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Background and Purpose: Extreme hypofractionated stereotactic body radiotherapy (SBRT) is a therapeutic alternative for localized low- or intermediate-risk prostate cancer. Despite the availability of several studies, the toxicity profile of SBRT has not been comprehensively described. This real-world evidence study assessed the efficacy and toxicities associated with this regimen, and potential prognosis factors for genitourinary toxicities., Materials and Methods: This retrospective study included 141 consecutive patients with localized prostatic adenocarcinoma treated with CyberKnife™ SBRT, as primary irradiation, at the Oscar Lambret Center between 2010 and 2020. The prescribed dose was 36.25 Gy in 5 fractions. Acute and late toxicities were graded according to the CTCAE (version 5.0). Biochemical recurrence-free survival (bRFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The cumulative incidence of biochemical recurrence (cBR) was estimated using the Kalbfleisch-Prentice method., Results: Among the included patients, 13.5 % had a history of transurethral resection of the prostate (TURP). The median follow-up was 48 months. At 5 years, bRFS, cBR, and OS were 72 % (95 %CI: 61-81), 7 % (95 %CI: 3-14), and 82 % (95 %CI: 73-89), respectively. Twenty-nine patients experienced at least one late toxicity of grade ≥ 2; genitourinary (N = 29), including 3 cases of chronic hematuria, and/or gastrointestinal (N = 1). The cumulative incidence of late urinary toxicity of grade ≥ 2 was 20.6 % at 5 years (95 %CI: 13.9-28.1). Multivariate analysis revealed that a history of TURP was significantly associated with late urinary toxicity of grade ≥ 2, after adjusting for clinical target volume (Odds Ratio = 3.06; 95%CI: 1.05-8.86; P  = 0.04)., Conclusion: Extreme hypofractionated SBRT is effective for localized prostate cancer with a low risk of late toxicity. A history of TURP is associated with a higher risk of late urinary toxicity. These findings may contribute to the optimal management of patients treated with this regimen, particularly those with a history of TURP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Background: Intensity-modulated conformal radiotherapy (IMRT) has become the technique of choice for the treatment of locally advanced or inoperable non-small cell lung cancer (NSCLC). Nevertheless, this technique presents dosimetric uncertainties, particularly in treating moving targets such as pulmonary neoplasms. Moreover, it theoretically increases the risk of isolated nodal failure (INF) due to reduced incidental irradiation., Objective: The objective of this study was to evaluate the efficacy and safety of IMRT in patients with inoperable NSCLC and to describe the pattern of relapses., Methods: Patients with locally advanced NSCLC treated with radiotherapy and chemotherapy between 2015 and 2018 at the Oscar Lambret Center were retrospectively included in the study. Overall and progression-free survival were estimated using the Kaplan-Meier method. The cumulative incidence of the different components of relapse was estimated using the Kalbfleisch and Prentice method. Prognostic factors for relapse/death were investigated using the Cox model. A comparison with literature data was performed using a one-sample log-rank test., Results: Seventy patients were included, and 65 patients (93%) had stage III disease. All the patients received chemotherapy, most frequently with cisplatin and navelbine. The dose received was 66 Gy administered in 33 fractions. The median follow-up and survival were 49.1 and 39.1 months, respectively. A total of 35 deaths and 43 relapses, including 29 with metastatic components, were reported. The overall survival rates at 1 and 2 years were 80.2% (95% confidence interval 68.3%-88.0%) and 67.2% (95% confidence interval 54.2%-77.3%), respectively. Locoregional relapse was observed in 14 patients, including two INF, one of which was located in the lymph node area adjacent to the clinical target volume. Median relapse-free survival was 15.2 months. No variable was statistically associated with the risk of relapse/death in multivariate analysis. Seven patients (10%) experienced grade 3 or higher toxicity., Conclusion: The use of IMRT for locally advanced or inoperable NSCLC led to favorable long-term clinical outcomes. The rate of locoregional relapse, particularly isolated lymph node failure, was low and comparable with that of the three-dimensional radiotherapy series, as was the rate of early and late toxicities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Le Roy, Wallet, Barthoulot, Leguillette, Lacornerie, Pasquier, Lartigau and Le Tinier.)

