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Background: Trastuzumab (T) combined with chemotherapy has been recently shown to improve outcome in HER2-positive breast cancer (BC). The aim of this study was to evaluate the toxic effects of concurrent radiation therapy (RT) and T administration in the adjuvant setting. Patients and methods: Data of 146 patients with stages II–III HER2-positive BC were recorded. Median age was 46 years. In all, 32 (23%) and 114 (77%) patients received a weekly and a 3-week T schedule, respectively. A median dose of 50 Gy was delivered after surgery. Internal mammary chain (IMC) was irradiated in 103 (71%) patients. Results: Grade >2 dermatitis and esophagitis were noted in 51% and 12%, respectively. According to the Common Toxicity Criteria v3.0 scale and HERA (HERceptin Adjuvant) trial criteria, respectively, 10% and 6% of the patients had a grade =2 of left ventricular ejection fraction (LVEF) decrease after RT. Multivariate analyses revealed two independent prognostic factors: weekly T administration (for LVEF decrease) and menopausal status (for dermatitis). Higher level of T cumulative dose (>1600 mg) was only borderline of statistical significance for acute esophagitis toxicity. Conclusion: We showed that weekly concurrent T and RT are feasible in daily clinical practice with, however, a decrease of LVEF. Cardiac volume sparing and patient selections for IMC irradiation are highly recommended. Longer follow-up is warranted to evaluate late toxic effects. [ABSTRACT FROM AUTHOR]

With the emergence of high-precision radiotherapy technologies such as stereotactic ablative radiotherapy (SABR), MR guided brachytherapy, image guided intensity modulated photon and proton radiotherapy and most recently daily adaptive radiotherapy, reirradiation is increasingly recognized as a viable treatment option for many patients. This includes those with recurrent, metastatic or new malignancies post initial radiotherapy. The primary challenge in reirradiation lies in balancing tumor control against the risk of severe toxicity from cumulative radiation doses to previously irradiated normal tissue. Although technology for precise delivery has advanced at a fast pace, clinical practice of reirradiation still mostly relies on individual expertise, as prospective evidence is scarce, the level of reporting in clinical studies is not standardized and of low quality - especially with respect to cumulative doses received by organs at risk. A recent ESTRO/EORTC initiative proposed a standardized definition of reirradiation and formulated general requirements for minimal reporting in clinical studies [1]. As a consequence we found it timely to convene for an international and interdisciplinary meeting with experts in the field to summarize the current evidence, identify knowledge gaps and explore which best practices can be derived for safe reirradiation. The meeting was held on 15.06.2023 in Zurich and was endorsed by the scientific societies SASRO, DEGRO and ESTRO. Here, we report on available evidence and research priorities in the field of reirradiation, as discussed during the meeting., 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.)

The impact of curative radiotherapy mainly depends on the total dose delivered to the tumor. However, despite recent technological advances, the dose delivered to surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. In the same population treated at one center with the same technique, individual radiosensitivity clearly exists, particularly in terms of late side effects that are, in principle, non-reversible. This article details the history of the radiation-induced lymphocyte apoptosis assay, from preclinical data to multicenter clinical trials. It puts the performance of such assays into perspective to define the optimal clinical situations for its use in daily practice., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: to evaluate an SRT approach in patients with at least 10 lesions at the time of BM initial diagnosis., Methods: This is a monocentric prospective cohort of patients treated by SRT, followed by a brain MRI every two months. Subsequent SRT could be delivered in cases of new BMs during follow-up. The main endpoints were local control rate (LCR), overall survival (OS), and strategy success rate (SSR). Acute and late toxicity were evaluated., Results: Seventy patients were included from October 2014 to January 2019, and the most frequent primary diagnosis was non-small-cell lung cancer (N = 36, 51.4%). A total of 1174 BMs were treated at first treatment, corresponding to a median number of 14 BMs per patient. Most of the patients (N = 51, 72.6%) received a single fraction of 20-24 Gy. At 1 year, OS was 62.3%, with a median OS of 19.2 months, and SSR was 77.8%. A cumulative number of 1537 BM were treated over time, corresponding to a median cumulative number of 16 BM per patient. At 1-year, the LCR was 97.3%, with a cumulative incidence of radio-necrosis of 2.1% per lesion. Three patients (4.3%) presented Grade 2 toxicity, and there was no Grade ≥ 3 toxicity. The number of treated BMs and the treatment volume did not influence OS or SSR ( p > 0.05)., Conclusions: SRT was highly efficient in controlling the BM, with minimal side effects. In this setting, an SRT treatment should be proposed even in patients with ≥10 BMs at diagnosis.

