@article{pmid35087753,

title = {Cost and Toxicity Comparisons of Two IMRT Techniques for Prostate Cancer: A Micro-Costing Study and Weighted Propensity Score Analysis Based on a Prospective Study},

author = {Ingrid Masson and Martine Bellanger and Geneviève Perrocheau and Marc-André Mahé and David Azria and Pascal Pommier and Nathalie Mesgouez-Nebout and Philippe Giraud and Didier Peiffert and Bruno Chauvet and Philippe Dudouet and Naji Salem and Georges Noël and Jonathan Khalifa and Igor Latorzeff and Catherine Guérin-Charbonnel and Stéphane Supiot},

doi = {10.3389/fonc.2021.781121},

issn = {2234-943X},

year  = {2022},

date = {2022-01-11},

urldate = {2021-01-01},

journal = {Front Oncol},

volume = {11},

pages = {781121},

abstract = {Background: Intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation.



Material and Methods: We used data from the "RCMI pelvis" prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting.



Results: The mean total cost for HT, €2019 3,069 (95% CI, 2,885-3,285) was significantly higher than the mean cost for VMAT €2019 2,544 (95% CI, 2,443-2,651) (p <.0001). The mean ± SD labor and accelerator cost for HT was €2880 (± 583) and €1978 (± 475) for VMAT, with 81 and 76% for accelerator, respectively. Acute GI and GU toxicity were more frequent in VMAT than in HT (p = .021 and p = .042, respectively). Late toxicity no longer differed between the two groups up to 24 months after completion of treatment.



Conclusion: Use of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35070993,

title = {Mapping of Recurrence Sites Following Adjuvant or Salvage Radiotherapy for Prostate Cancer Patients},

author = {Ana Gonzalez-Moya and Stéphane Supiot and Valérie Seegers and Thibaut Lizée and Florence Legouté and Tanguy Perennec and Gilles Calais},

doi = {10.3389/fonc.2021.787347},

issn = {2234-943X},

year  = {2022},

date = {2022-01-05},

urldate = {2021-01-01},

journal = {Front Oncol},

volume = {11},

pages = {787347},

abstract = {Introduction: Although salvage and adjuvant radiotherapy (RT) are effective in prostate cancer (PC) patients, 30%-40% of men will have disease progression. The objective was to describe the pattern of recurrence in PC patients with biochemical failure (BF) following postoperative RT.



Methods: We retrospectively analyzed 935 PC patients treated from 2009 to 2019 with adjuvant or salvage RT at the Institut de Cancérologie de l'Ouest. Of these, 205 (22%) developed BF of whom 166 underwent imaging. Patients with identified radiologic failure prior any specific treatment were included to determine the site of relapse categorized as local (L)-only, locoregional (LR), or metastatic (M) recurrence. Main disease characteristics and RT fields were examined in relation to sites of recurrence.



Results: One hundred forty-one patients were identified with 244 sites of failure on imaging. Of these, 108 patients had received RT to the PB alone and 33 RT to the PB and pelvic lymph nodes (PB+PLN). Androgen-deprivation therapy was used concomitantly in 50 patients (35%). The median PSA at imaging was 1.6 ng/ml (range, 0-86.7). In all, 74 patients (52%) had M disease (44% in the PB group and 79% in the PB+PLN group), 61 (43%) had LR failure (52% in the PB alone group and 15% in the PB+PLN group), and six (4%) had L-only failure, at a median of 26.7 months (range, 5-110.3) from RT. Metastases were in extra-pelvic LN (37 (15%)), bones (66 (27%)), and visceral organs (eight (3%)). Fifty-three (48%) of the pelvic LN failures in the PB group would have been encompassed by standard PLN RT volume.



Conclusion: We found that most patients evaluated for BF after postoperative RT recurred outside the RT field. Isolated pelvic nodal failure was rare in those receiving RT to the PB+PLN but accounted for half of failures in those receiving PB alone RT. Imaging directed salvage treatment could be helpful to personalize radiation therapy plan.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34816023,

title = {Cytokine release syndrome and tumor lysis syndrome in a multiple myeloma patient treated with palliative radiotherapy: A case report and review of the literature},

author = {Axel Cailleteau and Cyrille Touzeau and Bastien Jamet and Valentine Guimas and Emmanuel Jouglar and Stéphane Supiot},

doi = {10.1016/j.ctro.2021.11.004},

issn = {2405-6308},

year  = {2022},

date = {2022-01-01},

urldate = {2021-11-12},

journal = {Clin Transl Radiat Oncol},

volume = {32},

pages = {24--28},

abstract = {We present the case of a 53-year-old woman treated with analgesic radiotherapy for a multiple myeloma bone lesion of the forearm. After a first fraction of 5 Gray (Gy), she presented with an acute respiratory syndrome with fever a few hours after the treatment. The same symptoms occurred after the second fraction 3 days later. The patient recovered quickly thanks to intravenous hydration and suspension of the radiotherapy. Biological tests revealed a tumor lysis syndrome. We concluded that the clinical symptoms could be defined as cytokine release syndrome. This is the second time in the literature that cytokine release syndrome has been described following radiotherapy. First, we synthesize TLS and radiotherapy to determine how radiotherapy could be a trigger associated with other well-known factors. Furthermore, we discuss radiotherapy and cytokine release syndrome.



Summary: We present the case of a woman treated with analgesic radiotherapy for a multiple myeloma bone lesion. Following the first and the second treatment fraction, the patient presented with an acute respiratory syndrome with fever and biological tests revealed a tumor lysis syndrome. We concluded that the clinical symptoms could be defined as cytokine release syndrome. Furthermore, we discuss how radiotherapy could be a trigger of cytokine release syndrome and tumor lysis syndrome in association with chemotherapy drugs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34969622,

title = {Guide for paediatric radiotherapy procedures},

author = {A Laprie and V Bernier and L Padovani and V Martin and C Chargari and S Supiot and L Claude},

doi = {10.1016/j.canrad.2021.11.018},

issn = {1769-6658},

year  = {2021},

date = {2021-12-27},

urldate = {2021-12-27},

journal = {Cancer Radiother},

abstract = {A third of children with cancer receive radiotherapy as part of their initial treatment, which represents 800 paediatric irradiations per year in France carried out in 15 specialized centres approved on the recommendations of the French national cancer institute in decreasing order of frequency, the types of cancer that require irradiation are: brain tumours, neuroblastomas, Ewing's sarcomas, Hodgkin's lymphomas, soft tissue sarcomas including rhabdomyosarcomas, and nephroblastomas. The treatment guidelines follow the recommendations of the French society for childhood cancers (SFCE) or the French and European prospective protocols. The therapeutic indications, the technical and/and ballistic choices of complex cases are frequently discussed during bimonthly paediatric radiotherapy technical web-conferences. All cancers combined, overall survival being 80%, long-term toxicity logically becomes an important concern, making the preparation of treatments complex. The irradiation methods include all the techniques currently available: 3D conformational irradiation, intensity modulation radiation therapy, irradiation under normal or hypofractionated stereotaxic conditions, brachytherapy and proton therapy. We present the update of the recommendations of the French society for radiation oncology on the indications, the technical methods of realization and the organisation and the specificities of paediatric radiation oncology.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{pmid35004302,

