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Purpose: The optimal management of locally recurrent prostate cancer after definitive irradiation is still unclear but local salvage treatments are gaining interest. A retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity after salvage I-125 low-dose-rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer was conducted in a Comprehensive Cancer Center., Patients and Methods: A total of 94 patients treated with salvage LDR-BT between 2006 and 2021 were included. The target volume was either the whole-gland +/- a boost on the GTV, the hemigland, or only the GTV. The prescribed dose ranged from 90 to 145 Gy. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0., Results: Median follow-up was 34 months. Initial radiotherapy was external beam radiotherapy in 73 patients (78 %) with a median dose of 76 Gy and I-125 BT in 21 patients (22 %) with a prescribed dose of 145 Gy. Median PSA at salvage was 3.75 ng/ml with a median interval between first and salvage irradiation of 9.4 years. Salvage brachytherapy was associated with androgen deprivation therapy for 32 % of the patients. Only 4 % of the patients were castrate-resistant. Failure free survival was 82 % at 2 years and 66 % at 3 years. The only factors associated with failure-free survival on multivariate analysis were hormonosensitivity at relapse and European Association of Urology (EAU) prognostic group. Late grade 3 urinary and rectal toxicities occurred in 12 % and 1 % of the patients respectively.No significant difference in toxicity or efficacy was observed between the three implant volume groups., Conclusion: The efficacy and toxicity results are consistent with those in the LDR group of the MASTER meta -analysis. Salvage BT confirms to be an effective and safe option for locally recurrent prostate cancer. A focal approach could be interesting to reduce late severe toxicities, especially urinary., 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 Author(s).)

Purpose: The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies., Materials and Methods: A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation., Results: This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases., Conclusion: Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer., (Copyright © 2024 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Extracranial stereotactic radiotherapy has developed recently, since the years 1990-2000. Devices specifically dedicated to this type of treatment were then developed and shared the favors of radiation oncologists: Tomotherapy® and especially Cyberknife®, which offered the advantage of "tracking" with the possibility of real time motion correction, allowing an increase in the precision of targeting volumes. Recently, the latest generations of linear accelerators (Linac) have been developed, integrating much higher dose rates, an improved ballistic precision with a very short treatment duration time and the possibility of real time motion management (with notably the possibility of adaptive radiotherapy in real time with the development of "MLC tracking"). So are Linacs able to perform equivalent (not inferior) extracranial stereotactic radiotherapy treatments to those with Cyberknife®, the historical gold standard in this field? This article presents a comparison of these two treatment devices, by successively considering dose distributions in the irradiated volume, distant received doses from this volume (including the "integral dose"), problems linked to the duration of the sessions and those linked to motion management., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The issue of radiation-induced cancers must be taken into consideration during therapeutic irradiations. Risk factors for radiation-induced cancer include: the age of the patients, the volumes irradiated, the presence of risk cofactors and the exposure of critical organs. Those should be part of the therapeutic decision, in terms of indication, as well as choice of the radiotherapy technique (including repositioning systems). We present the update of the recommendations of the French society for radiation oncology on the modalities for preventing radiation-induced cancers., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Prostate brachytherapy techniques are described, concerning both permanent seed implant and high dose rate brachytherapy. The following guidelines are presented: brachytherapy indications, implant procedure for permanent low dose rate implants and high dose rate with source projector, as well as dose and dose-constraints objectives, immediate postoperative management, post-treatment evaluation, and long-term follow-up., (Copyright © 2021. Published by Elsevier Masson SAS.)

