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Background: Merkel cell carcinoma (MCC) is a rare type of neuroendocrine tumor. Palpebral localization represents 2.5% of MCCs. Surgery is not always possible due to the localization or comorbidities of elderly patients. We hypothesized that radiotherapy (RT) alone could be a curative treatment in patients contraindicated for oncological surgery. Methods: We performed a retrospective monocentric study of patients with localized eyelid MCC treated with curative intent using curative radiotherapy. Results: Overall, 11 patients with histologically confirmed eyelid MCC were treated with curative radiotherapy. The median age was 77 years old (range: 53–94). Curative RT was decided mainly due to difficult localization and significant co-morbidities. The median lesion dose was 57 Gy (range: 47–70). Most patients had adjuvant lymph nodes irradiation with a median dose of 50 Gy (n = 9; 82%). The median follow-up was 62 months (6–152 months). None of the seven deaths were MCC-related. None of our patients relapsed during follow-up. Side effects related to radiotherapy were mild (no grade ≥ 2) and rare (n = 3, 21%). Conclusion: Our data suggest that curative radiotherapy is an effective and safe treatment for Merkel cell carcinoma of the eyelid and periocular region. Radiotherapy alone allows limiting the aesthetic and functional sequelae in elderly and comorbid patients who are contraindicated for oncological surgery.

Hypofractionated radiotherapy of early-stage squamous cell carcinoma of the glottic larynx is a promising treatment option. This can be divided into radiotherapy with moderate hypofractionation (up to 2.5Gy per fraction), more intense hypofractionation (between 2.5 and 4.5Gy per fraction) and stereotactic radiotherapy (above 4.5Gy per fraction). Most studies evaluating moderate hypofractionation show a local control rate between 85 and 95%. Acute laryngeal toxicity is superior to conventional treatment, but only for grades 1 and 2, with no significant difference reported for severe toxicity. Stereotactic radiotherapy in this pathology is also an emerging entity, but some authors have reported significant toxicity. There are currently no standardized guidelines for treatment and management regimen. We conducted a systemic review of published prospective and retrospective trials to evaluate efficacy, toxicity, and discuss future directions.

Purpose This study examined the performance of a bladder volume measuring device, the BladderScan (BS) BVI9400. The use of the BS offers the possibility of assessing the bladder volume before positioning the patient and performing the daily image‐guided radiotherapy procedure. Patients often cannot lie down before entering the treatment vault. Therefore, the BS was also assessed in a standing position. Methods The repeatability precision was first evaluated, which is the variability of immediate repeated measures of the BS with same operator and subject. This was followed by the reproducibility precision of the BS in which the operator and subjects differ. Finally, the trueness was evaluated in terms of fixed and proportional bias of the results by applying weighted least‐squares fitting. Note that 53 and 85 patient measurements were carried out in supine and standing position, respectively, each consisting of three repeated BS measurements. These were compared with the computed tomography (CT)‐delineated bladder volume. Results Repeatability was dependent on measurement value (heteroscedasticity) with σ repeatability (BS) = ±15 cm3 ± 10%. However, the total agreement between BS and CT was low with the 95% limits of agreement (LOAs) exceeding ±200 cm3 due to poor patient reproducibility and presence of fixed and proportional bias. Only in the best case of male patients in the supine position, three BS measurements, and correction for the fixed and proportional bias, 95% LOAs of [–147, +114] cm3 were obtained between CT and BS. Conclusion The agreement of the BVI9400 BS with CT was found to be too low for radiotherapy applications.

Background: Stereotactic body radiotherapy (SBRT) has been reported as a safe and efficient therapy for treating refractory ventricular tachycardia (VT) despite optimal medical treatment and catheter ablation. However, data on the use of SBRT in patients with electrical storm (ES) is lacking. The aim of this study was to assess the clinical outcomes associated with SBRT in the context of ES. Methods: This retrospective study included patients who underwent SBRT in the context of ES from March 2020 to March 2021 in one tertiary center (CHU Lille). The target volume was delineated according to a predefined workflow. The efficacy was assessed with the following end points: sustained VT recurrence, VT reduced with antitachycardia pacing, and implantable cardioverter defibrillator shock. Results: Seventeen patients underwent SBRT to treat refractory VT in the context of ES (mean 67±12.8 age, 59% presenting ischemic heart disease, mean left ventricular ejection fraction: 33.7± 9.7%). Five patients presented with ES related to incessant VT. Among these 5 patients, the time to effectiveness ranged from 1 to 7 weeks after SBRT. In the 12 remaining patients, VT recurrences occurred in 7 patients during the first 6 weeks following SBRT. After a median 12.5 (10.5–17.8) months follow-up, a significant reduction of the VT burden was observed beyond 6 weeks (−91% [95% CI, 78–103]), P Conclusions: SBRT is associated with a significant reduction of the VT burden in the event of an ES; however, prospective randomized control trials are needed. In patients without incessant VT, recurrences are observed in half of patients during the first 6 weeks. VT tolerance and implantable cardioverter defibrillator programming adjustments should be integrated as part of an action plan defined before SBRT for each patient.

