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There is new data in the fractionation modalities and these are the really the practice-changing trials of last years: can we use hypo fractionated whole breast radiotherapy in patients presented with ductal carcinoma in situ? Can we realize hypofractionated whole breast radiotherapy with simultaneous integrated boost? What about hypofractionated irradiation after mastectomy with reconstruction? Can we do hypofractionation to lymph nodes without risk of increased toxicity? The purpose of this work is to respond with the last evidence-based recently presented or published data., (Copyright © 2024 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Regional nodal irradiation (RNI) for breast cancer delivers radiation in proximity to the shoulder and torso, and radiation exposure may contribute to long-term upper extremity and postural morbidity. To date, no studies have assessed the differential dosimetric impact of proton versus photon radiation on shoulder and torso anatomy. This study examined clinically relevant musculoskeletal (MSK) structures and assessed the dose delivered with each modality., Patients/material and Methods: Ten MSK structures were contoured on IMPT (intensity-modulated proton therapy) and VMAT (volumetric modulated arc therapy) plans for 30 patients receiving RNI. Relevant dose metrics were compared for each of the structures. Intensity-modulated proton therapy dose was calculated using the relative biological effective value of 1.1. Hypo-fractionated plans were scaled to the equivalent dose in 2 Gy fractions (EQD2) using an alpha/beta ratio of four. Wilcoxon signed rank sum tests compared doses. Select three-dimensional and optimised VMAT plans were also informally compared., Results and Interpretation: Each of the 10 structures received a statistically significantly lower dose with the use of IMPT compared with VMAT. Differences were greatest for posterior structures, including the trapezius, latissimus dorsi and glenohumeral joint. Mean absolute differences were as great as 23 Gy (supraspinatus D5cc) and up to 30-fold dose reductions were observed (deltoid D50cc). An average 3.7-fold relative dose reduction existed across all structures. Measures of low/intermediate dose (V15Gy and D50cc) showed the largest differences. Intensity-modulated proton therapy results in statistically lower radiation exposure to relevant shoulder and torso anatomy compared to photon radiation for patients requiring RNI. Prospective study is needed to correlate functional outcomes with radiation dose.

Background/aim: The application of volumetric-modulated arc therapy (VMAT) in postoperative radiotherapy for breast cancer has recently garnered considerable interest, especially when regional lymph node irradiation (RNI), is extended to include the internal mammary node (IMN) region, along with whole-breast or chest wall irradiation. This study aimed to assess both acute and late toxicities, as well as breast cancer outcomes, during the observation period., Patients and Methods: This retrospective study aimed to assess the safety and feasibility of VMAT in postoperative radiotherapy, including the IMN region, for patients with breast cancer at our hospital. We included 33 eligible patients who received postoperative VMAT radiotherapy, including the IMN region, between November 2018 and July 2021., Results: The primary indications for implementing VMAT were the presence of IMN metastases before primary systemic therapy or more than four axillary lymph node metastases. The median prescribed dose for the chest wall or conserved breast and regional lymph nodes was 50 Gy in 25 fractions. In 16 cases, a simultaneous boost (median, 10 Gy) was administered to residual lymph node metastases. VMAT facilitated a reduction in the mid- or high-dose range to organs at risk, exemplified by V 20Gy and V 40Gy of the ipsilateral lung, which were 24.10% and 6.84%, respectively, while ensuring adequate target dose irradiation, V 45Gy =95.23%. No serious adverse events, including symptomatic radiation pneumonitis, occurred during the 15-month median observation period., Conclusion: Our findings demonstrate the safety and effectiveness of postoperative radiotherapy for breast cancer, including the IMN region, when using VMAT., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Prostate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated., Material and Methods: The study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75Gy in 30 fractions of 2.5Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46Gy in 23 fractions with simultaneous integrated boost., Results: A total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4years and 3.96years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6months, 1year and 5years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6months, 1year and 5years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P=0.0028 for both)., Conclusion: External radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses., (Copyright © 2024 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Locoregional radiotherapy play an important role in controlling the disease after surgery in patients with breast cancer. Radiotherapy schedules vary from conventional fraction to hypofractionation. The purpose of this review is to get an insight into the data on regional nodal irradiation (RNI) with hypofractionation in patients with breast cancer. This systematic review was constructed in accordance with Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) framework. Electronic databases such as PubMed, Cochrane and EMBASE were searched from January 1, 2023 to March 31, 2023 to identify studies published in English language on hypofractionated RNI in post mastectomy patients. The search was carried out with the National Library of Medicine's Medical Subject Heading (MeSH) terms like "regional nodal irradiation," "hypofractionated" and "hypofractionation in breast cancer" with different Boolean operators (and/or). A manual search of reference lists of included articles was also performed to make sure there were no additional cases unidentified from the primary search. Studies deemed potentially eligible were identified and assessed by same independent reviewers to confirm eligibility. RNI data are mainly from a randomized study from Beijing and pooled data from START trials. There are also data from retrospective and single institutional studies and a few phase II studies with limited number of patients using different dose fractionations and techniques of radiotherapy. Doses used in these trials ranged from 26-47.7 Gy in 5-19 fractions over 1-4 weeks. Grade ≥ 2 pulmonary fibrosis and lymphedema rate ranged from 2%-7.9% and 3%-19.8% respectively. Grade ≥ 2 shoulder dysfunction and brachial plexopathy ranged from 0.2%-28% and 0%-< 1%, respectively. Late effects with a dose range of 26-40 Gy delivered in 5 to 15 fractions over 1-3 weeks were less/similar to conventional fraction. Current data showed lower/similar rates of toxicity with hypofractionated RNI compared with conventional fractionation RNI. Doses of 26 Gy to 40 Gy delivered in 5 to 15 fractions over 1-3 weeks are safe for RNI. With limited data, ultra-hypofractionation 26 Gy/5 fractions/1 week also seems to be safe. However, long-term outcome is awaited and many trials are going on to address its efficacy and safety., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: One of the current roadblocks to the widespread use of Total Marrow Irradiation (TMI) and Total Marrow and Lymphoid Irradiation (TMLI) is the challenging difficulties in tumor target contouring workflow. This study aims to develop a hybrid neural network model that promotes accurate, automatic, and rapid segmentation of multi-class clinical target volumes., Materials and Methods: Patients who underwent TMI and TMLI from January 2018 to May 2022 were included. Two independent oncologists manually contoured eight target volumes for patients on CT images. A novel Dual-Encoder Alignment Network (DEA-Net) was developed and trained using 46 patients from one internal institution and independently evaluated on a total of 39 internal and external patients. Performance was evaluated on accuracy metrics and delineation time., Results: The DEA-Net achieved a mean dice similarity coefficient of 90.1 % ± 1.8 % for internal testing dataset (23 patients) and 91.1 % ± 2.5 % for external testing dataset (16 patients). The 95 % Hausdorff distance and average symmetric surface distance were 2.04 ± 0.62 mm and 0.57 ± 0.11 mm for internal testing dataset, and 2.17 ± 0.68 mm, and 0.57 ± 0.20 mm for external testing dataset, respectively, outperforming most of existing state-of-the-art methods. In addition, the automatic segmentation workflow reduced delineation time by 98 % compared to the conventional manual contouring process (mean 173 ± 29 s vs. 12168 ± 1690 s; P < 0.001). Ablation study validate the effectiveness of hybrid structures., Conclusion: The proposed deep learning framework achieved comparable or superior target volume delineation accuracy, significantly accelerating the radiotherapy planning process., 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 © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

The IMN debate is still open and may never be closed for reasons outlined in this Comments and Controversies piece.