Stereotactic body radiation therapy (SBRT) has made the hypofractionation of high doses delivered in a few sessions more acceptable. While the benefits of hypofractionated SBRT have been attributed to additional vascular, immune effects, or specific cell deaths, a radiobiological and mechanistic model is still needed. By considering each session of SBRT, the dose is divided into hundreds of minibeams delivering some fractions of Gy. In such a dose range, the hypersensitivity to low dose (HRS) phenomenon can occur. HRS produces a biological effect equivalent to that produced by a dose 5-to-10 times higher. To examine whether HRS could contribute to enhancing radiation effects under SBRT conditions, we exposed tumor cells of different HRS statuses to SBRT. Four human HRS-positive and two HRS-negative tumor cell lines were exposed to different dose delivery modes: a single dose of 0.2 Gy, 2 Gy, 10 × 0.2 Gy, and a single dose of 2 Gy using a non-coplanar isocentric minibeams irradiation mode were delivered. Anti- γH2AX immunofluorescence, assessing DNA double-strand breaks (DSB), was applied. In the HRS-positive cells, the DSB produced by 10 × 0.2 Gy and 2 Gy, delivered by tens of minibeams, appeared to be more severe, and they provided more highly damaged cells than in the HRS-negative cells, suggesting that more severe DSB are induced in the "SBRT modes" conditions when HRS occurs in tumor. Each SBRT session can be viewed as hyperfractionated dose delivery by means of hundreds of low dose minibeams. Under current SBRT conditions (i.e., low dose per minibeam and not using ultra-high dose-rate), the response of HRS-positive tumors to SBRT may be enhanced significantly. Interestingly, similar conclusions were reached with HRS-positive and HRS-negative untransformed fibroblast cell lines, suggesting that the HRS phenomenon may also impact the risk of post-RT tissue overreactions.

Background: Genitourinary (GU) or gastrointestinal (GI) complications and tumor relapse can occur in the long term after radiotherapy for prostate cancer., Objective: To assess the late tolerance and relapse-free survival (RFS) in patients undergoing hypofractionated stereotactic boost therapy after external beam radiotherapy (EBRT) for intermediate-risk prostate cancer., Design Setting and Participants: Seventy-six patients with intermediate-risk prostate carcinoma between August 2010 and April 2013 were included. The first course delivered a dose of 46 Gy by conventional fractionation; the second course was a boost of 18 Gy (3 × 6 Gy) within 10 d., Outcome Measurements and Statistical Analysis: GU and GI toxicities were evaluated as the primary outcomes. The secondary outcomes were overall survival and RFS. The cumulative incidence of toxicity was calculated using a competing-risk approach. Overall survival and RFS were estimated using the Kaplan-Meier method., Results and Limitations: The median follow-up period was 88 mo (range, 81-99 mo). Sixty (79%) patients were treated with the CyberKnife and 16 (21%) using a linear accelerator. The cumulative incidences of GU and GI grade ≥2 toxicities at 120 mo were 1.4% (95% confidence interval [CI]: 0.1-6.6%) and 11.0% (95% CI: 5.1-19.4%), respectively. The overall survival and RFS rates at 8 yr were 89.1% (95% CI: 77-95%) and 76.9% (95% CI: 63.1-86.1), respectively., Conclusions: A very long follow-up showed low GU and GI toxicities after a hypofractionated stereotactic boost after EBRT for intermediate-risk prostate cancer. Dose escalation of the boost delivered by hypofractionated radiation therapy appears safe for use in future trials., Patient Summary: We found low toxicity and good survival rates after a short and high-precision boost after external beam radiotherapy for intermediate-risk prostate cancer, with a long-term follow-up of 88 mo. This long-term treatment is safe and should be considered in future trials., (© 2023 The Author(s).)