title = {Drug Intensification in Future Postoperative Radiotherapy Practice in Biochemically-Relapsing Prostate Cancer Patients},

author = {Axel Cailleteau and Paul Sargos and Fred Saad and Igor Latorzeff and Stéphane Supiot},

doi = {10.3389/fonc.2021.780507},

issn = {2234-943X},

year  = {2021},

date = {2021-12-24},

urldate = {2021-01-01},

journal = {Front Oncol},

volume = {11},

pages = {780507},

abstract = {Although salvage prostate bed radiotherapy is highly effective in biochemically-relapsing prostate cancer patients following prostatectomy, relapses remain frequent and improvements are needed. Randomized phase 3 trials have shown the benefit of adding androgen-depriving therapy to irradiation, but not all patients benefit from this combination. Preclinical studies have shown that novel agents targeting the androgen receptor, DNA repair, PI3K/AKT/mTOR pathways, or the hypoxic microenvironment may help increase the response to prostate bed irradiation while minimizing potential side effects. This perspective review focuses on the most relevant molecules that may have an impact when combined with salvage radiotherapy, and underlines the strategies that need to be developed to increase the efficacy of salvage post-prostatectomy radiotherapy in prostate cancer patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34955419,

title = {External radiotherapy for prostatic cancers},

author = {R de Crevoisier and S Supiot and G Créhange and P Pommier and I Latorzeff and O Chapet and D Pasquier and P Blanchard and U Schick and V Marchesi and P Sargos and C Hennequin},

doi = {10.1016/j.canrad.2021.11.017},

issn = {1769-6658},

year  = {2021},

date = {2021-12-20},

urldate = {2021-12-20},

journal = {Cancer Radiother},

abstract = {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.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{pmid34953712,

title = {Specificities of clinical research in radiotherapy},

author = {C Hennequin and D Azria and P Blanchard and G Créhange and É Deutsch and A Lisbona and É Moyal and D Pasquier and L Roca and S Supiot and P Giraud},

doi = {10.1016/j.canrad.2021.11.011},

issn = {1769-6658},

year  = {2021},

date = {2021-12-16},

urldate = {2021-12-16},

journal = {Cancer Radiother},

abstract = {The aim of this review is to present the specificities of clinical research in radiation oncology. Objectives are similar to all research in oncology: to improve the efficacy and to decrease toxic effects. Phase III trials remain the main methodology to demonstrate an improvement in efficiency, but phase I-II and registers are also important tools to validate an improvement in the therapeutic index with new technologies. In this article we discuss the special features of end-points, selection of population, and design for radiation oncology clinical trials. Quality control of delivered treatments is an important component of these protocols. Financial issues are also discussed, in the particular context of France.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{pmid34885179,

title = {Oncologic Impact and Safety of Pre-Operative Radiotherapy in Localized Prostate and Bladder Cancer: A Comprehensive Review from the Cancerology Committee of the Association Française d'Urologie},

author = {Paul Sargos and Stéphane Supiot and Gilles Créhange and Gaëlle Fromont-Hankard and Eric Barret and Jean-Baptiste Beauval and Laurent Brureau and Charles Dariane and Gaëlle Fiard and Mathieu Gauthé and Romain Mathieu and Guilhem Roubaud and Alain Ruffion and Raphaële Renard-Penna and Yann Neuzillet and Morgan Rouprêt and Guillaume Ploussard},

editor = {MDPI},

doi = {10.3390/cancers13236070},

issn = {2072-6694},

year  = {2021},

date = {2021-12-01},

urldate = {2021-12-01},

journal = {Cancers (Basel)},

volume = {13},

number = {23},

abstract = {Preoperative radiotherapy (RT) is commonly used for the treatment of various malignancies, including sarcomas, rectal, and gynaecological cancers, but it is preferentially used as a competitive treatment to radical surgery in uro-oncology or as a salvage procedure in cases of local recurrence. Nevertheless, preoperative RT represents an attractive strategy to prevent from intraoperative tumor seeding in the operative field, to sterilize microscopic extension outside the organ, and to enhance the pathological and/or imaging tumor response rate. Several clinical works support this research field in uro-oncology. In this review article, we summarized the oncologic impact and safety of preoperative RT in localized prostate and muscle-invasive bladder cancer. Preliminary studies suggest that both modalities can be complementary as initial primary tumor treatments and that a pre-operative radiotherapy strategy could be beneficial in a well-defined population of patients who are at a very high-risk of local relapse. Future prospective trials are warranted to evaluate the oncologic benefit of such a combination of local treatments in addition to new life-prolonging systemic therapies, such as immunotherapy, and new generation hormone therapies. Moreover, the safety and the feasibility of salvage surgical procedures due to non-response or local recurrence after pelvic RT remain poorly evaluated in that context.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34955420,

title = {Radiotherapy of bone metastases},

author = {S Thureau and S Supiot and E Jouglar and M Rogé and L Lebret and A Hadj Henni and G Beldjoudi and J-L Lagrange and J-C Faivre},

doi = {10.1016/j.canrad.2021.11.021},

issn = {1769-6658},

year  = {2021},

date = {2021-12-01},

urldate = {2021-12-01},

journal = {Cancer Radiother},

abstract = {We present the update of the recommendations of the French society of oncological radiotherapy on bone metastases. This is a common treatment in the management of patients with cancer. It is a relatively simple treatment with proven efficacy in reducing pain or managing spinal cord compression. More complex treatments by stereotaxis can be proposed for oligometastatic patients or in case of reirradiation. In this context, increased vigilance should be given to the risks to the spinal cord.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{pmid34881187,

title = {Post-Operative Radiotherapy in Prostate Cancer: Is It Time for a Belt and Braces Approach?},

author = {Nicolas Giraud and Nicolas Benziane-Ouaritini and Ulrike Schick and Jean-Baptiste Beauval and Ahmad Chaddad and Tamim Niazi and Mame Daro Faye and Stéphane Supiot and Paul Sargos and Igor Latorzeff},

doi = {10.3389/fonc.2021.781040},

issn = {2234-943X},

year  = {2021},

date = {2021-11-18},

urldate = {2021-11-18},

journal = {Front Oncol},

volume = {11},

pages = {781040},

abstract = {Approximately 30% of patients treated with radical prostatectomy (RP) for prostate cancers experience biochemical recurrence (BCR). Post-operative radiation therapy (RT) can be either offered immediately after the surgery in case of aggressive pathological features or proposed early if BCR occurs. Until recently, little data were available regarding the optimal RT timing, protocol, volumes to treat, and the benefit of adding androgen deprivation therapies to post-operative RT. In this review, we aim to pragmatically discuss current literature data on these points. Early salvage RT appears to be the optimal post-operative approach, improving oncological outcomes especially with low prostate-specific antigen (PSA) levels, as well as sparing several unnecessary adjuvant treatments. The standard RT dose is still 64-66 Gy to the prostate bed in conventional fractionation, but hypofractionation protocols are emerging pending on late toxicity data. Several scientific societies have published contouring atlases, even though they are heterogeneous and deserve future consensus. During salvage RT, the inclusion of pelvic lymph nodes is also controversial, but preliminary data show a possible benefit for PSA > 0.34 ng/ml at the cost of increased hematological side effects. Concomitant ADT and its duration are also discussed, possibly advantageous (at least in terms of metastasis-free survival) for PSA rates over 0.6 ng/ml, taking into account life expectancy and cardiovascular comorbidities. Intensified regimens, for instance, with new-generation hormone therapies, could further improve outcomes in carefully selected patients. Finally, recent advances in molecular imaging, as well as upcoming breakthroughs in genomics and artificial intelligence tools, could soon reshuffle the cards of the current therapeutic strategy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34391651,