Purpose This phase I study assessed the safety of first-in-class radioenhancer nanoparticles, NBTXR3, in elderly or frail patients with locally advanced head and neck squamous cell carcinoma (HNSCC), ineligible for chemoradiation. Methods Patients with stage III or IVA (American Joint Committee on Cancer (AJCC) guidelines, 7th edition, 2010) HNSCC of the oral cavity or oropharynx, aged ≥70 or ≥65 years and ineligible to receive cisplatin, amenable to radiotherapy (RT) with curative intent, received NBTXR3 as a single intratumoural (IT) injection followed by activation by intensity-modulated radiation therapy (IMRT; 70 Gy). The NBTXR3 dose corresponded to a percentage of the baseline tumour volume, measured by magnetic resonance imaging. The primary objectives were to determine the recommended phase II dose (RP2D), dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Safety and tolerability were assessed using National Cancer Institute CTCAE version 4.0. Antitumour activity was assessed by Response Evaluation Criteria in Solid Tumours 1.1. Results Nineteen patients were enrolled: 3 at the dose level of 5%, 3 at the dose level of 10%, 5 at the dose level of 15% and 8 at the dose level of 22% of the tumour volume. The MTD was not reached, and no DLTs or serious adverse event (SAEs) related to NBTXR3 were observed. Four adverse events related to NBTXR3 and/or the IT injection were reported (grade I–II). NBTXR3 remained in the injected tumour throughout RT, with no leakage in the surrounding healthy tissues. Specific RT-related toxicity was as expected with IMRT. The RP2D was determined as 22% baseline tumour volume. Preliminary signs of antitumour activity were observed. Conclusion Intratumoural injection of NBTXR3 followed by IMRT is feasible and demonstrated a good safety profile, supporting further evaluation at the RP2D in this patient population. Trial registration ClinicalTrials.gov NCT01946867 .

Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine.A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test.In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61-2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33-2.76, p = 0.93).No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.

Resume Les metastases sont les tumeurs cerebrales les plus frequentes. Apres chirurgie, la radiotherapie en conditions stereotaxiques du lit operatoire est devenue le standard. Les donnees de deux essais randomises montrent que la radiotherapie en conditions stereotaxiques permet un bon taux de controle local par rapport a la surveillance, tout en diminuant le risque de troubles cognitifs et d’alteration de la qualite de vie en comparaison avec l’irradiation de l’encephale en totalite. Le taux de controle local parait plus eleve apres radiotherapie en conditions stereotaxiques hypofractionnee par rapport a la radiotherapie en conditions stereotaxiques en seance unique. Des questions restent ouvertes, comme la definition des volumes cibles, le schema optimal en particulier pour les cavites operatoires de grande taille, les strategies pour diminuer le risque de recidive leptomeningee et la sequence therapeutique.

This study aimed to describe patient characteristics, treatment efficacy, and safety in patients with hepatocellular carcinoma (HCC) undergoing stereotactic body radiation therapy (SBRT). We retrospectively analyzed data of 318 patients with 375 HCC treated between June 2007 and December 2018. Efficacy (overall survival [OS], relapse-free survival, and local control) and acute and late toxicities were described. The median follow-up period was 70.2 months. Most patients were treated with 45 Gy in three fractions. The median (range) PTV volume was 90.7 (2.6–1067.6) cc. The local control rate at 24 and 60 months was 94% (91–97%) and 94% (91–97%), respectively. Relapse-free survival at 12, 24, and 60 months was 62% (55–67%), 29% (23–36%), and 13% (8–19%), respectively. OS at 12, 24, and 60 months was 72% (95%CI 67–77%), 44% (38–50%), and 11% (7–15%), respectively. Approximately 51% and 38% experienced acute and late toxicity, respectively. Child-Pugh score B-C, high BCLC score, portal thrombosis, high GTV volume, and higher PTV volume reported on total hepatic volume ratio were significantly associated with OS. SBRT is efficient for the management of HCC with a favorable toxicity profile. The outcome is highly related to the natural evolution of the underlying cirrhosis.

370 Background: When combined to preoperative radiation therapy (RT), CP and FFX regimen provide both high complete resection (R0) rate for EC/EGJ cancer (Adenis, ASCO 2022). However, it appeared that neoadjuvant chemoradiation (nCRT) with CP is associated with a severe postoperative morbidity rate higher than expected. We present here the expanded safety and efficacy analyses from the PROTECT trial. Methods: PROTECT is a randomized, phase 2 trial which included stage II/III and ECOG PS ≤2 EC or Siewert I-II EGJ cancers. Patients (pts) received FFX or CP with concurrent RT (41.4Gy, 1.8Gy, 23 fractions), followed by surgery 4-8 weeks after completion of nCRT (Messager, BMC Cancer 2016). Co-primary endpoints were proportion of R0 rate and proportion of Clavien-Dindo severe postoperative morbidity. Main secondary endpoints were nCRT and postoperative safety (NCI CTCAE v.4), DFS and OS. Results: 41/50 (82%) and 39/50 (78 %) pts received the planned chemo cycles and concurrent RT in FFX and CP arms, respectively. Grade (gr.) 3–4 AEs related to nCRT (FFX 14/50, 28%; CP 14/50, 28%) occurring in ≥5% of pts included lymphopenia (n=3, 6%; n=4, 8%), neutropenia (n=1, 2%; n=3, 6%), fatigue (n=2, 4%; n=0) and esophagitis-related to RT (n=1, 2%; n=1, 2%). No death was reported during nCRT. Surgery (FFX and CP; mini invasive: 15 and 15, hybrid: 22 and 21, open: 7 and 12) was performed in 44 and 48 pts, in FFX and CP groups, respectively. The main gr. III-V surgical complications (Clavien-Dindo scale) occurring in ≥5% of pts included esophageal fistula (n=2/43 evaluable pts, 6%; 8/48, 17%), conduit necrosis (n=2, 5%; n=1, 2%), ARDS (n=3, 7%; n=3, 6%), pleural effusion (n=3, 7%; n=4, 8%), and haemorrhage (n=0; n=3, 6%). There were no postoperative deaths. With a median follow-up of 54m, median DFS were 12.3m and 20m (HR=0.84; 95%CI: 0.52-1.35; p=0.48) and median OS were 31.7m and 45.8m (HR=0.79; 95%CI: 0.47-1.32; p=0.36) in FFX and CP arms, respectively. Prognostic factors significantly associated to DFS in univariate analysis were: R0 resection, TRG1-2 and ypT0N0 status. Conclusions: A higher than expected number of severe esophageal fistula was observed in the CP arm. We could not demonstrate a significant benefit of CP compared to FFX in terms of survival outcomes, but the study was not primarily designed to specifically address this issue. Clinical trial information: NCT02359968 .