Objectives: We aimed to compare the functional and radiographical outcomes of reconstruction of acute unstable acromioclavicular joint (ACJ) dislocation using Hook Plate (HP) versus Suture Endobutton (SE) fixation techniques., Methods: Forty-six consecutive patients with grade III to V ACJ dislocation according to Rockwood classification who underwent either HP or SE fixation in the period between January 2017 and June 2020 were evaluated. The treatment modalities were divided into either HP or SE fixation. The radiological assessment included standard anterior-posterior (AP) views to evaluate coracoclavicular (CC) distances for vertical reduction., Results: CC distances were grouped as preoperative (CC 1 ), early postoperative (CC 2 ), and late postoperative (CC 3 ). The distance variance between CC 2 and CC 3 was referred as ΔCC (CC 3 - CC 2 ). A statistically significant difference was found in ΔCC between the two groups (p=0.008). ΔCC was significantly higher in the SE group compared to the HP group (p<0.05). The Constant and UCLA Scores of patients in the SE group were found to be significantly higher than in the HP group patients., Conclusion: Clinical outcomes were more satisfactory in patients with acute unstable ACJ dislocation who underwent SE compared to HP procedures, at the end of the first year. Evidence Level IV; Case Series ., Competing Interests: All authors declare no potential conflict of interest related to this article.

A patient with a cutaneous lymphoma was treated on the same day for 2 distinct tumors using a 15 Gy single electron dose given in a dose rate of 0.08 Gy/second versus 166 Gy/second. Comparing the two treatments, there was no difference for acute reactions, late effects at 2 years and tumor control., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Personalized treatment and precision medicine have become the new standard of care in oncology and radiotherapy. Because treatment outcomes have considerably improved over the last few years, permanent side-effects are becoming an increasingly significant issue for cancer survivors. Five to ten percent of patients will develop severe late toxicity after radiotherapy. Identifying these patients before treatment start would allow for treatment adaptation to minimize definitive side effects that could impair their long-term quality of life. Over the last decades, several tests and biomarkers have been developed to identify these patients. However, out of these, only the Radiation-Induced Lymphocyte Apoptosis (RILA) assay has been prospectively validated in multi-center cohorts. This test, based on a simple blood draught, has been shown to be correlated with late radiation-induced toxicity in breast, prostate, cervical and head and neck cancer. It could therefore greatly improve decision making in precision radiation oncology. This literature review summarizes the development and bases of this assay, as well as its clinical results and compares its results to the other available assays.

Background: For patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC), surgery (S) followed by radiotherapy (RT) is a standard of care. Randomized controlled trials have shown that postoperative chemoradiation (CRT) increased the locoregional control (LRC) and overall survival (OS) in patient with R1-resection margin and/or extranodal extension (ENE). ENE has been introduced in the 8th TNM staging classification since its presence has been shown to have an independent adverse prognostic impact. The data supporting this finding were however mainly collected in the pre-CRT era., Objectives: The objective of this study was to challenge the adverse prognostic factor of ENE in the era of CRT., Methods: A retrospective cohort study was performed to evaluate patients diagnosed with LAHNSCC and undergoing a treatment by S and postoperative RT or CRT in Centre Léon Bérard, Lyon, France between 2003 and 2018. Patients with oral cavity, oropharyngeal, laryngeal and hypopharyngeal SCC were included., Results: 439 patients were included in the study. For patients with non-oropharyngeal p16-positive tumors without ENE, five-year OS, local control, and regional control (RC) reached 63.7%, 86.1%, and 94.9%, respectively; corresponding figures for patients with ENE reached, 42.6%, 77.5%, and 81.1%, respectively (p-value of 0.0006, 0.167, and 0.0005). In multivariable analysis, for non-oropharyngeal p16-positive tumors, ENE remained a poor prognostic factor for OS (RR = 1.74, 95%, CI = 1.16-2.61, p = 0.0069) and RC (RR 3.60, 95% CI =: 1.64-7.87, p = 0.0013)., Conclusion: In the era or postoperative chemoradiation, pathological ENE remains an adverse prognostic factor for OS and RC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: The current phase III EORTC 1420 Best-of trial (NCT02984410) compares the swallowing function after transoral surgery versus intensity modulated radiotherapy (RT) in patients with early-stage carcinoma of the oropharynx, supraglottis and hypopharynx. We report the analysis of the Benchmark Case (BC) procedures before patient recruitment with special attention to dysphagia/aspiration related structures (DARS)., Materials and Methods: Submitted RT volumes and plans from participating centers were analyzed and compared against the gold-standard expert delineations and dose distributions. Descriptive analysis of protocol deviations was conducted. Mean Sorensen-Dice similarity index (mDSI) and Hausdorff distance (mHD) were applied to evaluate the inter-observer variability (IOV)., Results: 65% (23/35) of the institutions needed more than one submission to achieve Quality assurance (RTQA) clearance. OAR volume delineations were the cause for rejection in 53% (40/76) of cases. IOV could be improved in 5 out of 12 OARs by more than 10 mm after resubmission (mHD). Despite this, final IOV for critical OARs in delineation remained significant among DARS by choosing an aleatory threshold of 0.7 (mDSI) and 15 mm (mHD)., Conclusions: This is to our knowledge the largest BC analysis among Head and neck RTQA programs performed in the framework of a prospective trial. Benchmarking identified non-common OARs and target delineations errors as the main source of deviations and IOV could be reduced in a significant number of cases after this process. Due to the substantial resources involved with benchmarking, future benchmark analyses should assess fully the impact on patients' clinical outcome.