Objective: Pelvic magnetic resonance imaging (MRI) is a key exam used for the initial assessment of loco-regional involvement of cervical cancer. In patients with locally advanced cervical cancer, MRI is used to evaluate the early response to radiochemotherapy before image-guided brachytherapy, the prognostic impact of which we aimed to study., Methods: Patients with locally advanced cervical cancer treated using concomitant radiochemotherapy followed by closure treatment between January 2010 and December 2015 were included in this study. Clinical, anatomopathological, radiological, therapeutic, and follow-up data were evaluated., Results: After applying the inclusion and exclusion criteria to the initially chosen 310 patients, 232 were included for evaluation (median follow-up period, 5.3 years). The median age was 50 years (range, 25-83 years), and the median tumor size was 47.5 mm (range, 0-105 mm). Based on the International Federation of Gynaecology and Obstetrics classification system, 9 patients were in stage IB2; 20, IB3; 2, IIA; 63, IIB; 4, IIIA; 7, IIIB; and 127, IIIC1 or higher. The re-evaluation MRI was performed at the median dose of 55.5 Gy, and median reduction in tumor size was 55.2% (range, -20-100%). There was a difference between the disease-free and overall survival rates of the patients with a tumor response greater or lesser than 50%. The risk of recurrence or death reduced by 39% in patients with a tumor size reduction >50%. The overall 5-year survival rate of patients with a response greater and lesser than 50% were 77.7% and 61.5%, respectively. The 5-year disease-free survival rate for these two groups of patients were 68.8% and 51.5%, respectively., Conclusion: Our study confirms the prognostic impact of tumor size reduction using MRI data obtained after radiochemotherapy in patients with locally advanced cervical cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cordoba, Durand, Escande, Taieb, Amor, Le Deley, Michel, Le Tinier, Hudry, Martinez, Leblanc, Becourt, Abdedaim, Bresson, Lartigau, Mirabel and Narducci.)

Background: Acute severe forms of COVID-19 infection are more likely in cancer patients and growing attention has been given to the persistent symptoms of the disease after severe COVID-19. However, mild illness is the dominant clinical presentation of COVID-19 infection. To investigate patients' behavior and the short- and longer-term pattern of the disease in cancer patients with mild COVID infection, a longitudinal online survey was conducted for 16 months during the pandemic in a large cohort of cancer patients from a French COVID-19 hot spot. An online questionnaire was administered at three time points between the first wave of the pandemic in France and the fourth wave. The questionnaire was completed by 1415 to 2224 patients, which queried patients' demographics, their behavior, and COVID infection patterns. Seventy percent of the patients were female, and 40% had a comorbid condition. More than one-third of the participants had breast cancer, and half were survivors. The rate of infection was 30% during wave 1 and 10% in wave 4; most patients had a mild COVID-19 infection. Twenty-five percent of infected patients during wave 4 did not seek medical advice. At wave 4, 87% of the patients received at least one dose of vaccine. Systematic compliance to shielding measures decreased over time. The short-term pattern of mild COVID changed between wave 1 and wave 4. Twenty-two percent of infected patients experienced persistent signs for more than 6 months with a negative impact on sleep, social behavior, and increased consumption of stress-relieving drugs. Our results showed a high prevalence of long-lasting symptoms in cancer patients with mild COVID-19 infection and inadequate behavior toward the disease and prevention measures among patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hajjaji, Lepoutre, Lakhdar, Bécourt, Bellier, Kaczmarek, Broyelle, Giscard and Lartigau.)

A rare but severe complication of curative-intent radiation therapy is the induction of second primary cancers. These cancers preferentially develop not inside the planning target volume (PTV) but around, over several centimeters, after a latency period of 1-40 years. We show here that normal human or mouse dermal fibroblasts submitted to the out-of-field dose scattering at the margin of a PTV receiving a mimicked patient's treatment do not die but enter in a long-lived senescent state resulting from the accumulation of unrepaired DNA single-strand breaks, in the almost absence of double-strand breaks. Importantly, a few of these senescent cells systematically and spontaneously escape from the cell cycle arrest after a while to generate daughter cells harboring mutations and invasive capacities. These findings highlight single-strand break-induced senescence as the mechanism of second primary cancer initiation, with clinically relevant spatiotemporal specificities. Senescence being pharmacologically targetable, they open the avenue for second primary cancer prevention., Competing Interests: EG, MT, CF, NM, EB, JB, Cd, JN, LS, CD, PB, AV, OM, LP, GG, OP, AP, FC, EL, NP, CA No competing interests declared, (© 2022, Goy et al.)