Purpose: Focal brachytherapy (F-BT) is a suitable technique for focal therapy in localized prostate cancer. It has the ability to adapt the seed implantation to the volume and location of the tumor. The aim of this study was to assess F-BT oncologic, functional, and toxicity midterm outcomes in men who underwent prostate cancer treatment., Methods and Materials: The study included 39 men with low- to intermediate-risk prostate cancer treated with F-BT between 2010 and 2015. The dose prescription was 145 Gy. Failure was defined as the presence of any residual prostate cancer in the treated area. The primary and secondary endpoints were the F-BT oncologic and functional outcomes, respectively. A 2-sided P value < .05 indicated statistical significance., Results: The mean follow-up time was 65 months (range, 43-104 months). After 24 months, 34 patients underwent control biopsies and 5 patients refused. The biopsies were negative in 27 cases (79%) and positive in 7 cases (21%), all outside the volume treated. Biochemical relapse-free survival at 5 years, disease-free survival, and overall survival were 96.8% ± 0.032%, 79.5% ± 0.076%, and 100%, respectively. The mean International Prostate Symptom Score at 2 months was significantly higher than initially (P = .0003), with no significant difference later. No late urinary, sexual, or rectal toxicity was observed. Salvage treatment was possible with good tolerance at 3.4 years of follow-up. Limitations of this study include the retrospective nature and lack of randomization., Conclusions: F-BT is a safe and effective treatment for selected patients presenting with low- or intermediate-risk localized prostate cancer., (Copyright © 2021. Published by Elsevier Inc.)

The French society of oncological radiotherapy (Société française de radiothérapie oncologique, SFRO) was created in 1990. On the occasion of its thirtieth annual congress, in October 2019, a session was devoted to it, with the objective of exposing its functioning, its actions and its productions during these three decades during which radiotherapy and oncology have undergone unprecedented transformations. We propose in this article to outline the content of this session., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The evolution of SARS-CoV-2 pneumonia to acute respiratory distress syndrome is linked to a virus-induced "cytokine storm", associated with systemic inflammation, coagulopathies, endothelial damage, thrombo-inflammation, immune system deregulation and disruption of angiotensin converting enzyme signaling pathways. To date, the most promising therapeutic approaches in COVID-19 pandemic are linked to the development of vaccines. However, the fight against COVID-19 pandemic in the short and mid-term cannot only rely on vaccines strategies, in particular given the growing proportion of more contagious and more lethal variants among exposed population (the English, South African and Brazilian variants). As long as collective immunity is still not acquired, some patients will have severe forms of the disease. Therapeutic perspectives also rely on the implementation of strategies for the prevention of secondary complications resulting from vascular endothelial damage and from immune system deregulation, which contributes to acute respiratory distress and potentially to long term irreversible tissue damage. While the anti-inflammatory effects of low dose irradiation have been exploited for a long time in the clinics, few recent physiopathological and experimental data suggested the possibility to modulate the inflammatory storm related to COVID-19 pulmonary infection by exposing patients to ionizing radiation at very low doses. Despite level of evidence is only preliminary, these preclinical findings open therapeutic perspectives and are discussed in this article., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 François, Helissey, Cavallero, Drouet, Libert, Cosset, Deutsch, Meziani and Chargari.)