Introduction: Local recurrence after lung SBRT for early stage NSCLC is rare but its treatment remains a challenge due to limited surgical options. We report a case series of 5 patients treated by stereotactic lung salvage reirradiation for local relapse after a previous lung SBRT., Material and Methods: Included patients presented an isolated primary lung relapse within at least the 50% isodose of the previous SBRT treatment. Typical reirradiation schedule was 60 Gy in 8 fractions at isodose 80% and was delivered by Cyberknife® using Synchrony® fiducial tracking system. Dose summations were performed to evaluate the safety of the reirradiation., Results: We identified 5 patients presenting peripheral lesions. All reirradiated lesions were locally controlled after a median follow-up of 11.1 months (6,7-12,2), while PFS at 6 months was 60% (n = 3). We did not notice any Grade 3 or more acute or late adverse event., Conclusion: We observed encouraging short-term outcome of lung SBRT reirradiation in patients presenting isolated local relapse of an early-stage NSCLC. Further studies are necessary to confirm the safety and efficiency of this salvage treatment approach., 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., (© 2021 The Authors.)

Background: Stage III N2 non-small cell lung cancer (NSCLC) is a very heterogeneous disease associated with a poor prognosis. A number of therapeutic options are available for patients with Stage III N2 NSCLC, including surgery [with neoadjuvant or adjuvant chemotherapy (CTx)/neoadjuvant chemoradiotherapy (CRT)] or CRT potentially followed by adjuvant immunotherapy. We have no clear evidence demonstrating a significant survival benefit for either of these approaches, the selection between treatments is not always straightforward and can come down to physician and patient preference. The very heterogeneous definition of resectability of N2 disease makes the decision-making process even more complex., Methods: We evaluated the treatment strategies for preoperatively diagnosed stage III cN2 NSCLC among Swiss thoracic surgeons and radiation oncologists. Treatment strategies were converted into decision trees and analysed for consensus and discrepancies. We analysed factors relevant to decision-making within these recommendations., Results: For resectable "non-bulky" mediastinal lymph node involvement, there was a trend towards surgery. Numerous participants recommend a surgical approach outside existing guidelines as long as the disease was resectable, even in multilevel N2. With increasing extent of mediastinal nodal disease, multimodal treatment based on radiotherapy was more common., Conclusions: Both, surgery- or radiotherapy-based treatment regimens are feasible options in the management of Stage III N2 NSCLC. The different opinions reflected in the results of this manuscript reinforce the importance of a multidisciplinary setting and the importance of shared decision-making with the patient., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-1210). The series “Radiotherapy in thoracic malignancies” was commissioned by the editorial office without any funding or sponsorship. PMP received an educational grant from AstraZeneca (educational grant to the Institution); outside the submitted work, he also received research support and educational grants to the department from Celgene, Roche and Takeda. The authors have no other conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Background and Purpose: Early-stage Hodgkin lymphoma (HL) is a highly curable disease but the treatment can induce late complications many years later. Irradiation of the healthy heart is inevitable during radiation treatment of mediastinal sites. We developed a novel method to induce a prolonged apnea-like state that can help decrease the dose to organs at risk during radiation therapy. We present the results of the first 8 HL patients treated routinely with percussion assisted radiation therapy (PART) in our clinic., Material and Methods: We used a newly developed high-frequency non-invasive ventilation system to suppress respiratory motion for prolonged periods and push the heart away from the treated volume., Results: All 8 patients were able to rapidly learn the technique and had an advantage to be treated by PART. We lowered the mean heart dose by an average of 3 Gy with similar target coverage compared to a classical free breathing treatment plan. They were all treated for 15 radiotherapy sessions by PART without any notable side effects., Conclusions: Percussion assisted radiation therapy can be used routinely to reduce the dose to the heart in Hodgkin lymphoma., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2019. Published by Elsevier B.V.)