Background Intramedullary metastasis (IMM) is a rare disease with poor prognosis. The incidence of IMMs has increased, which has been linked to improved systemic treatment in many cancers. Surgery and/or radiotherapy are the most commonly used treatments; only small-sample retrospective studies and case reports on stereotactic body radiotherapy (SBRT) have reported acceptable results in terms of local control and clinical improvement, with no reported toxicity. Thus, we performed this monocentric retrospective study on five cases treated with SBRT for IMMs, which we supplemented with a systematic review of the literature. Methods We included all patients treated for IMM with SBRT. The target tumor volume, progression-free survival, prescription patterns in SBRT, survival without neurological deficit, neurological functional improvement after treatment, and overall survival were determined. Results: Five patients treated with a median dose of 30 Gy in a median number of fractions of 5 (prescribed at a median isodose of 86%) included. The median follow-up duration was 23 months. Two patients showed clinical improvement. Three patients remained stable. Radiologically, 25% of patients had complete response and 50% had stable disease. No significant treatment-related toxicity was observed. Conclusion: SBRT appears to be a safe, effective, and rapid treatment option for palliative patients.

Purpose: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathological response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine. Method: A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant radiochemotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test.Results: In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete histological response was lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p=0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR]=1.26, 95% confidence interval [CI] 0.61–2.60, p=0.54) or overall survival (HR=0.95, 95% CI 0.33–2.76, p=0.93).Conclusion: There is a trend to a lower complete histological response with PPI co-medication in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.

Background and purpose Standard treatment of epidermoid anal cancer is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase I study aims to evaluate the addition of panitumumab (Pmab) to CRT and to determine the maximum tolerated dose (MTD) of Pmab and 5-FU in combination with CRT. Materials and methods Immunocompetent patients with locally advanced tumour without metastases (Stage T2, T3 or T4, whatever N stage; Stage N1–N3 whatever T stage) followed two RT periods (45 Gy in 5 weeks and 20 Gy in 2 weeks, separated by a 2-week break) with concomitant CT sessions of 5FU/MMC at RT weeks 1, 5 and 8. Pmab was administered on RT weeks 1, 3, 5, 8 and 10 according to a predefined dose escalation schedule. Results Ten patients were enroled. One was excluded due to unmet dose constraints respect. Three patients received dose level (DL) 0 (Pmab 3 mg/kg + 5FU 600 mg/m2/day) and six received DL-1 (Pmab 3 mg/kg + 5FU 400 mg/m2/day). Dose-limiting toxicities occurred in all patients at DL 0 and 2 at DL-1. Most common grade 3–4 toxicities observed at DL 0 were haematologic (100%), dermatitis (67%), and anaemia (67%). No death occurred. Four months after ending CRT, five and two patients had a local complete response and a partial response, respectively. One patient had a colostomy with abdomino-perineal amputation due to a tumour recurrence. Conclusions The MTD is 5FU at 400 mg/m2/day, MMC at 10 mg/m2 and Pmab at 3 mg/kg. The effect of the MTD on tumour response is evaluated in the phase 2 study.

4015 Background: Preoperative CRT with a FU/platinum regimen has been used for years for esophageal or junctional cancer before the CP regimen became a standard of care following the results of the CROSS study (van Hagen 2012). We aimed at evaluating the complete resection (R0) rate and severe postoperative morbidity rate associated with these 2 neoadjuvant regimens, each being combined with the radiation (RT) regime used in the CROSS trial. Methods: PROTECT is a multicenter, randomized, non-comparative, phase 2 trial (NCT02359968) in patients (pts) with resectable esophageal or Siewert type I-II junctional cancer, stage II (T1-2N1 or T3N0) or stage III (T3N1 or T4anyN) tumors (UICC-7 classification), and ECOG PS ≤2. Following randomization (balanced by ECOG PS 0 vs 1-2, stage II vs III, squamous-cell (SCC) vs adenocarcinoma (ADK), center), pts received CP (AUC2 CBP plus PCL 50mg/m² / week x 5 weeks), or Fx (FU 400 mg/m² bolus Day 1, then FU 1600 mg/m² continuous infusion over 2 days, plus OX 85 mg/m², and Folinic acid 200 mg/m², 2-h infusion, Day 1; 3 cycles every 2 weeks). RT technique was similar in both arms: 3D-conformal as published in the CROSS trial or IMRT (n = 35); total dose of 41.4Gy, 5 fractions of 1.8Gy / week, starting at Day 1 of chemotherapy. Surgery was performed 4 to 8 weeks after completion of CRT through a transthoracic or mini-invasive approach with a two field extended lymphadenectomy. Co-primary endpoints were R0 (failure: R1 or disease progression under CRT), and severe postoperative morbidity rate ≤30 days after surgery (Clavien-Dindo grade ≥ III). Based on a Bryant and Day 2-stage design (p0 = 75% and p1 = 90% for resection; p0 = 45% and p1 = 25% for morbidity; α = 10% and β = 15%), 48 evaluable pts were required by arm. Results: 100/104 pts recruited from 02/2015 to 08/2020, started the study treatment: 50 CP & 50 Fx. Overall, median age = 64 (range, 33-79); 82/100 males; 62 ADK and 38 SCC; 66 esophageal and 34 junctional site; 31 stage II; 68 stage III, 1 Nx. R0 resection was obtained in 46/50 CP pts (92.0%, 95% CI: 80.8-97.8%), and in 42/48 Fx pts (87.5%, 74.8-95.3%); 2 non evaluable pts because of event unrelated to disease progression. Severe postoperative adverse events (AEs) occurred in 34/91 pts who underwent surgery: 21/48 CP (43.8%, 29.5-58.8%) and 13/43 Fx (30.2%, 17.2-46.1%). Severe AEs were respiratory disorders (CP 26%; Fx 26%), esophageal fistula (CP 18%; Fx 6%), infection (CP 5%; Fx 3%), haemorrhage (CP 5%; Fx 0%) and gastric tube necrosis (CP 6%; Fx 3%). 5 pts died from AEs (3 CP, 2 Fx). A TRG1-2 was observed in 29/48 (60.4%, 95% CI: 44.3-74.2%) CP pts, and in 19/43 (44.2%, 29.1-60.1%) Fx pts. Conclusions: When combined to preoperative radiation therapy at 41.4Gy, both regimens (CP and Fx) provided short-term benefit on R0 resection; however, CP is associated with a severe postoperative morbidity rate higher than expected. Clinical trial information: NCT02359968.