The irradiation of non-malignant diseases, essentially for anti-inflammatory purpose, have been largely proposed and performed worldwide until the 1970-80s. At that time, the better assessment of the radio-induced malignancies, essentially in children and young patients, as well as the efficacy of the new anti-inflammatory drugs (steroids and non-steroids), led to the almost disappearance of those techniques, at least in France. In contrast, our German colleagues are still going on treating about 50,000 patients per year for non-malignant (more or less severe) diseases. After a short historical overview, the present article suggests that we were possibly going too far in the rejection of those low-dose irradiations for benign lesions. The recent emergence of new preclinical data, the better understanding of the risk of radio-induced secondary tumours (almost nil in the elderly), and the severity of some situations, such as the cytokine storm of the COVID-19, should probably lead us to reconsider those low - and sometimes very low (less than 1Gy) - irradiations for well-selected indications in the elderly., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Fundamentals in radiobiology commonly known as the '4R's' concept (ie, reoxygenation, repair, redistribution, and repopulation) have mostly been investigated for external beam radiotherapy. However, these fundamentals can be applied to brachytherapy (BT) by accounting for differences in dose rate, fractionation, and response to immunologic agents for this treatment modality. Many improvements have been achieved in the era of dosimetric optimization but still limited data are available regarding radiobiological opportunities for BT. As BT is characterized by a large degree of dose heterogeneity, a wide range of dose rates and fractionations exist within the implanted volume. Calculations based on the linear quadratic model can be used to estimate the dose-response equivalence between various BT modalities. Such models are helpful in daily practice and open possibilities in terms of radiobiological optimization. However, some limitations should be highlighted in terms of the applicability of the linear quadratic model. Furthermore, in vitro models do not account for the complex interplay between the tumor and its microenvironment, including vascularization and/or immune response. Recently, an improved understanding of the tumor's microenvironment has led to investigations of immunomodulatory agents in combination with radiotherapy. BT is a promising candidate to enhance the immunogenic response with concomitant immunotherapy. This review summarizes some of the main mechanisms involved in tissue response to BT. Preclinical data, clinical evidence, as well as novel approaches to radiobiology are highlighted., (Copyright © 2019.)

Particle, essentially, proton radiotherapy (RT) could provide some benefits over photon RT, especially in reducing the side effects of RT. We performed a systematic review to identify the performed randomised clinical trials (RCTs) and ongoing RCTs comparing particle RT with photon therapy. So far, there are no results available from phase 3 RCTs comparing particle RT with photon therapy. Furthermore, the results on side effects comparing proton and carbon ion beam RT with photon RT do vary. The introduction of new techniques in photon RT, such as image-guided RT (IGRT), intensity-modulated RT (IMRT), volumetric arc therapy (VMAT) and stereotactic body RT (SBRT) was already effective in reducing side effects. At present, the lack of evidence limits the indications for proton and carbon ion beam RTs and makes the particle RT still experimental., Competing Interests: The authors declare that they have no conflicts of interest., (© the authors; licensee ecancermedicalscience.)

The decision to reirradiate a volume which had been previously irradiated remains in 2019 one of the most difficult challenge for a radiation oncologist. Such a decision has to be based on a number of clinical and technological criteria, and the radiation oncologist will have to answer three main questions: i) can the patient clinically tolerate a second irradiation in the same previously irradiated area? While waiting for fully reliable individual tests of radiosensitivity, one has to take into account the tolerance of the first irradiation, as well as the comorbidities and/or habits which could impact the patient intrinsic radiosensitivity; ii) do the technical data of the first radiotherapy allow a re-irradiation? Unfortunately, and essentially when the discussion of re-irradiating the patient occurs many years (or even decades) after the first treatment, those precise technical data can be missing; iii) which technique should be used for the re-irradiation? In such a specific situation, the patient should be offered the more precise modern technology: stereotactic radiotherapy, protons, brachytherapy (low-, high-, or pulsed-dose rate). The indisputable improvement of the ballistic precision linked to our new technologies should lead to refine and to develop the indications of re-irradiation in the next future., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

In 1999, Brenner and Hall reported for prostate cancer a very low alpha/beta ratio (1.5Gy). In the following years, this value has been confirmed by a large series of papers, so that this very low alpha/beta ratio became a "dogma", on which a large number of hypofractionated schemes were being built. This was logical, since this very low value strongly suggested a beneficial advantage of hypofractionation for prostate cancer. However, more recently, several questions arose; first, a number of authors reported, from the analysis of their own data, values of alpha/beta ratio which were higher than the "dogma". Secondly, the three modern "superiority trials", aiming at demonstrating the advantages of hypofractionated schemes, actually failed to show such a superiority, in spite of high equivalent doses (calculated with an alpha/beta of 1.5Gy), reaching up to 84 - 90Gy. In 2018, three review papers/metanalyses shed a new light on what could be the value of the alpha/beta ratio for prostate cancer. In particular, those studies took into account a "time factor" (for repopulation), a parameter which had been either forgotten or underestimated before. In those three studies, the alpha/beta ratio was ranging from 2.7Gy to 4.9Gy. Those data do confirm the sensitivity to the fraction dose variation of prostate cancer, but this sensitivity could be lower than suggested by an alpha/beta ratio of 1.5Gy., (Copyright © 2019. Published by Elsevier Masson SAS.)