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints., Competing Interests: Conflict of interest statement A.I. declares the following relevant financial activities outside the submitted work: has received Grants from Transgene, Sanofi, Air Liquide, Nutritheragene; has received travel funding from Leo Pharma; Grant research support and travel funding from Carthera. J.G. declare the following financial personnal fees for activities outside the submitted work or served as consultant or advisory board/ has received symposium and travel funding from: Roche-Genentech, Novartis, Onxeo, Dachii Sankyo, MSD, Isai, Genomic Health, Ipsen, Macrogenics, Pfizer, Mylan, Lilly, Immunomedics, Sandoz. J.-P.S. declares the following financial personnal fees for activities outside the submitted work or served as consultant or advisory board/ has received Symposium and travel funding from: MSD, Lilly, Roche, Mylan, Pfizer, PFOncology, LeoPharma, Novartis, Biogaran, Astra Zeneca, Gilead, BMS. All the other authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Postoperative radiation therapy (poRT) of intracranial/skull base chondrosarcomas (CHSs) is standard treatment. However, consensus is lacking for poRT in extracranial CHS (eCHS) owing to their easier resectability and intrinsic radioresistance. We assessed the practice and efficacy of poRT in eCHS., Methods and Materials: This multicentric retrospective study of the French Sarcoma Group/Rare Cancer Network included patients with eCHS who were operated on between 1985 and 2015. Inverse propensity score weighting (IPTW) was used to minimize poRT allocation biases., Results: Of 182 patients, 60.4% had bone and 39.6% had soft-tissue eCHS. eCHS were of conventional (31.9%), myxoid (28.6%; 41 extraskeletal, 11 skeletal), mesenchymal (9.9%), or other subtypes. En-bloc surgery with complete resection was performed in 52.6% and poRT in 36.8% of patients (median dose, 54 Gy). Irradiated patients had unfavorable initial characteristics, with higher grade and incomplete resection. Median follow-up time was 61 months. Five-year incidence of local relapse was 10% with poRT versus 21.6% without (P = .050). Using the IPTW method, poRT reduced the local relapse risk (hazard ratio, 0.27; 95% confidence interval, 0.14-0.52; P < .001). Five-year disease-free survival (DFS) was 71.8% with poRT and 64.2% without (P = .680). Using the IPTW method, poRT improved DFS (hazard ratio, 0.51; 95% confidence interval, 0.30-0.85; P = .010). The benefit of poRT on local relapse and DFS was confirmed after exclusion of the extraskeletal subtype. There was no difference in overall survival. Prognostic factors of poorer DFS in multivariate analysis were deeper location, higher grade, incomplete resection, and no poRT., Conclusions: poRT should be offered in patients with eCHS and high-grade or incomplete resection, regardless of the histologic subtype., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ventricular tachycardia (VT) caused by myocardial scaring bears a significant risk of mortality and morbidity. Antiarrhythmic drug therapy (AAD) and catheter ablation remain the cornerstone of VT management, but both treatments have limited efficacy and potential adverse effects. Stereotactic body radiotherapy (SBRT) is routinely used in oncology to treat non-invasively solid tumors with high precision and efficacy. Recently, this technology has been evaluated for the treatment of VT. This review presents the basic underlying principles, proof of concept, and main results of trials and case series that used SBRT for the treatment of VT refractory to AAD and catheter ablation., (Copyright © 2020 Jumeau, Ozsahin, Schwitter, Elicin, Reichlin, Roten, Andratschke, Mayinger, Saguner, Steffel, Blanck, Vozenin, Moeckli, Zeverino, Vallet, Herrera-Siklody, Pascale, Bourhis and Pruvot.)