Background and Purpose: Given the substantial lack of knowledge, we aimed to assess clinical/dosimetry predictors of late hematological toxicity on patients undergoing pelvic-nodes irradiation (PNI) for prostate cancer (PCa) within a prospective multi-institute study., Materials and Methods: Clinical/dosimetry/blood test data were prospectively collected including lymphocytes count (ALC) at baseline, mid/end-PNI, 3/6 months and every 6 months up to 5-year after PNI. DVHs of the Body, ileum (BMILEUM), lumbosacral spine (BMLS), lower pelvis (BMPELVIS), and whole pelvis (BMTOT) were extracted. Current analysis focused on 2-year CTCAEv4.03 Grade ≥ 2 (G2+) lymphopenia (ALC < 800/μL). DVH parameters that better discriminate patients with/without toxicity were first identified. After data pre-processing to limit overfitting, a multi-variable logistic regression model combining DVH and clinical information was identified and internally validated by bootstrap., Results: Complete data of 499 patients were available: 46 patients (9.2 %) experienced late G2+ lymphopenia. DVH parameters of BMLS/BMPELVIS/BMTOT and Body were associated to increased G2+ lymphopenia. The variables retained in the resulting model were ALC at baseline [HR = 0.997, 95 %CI 0.996-0.998, p < 0.0001], smoke (yes/no) [HR = 2.9, 95 %CI 1.25-6.76, p = 0.013] and BMLS-V ≥ 24 Gy (cc) [HR = 1.006, 95 %CI 1.002-1.011, p = 0.003]. When acute G3+ lymphopenia (yes/no) was considered, it was retained in the model [HR = 4.517, 95 %CI 1.954-10.441, p = 0.0004]. Performances of the models were relatively high (AUC = 0.87/0.88) and confirmed by validation., Conclusions: Two-year lymphopenia after PNI for PCa is largely modulated by baseline ALC, with an independent role of acute G3+ lymphopenia. BMLS-V24 was the best dosimetry predictor: constraints for BMTOT (V10Gy < 1520 cc, V20Gy < 1250 cc, V30Gy < 850 cc), and BMLS (V24y < 307 cc) were suggested to potentially reduce the risk., 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 © 2024 Elsevier B.V. All rights reserved.)

Women with left-sided breast cancer receiving adjuvant radiotherapy have increased incidence of cardiac mortality due to ischemic heart disease; to date, no threshold dose for late cardiac/pulmonary morbidity or mortality has been established. We investigated the likelihood of cardiac death and radiation pneumonitis in women with left-sided breast cancer who received comprehensive lymph node irradiation. The differences in dosimetric parameters between free-breathing (FB) and deep inspiration breath hold (DIBH) techniques were also addressed. Based on NTCP calculations, the probability of cardiac death was significantly reduced with the DIBH compared to the FB technique ( p < 0.001). The risk of radiation pneumonitis was not clinically significant. There was no difference in coverage between FB and DIBH plans. Doses to healthy structures were significantly lower in DIBH plan than in FB plan for V20, V30, and ipsilateral total lung volume. Inspiratory gating reduces the dose absorbed by the heart without compromising the target range, thus reducing the likelihood of cardiac death.

Background: Total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI) have the advantages. However, delineating target lesions according to TMI and TMLI plans is labor-intensive and time-consuming. In addition, although the delineation of target lesions between TMI and TMLI differs, the clinical distinction is not clear, and the lymph node (LN) area coverage during TMI remains uncertain. Accordingly, this study calculates the LN area coverage according to the TMI plan. Further, a deep learning-based model for delineating LN areas is trained and evaluated., Methods: Whole-body regional LN areas were manually contoured in patients treated according to a TMI plan. The dose coverage of the delineated LN areas in the TMI plan was estimated. To train the deep learning model for automatic segmentation, additional whole-body computed tomography data were obtained from other patients. The patients and data were divided into training/validation and test groups and models were developed using the "nnU-NET" framework. The trained models were evaluated using Dice similarity coefficient (DSC), precision, recall, and Hausdorff distance 95 (HD95). The time required to contour and trim predicted results manually using the deep learning model was measured and compared., Results: The dose coverage for LN areas by TMI plan had V100% (the percentage of volume receiving 100% of the prescribed dose), V95%, and V90% median values of 46.0%, 62.1%, and 73.5%, respectively. The lowest V100% values were identified in the inguinal (14.7%), external iliac (21.8%), and para-aortic (42.8%) LNs. The median values of DSC, precision, recall, and HD95 of the trained model were 0.79, 0.83, 0.76, and 2.63, respectively. The time for manual contouring and simply modified predicted contouring were statistically significantly different., Conclusions: The dose coverage in the inguinal, external iliac, and para-aortic LN areas was suboptimal when treatment is administered according to the TMI plan. This research demonstrates that the automatic delineation of LN areas using deep learning can facilitate the implementation of TMLI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The development of large-field intensity-modulated radiation therapy (IMRT) has enabled the implementation of total marrow irradiation (TMI), total marrow and lymphoid irradiation (TMLI), and IMRT total body irradiation (TBI). IMRT TBI limits doses to organs at risk, primarily the lungs and in some cases the kidneys and lenses, which may mitigate complications. TMI/TMLI allows for dose escalation above TBI radiation therapy doses to malignant sites while still sparing organs at risk. Although still sparingly used, these techniques have established feasibility and demonstrated promise in reducing the adverse effects of TBI while maintaining and potentially improving survival outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This prospective phase I trial aimed to determine the recommended dose of 3-day total marrow and lymphoid irradiation (TMLI) for a myeloablative conditioning regimen by increasing the dose per fraction. The primary end-point of this single-institution dose escalation study was the recommended TMLI dose based on the frequency of dose-limiting toxicity (DLT) ≤100 days posthematopoietic stem cell transplantation (HSCT); a 3 + 3 design was used to evaluate the safety of TMLI. Three dose levels of TMLI (14/16/18 Gy in six fractions over 3 days) were set. The treatment protocol began at 14 Gy. Dose-limiting toxicities were defined as grade 3 or 4 nonhematological toxicities. Nine patients, with a median age of 42 years (range, 35-48), eight with acute lymphoblastic leukemia and one with chronic myeloblastic leukemia, received TMLI followed by unrelated bone marrow transplant. The median follow-up period after HSCT was 575 days (range, 253-1037). Three patients were enrolled for each dose level. No patient showed DLT within 100 days of HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. All patients achieved neutrophil engraftment at a median of 19 days (range, 14-25). One-year overall and disease-free survival rates were 83.3% and 57.1%, respectively. Three patients experienced relapse, and no nonrelapse mortality was documented during the observation period. One patient died due to disease relapse 306 days post-HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. The efficacy evaluation of this regimen is currently being planned in a phase II study., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Primary tumours of the salivary glands account for about 5 to 10% of tumours of the head and neck. These tumours represent a multitude of situations and histologies, where surgery is the mainstay of treatment and radiotherapy is frequently needed for malignant tumours (in case of stage T3-T4, nodal involvement, extraparotid invasion, positive or close resection margins, histological high-grade tumour, lymphovascular or perineural invasion, bone involvement postoperatively, or unresectable tumours). The diagnosis relies on anatomic and functional MRI and ultrasound-guided fine-needle aspiration for the diagnostic of benign or malignant tumors. In addition to patient characteristics, the determination of primary and nodal target volumes depends on tumor extensions and stage, histology and grade. Therefore, radiotherapy of salivary gland tumors requires a certain degree of personalization, which has been codified in the recommendations of the French multidisciplinary network of expertise for rare ENT cancers (Refcor) and may justify a specialised multidisciplinary discussion. Although radiotherapy is usually recommended for malignant tumours only, recurrent pleomorphic adenomas may sometimes require radiotherapy based on multidisciplinary discussion. An update of indications and recommendations for radiotherapy for salivary gland tumours in terms of techniques, doses, target volumes and dose constraints to organs at risk of the French society for radiotherapy and oncology (SFRO) was reported in this article., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

We present the update of the recommendations of the French society of oncological radiotherapy on external radiotherapy of prostate cancer. External radiotherapy is intended for all localized prostate cancers, and more recently for oligometastatic prostate cancers. The irradiation techniques are detailed. Intensity-modulated radiotherapy combined with prostate image-guided radiotherapy is the recommended technique. A total dose of 74 to 80Gy is recommended in case of standard fractionation (2Gy per fraction). Moderate hypofractionation (total dose of 60Gy at a rate of 3Gy per fraction over 4 weeks) in the prostate has become a standard of therapy. Simultaneous integrated boost techniques can be used to treat lymph node areas. Extreme hypofractionation (35 to 40Gy in five fractions) using stereotactic body radiotherapy can be considered a therapeutic option to treat exclusively the prostate. The postoperative irradiation technique, indicated mainly in case of biological recurrence and lymph node involvement, is detailed., (Copyright © 2021. Published by Elsevier Masson SAS.)