title = {[Postoperative radiotherapy for prostate cancer: when to propose it? What is the place for androgen deprivation?]},

author = {N Benziane-Ouaritini and P Sargos and J B Beauval and S Supiot and I Latorzeff},

doi = {10.1016/j.canrad.2021.07.005},

issn = {1769-6658},

year  = {2021},

date = {2021-10-25},

urldate = {2021-10-01},

journal = {Cancer Radiother},

volume = {25},

number = {6-7},

pages = {667--673},

abstract = {PURPOSE: While there is no high-level evidence showing superiority of surgery over radiation treatment, radical prostatectomy is the most common treatment option for patients with localized, non-metastatic disease. Nearly 30% of all patients undergoing surgery will develop a biochemical recurrence in 10 years. In fact, more than 30% of contemporary patients treated with RP will harbor aggressive disease characteristics at final pathology.



MATERIAL AND MEHODS: We conducted a review of the literature evaluating the timing of radiotherapy and the place of androgen deprivation after prostatectomie totale.



RESULTS: Four trials randomizing adjuvant radiotherapy and surveillance found an advantage in biochemical relapse-free survival in favor of immediate irradiation after radical prostatectomy, called adjuvant. However, in these studies, more than 40% of patients in the arm without adjuvant radiotherapy did not relapse at 10 years of follow-up. More recently, the question of the optimal time of this post-operative, adjuvant RT or during biological relapse has arisen through three trials (RADICALS-RT, RAVES, GETUG-AFU 17). These trials did not show a benefit for adjuvant radiotherapy in terms of event-free survival, a PSA-based endpoint, while confirming the toxicities observed during irradiation immediately after surgery. The optimal duration of hormonal therapy when associated with post-prostatectomy radiation therapy remains controversial.



CONCLUSION: Early salvage radiotherapy is a new standard of treatment and adjuvant radiotherapy could be reserved for very selected patients. The role of hormone therapy is well defined in salvage situation, but its duration is still being studied.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34391648,

title = {[Combination radiotherapy-immunotherapy in genitourinary cancer]},

author = {L Ollivier and V Guimas and E Rio and L Vaugier and I Masson and V Libois and M Labbé and D Fradin and V Potiron and S Supiot},

doi = {10.1016/j.canrad.2021.06.033},

issn = {1769-6658},

year  = {2021},

date = {2021-10-21},

urldate = {2021-10-01},

journal = {Cancer Radiother},

volume = {25},

number = {6-7},

pages = {565--569},

abstract = {Immunotherapy occupies a growing place in urologic oncology, mainly for kidney and bladder cancers. On the basis of encouraging preclinical work, the combination of immunotherapy with radiotherapy aims to increase the tumor response, including in metastatic tumors, which raises many hopes, which this article reviews.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34503149,

title = {Stereotactic Re-Irradiation for Local Recurrence after Radical Prostatectomy and Radiation Therapy: A Retrospective Multicenter Study},

author = {Tanguy Perennec and Loig Vaugier and Alain Toledano and Nathaniel Scher and Astrid Thomin and Yoann Pointreau and Guillaume Janoray and Renaud De Crevoisier and Stéphane Supiot},

doi = {10.3390/cancers13174339},

issn = {2072-6694},

year  = {2021},

date = {2021-08-01},

urldate = {2021-08-01},

journal = {Cancers (Basel)},

volume = {13},

number = {17},

abstract = {Prostate cancer recurrence in patients previously treated with radical prostatectomy and radiation therapy is challenging. Re-irradiation could be an option, but data regarding efficacy and safety are lacking. We retrospectively evaluated salvage re-irradiation for local recurrence after prostatectomy and external beam radiation therapy. We collected data from 48 patients who underwent salvage reirradiation with stereotactic radiation therapy for local prostate cancer recurrence in the prostatic bed at four French centers. Fifteen patients (31%) were on androgen deprivation therapy during stereotactic radiotherapy. Biochemical response and relapse-free survival were analyzed, and post-treatment toxicities were assessed according to the Common Terminology of Adverse Events criteria. Five patients had grade 3 late bladder toxicity (cystitis), three had grade 3 late incontinence, and one had grade 3 late chronic pain. At three months, 83% of patients had a positive biochemical response. The median follow-up was 22 months. At the end of the follow-up, 21 patients (43%) had a biochemical relapse. The median time to biologic relapse was 27 months. The biochemical relapse rates at 1 and 2 years were 80% and 52%, respectively. In conclusion, salvage re-irradiation for recurrent prostate cancer in the prostate bed may generate significant toxicity rates, and a prospective study with appropriate patient selection is needed to evaluate its effectiveness.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34221983,

title = {Late Gastrointestinal Tolerance After Prostate Radiotherapy: Is the Anal Canal the Culprit? A Narrative Critical Review},

author = {Paul Sargos and Mame Daro Faye and Manon Bacci and Stéphane Supiot and Igor Latorzeff and David Azria and Tamim M Niazi and Te Vuong and Véronique Vendrely and Renaud de Crevoisier},

doi = {10.3389/fonc.2021.666962},

issn = {2234-943X},

year  = {2021},

date = {2021-06-16},

urldate = {2021-01-01},

journal = {Front Oncol},

volume = {11},

pages = {666962},

abstract = {Introduction: Late gastro-intestinal toxicities (LGIT) secondary to pelvic radiotherapy (RT) are well described in the literature. LGIT are mainly related to rectal or ano-rectal irradiation; however, involvement of the anal canal (AC) in the occurrence of LGIT remains poorly described and understood.



Materials and Methods: The aim of this work was to explore the potential role of the AC in the development of LGIT after prostate irradiation and identify predictive factors that could be optimized in order to limit these toxicities. This narrative literature review was realized using the Pubmed database. We identified original articles published between June 1997 and July 2019, relating to LGIT after RT for localized prostate cancer and for which AC was identified independently. Articles defining the AC as part of an anorectal or rectal volume only were excluded.



Results: A history of abdominal surgery or cardio-vascular risk, anticoagulant or tobacco use, and the occurrence of acute GIT during RT increases the risk of LGIT. A dose-effect relationship was identified between dose to the AC and development of LGIT. Identification and contouring of the AC and adjacent anatomical structures (muscles or nerves) are justified to apply specific dose constraints. As a limitation, our review mainly considered on 3DCRT which is no longer the standard of care nowadays; we did not identify any reports in the literature using moderately hypofractionated RT for the prostate and AC specific dosimetry.