Objective: In the present study, we aimed to compare serum irisin levels in patients with fibromyalgia syndrome (FMS) and healthy control subjects and also investigate the relationship between irisin, disease activity and inflammation markers in patients., Methods: A total of 84 women, including 48 patients who were diagnosed with FMS and 36 healthy controls, were included in this study. The demographic characteristics of the patients and control group were recorded. VAS for pain and the Fibromyalgia Impact Questionnaire for the assessment of the physical function of the patients, SF36 was used for quality of life, and accompanying Beck Depression Inventory to assess depression was used. Blood samples were taken for analysis that irisin, and inflammatory markers of the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), high-sensitivity C-reactive protein (hs-CRP) and neutrophil/lymphocyte ratio (NLO). Serum irisin levels were determined using the Enzyme-Linked Immunosorbent Assay (ELISA) method., Results: Serum irisin level of the patients with FMS had no significant differences compared with the healthy control group. When we compared the values of ESR, CRP, hsCRP, NLO with FMS patients and healthy controls, there was no significant difference found between them (p>0.05). There was no significant correlation between inflammatory markers and level of serum irisin (p>0.05). In patients, there was no significant correlation between inflammatory markers and level of serum irisin (p>0.05)., Conclusion: Irisin, which is a myokine, was determined to have no significant role in the pathogenesis of FMS. Irisin had no association with disease activity and inflammatory markers. Also, the inflammation hypothesis was not supported, which suggested in FMS., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2019 by Istanbul Northern Anatolian Association of Public Hospitals.)

The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the target volume. Tumor sensitivity to radiotherapy may be particularly inconstant depending on location, histology, somatic genetic parameters and the capacity of the immune system to infiltrate the tumor. In addition, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. In a same population treated in one center with the same technique, it appears that individual radiosensitivity clearly exists, namely in terms of late side effects that are in principle non-reversible. This review details the different radiobiological approaches that have been developed to better predict the tumor response but also the radiation-induced late effects., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: When compared to conventional radiotherapy (RT) in pre-clinical studies, FLASH-RT was shown to reproducibly spare normal tissues, while preserving the anti-tumor activity. This marked increase of the differential effect between normal tissues and tumors prompted its clinical translation. In this context, we present here the treatment of a first patient with FLASH-RT., Material & Methods: A 75-year-old patient presented with a multiresistant CD30+ T-cell cutaneous lymphoma disseminated throughout the whole skin surface. Localized skin RT has been previously used over 110 times for various ulcerative and/or painful cutaneous lesions progressing despite systemic treatments. However, the tolerance of these RT was generally poor, and it was hypothesized that FLASH-RT could offer an equivalent tumor control probability, while being less toxic for the skin. This treatment was given to a 3.5-cm diameter skin tumor with a 5.6-MeV linac specifically designed for FLASH-RT. The prescribed dose to the PTV was 15 Gy, in 90 ms. Redundant dosimetric measurements were performed with GafChromic films and alanine, to check the consistency between the prescribed and the delivered doses., Results: At 3 weeks, i.e. at the peak of the reactions, a grade 1 epithelitis (CTCAE v 5.0) along with a transient grade 1 oedema (CTCAE v5.0) in soft tissues surrounding the tumor were observed. Clinical examination was consistent with the optical coherence tomography showing no decrease of the thickness of the epidermis and no disruption at the basal membrane with limited increase of the vascularization. In parallel, the tumor response was rapid, complete, and durable with a short follow-up of 5 months. These observations, both on normal skin and on the tumor, were promising and prompt to further clinical evaluation of FLASH-RT., Conclusion: This first FLASH-RT treatment was feasible and safe with a favorable outcome both on normal skin and the tumor., (Copyright © 2019. Published by Elsevier B.V.)