e16075 Background: Postoperative pulmonary complications are common after neoadjuvant CRT of locally advanced esophageal cancers. Using data from the French multicenter randomized phase II PROTECT trial (NCT02359968), we aimed to evaluate the dosimetric parameters which could be associated with the occurrence of postoperative respiratory morbidities in patients (pts) who underwent preoperative CRT. Methods: Key eligibility criteria for the PROTECT trial were stage II or III resectable adenocarcinoma or squamous cell carcinoma of the esophagus located below the carina. Pts received FOLFOX or Carboplatin-Paclitaxel, combined with radiotherapy (RT): total dose of 41.4 Gy, 5 fractions of 1.8 Gy per week, starting at day 1 of chemotherapy. The patient's position and definition of the target volumes and organs at risk were the same as in the CROSS trial (van Hagen, 2012). Pts were treated using 3D conformal RT or IMRT. Surgery occurred 4 to 8 weeks after completion of CRT through a transthoracic or mini-invasive approach with a two field extended lymphadenectomy. Pts recruited in the PROTECT trial up to Sept. 2019 who underwent surgery after CRT were eligible for this ancillary study. The primary endpoint of our translational study was the occurrence of postoperative respiratory morbidity, of any grade (Clavien-Dindo classification for early morbidity < 31 days; NCI-CTCAE v4 for later events), up to 1 year following surgery, considering disease progression or death as competing events. Cause-specific Cox models were used to model the risk of respiratory morbidity, considering the following factors: performance status, BMI, smoking, histological subtype, tumor site, FEV1, RT technique, time interval between CRT and surgery, and dosimetric parameters derived from the Dose-Volume Histogram analysis (mean lung dose, V10Gy, V20Gy and V30Gy, as other parameters strongly correlated to these 4 ones). Results: Among the 98 pts recruited in the PROTECT trial from Feb. 2015 to Sept. 2019, 78 underwent surgery after CRT and were included in our translational study. Median age was 63.5 years (range 33 to 79). Tumor was located at the middle or lower third of the esophagus for 67% of pts. Mean lung dose was 10.2 Gy (sd = 3.2). Mean PTV volume was 566 cc (sd = 272). A total of 33 pts experienced at least one respiratory morbidity (16 pneumonia, 7 pleural effusion, 4 ARDS, 21 miscellaneous events). The cumulative incidence of respiratory morbidity was 42% one month after surgery (95% CI, 32-54), 44% at 3 months (32-54), and 46% at 6 months (35-57). None of the dosimetric parameters and other studied factors appeared associated with postoperative respiratory morbidity. Conclusions: We did not identify dosimetric factors that could predict the risk of postoperative respiratory morbidity after treatment with preoperative CRT with FOLFOX or Carboplatin-Paclitaxel. Clinical trial information: NCT02359968.

Purpose Early stage Merkel cell carcinoma (MCC) is a rare and aggressive primary skin cancer. The standard of care for MCC is broad excision and adjuvant external beam radiation therapy (EBRT). However, for some patients, anesthesia is contraindicated, while others run the risk of serious aesthetic sequelae. In such cases, exclusive radiotherapy is an interesting alternative to surgery. Though limited data is available, this study evaluates exclusive radiotherapy for MCC, using data from the largest retrospective study to date. Methods All patients who were followed in our center between 1989 and 2019 for histologically proven early stage MCC were included in the study. They were treated either by surgery with a 2-cm clear margin followed by adjuvant radiotherapy (RT) or by exclusive RT. Survival rates with adjuvant and exclusive EBRT were analyzed using Cox model and Fine and Gray model depending on the type of survival. p value Results Eighty-four patients treated for MCC were included. Fifty-three of them (63.1%) were treated by exclusive RT, and 31 (36.9%) had surgical excision followed by adjuvant RT. Local relapse rate was 13.7% (95% CI 8.0–43.7) in the RT monotherapy group (group A) and 25.8% (95% CI 10.3–56.2) in the surgery + RT group (group B) (p = 0.42). No statistical difference was found for nodal relapse (p = 0.81), metastatic relapse (p = 0.10), disease free survival (p = 0.83) or overall survival (p = 0.98). Conclusion Our study suggests that exclusive radiotherapy for early Merkel cell carcinoma leads to a similar oncological outcome as combined treatment, with fewer aesthetic sequelae. The approach is interesting for elderly patients with comorbidities or patients for whom surgery would cause significant functional or aesthetic sequelae.