Objective: Xerostomia is the most common treatment-related toxicity after radiotherapy (RT) for head and neck carcinoma, reducing the quality of life of patients due to a decrease in salivary gland function., Methods: Salivary gland scintigraphy was performed to quantitatively evaluate the salivary gland functions in patients undergoing RT. It was done chronologically for 62 salivary glands of 31 patients before RT and retested 12 months later., Results: The salivary gland functions of most patients deteriorated post-RT and recovered when the radiation dose to the salivary gland was not high. The mean dose to the salivary gland was found to be the most reliable factor in deteriorating salivary gland function, and the tolerance dose was determined to be 46 Gy. The recovery rate of salivary gland function after 1 year of RT was 72% in the RT alone group ( n = 10), 56% in the conformal radiotherapy group ( n = 15), and 44% in the bioradiotherapy group ( n = 6)., Conclusion: Scintigraphy revealed that the salivary glands recovered from post-RT hypofunction when decreased doses were administered. The determined tolerance dose of 46 Gy may guide the approach to minimizing associated xerostomia in RT., Advances in Knowledge: In this study, the average tolerated dose to the salivary glands was 46 Gy.

Penile cancers are uncommon and should be treated in expert center. Radiotherapy indications are mainly limited to exclusive brachytherapy for early stage penile glans cancer. Brachytherapy yields to excellent outcome for disease control and organ and function preservation. Only scarce data are available for external beam radiation therapy. It could be considered as palliative setting for irradiation of the primary tumor. For lymph node irradiation, external beam radiation therapy (with or without chemotherapy) could be discussed either as neoadjuvant approach prior to surgery for massive inguinal lymph node invasion or as adjuvant approach in case of high-risk of relapse. However, these cases should be discussed on an individual basis, as the level of evidence is poor. We present the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for penile glans cancer., (Copyright © 2021. Published by Elsevier Masson SAS.)

Introduction of sentinel lymph node biopsy, initially in clinically node-negative and subsequently in patients presenting with involved axilla and downstaged by primary systemic therapy, allowed for significant decrease in morbidity compared to axillary lymph node dissection. Concurrently, regional nodal irradiation was demonstrated to improve outcomes in most node-positive patients. Additionally, over the last decades, introduction of more effective systemic therapies has resulted in improvements not only at distant sites, but also in locoregional control, creating space for de-escalation of locoregional treatments. We discuss the data on de-escalation in axillary surgery and irradiation, both in patients undergoing upfront surgery and primary systemic therapy, with special emphasis on the feasibility of omission of nodal irradiation in patients undergoing primary systemic therapy. In view of the accumulating evidence, omission of axillary irradiation may be considered in clinically node-positive patients converting after primary systemic therapy to pathologically negative nodes on sentinel lymph node biopsy (preferably also with in-breast pCR), presenting with lower initial nodal stage, older age and were treated with breast-conserving surgery followed by whole breast irradiation. Omission of regional nodal irradiation in patients with aggressive tumor phenotypes achieving a pCR is under investigation. In patients undergoing preoperative endocrine therapy the adoption of axillary management strategies utilized in case of upfront surgery seems more suitable than those used in post chemotherapy-based primary systemic therapy setting., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Long-term prospective patient-reported outcomes (PRO) after breast cancer adjuvant radiotherapy is scarce. TomoBreast compared conventional radiotherapy (CR) with tomotherapy (TT), on the hypothesis that TT might reduce lung-heart toxicity., Methods: Among 123 women consenting to participate, 64 were randomized to CR, 59 to TT. CR delivered 50 Gy in 25 fractions/5 weeks to breast/chest wall and regional nodes if node-positive, with a sequential boost (16 Gy/8 fractions/1.6 weeks) after lumpectomy. TT delivered 42 Gy/15 fractions/3 weeks to breast/chest wall and regional nodes if node-positive, 51 Gy simultaneous-integrated-boost in patients with lumpectomy. PRO were assessed using the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30. PRO scores were converted into a symptom-free scale, 100 indicating a fully symptom-free score, 0 indicating total loss of freedom from symptom. Changes of PRO over time were analyzed using the linear mixed-effect model. Survival analysis computed time to > 10% PRO-deterioration. A post-hoc cardiorespiratory outcome was defined as deterioration in any of dyspnea, fatigue, physical functioning, or pain., Results: At 10.4 years median follow-up, patients returned on average 9 questionnaires/patient, providing a total of 1139 PRO records. Item completeness was 96.6%. Missingness did not differ between the randomization arms. The PRO at baseline were below the nominal 100% symptom-free score, notably the mean fatigue-free score was 64.8% vs. 69.6%, pain-free was 75.4% vs. 75.3%, and dyspnea-free was 84.8% vs. 88.5%, in the TT vs. CR arm, respectively, although the differences were not significant. By mixed-effect modeling on early ≤2 years assessment, all three scores deteriorated, significantly for fatigue, P ≤ 0.01, without effect of randomization arm. By modeling on late assessment beyond 2 years, TT versus CR was not significantly associated with changes of fatigue-free or pain-free scores but was associated with a significant 8.9% improvement of freedom from dyspnea, P = 0.035. By survival analysis of the time to PRO deterioration, TT improved 10-year survival free of cardiorespiratory deterioration from 66.9% with CR to 84.5% with TT, P = 0.029., Conclusion: Modern radiation therapy can significantly improve long-term PRO., Trial Registration: Trial registration number ClinicalTrials.gov NCT00459628 , April 12, 2007 prospectively., (© 2021. The Author(s).)

Management of high-risk prostate cancers is still a subject of debate, because of the lack of randomized trial comparing surgery and radiotherapy. If external beam radiotherapy is proposed, it must be associated with a long-term androgen deprivation therapy, at least 18-months. Irradiation of pelvic lymph nodes seems to improve distant metastasis-free survival and is so indicated in most of the cases. Moderate hypofractionation is not validated for pelvic lymph nodes irradiation. A combination of external beam radiotherapy and brachytherapy improved biochemical control in randomized trials without impact on survival. But this combination has been evaluated in large retrospective studies and seems to improve specific and overall survivals. An integrated boost on the MRI-defined index lesion is another way of dose escalation and improved also biochemical control. Stereotactic radiotherapy is not a validated option at this moment. For each patient, according to the extension of the disease, age, comorbidities and also his willingness, the best approach must be chosen, ideally in multidisciplinary meeting., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Lymph node metastases presenting with locally advanced cervical cancer are poor prognostic features. Modern radiotherapy approaches enable dose escalation to radiologically abnormal nodes. This study reports the results of a policy of a simultaneous integrated boost (SIB) in terms of treatment outcomes., Materials and Methods: Patients treated with radical chemoradiation with weekly cisplatin for locally advanced cervical cancer including an SIB to radiologically abnormal lymph nodes were analysed. All patients received a dose of 45 Gy in 25 fractions and a SIB dose of 60 Gy in 25 fractions using intensity modulated radiotherapy/volumetric modulated arc therapy, followed by high dose rate brachytherapy of 28 Gy in 4 fractions. A control cohort with radiologically negative lymph nodes was used to compare impact of the SIB in node positive patients. Treatment outcomes were measured by overall survival (OS), post treatment tumour response and toxicities. The tumour response was based on cross sectional imaging at 3 and 12 months and recorded as local recurrence free survival (LRFS), regional recurrence free survival (RRFS) and distant recurrence free survival (DRFS)., Results: In between January 2015 and June 2017, a total of 69 patients with a median follow up of 30.9 months (23 SIB patients and 46 control patients) were identified. The complete response rate at 3 months was 100% in the primary tumour and 83% in the nodal volume receiving SIB. The OS, LRFS, RRFS and DRFS at 3 years of the SIB cohort were 69%, 91%, 79% and 77% respectively. High doses can be delivered to regional pelvic lymph nodes using SIB without excessive toxicity., Conclusion: Using a SIB, a total dose of 60 Gy in 25 fractions chemoradiation can be delivered to radiologically abnormal pelvic nodes with no increase in toxicity compared to node negative patients. The adverse impact of positive nodal status may be negated by high dose deposition using SIB, but larger prospective studies are required to confirm this observation.