Conclusion: These results suggest that the AC may have an important role in the development of LGIT after pelvic RT for prostate cancer. The individualization of the AC during planning should be recommended in prospective studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33920758,

title = {A Monte Carlo Determination of Dose and Range Uncertainties for Preclinical Studies with a Proton Beam},

author = {Arthur Bongrand and Charbel Koumeir and Daphnée Villoing and Arnaud Guertin and Ferid Haddad and Vincent Métivier and Freddy Poirier and Vincent Potiron and Noël Servagent and Stéphane Supiot and Grégory Delpon and Sophie Chiavassa},

doi = {10.3390/cancers13081889},

issn = {2072-6694},

year  = {2021},

date = {2021-04-15},

urldate = {2021-04-01},

journal = {Cancers (Basel)},

volume = {13},

number = {8},

abstract = {Proton therapy (PRT) is an irradiation technique that aims at limiting normal tissue damage while maintaining the tumor response. To study its specificities, the ARRONAX cyclotron is currently developing a preclinical structure compatible with biological experiments. A prerequisite is to identify and control uncertainties on the ARRONAX beamline, which can lead to significant biases in the observed biological results and dose-response relationships, as for any facility. This paper summarizes and quantifies the impact of uncertainty on proton range, absorbed dose, and dose homogeneity in a preclinical context of cell or small animal irradiation on the Bragg curve, using Monte Carlo simulations. All possible sources of uncertainty were investigated and discussed independently. Those with a significant impact were identified, and protocols were established to reduce their consequences. Overall, the uncertainties evaluated were similar to those from clinical practice and are considered compatible with the performance of radiobiological experiments, as well as the study of dose-response relationships on this proton beam. Another conclusion of this study is that Monte Carlo simulations can be used to help build preclinical lines in other setups.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33186618,

title = {Prostate Bed Delineation Guidelines for Postoperative Radiation Therapy: On Behalf Of The Francophone Group of Urological Radiation Therapy},

author = {Sophie Robin and Marjory Jolicoeur and Samuel Palumbo and Thomas Zilli and Gilles Crehange and Olivier De Hertogh and Talar Derashodian and Paul Sargos and Carl Salembier and Stéphane Supiot and Corina Udrescu and Olivier Chapet},

doi = {10.1016/j.ijrobp.2020.11.010},

issn = {1879-355X},

year  = {2021},

date = {2021-04-01},

urldate = {2021-01-01},

journal = {Int J Radiat Oncol Biol Phys},

volume = {109},

number = {5},

pages = {1243--1253},

abstract = {PURPOSE: Prostate bed (PB) irradiation is considered the standard postoperative treatment after radical prostatectomy (RP) for tumors with high-risk features or persistent prostate-specific antigen, or for salvage treatment in case of biological relapse. Four consensus guidelines have been published to standardize practices and reduce the interobserver variability in PB delineation but with discordant recommendations. To improve the reproducibility in the PB delineation, the Francophone Group of Urological Radiotherapy (Groupe Francophone de Radiothérapie Urologique [GFRU]) worked to propose a new and more reproducible consensus guideline for PB clinical target volume (CTV) definition.



METHODS AND MATERIALS: A 4-step procedure was used. First, a group of 10 GFRU prostate experts evaluated the 4 existing delineation guidelines for postoperative radiation therapy (European Organization for Research and Treatment of Cancer; the Faculty of Radiation Oncology Genito-Urinary Group; the Radiation Therapy Oncology Group; and the Princess Margaret Hospital) to identify divergent issues. Second, data sets of 50 magnetic resonance imaging studies (25 after RP and 25 with an intact prostate gland) were analyzed to identify the relevant anatomic boundaries of the PB. Third, a literature review of surgical, anatomic, histologic, and imaging data was performed to identify the relevant PB boundaries. Fourth, a final consensus on PB CTV definition was reached among experts.



RESULTS: Definitive limits of the PB CTV delineation were defined using easily visible landmarks on computed tomography scans (CT). The purpose was to ensure a better reproducibility of PB definition for any radiation oncologist even without experience in postoperative radiation therapy.



CONCLUSIONS: New recommendations for PB delineation based on simple anatomic boundaries and available as a CT image atlas are proposed by the GFRU. Improvement in uniformity in PB CTV definition and treatment homogeneity in the context of clinical trials are expected.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33762148,

title = {Perineal recurrence of prostate cancer along a brachytherapy needle track: A case report},

author = {I Sidibe and M Le Blanc-Onfroy and G Delpon and E Rio and M Crepel and M Lacour and J Rigaud and S Cazin and S Supiot},

doi = {10.1016/j.canrad.2020.06.027},

issn = {1769-6658},

year  = {2021},

date = {2021-03-21},

urldate = {2021-03-21},

journal = {Cancer Radiother},

volume = {25},

number = {5},

pages = {476--479},

abstract = {Metastatic recurrence in an atypical site, such as the perineum, can occur after prostatectomy, cryotherapy, or brachytherapy, but is uncommon. To our knowledge, this is only the third case of perineal recurrence of prostatic cancer along a low dose rate brachytherapy needle track. A 64-year-old man was referred to an urologist with an increased PSA of 6.9ng/mL in December 2008. There were no urinary symptoms. Prostatic biopsies revealed a Gleason 6 adenocarcinoma (3+3), and he was treated with low dose rate brachytherapy in May 2009. Sixty-seven seeds of iodine 125 were loaded under ultrasound control, and the PSA subsequently fell to a nadir of 1.19ng/mL in November 2015. Eight years (May 2017) after the initial treatment, the PSA rose to 5.2ng/mL. Pelvic MRI and choline PET revealed a nodule in the region of the left internal obturator muscle. Nodule biopsies confirmed prostatic origin. This perineal recurrence is thus most likely related to seeding of tumour cells along the track of a brachytherapy needle. To our knowledge, this is only the fourth case of perineal recurrence of prostatic cancer along a low-dose rate brachytherapy needle track. Perineal recurrence of prostatic cancer along a LDR brachytherapy needle track can occur. Improved imaging techniques may help to identify this type of recurrence earlier and optimise treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33137397,

title = {Towards homogenization of total body irradiation practices in pediatric patients across SIOPE affiliated centers. A survey by the SIOPE radiation oncology working group},

author = {Bianca A W Hoeben and Montserrat Pazos and Michael H Albert and Enrica Seravalli and Mirjam E Bosman and Christoph Losert and Tom Boterberg and Farkhad Manapov and Inna Ospovat and Soraya Mico Milla and Candan Demiroz Abakay and Jacob Engellau and Gregor Kos and Stéphane Supiot and Marc Bierings and Geert O Janssens},

doi = {10.1016/j.radonc.2020.10.032},

issn = {1879-0887},

year  = {2021},

date = {2021-02-01},

urldate = {2021-02-01},

journal = {Radiother Oncol},

volume = {155},

pages = {113--119},

abstract = {BACKGROUND AND PURPOSE: To reduce relapse risk, Total Body Irradiation (TBI) is part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) in pediatric acute leukemia. The study purpose was to evaluate clinical practices regarding TBI, such as fractionation, organ shielding and delivery techniques, among SIOPE affiliated radiotherapy centers.



METHODS: An electronic survey was sent out to 233 SIOPE affiliated centers, containing 57 questions about clinical practice of TBI. Surveys could be answered anonymously.