Background: Stereotactic body radiotherapy (SBRT) is a recognized treatment for colorectal cancer (CRC) metastases. We postulated that local responses could be improved by SBRT with a concomitant radiosensitizing agent (irinotecan). Methods: RADIOSTEREO-CAMPTO was a prospective multi-center phase 2 trial investigating SBRT (40&ndash, 48 Gy in 4 fractions) for liver and/or lung inoperable CRC oligometastases (&le, 3), combined with two weekly intravenous infusions of 40 mg/m2 Irinotecan. Primary outcome was the objective local response rate as per RECIST. Secondary outcomes were early and late toxicities, EORTC QLQ-C30 quality of life, local control and overall survival. Results: Forty-four patients with 51 lesions (liver = 39, lungs = 12) were included. Median age was 69 years (46&ndash, 84), 37 patients (84%) had received at least two prior chemotherapy treatments. Median follow-up was 48.9 months. One patient with two lung lesions was lost during follow-up. Assuming maximum bias hypothesis, the objective local response rate in ITT was 86.3% (44/51&mdash, 95% CI: [76.8&ndash, 95.7]) or 82.4% (42/51&mdash, 95% CI: [71.9&ndash, 92.8]). The observed local response rate was 85.7% (42/49&mdash, 95% CI: [75.9&ndash, 95.5]). The 1 and 2-year local (distant) progression-free survivals were 84.2% (38.4%) and 67.4% (21.3%), respectively. The 1 and 2-year overall survivals were 97.5% and 75.5%. There were no severe acute or late reactions. The EORTC questionnaire scores did not significantly worsen during or after treatment. Conclusions: SBRT with irinotecan was well tolerated with promising results despite heavily pretreated patients.

Simple Summary Exclusive chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas. Identifying novel prognostic factors could help to improve CRT outcomes, notably for locally advanced diseases where relapses still occur in around 35% of patients. In this study, we aim to assess the potential value of a pre-therapeutic MRI radiomic analysis added to standard clinical variables in order to build a logistic regression model predicting 2-year recurrence after CRT. In a population of 82 patients randomly divided in training (n = 54) and testing (n = 28) sets, after selection of optimal variables, a model using two radiomic (FirstOrder_Entropy and GLCM_JointEnergy) and two clinical (tumor size and CRT length) features was able to predict the 2-year recurrence with good performances in the testing set. Radiomic biomarkers provided valuable additional and independent information added to clinical data, and could help contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine. Abstract Purpose: Chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas (ASCC). Despite excellent results for T1-2 stages, relapses still occur in around 35% of locally advanced tumors. Recent strategies focus on treatment intensification, but could benefit from a better patient selection. Our goal was to assess the prognostic value of pre-therapeutic MRI radiomics on 2-year disease control (DC). Methods: We retrospectively selected patients with non-metastatic ASCC treated at the CHU Bordeaux and in the French FFCD0904 multicentric trial. Radiomic features were extracted from T2-weighted pre-therapeutic MRI delineated sequences. After random division between training and testing sets on a 2:1 ratio, univariate and multivariate analysis were performed on the training cohort to select optimal features. The correlation with 2-year DC was assessed using logistic regression models, with AUC and accuracy as performance gauges, and the prediction of disease-free survival using Cox regression and Kaplan-Meier analysis. Results: A total of 82 patients were randomized in the training (n = 54) and testing sets (n = 28). At 2 years, 24 patients (29%) presented relapse. In the training set, two clinical (tumor size and CRT length) and two radiomic features (FirstOrder_Entropy and GLCM_JointEnergy) were associated with disease control in univariate analysis and included in the model. The clinical model was outperformed by the mixed (clinical and radiomic) model in both the training (AUC 0.758 versus 0.825, accuracy of 75.9% versus 87%) and testing (AUC 0.714 versus 0.898, accuracy of 78.6% versus 85.7%) sets, which led to distinctive high and low risk of disease relapse groups (HR 8.60, p = 0.005). Conclusion: A mixed model with two clinical and two radiomic features was predictive of 2-year disease control after CRT and could contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine.

Resume Introduction Le cancer de l’œsophage localement avance peut relever d’une radiochimiotherapie preoperatoire. La radiotherapie est susceptible d’accroitre les complications pulmonaires postoperatoires. La plupart des contraintes de dose aux poumons utilisees en radiotherapie sont anciennes, et employees par extrapolation de la prise en charge des cancers pulmonaires. L’objectif de ce travail est de faire une revue critique des correlations rapportees dans la litterature entre criteres dosimetriques et complications pulmonaires postoperatoires. Methode Nous avons repertorie et selectionne les etudes publiees entre 1987 et 2019 selon la methode PRISMA. Les articles ont ete identifies sur la base d’une recherche PubMed et des connaissances des auteurs via les termes « cancer de l’œsophage », « radiochimiotherapie », « facteurs dosimetriques », « complications pulmonaires postoperatoires ». Resultats Quatorze articles ont ete selectionnes, et cinq n’ont pas mis en evidence de correlation entre facteurs dosimetriques et taux de complications pulmonaires postoperatoires. Le V20 (volume pulmonaire recevant plus de 20 Gy) etait identifie dans trois etudes comme facteur predictif de complications pulmonaires, de meme que le V10, le V15 et la dose moyenne pulmonaire (proche de 10 Gy) dans deux etudes. Le V30 ≥ 20 % etait identifie dans une etude. Discussion Les parametres dosimetriques associes aux complications pulmonaires postoperatoires les plus frequemment identifies sont le V20 et la dose pulmonaire moyenne. Seuls les resultats d’etudes prospectives pourront nous amener a preciser lequel de ces parametres est le plus pertinent pour predire le risque de complication pulmonaire postoperatoire.