Radiotherapy is an important component of cancer treatment, with approximately 50% of all cancer patients receiving radiation therapy during their course of illness. Nevertheless, solid tumors frequently exhibit hypoxic areas, which can hinder therapies efficacy, especially radiotherapy one. Indeed, hypoxia impacts the six parameters governing the radiotherapy response, called the « six Rs of radiation biology » (for Radiosensitivity, Repair, Repopulation, Redistribution, Reoxygenation, and Reactivation of anti-tumor immune response), by inducing pleiotropic cellular adaptions, such as cell metabolism rewiring, epigenetic landscape remodeling, and cell death weakening, with significant clinical repercussions. In this review, according to the six Rs, we detail how hypoxia, and associated mechanisms and pathways, impact the radiotherapy response of solid tumors and the resulting clinical implications. We finally illustrate it in hypoxic endocrine cancers through a focus on anaplastic thyroid carcinomas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rakotomalala, Escande, Furlan, Meignan and Lartigau.)

Background/purpose: Dose-escalated external beam radiotherapy (RT) is effective in the control of prostate cancer but is associated with a greater incidence of rectal adverse events. We assessed the dosimetric gain and safety profile associated with implantation of a new biodegradable rectal spacer balloon., Materials/methods: Patients scheduled for image-guided, intensity-modulated RT for intermediate-risk prostate cancer were prospectively included in the French multicenter BioPro-RCMI-1505 study (NCT02478112). We evaluated the dosimetric gain, implantation feasibility, adverse events (AEs), and prostate-cancer-specific quality of life associated with use of the balloon spacer., Results: After a scheduled review of the initial recruitment target of 50 patients by the study's independent data monitoring committee (IDMC), a total of 24 patients (including 22 with dosimetry data) were included by a single center between November 2016 and May 2018. The interventional radiologist who implanted the balloons considered that 86% of the procedures were easy. 20 of the 24 patients (83.3%) received IMRT and 4 (16.7%) received volumetric modulated arc therapy (78-80 Gy delivered in 39 fractions). The dosimetric gains associated with spacer implantation were highly significant (p<0.001) for most variables. For the rectum, the median (range) relative gain ranged from 15.4% (-9.2-47.5) for D20cc to 91.4% (36.8-100.0) for V70 Gy (%). 15 patients (62%) experienced an acute grade 1 AE, 8 (33%) experienced a late grade 1 AE, 1 (4.2%) experienced an acute grade 2 AE, and 3 experienced a late grade 2 AE. No grade 3 AEs were reported. Quality of life was good at baseline (except for sexual activity) and did not markedly worsen during RT and up to 24 months afterwards., Conclusion: The use of a biodegradable rectal spacer balloon is safe, effective and associated with dosimetric gains in modern RT for intermediate-risk prostate cancer., Competing Interests: The authors declare that this study received funding from BioProtect Ltd and AQUILAB. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2021 Latorzeff, Bruguière, Bogart, Le Deley, Lartigau, Marre and Pasquier.)

Background: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France., Patients and Methods: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses., Results: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years., Conclusions: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years., Competing Interests: Disclosure JYB reports research support and honoraria from Troche, BMS, MSD, PharmaMar, Bayer, Deciphera, GSK, Novartis, and AstraZeneca. JPD reports institutional fees for advisory or speaker roles for Genentech, Roche, BMS, MSD, and Novartis, and institutional grants for research projects with Genentech, Roche, BMS, MSD, Debiopharm, and Astra Zeneca. JCS reports shares from AstraZeneca, Daiichi Sankyo, Gritstone, and is also a full-time employee of AstraZeneca from September 2017 to December 2019. All other authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Salvage radiotherapy is the only curative treatment for biochemical progression after radical prostatectomy. Macroscopic recurrence may be found in the prostatic bed. The purpose of our study is to evaluate the effectiveness of salvage radiotherapy of the prostate bed with a boost to the area of the macroscopic recurrence., Material and Methods: From January 2005 to January 2020, 89 patients with macroscopic recurrence in the prostatectomy bed were treated with salvage radiotherapy +/- hormone therapy. The average PSA level prior to radiotherapy was 1.1 ng/mL (SD: 1.6). At the time of biochemical progression, 96% of the patients had a MRI that revealed the macroscopic recurrence, and 58% had an additional choline PET scan. 67.4% of the patients got a boost to the macroscopic nodule, while 32.5% of the patients only underwent radiotherapy of the prostate bed without a boost. The median total dose of radiotherapy was 70 Gy (Min.: 60 - Max.: 74). The most commonly-used regimen was radiotherapy of the prostatectomy bed with a concomitant boost. 48% of the patients were concomitantly treated with hormone therapy., Results: After a median follow-up of 53.7 months, 77 patients were alive and 12 had died, of which 4 following metastatic progression. The 5-year and 8-year survival rates (CI95%) are, respectively, 90.2% (78.9-95.6%) and 69.8% (46.4-84.4%). The 5-year biochemical progression-free survival rate (CI95%) is 50.8% (36.7-63.3). Metastatic recurrence occurred in 11.2% of the patients. We did not find any statistically significant impact from the various known prognostic factors for biochemical progression-free survival. No toxicity with a grade of > or = to 3 was found., Conclusions: Our series is one of the largest published to date. Salvage radiotherapy has its place in the management of patients with biochemical progression with local recurrence in the prostate bed, with an acceptable toxicity profile. The interest of the boost is to be evaluated in prospective trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zaine, Vandendorpe, Bataille, Lacornerie, Wallet, Mirabel, Lartigau and Pasquier.)