RESULTS: From over 25 countries, 82 responses were collected. For TBI-performing centers, 40/48 irradiated ≤10 pediatric patients annually (range: 1-2 to >25). Most indications concerned acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Four different fractionation schedules were used, of which 12 Gy in 6 fractions was applied in 91% for ALL and 86% for AML. Dose reduction to the lungs, mostly to a mean dose of 8-10 Gy, was applied by 28/33 centers for ALL and 19/21 centers for AML, in contrast to much less applied dose reduction to the kidneys (7/33 ALL and 7/21 AML), thyroid (2/33 ALL and 2/21 AML), liver (4/33 ALL and 3/21 AML) and lenses (4/33 ALL and 4/21 AML). Conventional TBI techniques were used by 24/29 responding centers, while 5/29 used advanced optimized planning techniques.



CONCLUSION: Across SIOPE, there is a high level of uniformity in fractionation and use of lung shielding. Practices vary regarding other organs-at-risk shielding and implementation of advanced techniques. A SIOPE radiotherapy working group will be established to define international guidelines for pediatric TBI.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33478838,

title = {Brachytherapy boost (BT-boost) or stereotactic body radiation therapy boost (SBRT-boost) for high-risk prostate cancer (HR-PCa)},

author = {G Peyraga and T Lizee and J Khalifa and E Blais and G Mauriange-Turpin and S Supiot and S Krhili and P Tremolieres and P Graff-Cailleaud},

doi = {10.1016/j.canrad.2020.11.004},

issn = {1769-6658},

year  = {2021},

date = {2021-01-18},

urldate = {2021-06-01},

journal = {Cancer Radiother},

volume = {25},

number = {4},

pages = {400--409},

abstract = {Systematic review for the treatment of high-risk prostate cancer (HR-PCa, D'Amico classification risk system) with external body radiation therapy (EBRT)+brachytherapy-boost (BT-boost) or with EBRT+stereotactic body RT-boost (SBRT-boost). In March 2020, 391 English citations on PubMed matched with search terms "high risk prostate cancer boost". Respectively 9 and 48 prospective and retrospective studies were on BT-boost and 7 retrospective studies were on SBRT-boost. Two SBRT-boost trials were prospective. Only one study (ASCENDE-RT) directly compared the gold standard treatment [dose-escalation (DE)-EBRT+androgen deprivation treatment (ADT)] versus EBRT+ADT+BT-boost. Biochemical control rates at 9 years were 83% in the experimental arm versus 63% in the standard arm. Cumulative incidence of late grade 3 urinary toxicity in the experimental arm and in the standard arm was respectively 18% and 5%. Two recent studies with HR-PCa (National Cancer Database) demonstrated better overall survival with BT-boost (low dose rate LDR or high dose rate HDR) compared with DE-EBRT. These recent findings demonstrate the superiority of EBRT+BT-boost+ADT versus DE-EBRT+ADT for HR-PCa. It seems that EBRT+BT-boost+ADT could now be considered as a gold standard treatment for HR-PCa. HDR or LDR are options. SBRT-boost represents an attractive alternative, but the absence of randomised trials does not allow us to conclude for HR-PCa. Prospective randomised international phase III trials or meta-analyses could improve the level of evidence of SBRT-boost for HR-PCa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33461061,

title = {Radical radiotherapy for paediatric solid tumour metastases: An overview of current European protocols and outcomes of a SIOPE multicenter survey},

author = {Sophie C Huijskens and Petra S Kroon and Mark N Gaze and Lorenza Gandola and Stephanie Bolle and Stephane Supiot and Candan D Abakay and Aikaterini Alexopoulou and Jelena Bokun and Marzanna Chojnacka and Alexandre Escande and Jordi Giralt and Semi Harrabi and John H Maduro and Henry Mandeville and Anna Mussano and Aleksandra Napieralska and Laetitia Padovani and Giovanni Scarzello and Beate Timmermann and Line Claude and Enrica Seravalli and Geert O Janssens},

doi = {10.1016/j.ejca.2020.12.004},

issn = {1879-0852},

year  = {2021},

date = {2021-01-16},

urldate = {2021-01-01},

journal = {Eur J Cancer},

volume = {145},

pages = {121--131},

abstract = {PURPOSE/OBJECTIVE: About 20% of children with solid tumours (ST) present with distant metastases (DM). Evidence regarding the use of radical radiotherapy of these DM is sparse and open for personal interpretation. The aim of this survey was to review European protocols and to map current practice regarding the irradiation of DM across SIOPE-affiliated countries.



MATERIALS/METHODS: Radiotherapy guidelines for metastatic sites (bone, brain, distant lymph nodes, lung and liver) in eight European protocols for rhabdomyosarcoma, non-rhabdomyosarcoma soft-tissue sarcoma, Ewing sarcoma, neuroblastoma and renal tumours were reviewed. SIOPE centres irradiating ≥50 children annually were invited to participate in an online survey.



RESULTS: Radiotherapy to at least one metastatic site was recommended in all protocols, except for high-risk neuroblastoma. Per protocol, dose prescription varied per site, and information on delineation and treatment planning/delivery was generally missing. Between July and September 2019, 20/27 centres completed the survey. Around 14% of patients were deemed to have DM from ST at diagnosis, of which half were treated with curative intent. A clear cut-off for a maximum number of DM was not used in half of the centres. Regardless of the tumour type and site, conventional radiotherapy regimens were most commonly used to treat DM. When stereotactic radiotherapy was used, a wide range of fractionation regimens were applied.



CONCLUSION: Current radiotherapy guidelines for DM do not allow a consistent approach in a multicentre setting. Prospective (randomised) trials are needed to define the role of radical irradiation of DM from paediatric ST.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34595122,

title = {Interaction Between Modern Radiotherapy and Immunotherapy for Metastatic Prostate Cancer},

author = {Luc Ollivier and Maureen Labbé and Delphine Fradin and Vincent Potiron and Stéphane Supiot},

doi = {10.3389/fonc.2021.744679},

issn = {2234-943X},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Front Oncol},

volume = {11},

pages = {744679},

abstract = {Prostate cancer is the most frequently diagnosed cancer in men and a leading cause of cancer-related death. In recent decades, the development of immunotherapies has resulted in great promise to cure metastatic disease. However, prostate cancer has failed to show any significant response, presumably due to its immunosuppressive microenvironment. There is therefore growing interest in combining immunotherapy with other therapies able to relieve the immunosuppressive microenvironment. Radiation therapy remains the mainstay treatment for prostate cancer patients, is known to exhibit immunomodulatory effects, depending on the dose, and is a potent inducer of immunogenic tumor cell death. Optimal doses of radiotherapy are thus expected to unleash the full potential of immunotherapy, improving primary target destruction with further hope of inducing immune-cell-mediated elimination of metastases at distance from the irradiated site. In this review, we summarize the current knowledge on both the tumor immune microenvironment in prostate cancer and the effects of radiotherapy on it, as well as on the use of immunotherapy. In addition, we discuss the utility to combine immunotherapy and radiotherapy to treat oligometastatic metastatic prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34118357,

title = {Recommendations for planning and delivery of radical radiotherapy for localized urothelial carcinoma of the bladder},

author = {Jonathan Khalifa and Stéphane Supiot and Géraldine Pignot and Christophe Hennequin and Pierre Blanchard and David Pasquier and Nicolas Magné and Renaud de Crevoisier and Pierre Graff-Cailleaud and Olivier Riou and Morgane Cabaillé and David Azria and Igor Latorzeff and Gilles Créhange and Olivier Chapet and Morgan Rouprêt and Sarah Belhomme and Arnaud Mejean and Stéphane Culine and Paul Sargos},

doi = {10.1016/j.radonc.2021.06.011},

issn = {1879-0887},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Radiother Oncol},

volume = {161},

pages = {95--114},

abstract = {PURPOSE: Curative radio-chemotherapy is recognized as a standard treatment option for muscle-invasive bladder cancer (MIBC). Nevertheless, the technical aspects for MIBC radiotherapy are heterogeneous with a lack of practical recommendations.