Summary Background Reversion of an implantable cardioverter defibrillator (ICD) to back-up mode degrades the operating capabilities of the device, puts patients at risk and requires rapid intervention by a manufacturer's technician. Aim To illustrate the usefulness of remote monitoring of ICDs for the early detection of reversion to back-up mode. Methods In our centre, all patients implanted with an ICD, with or without resynchronisation, were offered remote monitoring as soon as the technology became available. Alerts triggered by the remote monitoring system were included prospectively in a register. During a mean follow-up of 5.7 ± 1.3 years, a total of 1594 patients with an ICD (441 with resynchronisation function) followed with remote monitoring were included in the register. Results Among 15,874 alerts, only 10 were related to a reversion to back-up mode. Among those, seven reversions were caused by radiotherapy, two were fake events and one was caused by magnetic resonance imaging. Except for the two fake events, the eight other patients had an emergency admission for the resetting and reprogramming of their ICD. None of the reversion to back-up mode alerts was followed by a clinical alert (i.e. a shock alert) before the ICD problem was resolved. Conclusions Reversion to back-up mode is a very rare event, accounting for 0.06% of total alerts; remote monitoring facilitates the early detection of this critical event to resolve the problem faster than the next scheduled follow-up. Remote monitoring can prevent serious damage to the patient and avoids systematic ambulatory control of the ICD after each radiotherapy session.

Stereotactic radiotherapy (SRT) of brain metastases (BM) results are often reported in the heterogeneous primitive population. Here, we report our experience in consecutively treated patients who underwent SRT alone for BM from non-small cell lung cancer (NSCLC). This retrospective analysis included consecutive patients with no history of cerebral treatment who underwent Cyberknife™ SRT for BM from NSCLC in our institution from 2007 to 2016. One hundred patients were included in the study, with a median follow-up of 33 months (20–64). Mean age was 63 years (SD ± 10); 88% had Karnofsky Performance Status (KPS) > 70; 67% had unique BM; 18 patients received single-fraction SRT (20–25 Gy), and 82 received hypo-fractionated SRT (HSRT) (24–36 Gy in 3–5 fractions). We reported a complication rate of 17% (2% of G3-4). Median survival was 10.1 months [95% confidence interval (CI) 7.8–13.9]. At 1 year, local and cerebral control rates were respectively 78.7% (95% CI 70–86.5%) and 43% (95% CI 33.5–53%). Thirty patients underwent salvage treatment (whole brain radiation therapy, n = 13; SRT, n = 14; surgery, n = 3). Cyberknife™-based SRT is an effective treatment associated with high local control rate with low morbidity for patients with NSCLC’s BM. Close follow-up is necessary to perform salvage treatment.

Several molecules are being investigated for their ability to enhance the anti-tumor effect of radiotherapy. The widely prescribed antidiabetic drug metformin has been suggested to possess anti-cancer activity; data indicate that metformin could also enhance radiation sensitivity. The purpose of this review is to summarize current knowledge on the specific effect of metformin in the field of RT, while also discussing the many unknowns that persist. Preclinical models point to multiple mechanisms involved in the radiosensitizing effects of metformin that are mainly linked to mitochondrial complex I inhibition and AMP-activated protein kinase. Transposition of results from bench to bedside will be discussed through the lens of the drug concentration, its potential limits in human settings, and possible alternatives. Clinical data suggest metformin improves progression-free and overall survival in patients for many different cancers treated with RT; nevertheless, the results are not always consistent. The main limitations of the reviewed literature are the retrospective nature of studies, and most of the time, a lack of information on MTF treatment duration and the administered dosages. Despite these limitations, the possible mechanisms of the role of metformin and its utility in enhancing radiotherapy treatments are analyzed. Ongoing clinical trials are also discussed.

Purpose Liver transplantation is the standard definitive treatment for nonmetastatic hepatocellular carcinoma (HCC). However, less than 5% of patients are ultimately candidates as a result of frequent comorbidities and graft shortage. The aim of this study was to evaluate stereotactic body radiation therapy (SBRT) as an ablative treatment for inoperable HCC. Methods and Materials A prospective phase 2 trial included newly diagnosed single HCC lesions that were without extrahepatic extension and that were deemed unsuitable for standard locoregional therapies, with a tumor size ranging from 1 to 6 cm. The SBRT dose was 45 Gy in 3 fractions. Primary endpoint was the local control of irradiated HCC at 18 months, defined by Response Evaluation Criteria in Solid Tumors. Results Forty-three patients were treated and evaluable. Median follow-up was 4.0 years (range, 1.2-4.6 years). All 43 patients had cirrhosis; 37 (88%) were Child–Pugh grade A and 5 (12%) grade B (1 missing data). No patients had received prior local treatment. Thirteen patients (31%) presented grade ≥3 acute adverse events, including 8 patients with an abnormality of the liver function tests (19%). Three patients (10%) experienced a decline in Child–Pugh at 3 months post-SBRT. The 18-month local control rate was 98% (95% confidence interval, 85%-99%). The 18-month overall survival rate was 72% (range, 56%-83%). Median overall survival was 3.5 years. Conclusions Local control and overall survival after SBRT for untreated solitary HCC were excellent despite candidates being unfit for transplantation, resection, ablation, or embolization treatments. SBRT should be considered as a bridge to transplant or as definitive therapy for those ineligible for transplant.