For more than a decade, the majority of radiation oncology centres have been delivering intensity-modulated radiotherapy (then volumetric-modulated arctherapy) with 6 MV photons as their standard of care. This « dogma » had been supported by the usual absence of dosimetric advantages with high-energy photons (15 to 18 MV or more), at least for the planning target volume and the dose received by the adjacent organs at risk, and by the neutron component as soon as the photon energy exceeds 10 MV. Recent data could question such a dogma. First, in 2019, one cannot avoid taking into account the integral dose, delivered outside the treated volume. Actually, most available data show that integral dose is higher with low energy photons (as 6 MV) than with higher energies. Moreover, recent studies have shown that the neutron component at high energies may have been overestimated in the past; in fact, the neutron dose appears to be lower, and sometimes much lower, than the dose we accept for imaging. Finally, a few cohort studies did not show any increase in second cancers incidence after high-energy photon radiotherapy. In such a context, the American Association of Physicists in Medicine (AAPM) TG 158 document, released a few months ago, clearly states that there is a trade-off between high- and low-energy treatments. High-energy therapy is associated with neutron production, while low-energy therapy results in higher stray photon dose. According to the AAPM, « the optimal energy is likely an intermediate such as 10 MV »., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate the dose distribution of additional radioactive seeds implanted during salvage permanent prostate implant (sPPI) after a primary permanent prostate implant (pPPI)., Methods and Materials: Patients with localized prostate cancer were primarily implanted with iodine-125 seeds and had a dosimetric assessment based on day 30 postimplant CT (CT1). After an average of 6 years, these patients underwent sPPI followed by the same CT-based evaluation of dosimetry (CT2). Radioactive seeds on each CT were detected. The detected primary seeds on CT1 and CT2 were registered and then removed from CT2 referred as a modified CT2 (mCT2). Dosimetry evaluations (D 90 and V 100 ) of sPPI were performed with dedicated planning software on CT2 and mCT2. Indeed, prostate volume, D 90 , and V 100 differences between CT2 and either CT1 or mCT2 were calculated, and values were expressed as mean (standard deviation)., Results: The mean prostate volume difference between sPPI and pPPI over the 6 patients was 9.85 (7.32) cm 3 . The average D 90 and V 100 assessed on CT2 were 486.5 Gy (58.9) and 100.0% (0.0), respectively, whereas it was 161.3 Gy (47.5) and 77.3% (25.2) on mCT2 (p = 0.031 each time). The average D 90 the day of sPPI [145.4 Gy (11.2)] was not significantly different from that observed on mCT2 (p = 0.56)., Conclusion: Postimplant D 90 and V 100 of sPPI after pPPI can be estimated on CT images after removing the primary seeds., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Salvage brachytherapy after a first prostate radiation therapy is an emerging technique, which has to be considered in the therapeutic armamentarium in the clinically challenging context of patients with isolated local failure from prostate cancer who may still be considered for cure. These occult failures are more and more frequently diagnosed at an early stage, thanks to targeted biopsies and advances in imaging modalities, such as multiparametric MRI and PET-CT. Salvage brachytherapy benefits from the implantation accuracy of brachytherapy procedures using 3D dosimetry and has resulted in more than 50% tumour control rates with long-term. Incontinence rates are always below those of other salvage treatments such as radical prostatectomy, HIFU or cryotherapy. Today, a consensus has been reached to better define good candidates for salvage brachytherapy with respect to disease characteristics at baseline and at failure. No consensus has been clearly defined yet regarding the choice of the technique (low or high dose rate), the total dose to be delivered, or the volume to be implanted (whole gland or focal). While we await robust data from recently completed phase II studies and given the heterogeneous results in the literature, this technique (although already included in the last 2016 NCCN guidelines) remains to be precisely evaluated, optimally within the frame of controlled trials., (Copyright © 2017. Published by Elsevier SAS.)