Purpose: In breast cancer, radiotherapy is an essential component of the treatment. However, indications of irradiation of the internal mammary chain and axillary area are debatables. Axillary recurrence in patients with invasive breast carcinoma remains an issue. Currently, the substitution of axillary lymph node dissection by sentinel node biopsy leads to revisit the role of axillary irradiation. Breast irradiation including level I, II and III might decrease the risk of axillary recurrence., Material and Methods: A literature search was performed in PubMed and the Cochrane library to identify articles publishing data regarding dose-volume analysis of axillary levels in breast irradiation aiming to determine the potential therapeutic implications., Results: Eleven articles were retained. A total of 375 treatment plans were analyzed. The results concerning the irradiation technique, initial dose prescribed to breast, delineated volumes and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I-III with 3D-conformal radiotherapy using standard fields were between 24Gy and 43.5Gy, 3Gy and 32.5Gy and between 1.0Gy and 20.5Gy respectively. The average doses delivered to axilla levels I-III with 3D-conformal radiotherapy using high tangential fields were between 38Gy and 49.7Gy, 11Gy and 47.1Gy and 5Gy 38.7Gy, 32.1Gy and 5Gy (result available for only one study) respectively. Finally, the average doses delivered to axilla levels I-III with intensity modulated radiation therapy were between 14.5Gy and 42.6Gy, 3.4Gy and 35Gy and between 1.2Gy and 25.5Gy respectively., Conclusions: Incidental axillary dose seems insufficient to be therapeutic regardless of the irradiation technique. There are meaningful differences between intensity modulated radiation therapy and 3D-conformal radiotherapy., (Copyright © 2020. Published by Elsevier Masson SAS.)

Purpose: The aims of this study were: determination of the CTV to PTV margins for prostate and pelvic lymph nodes. Investigation of the impact of registration modality (pelvic bones or prostate) on the CTV to PTV margins of pelvic lymph nodes. Investigation of the variations of bladder and rectum over the treatment course. Investigation of the impact of bladder and rectum variations on prostate position., Patients and Methods: This study included 15 patients treated for prostate adenocarcinoma. Daily kilo voltage images and weekly CBCT scans were performed to assess prostate displacements and common and external iliac vessels motion. These data was used to calculate the CTV to PTV margins using Van Herk equation in the setting of a daily bone registration. We also compared the CTV to PTV margins of pelvic lymph nodes according to registration method; based on pelvic bone or prostate. We delineated bladder and rectum on all CBCT scans to assess their variations over treatment course at 4 anatomic levels [1.5cm above pubic bone (PB), superior edge, mid- and inferior edge of PB]., Results: Using Van Herk equation, the prostate CTV to PTV margins (bone registration) were 8.03mm, 5.42mm and 8.73mm in AP, ML and SI direction with more than 97% of prostate displacements were less than 5mm. The CTV to PTV margins ranged from 3.12mm to 3.25mm for external iliac vessels and from 3.12mm to 4.18mm for common iliac vessels. Compared to registration based on prostate alignment, bone registration resulted in an important reduction of the CTV to PTV margins up to 54.3% for external iliac vessels and up to 39.6% for common iliac vessels. There was no significant variation of the mean bladder volume over the treatment course. There was a significant variation of the mean rectal volume before and after the third week of treatment. After the third week, the mean rectal volume seemed to be stable. The uni- and multivariate analysis identified the anterior wall of rectum as independent factor acting on prostate motion in AP direction at 2 levels (superior edge of, mid PB). The right rectal wall influenced the prostate motion in ML direction at inferior edge of PB. The bladder volume tends toward significance as factor acting on prostate motion in AP direction., Conclusions: We recommend CTV to PTV margins of 8mm, 6mm and 9mm in AP, ML and SI directions for prostate. And, we suggest 4mm and 5mm for external and common iliac vessels respectively. We also prefer registration based on bony landmarks to minimize bowel irradiation. More CBCT scans should be performed during the first 3weeks and especially the first week to check rectum volume., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Little is known about the toxicity of additional pelvic lymph node irradiation in men receiving intensity modulated radiation therapy (IMRT) for prostate cancer. The aim of this study was to compare patient-reported outcomes after IMRT to the prostate only (PO-IMRT) versus the prostate and pelvic lymph nodes (PPLN-IMRT)., Methods and Materials: Patients who received a diagnosis of high-risk or locally advanced prostate cancer in the English National Health Service between April 2014 and September 2016 who were treated with IMRT were mailed a questionnaire at least 18 months after diagnosis. Patient-reported urinary, sexual, bowel, and hormonal functional domains on a scale from 0 to 100, with higher scores indicating better outcomes, and generic health-related quality of life were collected using the Expanded Prostate Cancer Index Composite 26-item version and EQ-5D-5L. We used linear regression to compare PPLN-IMRT versus PO-IMRT with adjustment for patient, tumor, and treatment characteristics., Results: Of the 7017 men who received a questionnaire, 5468 (77.9%) responded; 4196 (76.7%) had received PO-IMRT and 1272 (23.3%) PPLN-IMRT. Adjusted differences in the Expanded Prostate Cancer Index Composite 26-item version domain scores were smaller than 1 (P always >.2), except for sexual function, with men who had PPNL-IMRT reporting a lower mean score (adjusted difference, 2.3; 95% confidence interval, 0.9-3.7; P = .002). This did not represent a clinically relevant difference. There was no significant difference in health-related quality of life (P = .5)., Conclusions: Additional pelvic lymph node irradiation does not lead to clinically meaningful increases in the toxicity of IMRT for prostate cancer according to patient-reported functional outcomes and health-related quality of life., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Clinical trials support adjuvant regional nodal irradiation (RNI) after breast-conserving surgery or mastectomy for patients with lymph node-positive breast cancer. Advanced treatment planning techniques (eg, intensity modulated radiation therapy [IMRT]) can reduce dose to organs at risk (OARs) in this situation. However, uncertainty persists about when IMRT is clinically indicated (vs 3-dimensional conformal radiation therapy [3DCRT]) for RNI. We hypothesized that an adaptive treatment planning algorithm (TPA) for IMRT adoption would allow OAR constraints for RNI to be met when 3DCRT could not without significantly changing toxicity and locoregional recurrence (LRR) patterns., Methods and Materials: Since 2013, all RNI patients also underwent an adaptive TPA that began with 3DCRT and then changed to IMRT when OAR constraints (mean heart dose ≤500 cGy; ipsilateral lung V20 ≤35%) could not be met. Patients received 2 Gy/d to the prospectively contoured target volumes (including internal mammary nodes). We retrospectively evaluated the dosimetry and clinical outcomes of the treatment groups (IMRT vs 3DCRT). The primary endpoint was the cumulative incidence of LRR as the site of first recurrence, and we specifically address patterns of failure based on dose to the posterior supraclavicular nodal region (SCL-post)., Results: Two hundred forty patients (60% stage III; mean 4.0 + nodes) underwent an adaptive-TPA for RNI after mastectomy (74%) or breast-conserving surgery (26%), resulting in 168 patients treated with 3DCRT and 72 patients treated with IMRT. There were 7 LRRs (2 IMRT, 5 3DCRT) resulting in 4-year LRR of 2.8% for IMRT versus 1.8% for 3DCRT (P = .99). Three patients (2 IMRT, 1 3DCRT) had SCL nodal failures (1 in the SCL-post)., Conclusions: An adaptive TPA for use of IMRT when 3DCRT does not meet critical OAR constraints resulted in rare high-grade toxicity and no difference in failure patterns between patients treated with IMRT and 3DCRT. These data should provide reassurance that IMRT maintains the therapeutic ratio by preserving cancer control outcomes without excess toxicity when 3DCRT fails to meet OAR constraints., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The aim of this paper is to investigate the outcome of patients treated with mastectomy, immediate breast reconstruction (IBR) and post-mastectomy radiotherapy (PMRT) and the risk of late complications., Material and Method: All patients had post-mastectomy, immediate reconstructive surgical procedure by using autologous abdominal implant; tissue expander (TE)/permanent prosthesis (PP); or even combined procedures. Adjuvant external beam radiotherapy treatment (EBRT) was delivered to the reconstructed chest wall and supraclavicular nodes, for a total dose of 50 Gy in 25 fractions. The Kaplan-Meyer analysis evaluates patients' rate of late side effects, Overall Survival (OS), Progression Free survival (PFS), Local-regional free survival (LRFS) and Metastasis Free Survival (MFS). The univariate analysis investigates the correlation between late toxicity and related factors., Results: Between November 2003 and October 2016, 91 breast cancer patients were treated with IBR and PMRT. Twenty-three (25.3%) patients experimented late toxicity. Overall, 16 (17.6%) patients experienced late complications which required a surgical approach. The 1- 2- 5- years late toxicity rates were 96.6%, 87.1% and 77.9%, respectively. The type of reconstruction was not statistically related with late toxicity rate (P = 0.35). The median follow-up period was 59 months (range 6-142 months). Median OS was not reached, the 1- 2- 5-years OS rates were 100%, 95.4% and 81% respectively., Conclusion: This study underlines that the type of reconstruction does not influence late toxicity rate. Moreover, IBR followed by adjuvant radiotherapy, has showed acceptable late toxicity profile and no influence on OS.