Preoperative chemoradiotherapy is an option for locally advanced esophageal cancer. Radiation therapy may increase postoperative pulmonary complications. Usual lungs dose constraints in radiotherapy are old and used by extrapolation of lung cancer management. Our objective is to review the literature on correlations between postoperative lung toxicity and dosimetric factors.This literature review identified and selected studies published between 1987 and 2019 using the PRISMA method. The articles were identified on the basis of a PubMed search and the author's knowledge, using the following terms: "esophageal cancer"; "chemoradiotherapy"; "dosimetric factors"; "postoperative pulmonary complications".Fourteen articles were selected, and five did not demonstrate a correlation between dosimetric factors and the postoperative pulmonary complications rate. The V20 (lung volume receiving more than 20Gy) was identified in three studies, like the V10, V15 and mean lung dose (around 10Gy) in two studies. The V30≥20% was identified in one study.The most frequently identified dosimetric predictors for postoperative pulmonary complications are the V20 and the mean lung dose. Results of prospective studies would lead us to specify which of these parameters is most relevant for predicting the risk of postoperative pulmonary complications.

PURPOSE/OBJECTIVE(S) Concurrent radiotherapy (RT) with high-dose cisplatin, or cetuximab in case of intolerance to cisplatin, are the non-surgical standard treatment for locally advanced head and neck squamous cell carcinoma (LA HNSCC). However, elderly patients, patients with poor performance status, comorbidities, and/or intolerance may not benefit from these treatments and represent a high unmet medical need. New approaches are thus needed to improve the patient clinical outcomes without adding toxicity. NBTXR3, composed of functionalized hafnium oxide nanoparticles, is injected once intratumorally and activated by RT. NBTXR3 increases the RT energy deposit inside tumor cells and subsequently increases tumor cell death compared to RT alone, without adding toxicity to healthy tissues. We present here current results of the dose expansion part of the phase I study evaluating NBTXR3 plus intensity modulated radiation therapy (IMRT) in this population (ClinicalTrials.gov: NCT01946867). MATERIALS/METHODS Patients with stage III-VA or T3/T4 (AJCC/UICC TNM staging system 8th ed.) HNSCC of the oropharynx or oral cavity, ineligible to cisplatin or cetuximab and amenable for RT, received a single intratumoral injection of NBTXR3 and IMRT (70 Gy in 35 fractions /7 weeks). A classical 3 + 3 dose escalation design has tested four doses of NBTXR3, equivalent to 5, 10, 15, and 22% of baseline theoretical tumor volume. The RP2D established as 22% of baseline tumor volume is further tested in the dose expansion part of the study. The primary endpoints of the dose expansion part are objective response rate (ORR) and complete response rate (CRR) of the primary tumor, by imaging according to RECIST v1.1. Safety is also evaluated. RESULTS As of August 13, 2020, 43 patients have been treated in the dose expansion part of the study. The median age was 70.7 years old (range: 50.7- 89.9), 70% of patients had cardiac disorder risk, 44% had gastrointestinal disorder risk and 44% metabolic and nutrition disorder risk. The median tumor volume was 42.8 mL (range: 1.3 - 222.3). In the evaluable population for efficacy (N = 31), the ORR of the primary lesion was 83.9% and the CRR 67.7% at a median time of 7.8 months after NBTXR3 injection. Three patients (7%) experienced at least one serious adverse event (AE) related to the injection procedure and/or NBTXR3 which represented less than 1% of all reported AEs. RT-related toxicity was as expected with IMRT. Three deaths due to AEs related to RT and other causes were reported. The recruitment is ongoing and updated efficacy and safety results will be presented. CONCLUSION NBTXR3 intratumoral administration followed by IMRT may represent an option in elderly in elderly patients or patients with multiple comorbidities with LA-HNSCC who have limited therapeutic options. NBTXR3 activated by RT showed promising anti-tumor efficacy, supporting further evaluation in a phase III randomized trial.

Introduction Le carcinome de Merkel (CM) est un carcinome cutane rare mais agressif atteignant une population souvent âgee. Les recommandations actuelles preconisent une exerese large de la lesion primitive, avec marges de 2 cm, suivie de radiotherapie (RT) adjuvante. En pratique, ces recommandations sont souvent difficilement applicables, en raison du prejudice esthetique et fonctionnel qu’induirait la chirurgie ou de contre-indications a l’anesthesie. Quelques etudes sur de petits effectifs suggerent une efficacite de la radiotherapie exclusive. Nous rapportons la plus grande cohorte de patients traites par RT exclusive. Materiel et methodes Tous les patients presentant un CM de stade localise traites au CHU de Lille entre 1989 et 2019 ont ete inclus. Ces patients ont ete repartis en 2 groupes de traitement : chirurgie avec marge > 2 cm et radiotherapie adjuvante ou radiotherapie exclusive sans chirurgie prealable. Les patients traites par chirurgie avec marge Resultats Les donnees de 175 patients atteints de CM de stade localise ont ete analysees. Parmi eux, 84 patients ont ete inclus, dont 53 patients traites par radiotherapie exclusive et 31 patients par chirurgie avec marge > 2 cm et radiotherapie adjuvante. Le diametre tumoral etait de 2,0 cm dans le groupe « RT exclusive » et de 2,5 cm dans le groupe « chirurgie + RT ». La tumeur primitive etait plus frequemment localisee en region cervico-cephalique dans le groupe « RT exclusive » (81,1 %) que dans le groupe « chirurgie + RT » (22,6 %). La dose mediane d’irradiation delivree sur la lesion etait de 60 Gy dans le groupe « RT exclusive » et de 50 Gy dans le groupe « chirurgie + RT ». 75,5 % des patients du groupe « RT exclusive » et 77,4 % des patients du groupe « chirurgie + RT » ont recu une irradiation ganglionnaire, avec une dose mediane de 50 Gy dans les 2 groupes. Le suivi median etait de 64 mois dans le groupe « RT exclusive » et de 95 mois dans le groupe « chirurgie + RT ». Il n’y avait pas de difference significative concernant la recidive locale entre les 2 groupes (respectivement 13,7 % et 25,8 % ; p = 0,42). De meme, aucune difference n’a ete mise en evidence entre les 2 groupes concernant la recidive ganglionnaire (p = 0,81) ou metastatique (p = 0,10). Il n’y avait pas de difference sur la survie sans progression a 5 ans (40,0 % vs 43,0 % ; HR = 0,95 (IC95 % : 0,55–1,65) ou sur la survie globale a 5 ans (50,8 % vs 51,0 % ; HR 1,05 (IC95 % : 0,44–2,5). Discussion Notre etude confirme la place de la radiotherapie exclusive sans chirurgie prealable dans le traitement du carcinome de Merkel, comme alternative au traitement de reference. Cette approche semble interessante pour les patients âges, atteints de comorbidites, ou sur les zones d’abord chirurgical difficile afin de limiter les sequelles fonctionnelles et esthetiques.