METHODS AND MATERIALS: In 2018, a workshop identified the need for two cooperative groups to develop consistent, evidence-based guidelines for irradiation technique in the delivery of curative radiotherapy. Two radiation oncologists performed a review of the literature addressing several topics relative to radical bladder radiotherapy: planning computed tomography acquisition, target volume delineation, radiation schedules (total dose and fractionation) and dose delivery (including radiotherapy techniques, image-guided radiotherapy (IGRT) and adaptive treatment modalities). Searches for original and review articles in the PubMed and Google Scholar databases were conducted from January 1990 until March 2020. During a meeting conducted in October 2020, results on 32 topics were presented and discussed with a working group involving 15 radiation oncologists, 3 urologists and one medical oncologist. We applied the American Urological Association guideline development's method to define a consensus strategy.



RESULTS: A consensus was obtained for all 34 except 4 items. The group did not obtain an agreement on CT enhancement added value for planning, PTV margins definition for empty bladder and full bladder protocols, and for pelvic lymph-nodes irradiation. High quality evidence was shown in 6 items; 8 items were considered as low quality of evidence.



CONCLUSION: The current recommendations propose a homogenized modality of treatment both for routine clinical practice and for future clinical trials, following the best evidence to date, analyzed with a robust methodology. The XXX group formulates practical guidelines for the implementation of innovative techniques such as adaptive radiotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33358745,

title = {[Stereotactic radiotherapy in urologic cancers: Reports from the 3rd international meeting of the Groupe Francophone de Radiothérapie Urologique (GFRU)]},

author = {Tanguy Perennec and Stéphane Supiot},

doi = {10.1016/j.bulcan.2020.10.015},

issn = {1769-6917},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Bull Cancer},

volume = {108},

number = {1},

pages = {125--128},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33303195,

title = {[Innovation in radiotherapy in 2021]},

author = {Ingrid Masson and Marie Dutreix and Stéphane Supiot},

doi = {10.1016/j.bulcan.2020.10.005},

issn = {1769-6917},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Bull Cancer},

volume = {108},

number = {1},

pages = {42--49},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34247896,

title = {OLIGOPELVIS GETUG P07, a Multicenter Phase II Trial of Combined High-dose Salvage Radiotherapy and Hormone Therapy in Oligorecurrent Pelvic Node Relapses in Prostate Cancer},

author = {Stéphane Supiot and Loig Vaugier and David Pasquier and Xavier Buthaud and Nicolas Magné and Didier Peiffert and Paul Sargos and Gilles Crehange and Pascal Pommier and Genevieve Loos and Ali Hasbini and Igor Latorzeff and Marlon Silva and Fabrice Denis and Jean-Léon Lagrange and Cyrille Morvan and Loic Campion and Audrey Blanc-Lapierre},

doi = {10.1016/j.eururo.2021.06.010},

issn = {1873-7560},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Eur Urol},

volume = {80},

number = {4},

pages = {405--414},

abstract = {BACKGROUND: Oligorecurrent pelvic nodal relapse in prostatic cancer is a challenge for regional salvage treatments. Androgen depriving therapies (ADTs) are a mainstay in metastatic prostate cancer, and salvage pelvic radiotherapy may offer long ADT-free intervals for patients harboring regional nodal relapses.



OBJECTIVE: To assess the efficacy of the combination of ADT and salvage radiotherapy in men with oligorecurrent pelvic node relapses of prostate cancer.



DESIGN, SETTING, AND PARTICIPANTS: We performed an open-label, phase II trial of combined high-dose intensity-modulated radiotherapy and ADT (6 mo) in oligorecurrent (five or fewer) pelvic node relapses in prostate cancer, detected by fluorocholine positron-emission tomography computed tomography imaging.



OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was 2-yr progression-free survival defined as two consecutive prostate-specific antigen levels above the level at inclusion and/or clinical evidence of progression as per RECIST 1.1 and/or death from any cause.



RESULTS AND LIMITATIONS: Between August 2014 and July 2016, 67 patients were recruited in 15 centers. Half of the patients had received prior prostatic irradiation. The median age was 67.7 yr. After a median follow-up of 49.4 mo, 2- and 3-yr progression-free survival rates were 81% and 58%, respectively. Median progression-free survival was 45.3 mo. The median biochemical relapse-free survival (BRFS) was 25.9 mo. At 2 and 3 yr, the BRFS rates were 58% and 46%, respectively. Grade 2 + 2-yr genitourinary and gastrointestinal toxicities were 10% and 2%, respectively.



CONCLUSIONS: Combined high-dose salvage pelvic radiotherapy and ADT appeared to prolong tumor control in oligorecurrent pelvic node relapses in prostate cancer with limited toxicity. After 3 yr, nearly half of patients were in complete remission. Our study showed initial evidence of benefit, but a randomized trial is required to confirm this result.



PATIENT SUMMARY: In this report, we looked at the outcomes of combined high-dose salvage pelvic radiotherapy and 6-mo-long hormone therapy in oligorecurrent pelvic nodal relapse in prostatic cancer. We found that 46% of patients presenting with oligorecurrent pelvic node relapses in prostate cancer were in complete remission after 3 yr following combined treatment at the cost of limited toxicity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34016489,

title = {Discontinuous stereotactic body radiotherapy schedule increases overall survival in early-stage non-small cell lung cancer},

author = {L Duvergé and P-Y Bondiau and L Claude and S Supiot and L Vaugier and F Thillays and J Doyen and C Ricordel and H Léna and J Bellec and E Chajon and R de Crevoisier and J Castelli},

doi = {10.1016/j.lungcan.2021.05.016},

issn = {1872-8332},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Lung Cancer},

volume = {157},

pages = {100--108},

abstract = {OBJECTIVES: The duration of stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) may affect patient outcomes. We aimed to determine the impact of a continuous versus discontinuous SBRT schedule on local control (LC) and overall survival (OS) in NSCLC patients.



MATERIALS AND METHODS: Consecutive NSCLC stage I patients (475) treated with SBRT in four centers were retrospectively analyzed. The delivered dose ranged from 48 to 75 Gy in 3-10 fractions. Based on the ratio between the treatment duration (TD) and number of fractions (n), patients were divided into two groups: continuous schedule (CS) (TD ≤ 1.6n; 239 patients) and discontinuous schedule (DS) (TD > 1.6n; 236 patients). LC and OS were compared using Cox regression analyses after propensity score matching (216 pairs).