Randomized trials demonstrated similar overall survival between mastectomy and breast-conservative surgery followed by adjuvant radiation therapy. Breast-conservative surgery, with adjuvant radiation therapy, with or without neoadjuvant systemic therapy has become the standard of care for women with early or locally advanced breast cancer. Nevertheless, certain cardiac, lung or cutaneous toxicities may alter the long-term body image and the quality of life of a limited number of patients who consider having had "overtreatment" or treatment outside the best knowledge of science. In case of low-risk breast cancer, several trials have evaluated the carcinologic outcome in absence of radiation therapy after breast-conservative surgery. Local recurrences increased in case of breast-conservative surgery alone but without impact on overall survival. Multiple debates have emerged in order to select the most appropriate evaluation criteria. Finally, a large consensus has considered that reducing local recurrences is important but with modern technologies and after identifying patients of individual radiosensitivity. Indeed, in case of a low absolute risk of local recurrence, radiation therapy techniques have been developed to allow a focal treatment especially for patients with high risk of developing late effects. This kind of compromise takes into account the reduction risk of local recurrences but also the probability of developing radiation-induced cutaneous sequelae. In the same way, for patients considered at high risk of recurrence, the huge volumes need specific techniques to better cover the targets while protecting the surrounding critic organs such as heart and lung. Intensity-modulated radiation therapy and the local high boost may help to decrease local recurrences of these more extended and aggressive diseases while considering the individual radiosensitivity that paves the way of long-term sequelae. In this article, we detail a personalized approach of breast radiation therapy considering the absolute risk of local recurrences and the probability of radiation-induced toxicity appearance., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Over the past decades, technological advances have transformed radiation therapy (RT) into a precise and powerful treatment for cancer patients. Nevertheless, the treatment of radiation-resistant tumors is still restricted by the dose-limiting normal tissue complications. In this context, FLASH-RT is emerging in the field. Consisting of delivering doses within an extremely short irradiation time, FLASH-RT has been identified as a promising new tool to enhance the differential effect between tumors and normal tissues. Indeed, preclinical studies on various animal models and a veterinarian clinical trial have recently shown that compared to conventional dose-rate RT, FLASH-RT could control tumors while minimizing normal tissue toxicity. In the present review, we summarize the main data supporting the clinical translation of FLASH-RT and explore its feasibility, the key irradiation parameters and the potential technologies needed for a successful clinical translation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: Larynx cancer represents one of the most frequently diagnosed head and neck malignancies, which is most often confined to the glottic area. The aim of this study was to report the oncological outcome and identify prognostic factors in early-stage glottic squamous cell carcinoma treated with radiotherapy. Material and Methods: Patients ( n = 761) diagnosed and treated in 10 centers between 1990 and 2015 were retrospectively analyzed. Probabilities of loco-regional control (LRC) and overall survival (OS) were calculated and possible prognostic factors were analyzed using Cox proportional hazards models. Results: The median follow-up was 63 months (range: 2-243). Three hundred and sixty-four, 148 and 249 patients had cT1a, cT1b, and cT2 stage I-II disease, respectively. Five and 10-years LRC/OS rates in the whole cohort were 83/82% and 80/68%, respectively. Three patients developed distant recurrences. In univariate analysis, male sex (HR: 3.49; 95% CI: 1.47-11.37; p < 0.01), T2 vs. T1a (HR: 1.62; 95% CI: 1.08-2.43; p = 0.02) and anterior commissure involvement (ACI) (HR: 1.66; 95% CI: 1.38-2.45; p < 0.01) were associated with impaired LRC. In multivariate analysis, male sex (HR: 3.42; 95% CI: 1.44-11.17; p < 0.01) and ACI (HR: 1.51; 95% CI: 1.01-2.28; p = 0.047) remained poor prognostic factors. No relation of treatment technique and biologically equivalent dose (BED) to oncological outcome was identified except for higher BED 10 (L = 25; T = 1) yielding better LRC in T1a tumors ( p = 0.04) in univariate analyses. Conclusion: Our results highlight the negative impact of ACI on tumor control. A less-expected finding was the impact of sex on tumor control. Further research is needed to validate its prognostic value and investigate any related biologic or behavioral factors, which may be modified to improve oncologic outcome., (Copyright © 2019 Elicin, Ermiş, Oehler, Aebersold, Caparrotti, Zimmermann, Studer, Henke, Adam, Anschuetz, Ozsahin, Guckenberger, Shelan, Kaydıhan, Riesterer, Prestwich, Spielmann, Giger and Şen.)