Orcid: 0000-0001-6019-7309. In the treatment of breast cancer, intensity-modulated radiation therapy (IMRT) reportedly reduces the high-dose irradiation of at-risk organs and decreases the frequency of adverse events (AEs). Comparisons with conventional radiotherapy have shown that IMRT is associated with lower frequencies of acute and late-onset AEs. Here, we extended a prospective, observational, single-center study of the safety of IMRT to a second investigating center. Patients scheduled for adjuvant IMRT after partial or total mastectomy were given a dose of 50 Gy (25 fractions of 2 Gy over 5 weeks), with a simultaneous integrated boost in patients having undergone conservative surgery. 300 patients were included in the study, and 288 were analyzed. The median follow-up period was 2.1 years. The 2-year disease-free survival rate [95% CI] was 93.4% [89.2-96.0%]. Most AEs were mild. The most common AEs were skin-related-mainly radiodermatitis [in 266 patients (92.4%)] and hyperpigmentation (in 178 (61.8%)). 35% and 6% of the patients presented with grade 2 acute skin and esophageal toxicity, respectively. Only 4 patients presented with a grade 3 event (radiodermatitis). Smoking (odds ratio) [95% CI] = 2.10 [1.14-3.87]; p = 0.017), no prior chemotherapy (0.52 [0.27-0.98]; p = 0.044), and D98% for subclavicular skin (1.030 [1.001-1.061]; p = 0.045) were associated with grade ≥ 2 acute AEs. In a univariate analysis, the mean dose, (p < 0.0001), D2% (p < 0.0001), D50% (p = 0.037), D95% (p = 0.0005), D98% (p = 0.0007), V30Gy (p < 0.0001), and V45Gy (p = 0.0001) were significantly associated with grade ≥ 1 acute esophageal AEs. In a multivariate analysis, D95% for the skin (p < 0.001), D98% for the subclavicular skin and low D95% for the internal mammary lymph nodes were associated with grade ≥ 1 medium-term AEs. The safety profile of adjuvant IMRT after partial or total mastectomy is influenced by dosimetric parameters., Trial Registration: ClinicalTrials.gov NCT02281149.

The objective of this study was to evaluate the acute and medium-term toxicities, the quality of life, and aesthetic results of patients with breast cancer (BC) treated with tomotherapy. This was a prospective study, including patients with BC treated by tomotherapy. Radiation therapy delivered 50 Gy in 25 fractions to the breast or chest wall and to lymph node areas, with a simultaneous integrated boost at a dose of 60 Gy at the tumor bed in cases of breast conservative surgery. We included 288 patients, 168 and 120 treated with breast-conserving surgery and mastectomy respectively. Two hundred sixty patients (90.3%) received lymph node irradiation. Median follow-up was 25 months (6-48). Acute dermatitis was observed in 278 patients (96.5%), mostly grade 1 (59.7%). The aesthetic aspect of the breast at one year was reported as "good" or "excellent" in 84.6% of patients. The patients' quality of life improved over time, especially those treated with chemotherapy. The two-year overall survival and disease-free survival were 97.8% (95% confidence interval (CI): 94.1-99.2%), and 93.4% (95% CI: 89.2-96.0%) respectively. Tomotherapy for locally advanced BC has acceptable toxicity, supporting its use in this indication; however, longer follow-up is needed to assess long-term outcomes.

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.