Introduction Le carcinome de Merkel (CM) est une tumeur neuroendocrine rare (265 cas/an en France). La localisation palpebrale represente 2,5 % des CM (± 200 cas dans la litterature). Il se presente par une papule violacee souvent confondue avec des kystes dermoides, chalazions ou carcinomes basocellulaires. La chirurgie n’est pas toujours possible en raison de la localisation ou des comorbidites des patients âges. La radiotherapie (RT) exclusive se presente alors comme une alternative de choix. Materiel et methodes Nous presentons une etude descriptive monocentrique retrospective de la prise en charge des CMs peri-orbitaires localises discutes en RCP d’onco-dermatologie au CHU de Lille a visee curative apres confirmation histologique. Les patients ayant des atteintes ganglionnaires et metastatiques etaient exclus. Resultats Quatorze patients ont ete traites, d’âge median de 79 ans [53–94 ans], avec hemopathie associee dans 14 % (2/14) des cas. La taille mediane des lesions etait de 14,5 mm [4–20 mm]. Le traitement a consiste en une RT exclusive pour 50 % (7/14) des cas. Pour les patients operes, les marges etaient de 5,5 mm [1–10 mm], tous ont recu une RT adjuvante. La RT exclusive etait decidee principalement en raison d’une localisation difficile (85,7 % soit 6/7) et des comorbidites importantes (14,3 % soit 1/7). La dose mediane lesionnelle etait de 57 Gy [30–70 Gy]. Parmi les traitements par RT exclusive, 57 % (4/7) ont recu un boost lesionnel (mediane 12 Gy). Les territoires de drainages ont ete irradies avec une mediane de 50 Gy [43–57 Gy], dont 2 avec un boost ganglionnaire. Un hypofractionnement etait realise pour 4 patients. Le suivi median etait de 42 mois [2–128 mois]. Aucun des huit deces n’etait lie au CM. Aucune rechute n’a ete diagnostiquee. Les effets secondaires lies a la radiotherapie etaient legers (conjonctivite, radioepithelite, epistaxis et alopecie). Un patient a presente une regression spontanee avant traitement. Discussion Devant la rarete et la complexite de PEC de ces lesions periorbitaires, aucun essai randomise n’existe a ce jour. La RT exclusive des CMs associee a une radiotherapie ganglionnaire est preconisee par certains auteurs. Nous rapportons la plus grande serie de CM peri-oculaires localises traites par RT exclusive. Seuls 5 autres cas ont ete rapportes dans la litterature. Aucun n’a presente de rechute a notre connaissance. Les limites de notre etude sont le petit effectif de patients et les modalites retrospectives monocentriques. En cas de chirurgie, une radiotherapie adjuvante precoce du lit tumoral doit etre envisagee devant le risque de recidive rapide lie aux faibles marges. Au vu de ces donnees, il semble que la radiotherapie exclusive soit une alternative pour les CMs peri-oculaires chez les personnes âgees avec comorbidites.

Introduction L’ipilimumab associe a la radiochirurgie a demontre une augmentation de la survie globale par rapport a la radiochirurgie seule chez des patients atteints d’un melanome metastatique avec metastases cerebrales. Nous rapportons les resultats de survie a 5 ans d’un essai de phase 2 ( NCT02662725 ). Materiel et methodes Cette etude ouverte multicentrique de phase 2 a evalue l’efficacite d’administration d’ipilimumab (10 mg/kg) associee a la radiochirurgie (1 fraction a 20-25 Gy) dans une cohorte de patients atteint de melanome avec 1 a 3 metastases cerebrales sans indication de corticosteroide. L’objectif principal etait de montrer une augmentation d’au moins 50 % du temps median de survie globale par rapport a une cohorte historique de controle de 333 patients avec des caracteristiques comparables ayant beneficie de radiochirurgie seule. Les criteres secondaires etaient les taux de reponses intra et extra-cerebrale, la survie sans progression et la securite. Resultats Un total de 73 patients ont ete inclus dans l’etude, 57 ont beneficie de l’ipilimumab associe a la radiochirurgie. L’âge median etait de 54 ans (47–67). Une survie significativement prolongee par rapport a la population de reference a ete observee, avec une survie globale mediane de 19,1 mois, contre 5,6 mois dans la population de reference (HR = 0,29 ; IC 95 % = 0,19–0,39 ; p Discussion Cette analyse sur 5 ans represente le plus long suivi a ce jour d’utilisation de l’ipilimumab a haute dose combine a la radiochirurgie et suggere une efficacite superieure sur la survie globale avec un profil de securite satisfaisant chez les patients atteints d’un melanome avec metastases cerebrales.