenectomy. The overall median survival of all 102 patients in the study was 17 months, with a 5-year survival of 10%. For patients who underwent resection, the median survival was 23 months. Correspondingly, the median survival was 11 months for the 40 unresected patients (p = 0.002). The 5-year survivals for resected and unresected patients were 18 and 0% (p = 0.01), respectively. A complete pathological response to neoadjuvant CRT was noted for 8 patients (13%). Margin and lymph node positivity was present in 5 (8%) and 15 (24%) patients, respectively. There was documented local recurrence in 8 (13%) and distant recurrence in 36 (58%) patients, with the liver being the most common site. CONCLUSION: Neoadjuvant 5-fluorouracil-based CRT had a limited impact on survival but appeared to be associated with improved local control.