Purpose: PET/CT is a standard medical imaging used in the delineation of gross tumor volume (GTV) in case of radiation therapy for lung tumors. However, PET/CT could present some limitations such as resolution and standardized uptake value threshold. Moreover, chest MRI has shown good potential in diagnosis for thoracic oncology. Therefore, we investigated the influence of chest MRI on inter-observer variability of GTV delineation. Methods and Materials: Five observers contoured the GTV on CT for 14 poorly defined lung tumors during three contouring phases based on true daily clinical routine and acquisition: CT phase, with only CT images; PET phase, with PET/CT; and MRI phase, with both PET/CT and MRI. Observers waited at least 1 week between each phases to decrease memory bias. Contours were compared using descriptive statistics of volume, coefficient of variation (COV), and Dice similarity coefficient (DSC). Results: MRI phase volumes (median 4.8 cm 3 ) were significantly smaller than PET phase volumes (median 6.4 cm 3 , p = 0.015), but not different from CT phase volumes (median 5.7 cm 3 , p = 0.30). The mean COV was improved for the MRI phase (0.38) compared to the CT (0.58, p = 0.024) and PET (0.53, p = 0.060) phases. The mean DSC of the MRI phase (0.67) was superior to those of the CT and PET phases (0.56 and 0.60, respectively; p < 0.001 for both). Conclusions: The addition of chest MRI seems to decrease inter-observer variability of GTV delineation for poorly defined lung tumors compared to PET/CT alone and should be explored in further prospective studies.

Purpose: This study aimed to describe our institutional experience in the use of stereotactic body radiation therapy (SBRT) for the management of adrenal gland metastases from multiple primary cancers. Materials and Methods: We retrospectively reviewed 31 patients who underwent SBRT as treatment for 33 adrenal gland lesions in the academic radiotherapy department of Oscar Lambret cancer center between May 2011 and September 2018. The primary study endpoints were 1- and 2-year local control rates, defined as the absence of progression at the treatment site based on the response evaluation criteria in solid tumors (RECIST). Toxicities were graded in accordance with the Common Terminology Criteria for Adverse Events version 4.03. Results: The average tumor volume was 33.5 cm 3 (standard deviation: 51.7 cm 3 ), and the prescribed dose ranged from 30 to 55 Gy given in 3-9 fractions. The median biological effective dose was 112.5 Gy (range: 45-115.5 Gy), assuming α/β = 10. Considering progression at distant sites or death as competing events, the 1- and 2-year actuarial local control rates were 96.5% (95% confidence interval: 84.9-99.7) and 92.6% (95% confidence interval: 79.2-98.7), respectively. According to RECIST, a complete response was achieved in 10 (32.3%) lesions, a partial response in 10 (32.3%) lesions, and stability in 8 (25.8%) lesions. Three patients presented with local relapse at 8.8, 14, and 49.4 months. After a median follow-up of 18 months (range: 4.4-66.4), the median overall survival was 33.5 months (95% confidence interval: 17-not reached), while the median progression-free survival was 7.4 months (95% confidence interval: 3.8-14.1). Treatment-related toxicity was grade 1 or 2 in 42.4% of patients, including nausea (27.3%), abdominal pain (18.2%), vomiting (15.2%), and asthenia (9.1%). None of the patients developed acute grade ≥3 or late toxicity. Conclusion: SBRT seems to be a safe and effective treatment for adrenal gland metastases in patients whose primary tumor and metastatic spread are controlled by systemic treatment. With a 2-year local control rate of 92.6%, SBRT may be considered as one of the first-line treatments in oligometastatic patients with adrenal metastases.