Background: Biomarkers for predicting late normal tissue toxicity to radiotherapy are necessary to personalize treatments and to optimize clinical benefit. Many radiogenomic studies have been published on this topic. Conversely, proteomics approaches are not much developed, despite their advantages., Methods: We used the isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approach to analyze differences in protein expression levels in ex-vivo irradiated (8 Gy) T lymphocytes from patients with grade ≥ 2 radiation-induced breast fibrosis (grade ≥ 2 bf+) and patients with grade < 2 bf + after curative intent radiotherapy. Patients were selected from two prospective clinical trials (COHORT and PHRC 2005) and were used as discovery and confirmation cohorts., Results: Among the 1979 quantified proteins, 23 fulfilled our stringent biological criteria. Immunoblotting analysis of four of these candidate proteins (adenylate kinase 2, AK2; annexin A1; heat shock cognate 71 kDa protein; and isocitrate dehydrogenase 2) confirmed AK2 overexpression in 8 Gy-irradiated T lymphocytes from patients with grade ≥ 2 bf + compared with patients with grade < 2 bf+. As these candidate proteins are involved in oxidative stress regulation, we also evaluated radiation-induced reactive oxygen species (ROS) production in peripheral blood mononuclear cells from patients with grade ≥ 2 bf + and grade < 2 bf+. Total ROS level, and especially superoxide anion level, increased upon ex-vivo 8 Gy-irradiation in all patients. Analysis of NADPH oxidases (NOXs), a major source of superoxide ion in the cell, showed a significant increase of NOX4 mRNA and protein levels after irradiation in both patient groups. Conversely, only NOX4 mRNA level was significantly different between groups (grade ≥ 2 bf + and grade < 2 bf+)., Conclusion: These findings identify AK2 as a potential radiosensitivity candidate biomarker. Overall, our proteomic approach highlights the important role of oxidative stress in late radiation-induced toxicity, and paves the way for additional studies on NOXs and superoxide ion metabolism.

Stereotactic body radiotherapy (SBRT) is routinely used in oncology to treat non-invasively solid tumors with high precision and efficacy. Recently, this technology has been evaluated in the treatment of ventricular tachycardia (VT). This article presents the basic underlying principles, proofs of concept and main results of clinical studies that used SBRT for the treatment of VT., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background and Purpose: In 2000, a panel of experts published a proposal for the selection of lymph node target volumes for definitive head and neck radiation therapy (Radiother Oncol, 2000; 56: 135-150). Hereunder, this selection is updated and extended to also cover primary sites not previously covered., Patients and Methods: The lymphatic spread of head and neck cancers into neck lymph nodes was comprehensively reviewed based on radiological, surgical and pathological literature regarding both initial involvement and patterns of failure. Then a panel of worldwide head and neck radiotherapy experts agreed on a consensus for the selection of both high- and low-risk lymph node target volumes for the node negative and the node positive neck., Results: An updated selection of lymph node target volumes is reported for oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, nasal cavity and carcinoma of unknown primary as a function of the nodal staging (UICC 8th edition)., Conclusions: The selection of lymph node target volumes for head and neck cancers treated with IMRT/VMAT or other highly conformal techniques (e.g. proton therapy) requires a rigorous approach. This updated proposal of selection should help clinicians for the selection of lymph nodes target volumes and contribute to increase consistency., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Head and neck cancer (HNC) is an immunosuppressive disease that demonstrates heterogeneous molecular characteristics and features of tumor-host interaction. Beside radiotherapy and surgery, the current standard of care in systemic treatment involves the use of cytotoxic chemotherapy, monoclonal antibodies (mAbs), and tyrosine kinase inhibitors (TKIs). There are also other modalities being developed under the category of immunotherapy, but they are overshadowed by the recent advancements of immune checkpoint inhibitors., Areas Covered: This systematic review covers recent advancements in 'patient-specific' treatment modalities, which can be only administered to a given patient., Expert Opinion: Currently, patient-specific treatment modalities in HNC mainly consist of active immunotherapy using adoptive cell therapies and/or gene engineered vectors. Despite the slow pace of development, the interest continues in these treatment modalities. The future of HNC treatment is expected to be guided by biomarkers and personalized approaches with tailored combinations of local treatments (radiotherapy, surgery), systemic agents and immune system modulation. Systematic research is required to generate robust data and obtain a high-level of evidence for the effectiveness of such treatment modalities.

Purpose: Helical tomotherapy (HT) has been recently introduced in the neoadjuvant treatment of locally advanced rectal cancer. Aim of this study is to report the toxicity and local control rates of a large series of locally advanced rectal cancer patients treated with neoadjuvant chemotherapy and HT under daily image guidance followed by surgery., Methods: Data from 117 locally advanced rectal cancer patients treated at two Swiss Radiotherapy departments were collected and analyzed. Radiotherapy consisted of 45 Gy (1.8 Gy/fraction, 5 fractions/week delivered in 5 weeks) to the regional pelvic lymph nodes. Seventy patients also received a simultaneous integrated boost (SIB) up to 50 Gy to the tumor and involved nodes (2 Gy/fraction, 5 fractions/week delivered in 5 weeks). Chemotherapy consisted of capecitabine 825 mg/m 2 , twice daily, during the irradiation days. After a median interval of 59 days [95% confidence interval (CI) 53-65 days), all patients underwent surgery., Results: Median follow-up was 45 months (range 4-90 months). The overall rate of acute grade 2-4 toxicity was 18.8% (n = 22). Four patients (3.4%) presented a grade 3 dermatitis (n = 1) or diarrhea (n = 3), and 1 (0.8%) demonstrated grade 4 rectal toxicity. No patients presented with grade ≥ 3 hematologic toxicity. Six patients (5.1%) had late grade 3 gastrointestinal toxicity. The 4-year local control rate was 88.4% (95% CI 87.5-88.5%)., Conclusions: Neoadjuvant chemoradiotherapy delivered with HT under daily image guidance is well tolerated and shows a high 4-year local control rates.