Objective: To perform a state of the art about indications and limits of ablative therapies for localized prostate cancer., Methods: A review of the scientific literature was performed in Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of keywords. Publications obtained were selected based on methodology, language and relevance. After selection, 107 articles were analysed., Results: The objective to combine reduction of side effects and oncological control has induced recent development of several ablative therapies. Beyond this heterogeneity, some preferential indications appear: unilateral cancer of low risk (but with significant volume, excluding active surveillance) or intermediate risk (excluding majority of grade 4); treatment targeted the index lesion, by quarter or hemi-ablation, based on biopsy and mpMRI. In addition, indications must considered specific limits of each energy, such as gland volume and tumor localization., Conclusion: Based on new imaging and biopsy, ablative therapies will probably increased its role in the future in management of localize prostate cancer. The multiple ongoing trials will certainly be helpful to better define their indications and limits., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: To perform a state of the art about methods of evaluation and present results in ablative therapies for localized prostate cancer., Methods: A review of the scientific literature was performed in Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of keywords. Publications obtained were selected based on methodology, language and relevance. After selection, 102 articles were analysed., Results: Analyse the results of ablative therapies is presently difficult considering the heterogeneity of indications, techniques and follow-up. However, results from the most recent and homogeneous studies are encouraging. Oncologically, postoperative biopsies (the most important criteria) are negative (without any tumor cells in the treated area) in 75 to 95%. Functionally, urinary and sexual pre-operative status is spared (or recovered early) in more than 90% of the patients treated. More and more studies underline also the correlation between the results and the technique used considering the volume of the gland and, moreover, the "index lesion" localization., Conclusion: The post-treatment pathological evaluation by biopsies (targeted with MRI or, perhaps in a near future, with innovative ultrasonography) is the corner stone of oncological evaluation of ablative therapies. Ongoing trials will allow to standardize the follow-up and determine the best indication and the best techniques in order to optimize oncological and functional results for each patient treated., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

For prostate cancer, hypofractionation has been based since 1999 on radiobiological data, which calculated a very low alpha/beta ratio (1.2 to 1.5Gy). This suggested that a better local control could be obtained, without any toxicity increase. Consequently, two types of hypofractionated schemes were proposed: "moderate" hypofractionation, with fractions of 2.5 to 4Gy, and "extreme" hypofractionation, utilizing stereotactic techniques, with fractions of 7 to 10Gy. For moderate hypofractionation, the linear-quadratic (LQ) model has been used to calculate the equivalent doses of the new protocols. The available trials have often shown a "non-inferiority", but no advantage, while the equivalent doses calculated for the hypofractionated arms were sometimes very superior to the doses of the conventional arms. This finding could suggest either an alpha/beta ratio lower than previously calculated, or a negative impact of other radiobiological parameters, which had not been taken into account. For "extreme" hypofractionation, the use of the LQ model is discussed for high dose fractions. Moreover, a number of radiobiological questions are still pending. The reduced overall irradiation time could be either a positive point (better local control) or a negative one (reduced reoxygenation). The prolonged duration of the fractions could lead to a decrease of efficacy (because allowing for reparation of sublethal lesions). Finally, the impact of the large fractions on the microenvironment and/or immunity remains discussed. The reported series appear to show encouraging short to mid-term results, but the results of randomized trials are still awaited. Today, it seems reasonable to only propose those extreme hypofractionated schemes to well-selected patients, treating small volumes with high-level stereotactic techniques., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)