Objective: Our study aimed to compare regional node coverage and doses to the organ at risk (OAR) using conventional technique (CT) vs "AMAROS" (AT) vs intensity-modulated radiation therapy (IMRT) techniques in patients receiving regional nodal irradiation (RNI) for breast cancer (BC)., Methods: We included 30 consecutive patients with BC who received RNI including axillary nodes. Two independent and blinded dosimetric RNI plans were generated for all patients. For target volume coverage, we analyzed the V95%, the D95%, the mean and the minimal dose within the nodal station. For hotspots within nodal target volume, we used the V105%, the V108% and the maximal doses. For OAR, lung V20, mean lung and heart doses, the maximal dose to the brachial plexus and the axillary-lateral thoracic vessel junction region were compared between the three techniques., Results: Target volume coverage and hotspots: Mean V95% in stations I, II, III and IV were 35.8% and 75% respectively with CV, 22.59 and 59.9% respectively with AT technique and 45.58 and 99.6% respectively with IMRT with statistically significant differences ( p < 0.001). Mean V105% (cc) in axillary and supraclavicular stations were 21.3 and 6.4 respectively with CV, 1.2 and 0.02 respectively with AT technique and 0.5 and 0.4 respectively with IMRT with statistically significant differences ( p < 0.001)..OARs: The mean ipsilateral lung V20 was 16.9%, 16.4 and 13.3% with CT, AT and IMRT respectively. The mean heart dose (Gy) was 0.3, 0.2 and 0.2 with CT, AT and IMRT respectively. The maximal dose to the plexus brachial (Gy) was 50.3, 46.3 and 47.3 with CT, AT and IMRT respectively. The maximal dose to the axillary-lateral thoracic vessel junction (Gy) was 52.3, 47.3 and 47.6 with CT, AT and IMRT respectively. The differences were statistically significant for all OAR ( p < 0.001)., Conclusion: AT is a valuable technique for RNI including axilla in patients with limited sentinel lymph node biopsy involvement without additional axillary lymph node dissection since it decreases hotspots in the target volume and lowers the radiation exposure of the OAR. For more advanced tumors or patients who did not respond to primary systemic therapy, CT or IMRT should be considered because of their better coverage of the potentially residual nodal disease. IMRT combines several advantages of offering high conformal plans, limited hotspots and protection of main OAR. The clinical impact of these dosimetric differences need to be addressed., Advances in Knowledge: This study is to our knowledge the first to compare conventional three-dimensional and IMRT techniques for regional nodal irradiation for each nodal station in breast cancer in a context of increasing utilization of axillary irradiation .

Objective: To analyze the effect of intra- and interfractional motion during breast intensity modulated radiation therapy (IMRT) by calculating dose distribution based on four-dimensional computed tomography (4DCT)., Methods: 20 patients diagnosed with left breast cancer were enrolled. Three-dimensional CT (3DCT) along with 10 phases of 4DCT were collected for each patient, with target volumes independently delineated on both 3DCT and all phases of 4DCT. IMRT plans were generated based on 3DCT (43.2 Gy in 16 fractions). The plan parameters for each segment were split into phases based on time duration estimates for each respiratory phase, with phase-specific dose distributions calculated and summated (4D-calculated dose). The procedure is repeated for 16 fractionations by randomly allocating starting phase using random-number generation to simulate interfractional discrepancy caused by different starting phase. Comparisons of plan quality between the original and 4D-calculated doses were analyzed., Results: There was a significant distortion in 4D-calculated dose induced by respiratory motion in terms of conformity and homogeneity index compared to those of the original 3D plan. Mean doses of the heart and the ipsilateral lung were significantly higher in the 4D-calculated doses compared to those of the original 3D plan (0.34 Gy, p = 0.010 and 0.59 Gy, p < 0.001), respectively). The mean internal mammary lymph node (IMN) dose was significantly greater in the 4D-calculated plan, compared to the original 3D plan (1.42 Gy, p < 0.001)., Conclusions: IMN doses should be optimized during the dose-calculation for the free-breathing left breast IMRT., Advances in Knowledge: The interplay effect between respiratory motion and multileaf collimator modulation caused discrepancies in dose distribution, particularly in IMN.

Objectives: To evaluate the feasibility and optimal restricted angle of the complete-directional-complete block (CDCB) technique in helical tomotherapy (HT) by including regional nodal irradiation (RNI) with the internal mammary node (IMN) in left-sided breast cancer., Methods: Ten left-sided breast cancer patients treated with 50 Gy in 25 fractions were compared with five-field intensity-modulated radiation therapy (5F-IMRT) and six types of HT plans. In the HT plans, complete block (CB), organ-based directional block (OBDB) and CDCB with different restricted angles were used., Results: The conformity index (CI) between the CDCB 0,10,15,20 and 5F-IMRT groups was similar. Compared to CB, OBDB and 5F-IMRT, CDCB 20 resulted in a decreased ipsilateral mean lung dose. The low-dose region (V 5 ) of the ipsilateral lung in OBDB (84.0%) was the highest among all techniques ( p < 0.001). The mean dose of the heart in CB was significantly reduced (by 11.5-22.4%) compared with other techniques. The V 30 of the heart in CDCB 20 (1.9%) was significantly lower than that of CB, OBDB and 5F-IMRT. Compared to the mean dose of the left anterior descending (LAD) artery of 5F-IMRT (27.0 Gy), CDCB 0 , CDCB 10 , CDCB 15 , CDCB 20 and OBDB reduced the mean dose effectively by 31.7%, 38.3%, 39.6%, 42.0 and 56.2%, respectively. Considering the parameters of the organs-at-risk (OARs), CDCB 10,15,20 had higher expectative values than the other techniques ( p = 0.01)., Conclusions: HT with the CDCB technique is feasible for treating left-sided breast cancer patients. The CDCB 10-20 techniques not only achieved similar planning target volume coverage, homogeneity and dose conformity but also allowed better sparing of the heart and bilateral lungs., Advances in Knowledge: For left-sided breast cancer patients whose RNI field includes the IMN, heart avoidance is an important issue. The CDCB technique achieved good PTV coverage, homogeneity and dose conformity and allowed better sparing of the mean dose of the lung, the LAD artery, and the heart and reduced the V 30 of the heart.