Introduction: Prostate cancer is the third most important cancer in terms of mortality in men. No standard local treatment exists for patients with an intraprostatic recurrence after radiotherapy. Stereotatic body radiotherapy (SBRT) could be a curative treatment for local recurrence. The phase I/II primary objective is the selection of the recommended dose for salvage-SBRT and to estimate the efficacy., Methods and Analysis: We plan to perform a multicentre prospective phase I/II study including at least 47 patients. Eligible patients are patients with biochemical recurrence occurring at least 2 years after external radiotherapy for prostatic adenocarcinoma by the Phoenix definition (prostate-specific antigen (PSA) nadir +2 ng/mL) and histologically proven intraprostatic recurrence only (stage T1-T2 on relapse, PSA level ≤10 ng/mL, PSA doubling time >10 months, absence of pelvic or metastatic recurrence proven by choline or PSMA positron emission tomography scan, and pelvic and prostatic assessment by multiparametric MRI). The phase I primary objective is the selection of the recommended dose for salvage-SBRT (5×6, 6×6 or 5×5 Gy) based on dose-limiting toxicity (DLT). The dose of salvage-SBRT will be selected using a time-to-event continual reassessment method based on DLT defined as grade ≥3 gastrointestinal or urinary toxicity or any other grade 4 adverse event. The phase II primary outcome is to estimate the efficacy of the salvage-SBRT in terms of biochemical relapse-free survival rate (Phoenix definition: increase in serum total PSA ≥2 ng/mL above the nadir). Phase II secondary outcomes are acute and late toxicities, quality of life, clinical progression-free survival defined as the time interval between the date of registration and the date of clinical progression or death irrespective of the cause., Ethics and Dissemination: The study has received ethical approval from the Ethics committee 'Ile-de-France III'. Academic dissemination will occur through publication and conference presentations., Trial Registration Number: NCT03438552., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The aim of this study was to assess, in a large series, the efficacy and tolerance of post-operative adjuvant hypofractionated stereotactic radiation therapy (HFSRT) for brain metastases (BMs). Materials and Methods: Between July 2012 and January 2017, 160 patients from 2 centers were operated for BM and treated by HFSRT. Patients had between 1 and 3 BMs, no brainstem lesions or carcinomatous meningitis. The primary endpoint was local control. Secondary endpoints were distant brain control, overall survival (OS) and tolerance to HFSRT. Results: 73 patients (46%) presented with non-small cell lung cancer (NSCLC), 23 (14%) had melanoma and 21 (13%) breast cancer. Median age was 58 years (range, 22-83 years). BMs were synchronous in 50% of the cases. The most frequent prescription regimens were 24 Gy in 3 fractions ( n = 52, 33%) and 30 Gy in 5 fractions ( n = 37, 23%). Local control rates at 1 and 2 years were 88% [95%CI, 81-93%] and 81% [95%CI, 70-88%], respectively. Distant control rate at 1 year was 48% [95%CI, 81-93%]. In multivariate analysis, primary NSCLC was associated with a significant reduction in the risk of death compared to other primary sites (HR = 0.57, p = 0.007), the number of extra-cerebral metastatic sites (HR = 1.26, p = 0.003) and planning target volumes (HR = 1.15, p = 0.012) were associated with a lower OS. There was no prognostic factor of time to local progression. Median OS was 15.2 months [95%CI, 12.0-17.9 months] and the OS rate at 1 year was 58% [95% CI, 50-65%]. Salvage radiotherapy was administered to 72 patients (45%), of which 49 received new HFSRT. Ten (7%) patients presented late grade 2 and 4 (3%) patients late grade 3 toxicities. Thirteen (8.9%) patients developed radiation necrosis. Conclusions: This large multicenter retrospective study shows that HFSRT allows for good local control of metastasectomy tumor beds and that this technique is well-tolerated by patients.

Radiotherapy after breast conserving surgery and mastectomy with node positive disease has been shown to reduce risk of recurrence and mortality in the treatment of breast cancer. Intensity-modulated radiation therapy (IMRT) after conservative surgery offers several advantages over conventional RT including improved acute and late toxicity and quality of life (QoL). We undertook this study to prospectively evaluate acute (≤90 days after last dose of radiotherapy) and long-term (>90 days) cutaneous, esophageal, and fibrosis toxicity and QoL in breast cancer patients treated by adjuvant IMRT after breast surgery. We included patients with complex volumes for which 3D RT does not allow a good coverage of target volumes and sparing organs at risk. We report here an interim analysis with a median follow-up of 13.1 months (range, 6.5-25.9 months). Most of the acute toxicity was cutaneous (95.9%) and oesophageal (59.6%), and mostly grade 1 and 2. Medium-term cutaneous toxicity rate was 25.6%, and mostly grade 1. Medium-term esophageal toxicity was rare (1.8%). In this series acute oesophageal toxicity was found to be associated with dosimetric factors. QoL was well preserved throughout the study, and aesthetic outcomes were good. Based on these data, tomotherapy may be a favorable alternative to other techniques in patients needing a complex irradiation of the breast and lymph node volumes.