Primary extranodal non-Hodgkin's lymphomas (EN-NHL) are a heterogeneous group of malignancies that involve numerous entities with significant difference in terms of tumor site locations, prognostic factors, biology expression, and therapeutic options. In the literature, many EN-NHL types were reported from limited series which only allowed narrow views for elucidating prognostic factors and defining the role of loco-regional therapies in the era of new systemic and biologically targeted therapies. The Rare Cancer Network (RCN), an international multidisciplinary consortium, has published a number of reports on several EN-NHL sites which included many gland locations. In this review, we will focus on the recent literature for a selected number of EN-NHL types in both exocrine and endocrine gland locations. We aim to provide renewed and clear messages for the best practice in 2019 for diagnosis, histopathology, treatments, and also their prognostic implications. We believe that better understanding of molecular and genetic characteristics of these particular diseases is crucial for an appropriate management in the era of personalized treatment developments., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: The trigeminal nerve (V) is a major route of tumor spread in several head and neck cancers. However, only limited data are currently available for its precise contouring, although this is absolutely necessary in the era of intensity-modulated radiation therapy (IMRT). The purpose of this article is to present practical clinical guidelines for contouring the trigeminal nerve (V) in head and neck cancers at risk of spread along this nerve., Method: The main types of head and neck cancers associated with risks of spread along the trigeminal nerve (V) and its branches were comprehensively reviewed based on clinical experience, literature-based patterns of failure, anatomy and radio-anatomy. A consensus for contouring was proposed based on a multidisciplinary approach among head and neck oncology experts including radiation oncologists (JBi, ML, MO, VG and JB), a radiologist (VD) and a surgeon (CS). These practical clinical guidelines have been endorsed by the GORTEC (Head and Neck Radiation Oncology Group)., Results: We provided contouring and treatment guidelines, supported by detailed figures and tables to help, for the trigeminal nerve and its branches: the ophthalmic nerve (V1), the maxillary nerve (V2) and the manidibular nerve (V3). A CT- and MRI-based atlas was proposed to illustrate the whole trigeminal nerve pathway with its main branches., Conclusion: Trigeminal nerve (V) invasion is an important component of the natural history of various head and neck cancers. Recognizing the radio-anatomy and potential routes of invasion is essential for optimal contouring, as presented in these guidelines., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Locally advanced oesophageal cancer treatment requires a multidisciplinary approach with the combination of chemotherapy and radiotherapy for preoperative and definitive strategy. Preoperative chemoradiation improves the locoregional control and overall survival after surgery for locally advanced oesophageal cancer. Definitive chemoradiation can also be proposed for non-resectable tumours or medically inoperable patients. Besides, definitive chemoradiation is considered as an alternative option to surgery for locally advanced squamous cell carcinomas. Chemotherapy regimen associated to radiotherapy consists of a combination of platinum derived drugs (cisplatinum or oxaliplatin) and 5-fluorouracil or a weekly scheme combination of carboplatin and paclitaxel according to CROSS protocol in a neoadjuvant strategy. Radiation doses vary from 41.4Gy to 45Gy for a preoperative strategy or 50 to 50.4Gy for a definitive treatment. The high risk of lymphatic spread due to anatomical features could justify the use of an elective nodal irradiation when the estimated risk of microscopic involvement is higher than 15% to 20%. An appropriate delineation of the gross tumour volume requires an exhaustive and up-to-date evaluation of the disease. Intensity-modulated radiation therapy represents a promising approach to spare organs-at-risk. This critical review of the literature underlines the roles of radiotherapy for locally advanced oesophageal cancers and describes doses, volumes of treatment, technical aspects and dose constraints to organs-at-risk., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)