Squamous cell carcinoma of oral cavity (OSCC) is predominantly managed with surgery. Post-operative radiotherapy (PORT) and chemoradiotherapy (POCRT) enhance disease control in OSCC patients with adverse anatomic and pathologic primary and nodal features. Knowledge about disease behavior, surgery and radiotherapy advances, and the emergence of new systemic agents prompt refinement of PORT volumes and POCRT regimens. Traditional and emerging prognostic models that include adverse histopathological features underpin such approaches. This review summarizes research over recent decades with emphasis on the 2015 to Feb 2019 period describing: (1) Indications for PORT and/or POCRT, addressing surgical "margin status" including the definition of a "clear" margin to permit withholding PORT/POCRT; these concepts include characterizing the specimen yielding these measurements, the optimal time point to assess these findings, and the putative value of a "revised margin" performed during the same operative procedure, (2) Emerging prognostic factors including nodal burden (total number of involved lymph nodes) and perineural invasion, (3) PORT volume design, dose/fractionation and optimal surgery-to-PORT interval, (4) Chemotherapy dose, schedule, and agents, and (5) On-going clinical trials involving systemic agents and combinations of chemotherapy with immunotherapy., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Intensity modulated proton therapy (IMPT) of locally advanced prostate cancer can spare the bowel considerably compared with modern photon therapy, but simultaneous treatment of the prostate (p), seminal vesicles (sv), and lymph nodes is challenging owing to day-to-day organ motion and range uncertainties. Our purpose was, therefore, to generate a plan library for use in adaptive IMPT to mitigate these uncertainties., Methods and Materials: We retrospectively included 27 patients with a series of computed tomography scans throughout their treatment representing day-to-day variation. In 18 of the patients, target motion was analyzed using rigid shifts of prostate gold markers relative to bony anatomy. A plan library with different p and sv planning target volume (p/sv-PTV) positions was defined from the distribution and direction of these shifts. Delivery of IMPT using plan selection from the library was simulated for image guidance on bony anatomy, in the remaining patients and compared with nonadaptive IMPT., Results: The plan library consisted of 3 small margin p/sv-PTVs: (1) p/sv-PTV shifted 1.5 systematic error (Σ) of the population mean in the anterior and cranial directions, (2) p/sv-PTV shifted 1.5Σ in the posterior and caudal directions, and (3) p/sv-PTV in the planning position. The conventional p/sv-PTV was also available for backup. Plan selection compared with nonadaptive IMPT resulted in a reduction of the rectum volume receiving 60 Gy relative biological effect (RBE) (V60 GyRBE ) from on average 12 mL to 9 mL. For the bladder the average V45 GyRBE was reduced from 36% to 30%. Large and small bowel doses were also reduced, whereas target coverage was comparable or improved compared with nonadaptive IMPT., Conclusions: Plan selection based on a population model of rigid target motion was feasible for all patients. Compared with conventional IMPT, plan selection resulted in significant dosimetric sparing of rectum and bladder without compromising target coverage., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Lymph node irradiation in breast cancer has gained complexity due to recently published studies and technical innovations which then led to changes in international guidelines. We sought to determine real-time variability in lymph node irradiation in clinical practice in German-speaking countries., Methods: The Department of Radiation Oncology, Technical University of Munich (TUM), developed an online-based questionnaire focusing on the indication, target definition, and treatment technique of lymph node irradiation in patients with breast cancer. The invitation to participate in the survey was sent to members of the German Society of Radiation Oncology (DEGRO) by e‑mail. The results of the survey were exported from the online platform into SPSS for a detailed analysis., Results: In total, 100 physicians completed the questionnaire between 05/2019 and 06/2019. Despite the existence of several treatment and contouring guidelines, we observed large variability of lymph node irradiation: The guideline recommendation for internal mammary irradiation is not consistently implemented in clinical practice and irradiation of the axilla after positive SLNB (sentinel lymph node biopsy) or ALND (axillary lymph node dissection) is handled very differently. Furthermore, in most clinics, the ESTRO (European Society for Therapeutic Radiology and Oncology) contouring consensus is not used, and PTV (planning target volume) definitions and margins vary considerably., Conclusion: Further clinical studies should be performed with a particular focus on radiotherapy for lymphatic drainage to support and amend the existing guidelines. These studies should establish a more standardized treatment of the lymph node regions in clinical practice. Quality assurance should enforce broad implementation of consensus recommendations.

Adjuvant radiotherapy is a key treatment in early-stage breast cancer. The meta-analysis by the Early Breast Cancer Trialist's Collaborative Group (EBCTCG) has demonstrated a decreased risk of locoregional relapse and death after whole-breast radiotherapy. Prophylactic lymph nodes irradiation in breast cancer has also proven to be beneficial in several therapeutic trials. At a time when three-dimensional conformal radiotherapy has become the standard procedure and with the development of intensity-modulated radiation therapy, defining nodal volumes is essential and practices should be harmonized to assess and compare the efficiency and toxicity of radiotherapy. Furthermore, the indication of lymph nodes irradiation has to take into account the risk/benefit balance as expanding the irradiated volume can increase radio-induced toxicity. Selection of patients receiving this treatment is essential. The aim of this update is to define nodal volumes, to precise the indications of their irradiation and to present the expected benefits as well as the potential side effects., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The aim of this study was to compare five different techniques for chest wall (CW) and lymphatic irradiation in patients with left-sided breast carcinoma., Methods: Three-dimensional conformal radiotherapy (3DCRT), forward-planned intensity-modulated radiotherapy (FP-IMRT), inverse-planned IMRT (IP-IMRT; 7- or 9-field), and hybrid IP-/FP-IMRT were compared in 10 patients. Clinical target volume (CTV) included CW and internal mammary (IM), supraclavicular (SC), and axillary nodes. Planning target volumes (PTVs), CTVs, and organs at risks (OARs) doses were analyzed with dose-volume histograms (DVHs)., Results: No differences could be observed among the techniques for doses received by 95% of the volume (D95%) of lymphatics. However, the FP-IMRT resulted in a significantly lower D95% dose to the CW-PTV compared to other techniques (P = 0.002). The 9-field IP-IMRT achieved the lowest volumes receiving higher doses (hotspots). Both IP-IMRT techniques provided similar mean doses (Dmean) for the left lung which were smaller than the other techniques. There was no difference between the techniques for maximum dose (Dmax) of right breast. However, FP-IMRT resulted in lower Dmean and volume of right breast receiving at least 5 Gy doses compared to other techniques., Conclusion: The dose homogeneity in CW-CTV was better using IMRT techniques compared to 3DCRT. Especially 9-field IP-IMRT provided a more homogeneous dose distribution in IM and axillary CTVs. Moreover, the OARs volumes receiving low radiation doses were larger with IP-IMRT technique, while volumes receiving high radiation doses were larger with FP-IMRT technique. Hybrid IMRT plans were found to have the advantages of both FP- and IP-IMRT techniques., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Stereotactic body radiation therapy is still controversial for inoperable patients with central lung lesion. We report the case of a 59-year-old woman with previous history of head and neck squamous cell carcinoma who was treated by lung stereotactic body irradiation for an inoperable lymph node in station 10R. One year after, a fibroscopy showed a necrosis of the right main bronchus mucosae and the CT showed a radio-induced aneurysm protruding into the right inferior lobular bronchus. The patient eventually died a few hours later with a massive haemoptysis. This case highlights the potential toxicity of central lung stereotactic body radiation therapy and raises the question of its legitimacy., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: To assess the comparative efficacy and safety of elective nodal irradiation (ENI) and involved-field irradiation (IFI) in patients with esophageal cancer (EC) receiving neoadjuvant chemoradiotherapy plus surgery (nCRTS)., Material and Methods: PubMed, Embase, Cochrane Library, Web of Science and major meetings were searched for randomized controlled trials (RCTs) that compared at least two of the following treatment regimens: nCRTS, neoadjuvant chemotherapy plus surgery (nCTS), and surgery (S) alone. Overall survival (OS) was the primary outcomes of interest, reported as hazard ratio (HR) and 95% confidence intervals (CIs). A Bayesian network meta-analysis was performed to compare all regimens simultaneously., Results: Twenty-nine RCTs with a total of 5212 patients were included in the meta-analysis. Both nCRTS adopting ENI (nCRTS-ENI) (HR = 0.63, 95% CI: 0.48-0.83) and nCRTS adopting IFI (nCRTS-IFI) (HR = 0.75, 95% CI: 0.66-0.86) significantly improved OS compared to S alone. No significant differences in OS, locoregional recurrence, distant metastases, R0 resection and postoperative mortality were observed between nCRTS-ENI and nCRTS-IFI. In subgroup analyses, nCRTS-IFI showed a significant OS advantage over nCTS (HR = 0.78, 95% CI: 0.63-0.96) and S alone (HR = 0.50, 95% CI: 0.38-0.68) for esophagus squamous cell carcinoma (ESCC), but nCRTS-ENI did not; nCRTS-ENI using three-dimensional radiotherapy (3D-RT) resulted in an improved OS compared to that with 2D-RT (HR = 0.58, 95% CI: 0.34-0.99). Based on treatment ranking in term of OS, nCRTS-IFI (0.90) and nCRTS-ENI (0.96) was ranked the most effective treatment for ESCC and esophagus adenocarcinoma (EAC), respectively., Conclusion: Either adopting ENI or IFI, nCRTS is likely to be the optimal treatment for resectable EC, and nCRTS-IFI and nCRTS-ENI seem to be more effective for patients with ESCC and EAC, respectively. Future head to head comparison trials are needed to confirm these findings.