Objectives: To report the preliminary results of salvage re-irradiation in the prostatic bed after radical prostatectomy and salvage external beam radiation therapy (EBRT) using robotic stereotactic body radiation therapy (SBRT) with Cyberknife® for local recurrence of prostate cancer. Materials and Methods: Retrospective monocentric analysis was performed on patients treated with SBRT for isolated macroscopic recurrence in the prostatic bed. All patients had radical prostatectomy and salvage or adjuvant EBRT. Local recurrence was documented using magnetic resonance imaging (MRI) and positron emission tomography (PET). Biochemical recurrence was defined as 2 rises in prostate-specific antigen (PSA) of ≥ 0.2 ng/mL above nadir. Internal gold fiducials were used for the tracking of tumor motion during SBRT. The prescription dose was 36 Gy in 6 fractions for all patients. Toxicity was scored according to the CTCAE v4.0. Results: Between July 2011 and November 2017, 12 patients were treated with SBRT for prostatic bed recurrence with a median follow-up of 34.2 (range, 3.5-64.4) months. Isolated non-metastatic recurrence in the prostatic bed was seen at MRI and PET imaging. Two patients were treated with 6 months androgen deprivation therapy (ADT) concomitant with re-irradiation. The median planning target volume was 4.5 cm 3 (range, 1.2-13.3). A PSA decrease after SBRT was found in 10 (83%) patients. The 1 and 2 years biochemical recurrence-free survival rates were 79 and 56%, respectively. Biochemical recurrence was observed for 6 patients (50%) after a median time of 18 (4-42) months. Toxicity showed: 3 patients (25%) with grade 1 cystitis and 1 patient (8%) with acute grade 2 proctitis at 4 months. One patient (13%) had grade 1 cystitis at 12 months. Conclusion: Re-irradiation for local recurrence in the prostatic bed using Cyberknife® after surgery and salvage or adjuvant EBRT is well-tolerated and associated with 2 years biochemical recurrence-free survival rates of 56%. Longer follow-up and larger series are necessary.

We evaluated efficacy and tolerance of hypofractionated stereotactic radiation treatment (hFSRT) in the management of intracranial meningiomas. Between December 2008 and June 2016, 126 patients with 136 intracranial meningiomas were treated with robotic hFSRT. hFSRT was performed as primary irradiation and as a salvage option for the local recurrence after prior radiotherapy. The median prescription dose was 25 Gy (12-40) with a median number of fractions of 5 (3-10). After a median follow-up of 20.3 months (range 1-77 months), the 24-months local control (LC) rate was 81% in the primary hFSRT group and 39% after hFSRT in the re-irradiation group (p=0.002). The clinical control rate of symptoms in the overall population was 95% (95% CI: 89-98%). Progression-free survival (PFS) in the overall population at 24 months was 70% (95% CI: 60%-79%). In the primary hFSRT group, PFS was significantly lower with the most hypofractionated schedules of 21-23 Gy in 3 fractions vs. 25-40 Gy in 5-10 fractions: 62% vs. 92% (p = 0.0006). The incidence of radionecrosis at 24 months was significantly lower in the primary hFSRT group, at 2% vs. 20% in the re-irradiation hFSRT group (p = 0.002).

We evaluated the feasibility of using the kinetic of diffusion-weighted MRI (DWI) and the normalized apparent coefficient diffusion (ADC) map value as an early biomarker in patients treated by external beam radiotherapy (EBRT). Twelve patients were included within the frame of a multicenter phase II trial and treated for intermediate risk prostate cancer (PCa). Multiparametric MRI was performed before treatment (M0) and every 6 months until M24. Association between nADC and PSA or PSA kinetic was evaluated using the test of nullity of the Spearman correlation coefficient. The median rates of PSA at the time of diagnosis, two years and four years after EBRT were 9.29 ng/ml (range from 5.26 to 17.67), 0.68 ng/ml (0.07-2.7), 0.47 ng/ml (0.09-1.39), respectively. Median nADC increased from 1.14 × 10 -3 mm 2 /s to 1.59 × 10 -3 mm 2 /s between M0 and M24. Only one patient presented a decrease of nADC (1.35 × 10 -3  mm 2 /s and 1.11 × 10 -3  mm 2 /s at M0 and M12 respectively). The increase in nADC at M6 was correlated with PSA decrease at M18, M24 and M30 (p < 0.05). The increase in nADc at M12 was correlated with PSA decrease at M36 (p = 0.019). Early nADC variation were correlated with late PSA decrease for patients with PCa treated by EBRT.