RESULTS: The median follow-up period was 41 months. Multivariate analysis showed that the DS (hazard ratio (HR): 0.42; 95 % confidence interval (CI): 0.22-0.78) and number of fractions (HR: 1.24; 95 % CI: 1.07-1.43) were significantly associated with LC. The DS (HR: 0.67; 95 % CI: 0.51-0.89), age (HR: 1.02; 95 % CI: 1-1.03), WHO performance status (HR: 2.27; 95 % CI: 1.39-3.7), and T stage (HR: 1.4; 95 % CI: 1.03-1.87) were significantly associated with OS. The 3-year LC and OS were 92 % and 64 % and 81 % and 53 % for DS and CS treatments, respectively (p < 0.01). Cox analysis confirmed that the discontinuous SBRT schedule significantly increased LC and OS.



CONCLUSION: DS is associated with significantly improved LC and OS in early-stage NSCLC patients treated with SBRT.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1093/neuonc/noaa222.321,

title = {HGG-40. Exceptional synchronous occurence of a BRAF V600E mutant glioblastoma and a H3.3K27M mutant diffuse intrinsic Pontine glioma: a case report},

author = {Emilie De Carli and Blandine Boisselier and Luc Le Fournier and Stéphane Supiot and Coralie Mallebranche and Stéphanie Proust-Houdemont and Mylène Duplan and Isabelle Pellier and Audrey Rousseau},

url = {https://doi.org/10.1093/neuonc/noaa222.321},

doi = {10.1093/neuonc/noaa222.321},

issn = {1522-8517},

year  = {2020},

date = {2020-12-04},

urldate = {2020-01-01},

journal = {Neuro-Oncology},

volume = {22},

number = {Supplement_3},

pages = {iii351-iii351},

abstract = {We report herein the case of a 17-year-old female who presented with intracranial hypertension and diplopia. Magnetic resonance imaging showed a large left cystic and solid temporoparietal lesion, associated with an infiltrating lesion of the brainstem, hypointense in T1 and hyperintense in FLAIR sequences, without enhancement after injection of gadolinium. Complete resection of the parietal mass and biopsy of the brainstem lesion were performed. Histopathological analysis of the parietal mass showed glioblastoma (WHO grade IV) with no IDH1/2 or H3.3/H3.1 gene mutation detected by Sanger sequencing. Immunohistochemistry found the expression of the proteins of mismatch repair system. Whole exome and RNA sequencing identified a BRAF-V600E mutation. The brainstem lesion was a diffuse midline glioma, H3K27M-mutant (grade IV) according to the 2016 WHO classification. Pan-genomic SNP arrays of the 2 tumors showed distinct genetic alterations. The parietal glioblastoma displayed complex genomic alterations whereas the brainstem glioma harbored chromosome 7q gain, chromosome 9p and 10 losses, and RB, TP53 and CDKN2A homozygous deletions. The patient was treated by concomitant radiochemotherapy (according to Stupp protocol). After 12 cycles of temozolomide, there was complete remission persistant in the parietal lobe. The brainstem tumor was stable but progressed after 3 months of temozolomide discontinuation. Treatment with mTOR inhibitors was initiated. At 21-month follow-up, the patient remains with few symptoms. No predisposition syndrome was identified in the patient or her family. Concurrent glioblastomas with distinct driver gene mutations are exceptional.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{MYLONA20201189,

title = {Rectal and Urethro-Vesical Subregions for Toxicity Prediction After Prostate Cancer Radiation Therapy: Validation of Voxel-Based Models in an Independent Population},

author = {Eugenia Mylona and Martin Ebert and Angel Kennedy and David Joseph and James Denham and Allison Steigler and Stephane Supiot and Oscar Acosta and Renaud Crevoisier},

url = {https://www.sciencedirect.com/science/article/pii/S0360301620314176},

doi = {https://doi.org/10.1016/j.ijrobp.2020.07.019},

issn = {0360-3016},

year  = {2020},

date = {2020-12-01},

urldate = {2020-01-01},

journal = {International Journal of Radiation Oncology*Biology*Physics},

volume = {108},

number = {5},

pages = {1189-1195},

abstract = {Purpose 

Recent voxel-based studies have shown that the dose to specific rectal and urethro-vesical subregions is predictive of toxicities after prostate cancer intensity modulated radiation therapy. The objective of this study was to validate the discriminatory power of these subregions with respect to the whole organs in a large independent population. 

Methods and Materials 

The validation cohort consisted of 450 patients from the TROG03.04-RADAR trial treated with 3-dimensional conformal radiation therapy at 66 to 74 Gy. Previous voxel-based analyses identified an inferoanterior rectal subregion as predictive of rectal bleeding and 5 subregions in the urethra and the posterior and superior part of the bladder as predictive of urinary incontinence, dysuria, retention, and hematuria. In the validation cohort, these subregions were segmented in each patient’s anatomy. Dose-volume histograms (DVHs) of the whole organs and the 6 subregions were compared bin-wise between patients with and without toxicities. The discriminatory power of DVHs for grade ≥2 toxicity endpoints was assessed using the area under the receiver operating characteristic curve (AUC). 

Results Subregion DVHs were significantly different between patients with and without toxicities for late rectal bleeding (V44-V74), acute urinary incontinence (V68-V72), late dysuria (V56-V68), and late retention (V14-V64). The dose to the rectal subregion and the whole rectum were equally predictive of rectal bleeding (V68; AUC = 0.61). The doses to 3 out of the 5 urethro-vesical subregions were found to be more predictive than the dose to the whole bladder: in the urethra for acute incontinence (V71 AUC = 0.69 vs V71 AUC = 0.66), in the posterior part of the bladder for late dysuria (V65 AUC = 0.66 vs V68 AUC = 0.59), and late retention (V39 AUC = 0.74 vs no significant AUC). 

Conclusions 

Three subregions located in the urethra and the bladder were successfully validated as more predictive of urinary toxicity than the whole bladder for urinary incontinence, retention, and dysuria. Sparing the posterior part of the bladder in particular in treatment planning may reduce the risk of late urinary retention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{CARRIE20201204,

title = {Exclusive Hyperfractionated Radiation Therapy and Reduced Boost Volume for Standard-Risk Medulloblastoma: Pooled Analysis of the 2 French Multicentric Studies MSFOP98 and MSFOP 2007 and Correlation With Molecular Subgroups},

author = {Christian Carrie and Virginie Kieffer and Dominique Figarella-Branger and Julien Masliah-Planchon and Stéphanie Bolle and Valérie Bernier and Anne Laprie and Stéphane Supiot and Julie Leseur and Jean-Louis Habrand and Claire Alapetite and Christine Kerr and Christelle Dufour and Line Claude and Sophie Chapet and Aymeri Huchet and Pierre-Yves Bondiau and Alexandre Escande and Gilles Truc and Tan Dat Nguyen and Caroline Pasteuris and Céline Vigneron and Xavier Muracciole and Franck Bourdeaut and Romain Appay and Bernard Dubray and Carole Colin and Céline Ferlay and Sophie Dussart and Sylvie Chabaud and Laetitia Padovani},

url = {https://www.sciencedirect.com/science/article/pii/S0360301620337433},

doi = {https://doi.org/10.1016/j.ijrobp.2020.07.2324},

issn = {0360-3016},

year  = {2020},

date = {2020-12-01},

urldate = {2020-01-01},

journal = {International Journal of Radiation Oncology*Biology*Physics},

volume = {108},

number = {5},

pages = {1204-1217},

abstract = {Purpose 

Medulloblastoma has recently been characterized as a heterogeneous disease with 4 distinct molecular subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4, with a new definition of risk stratification. We report progression-free survival, overall survival, and long-term cognitive effects in children with standard–risk medulloblastoma exclusively treated with hyperfractionated radiation therapy (HFRT), reduced boost volume, and online quality control, and we explore the prognostic value of biological characteristics in this chemotherapy-naïve population. 