Lung cancer treatment is a heavy workload for radiation oncologist and that field showed many evolutions over the last two decades. The issue about target volume was raised when treatment delivery became more precise with the development of three-dimensional conformal radiotherapy. Initially based upon surgical series, numerous retrospective and prospective studies aimed to evaluate the risk of elective nodal failure of involved-field radiotherapy compared to standard large field elective nodal irradiation. In every setting, locally advanced non-small cell lung cancer, localized non-small cell lung cancer, localized small cell lung cancer, exclusive chemoradiation or postoperative radiotherapy, most of the studies showed no significant difference between involved-field radiotherapy or elective nodal irradiation with elective nodal failure rate under 5% at 2 years, provided staging had been done with modern imaging and diagnostic techniques (positron emission tomography scan, endoscopy, etc.). Moreover, if reducing irradiated volumes are safe regarding recurrences, involved-field radiotherapy allowed dose escalation while reducing acute and late oesophageal, cardiac and pulmonary toxicities. Consequently, major clinical trials involving radiotherapy initiated in the last two decades and international clinical guidelines recommended omission of elective nodal irradiation in favour of in-field radiotherapy., (Copyright © 2019. Published by Elsevier Masson SAS.)

Purpose: The ongoing phase 2/3 PRODIGE 26/CONCORDE trial compares chemoradiation therapy with and without dose escalation in patients with locally advanced or unresectable esophageal cancer. The results of a benchmark case procedure are reported here to evaluate the protocol compliance of participating centers as part of quality assurance for radiation therapy., Methods and Materials: Volume delineation, target coverage, and dose constraints to the organs at risk (OARs) were assessed on treatment plans of a common benchmark case performed by each participating center. The centers were classified in 3 categories: per protocol, minor acceptable deviation (MiD), or major unacceptable deviation (MaD). A plan was rejected if ≥4 MiDs or 1 MaD were found., Results: Thirty-5 centers submitted 43 plans. Among them, 14 (32.6%) were per protocol, 19 (44.2%) presented at least 1 MiD, 2 (4.6%) presented at least 1 MaD, and 8 (18.6%) presented both MiD and MaD. Overall, 11 (25.6%) plans were rejected. Only 1 plan was rejected because gross tumor volume was not correctly delineated. The OAR delineation was respected in all cases. Dose constraints to the OARs were respected in the majority of cases except for the heart, where one-third of the plans presented a deviation. As for the target volume, 3 plans (5.8%) had a major underdosage and 1 plan (1.9%) had a major overdosage. Overall, 58% of all treatments were planned with intensity modulated radiation therapy, whereas 42% were planned with 3-dimensional chemoradiation therapy. Significantly more plans in the intensity modulated radiation therapy group were accepted compared with the 3-dimensional chemoradiation therapy group (P = .03)., Conclusion: The high frequency of protocol deviations underlines the importance of a quality assurance program in clinical trials. Further work should assess the impact of quality assurance for radiation therapy on patient outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The conservative treatment of squamous cell carcinoma of anal canal by irradiation is recommended as first indication. Despite its rarity, significant improvements were obtained by retrospective or prospective clinical studies these 20 past years, evaluating concomitant chemotherapy and IMRT. Nevertheless, the individualisation of the treatment, over dose distribution, has poor data available. Fractionation remains classic (1.8-2.0Gy/Fr), but the optimal dose level remains under discussion. The strategy concerning the volumes and doses for the prophylactic volumes remains under discussion. This paper will describe the data published, and the recommendations of working Groups, and the main options under evaluation. To conclude, today only the absence of gap is recommended, the benefit of a one-step schedule reducing the treatment time, then increasing local control and survival, but personalised schedules remain under investigation., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The selection of target volumes for head and neck cancer radiation therapy, particularly prophylactic volumes that reflect infra-clinic spreads, is a complex process. It is based on the knowledge of the natural history of these tumors and must take into consideration the special challenges due to the diversity and complexity of head and neck anatomy. The dosimetric and ballistic precision provided by modern radiation techniques has required strong strategic deliberation to ensure the relevance and reproducibility of target volumes. Specifically, regarding cervical lymph node volumes, two issues emerged. What lymph node area to select depending on the location and the staging of the primary tumor? How to convey that choice in the process of treatment planning and delivery? This debate has been progressively enriched over time resulting in the publication of several international guidelines to standardize the terminology of head and neck lymph node areas and to lay solid science-based foundations to drive practices. This abundance of information makes these guidelines complex, but their accurate understanding is required for adequate usage. We provide an overview of the main published recommendations for the selection of lymph node target volumes when treating oral cavity and pharyngo-laryngeal squamous cell carcinoma with radiation therapy., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Despite representing a 1% of diagnosed cancer cases in the USA and up to 5% in eastern Asia and Africa, oesophageal cancer still holds numerous questions concerning the best therapeutic management. For squamous cell carcinoma, while radiochemotherapy has proven itself to be the gold standard as part of the trimodality or alone as a definitive treatment, radiotherapy modalities are still debated especially regarding lymph node irradiation. Involved nodes irradiation was developed with the aim of maintaining clinical outcomes and enhancing quality of life but lacks grade 1 evidence. In this article, we aim to summarize the state of art regarding lymph node irradiation, discuss the impact of target definition, delivery techniques, concomitant treatment and the perspectives. Being highly connected to the lymph vessels, lymphatic metastases are frequent and can locate from the neck to the coeliac area with each node having a different prognostic significance. Regarding the comparison between elective nodal irradiation and involved nodes irradiation, evidence-based medicine mostly relies on retrospective studies. Pooled, it suggests similar clinical outcomes with lower acute toxicities in favour of involved nodes irradiation. However, delivery techniques, doses and concomitant treatment were not consensual. Studies are ongoing evaluating the impact of radiation delivery techniques and the choice of concomitant treatment, i.e. immunotherapy. Modern techniques of imaging, radiation therapy progressing each day and alternative treatment modalities being tested, the need of randomized controlled trials has never been so high. Elective nodal irradiation should remain the standard of care while phase 3 trials explore the safety of involved nodal irradiation., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The risk of lymph node invasion, in case of prostate cancer, increases with the clinical stage of the disease, the Gleason score of prostate biopsies and the value of PSA at diagnosis. Historically, beyond 15% risk of lymph node involvement, irradiation of the pelvic areas was performed with prostate radiotherapy (RT) to take into account the risk of occult lymph node metastasis in patients at risk, but the benefit of this therapeutic approach remains to be demonstrated. The data from surgical lymph node dissection seem to question the risk levels, the escalation of the dose on the prostate increases the survival without relapse, the contribution of image-guided radiotherapy, (IGRT) and modulation of intensity (IMRT), decreases the toxicity of pelvic RT. This article reviews the principles of prophylactic ganglion irradiation for prostate cancer and discusses its relevance, current uncertainties, and prospective trials., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Locoregional therapy for oligometastatic prostate cancer has generated great interest. However, its benefit for castration-resistant prostate cancer (CRPC) has not been fully demonstrated. Our objective was to evaluate the treatment outcome of progressive site-directed therapy (PSDT) for oligoprogressive CRPC (OP-CRPC)., Methods and Materials: This study cohort consisted of 101 patients with CRPC who underwent whole-body diffusion-weighted magnetic resonance imaging between 2014 and 2018, when a new line of anticancer therapy was being considered. For OP-CRPC, PSDT with radiation therapy and unchanged continuation of systemic therapy were recommended., Results: Thirty-eight patients received a diagnosis of OP-CRPC, and 23 (61%) underwent PSDT at a median prostate-specific antigen (PSA) level of 7.8 ng/mL. The regional radiation therapy targets were the prostate/pelvic lymph nodes (n = 7), bone (n = 15), or both (n = 1). A decrease in PSA levels of at least 50% in response to PSDT (50% PSA decline) was observed in 16 cases (70%); the median time to PSA progression was 8.7 months. Intrapelvic localization of progressive lesions was a significant predictor of time to PSA progression (hazard ratio, 6.6; P = .007) as well as volumes of abnormal signal intensity on whole-body diffusion-weighted magnetic resonance imaging (hazard ratio, 0.5; P = .045). A 50% PSA decline was achieved in 16 of the 18 patients with intrapelvic OP-CRPC (89%) and in none of the 5 patients with non-intrapelvic OP-CRPC (P < .001). Intrapelvic OP-CRPC had a significantly longer time to PSA progression than non-intrapelvic OP-CRPC (10.1 vs 4.8 months, P = .0014)., Conclusions: PSDT can be an effective treatment option for OP-CRPC. Progressive site localization was an important factor in good PSA response., (Copyright © 2019 Elsevier Inc. All rights reserved.)

There are many treatment options for localized prostate cancers, including active surveillance, brachytherapy, external beam radiotherapy, and radical prostatectomy. Quality of life remains a primary objective in the absence of superiority of one strategy over another in terms of specific survival with similar long-term biochemical control rates. Despite a significant decrease in digestive and urinary toxicities thanks to IMRT and IGRT, external radiotherapy remains a treatment that lasts approximately 2 months or 1.5 months, when combined with a brachytherapy boost. Given the specific radiosensitivity of this tumor, several randomized studies have shown that a hypofractionated scheme is not inferior in terms of biochemical control and toxicities, allowing to divide the number of fractions by a factor 2 to 8. Given that SBRT becomes a validated therapeutic option for a selected population of patients with localized prostate cancer, extreme hypofractionation is becoming a strong challenger of conventional external radiotherapy or brachytherapy., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The purpose of this article was to report the treatment effect of image-guided high-dose-rate interstitial brachytherapy boost in the radical radiotherapy for a huge metastatic carcinoma of cervical lymph nodes from an unknown primary site. The patient was a 75-year-old male. A diagnostic biopsy showed metastatic squamous cell carcinoma and the tumour size was 7.5×6.5×11.5cm 3 before treatment (N3; AJCC 7th). After external beam radiotherapy with a dose of 60Gy in 30 fractions, the residual tumour (6.2×4.7×6.0cm 3 ) was treated with image-guided high-dose-rate interstitial brachytherapy boost under ultrasound guidance. The brachytherapy dose was 16Gy in four fractions of 4Gy each. Removal of the huge metastatic tumour was securely achieved by high dose rate interstitial brachytherapy guided with ultrasound scanning. The refractory tumour in the patients healed uneventfully after image-guided high-dose-rate interstitial brachytherapy without recurrence during the 24 months of follow-up. The image-guided high-dose-rate interstitial brachytherapy boost may be a proposed treatment strategy for metastatic carcinoma of cervical lymph nodes from an unknown primary site with radical radiotherapy, especially for huge residual tumour., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

This article provides a proposal for the selection and delineation of clinical target volumes for the treatment with radiation of submandibular glands tumours. This article does not deal with external radiotherapy indications but specifies the volumes to be treated if radiotherapy is chosen. High-risk and low-risk peritumoral clinical target volumes are described based on the probability of local tumoral spread. High-risk and low-risk clinical target volumes are illustrated on CT-scan slices. A proposal for the selection of nodal clinical target volumeis also proposed., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Nonmyeloablative total lymphoid irradiation and antithymocyte globulin (TLI-ATG) conditioning is protective against graft-versus-host disease (GVHD), while retaining graft-versus-tumor activity across various hematologic malignancies. We report our comprehensive experience using TLI-ATG conditioning in 612 patients with hematologic malignancies who underwent allogeneic transplantation at Stanford University from 2001 to 2016. All patients received granulocyte colony-stimulating factor-mobilized peripheral blood grafts and cyclosporine and mycophenolate mofetil for GVHD prophylaxis. The median age was 60 years (range, 21-78), with a median follow-up of 6.0 years (range, 1.0-16.4). Common diagnoses included acute myeloid leukemia (AML; n = 193), myelodysplastic syndrome (MDS; n = 94), chronic lymphocytic leukemia (CLL; n = 80), non-Hodgkin lymphoma (NHL; n = 175), and Hodgkin lymphoma (HL; n = 35). Thirty-four percent of patients had a comorbidity index ≥3, 30% had a high to very high disease risk index, and 56% received unrelated donor grafts, including 15% with HLA-mismatched donors. Ninety-eight percent underwent transplant in the outpatient setting, and 57% were never hospitalized from days 0 through 100. The 1-year rates of nonrelapse mortality (NRM), grade II-IV acute GVHD, and extensive chronic GVHD were 9%, 14%, and 22%, respectively. The 4-year estimates for overall and progression-free survival were 42% and 32% for AML, 30% and 21% for MDS, 67% and 43% for CLL, 68% and 45% for NHL, and 78% and 49% for HL. Mixed chimerism correlated with the risk of relapse. TLI-ATG conditioning was well tolerated, with low rates of GVHD and NRM. Durable remissions were observed across hematologic malignancies, with particularly favorable outcomes for heavily pretreated lymphomas. Several efforts are underway to augment donor chimerism and reduce relapse rates while maintaining the favorable safety and tolerability profile of this regimen., (© 2019 by The American Society of Hematology.)

Purpose: Controversy surrounds the benefit of pelvic lymph node irradiation (PLN-RT) in localized prostate cancer (CaP). Our objective was to determine the practice patterns and predictors of PLN-RT in a national cohort., Materials and Methods: The National Cancer Data Base (2005-2015) was leveraged to obtain men diagnosed with nonmetastatic CaP treated with external beam radiotherapy (n = 197,378). Multivariable logistic regressions were used to assess temporal trends and factors associated with PLN-RT., Results: PLN-RT occurred in 37% of patients overall, which increased to 41% by 2015. When stratified by risk group, there was no significant difference in PLN-RT over time in low, favorable intermediate, unfavorable intermediate, or high-risk CaP. PLN-RT increased for men with very high-risk disease (51%-60%; odds ratio per year 1.34, 95% confidence inrerval 1.06-1.70, P = 0.013). Increased odds of PLN-RT was associated with higher risk disease, addition of hormone therapy, treatment at community hospitals, and shorter patient travel distance to treatment facilities. Surprisingly, 26% and 34% of low and favorable intermediate risk CaP received PLN-RT, respectively. Predictors of PLN-RT among these patients included treatment at a community practice and use of brachytherapy or hormone therapy., Conclusions: PLN-RT occurred in about one-third of men receiving external beam radiotherapy and increased over time, mostly in men with very high-risk CaP for unclear reasons. Of concern, over one-quarter of low-risk men receive PLN-RT. Further work is needed to understand the heterogeneity in PLN-RT use. We await the completion of RTO G 09-24 to better understand the role of PLN-RT for men with localized CaP., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: There is limited data on stereotactic ablative radiation therapy (SABR) in high-risk prostate cancer (PCa), especially regarding the role of elective nodal irradiation (ENI). This study compares 2 prospective phase 2 trials using SABR in high-risk PCa, with and without ENI., Methods and Materials: Patients had high-risk PCa. Those in trial 1 received 40 Gy in 5 fractions to the prostate and 30 Gy in 5 fractions to the seminal vesicles. Patients in trial 2 received 40 Gy in 5 fractions to the prostate and 25 Gy in 5 fractions to the pelvis and seminal vesicles. National Cancer Institute Common Terminology Criteria for Adverse Events toxicities were collected. Biochemical failure (BF) was defined as nadir + 2, and the 4-year prostate-specific antigen (PSA) response rate (4yPSARR) was <0.4 ng/mL., Results: Sixty patients were included (trial 1, n = 30; trial 2, n = 30). Median follow-up was 5.6 years and 4.0 years. The median nadir PSA was 0.02 ng/mL for both trials. Six patients had BF, all from trial 1. The BF rate was 14.6% at 5 years in trial 1 and 0% in trial 2. Sixty-three percent of patients in trial 1 and 93% in trial 2 had a 4yPSARR. Two patients died in trial 1, 1 from metastatic disease. One patient in trial 2 died of other causes. No other patients developed metastatic disease, and 1 patient in trial 1 had castrate resistant PCa. Overall survival at 5 years was 93.2% and 96.7% (P = .86). There was significantly worse late gastrointestinal and sexual toxicity in trial 1, but there was no difference in late genitourinary toxicity., Conclusions: SABR in high-risk PCa yields biochemical control rates that may be comparable to that of other radiation therapy modalities. ENI using SABR is feasible and may lead to a significant improvement in biochemical control and in 4yPSARR, without an increase in late gastrointestinal or genitourinary toxicity. Longer follow-up would provide a better assessment of biochemical control. Well-conducted phase 3 trials are needed to fully establish the role of SABR and ENI in high-risk PCa., (Copyright © 2018 Elsevier Inc. All rights reserved.)