Methods and Materials 

Patients with standard–risk medulloblastoma were enrolled in 2 successive prospective multicentric studies, MSFOP 98 and MSFOP 2007, and received exclusive HFRT (36 Gy, 1 Gy/fraction twice daily) to the craniospinal axis followed by a boost at 68 Gy restricted to the tumor bed (1.5 cm margin), with online quality assurance before treatment. Patients with MYC or MYCN amplification were not excluded at the time of the study. We report progression-free survival and overall survival in the global population, and according to molecular subgroups as per World Health Organization 2016 molecular classification, and we present cognitive evaluations based on the Wechsler scale. 

Results Data from 114 patients included in the MSFOP 98 trial from December 1998 to October 2001 (n = 48) and in the MSFOP 2007 from October 2008 to July 2013 (n = 66) were analyzed. With a median follow-up of 16.2 (range, 6.4-19.6) years for the MSFOP 98 cohort and 6.5 (1.6-9.6) years for the MSFOP 2007 cohort, 5-year overall survival and progression-free survival in the global population were 84% (74%-89%) and 74% (65%-81%), respectively. Molecular classification was determined for 91 patients (WNT [n = 19], SHH [n = 12], and non-WNT/non-SHH [n = 60]—including group 3 [n = 9], group 4 [n = 29], and not specified [n = 22]). Our results showed more favorable outcome for the WNT-activated subgroup and a worse prognosis for SHH-activated patients. Three patients had isolated extra–central nervous system relapse. The slope of neurocognitive decline in the global population was shallower than that observed in patients with a normofractionated regimen combined with chemotherapy. 

Conclusions 

HFRT led to a 5-year survival rate similar to other treatments combined with chemotherapy, with a reduced treatment duration of only 6 weeks. We confirm the MSFOP 98 results and the prognostic value of molecular status in patients with medulloblastoma, even in the absence of chemotherapy. Intelligence quotient was more preserved in children with medulloblastoma who received exclusive HFRT and reduced local boost, and intelligence quotient decline was delayed compared with patients receiving standard regimen. HFRT may be appropriate for patients who do not consent to or are not eligible for prospective clinical trials; for patients from developing countries for whom aplasia or ileus may be difficult to manage in a context of high cost/effectiveness constraints; and for whom shortened duration of RT may be easier to implement.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{BELKACEMI2020892,

title = {Patterns of practice of androgen deprivation therapy combined to radiotherapy in favorable and unfavorable intermediate risk prostate cancer. Results of The PROACT Survey from the French GETUG Radiation Oncology group},

author = {Y Belkacemi and I Latorzeff and A Hasbini and G Coraggio and D Pasquier and A Toledano and C Hennequin and A Bossi and O Chapet and G Crehange and S Guerif and T Duberge and N Allouache and P Clavere and E Gross and S Supiot and D Azria and M Bolla and P Sargos},

url = {https://www.sciencedirect.com/science/article/pii/S1278321820302924},

doi = {https://doi.org/10.1016/j.canrad.2020.03.014},

issn = {1278-3218},

year  = {2020},

date = {2020-12-01},

urldate = {2020-12-01},

journal = {Cancer/Radiothérapie},

volume = {24},

number = {8},

pages = {892-897},

abstract = {Summary 

Purpose 

The intermediate-risk (IR) prostate cancer (PCa) group is heterogeneous in terms of prognosis. For unfavorable or favorable IR PCa treated by radiotherapy, the optimal strategy remains to be defined. In routine practice, the physician's decision to propose hormonal therapy (HT) is controversial. The PROACT survey aimed to evaluate pattern and preferences of daily practice in France in this IR population. 

Materials and methods 

A web questionnaire was distributed to French radiotherapy members of 91 centers of the Groupe d’Etude des Tumeurs Uro-Genitales (GETUG). The questionnaire included four sections concerning: (i) the specialists who prescribe treatments and multidisciplinary decisions (MTD) validation; (ii) the definition of IR subsets of patients; (iii) radiotherapy parameters; (iv) the pattern of practice regarding cardiovascular (CV) and (iv) metabolic evaluation. A descriptive presentation of the results was used. 

Results 

Among the 82 responses (90% of the centers), HT schedules and irradiation techniques were validated by specific board meetings in 54% and 45% of the centers, respectively. Three-fourths (76%) of the centers identified a subset of IR patients for a dedicated strategy. The majority of centers consider PSA>15 (77%) and/or Gleason 7 (4+3) (87%) for an unfavorable IR definition. Overall, 41% of the centers performed systematically a CV evaluation before HT prescription while 61% consider only CV history/status in defining the type of HT. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR patients. Finally, weight (80%), metabolic profile (70%) and CV status (77%) of patients are considered for follow-up under HT. 

Conclusion 

To the best of our knowledge, this is the first survey on HT practice in IR PCa. The PROACT survey indicates that three-quarters of the respondents identify subsets of IR-patients in tailoring therapy. The CV status of the patient is considered in guiding the HT decision, its duration and type of drug. 

Résumé 

Objectif de l’étude 

Le cancer de la prostate de risque intermédiaire est hétérogène en termes de pronostic. La stratégie optimale pour le cancer de la prostate de risque intermédiaire favorable ou défavorable n’est pas encore bien définie. Dans la pratique quotidienne, la décision médicale de proposer l’hormonothérapie reste controversée. L’enquête PROACT avait pour objectif d’évaluer les pratiques en France sur les indications de l’hormonothérapie associée à la radiothérapie. 

Matériel et méthodes 

Un questionnaire électronique a été distribué à 91 centres français membres du Groupe d’étude des tumeurs uro-génitales (GETUG). Le questionnaire incluait quatre sections : choix de l’hormonothérapie, pratiques de la radiothérapie, évaluation cardiovasculaire et métabolique avant l’hormonothérapie. Les résultats sont présentés de façon descriptive. 

Résultats 

Parmi les 82 réponses (90 % de centres), le schéma d’hormonothérapie et la technique d’irradiation sont validés lors de réunions de concertation pluridisciplinaires (RCP) dans respectuvement 54 % et 45 % des centrest. Trois-quarts (76 %) des centres ont déclaré identifier des sous-groupes de patients atteints de cancer de risque intermédiaire pour des stratégies dédiées. La plupart des centres considèrent une concentration de PSA de plus de 15ng/mL (77 %) et/ou un score de Gleason de 7 (4+3) (87 %) pour la définition du risque intermédiaire défavorable. Quarante et un pour cent des centres ont déclaré réaliser une évaluation cardiovasculaire systématique avant la prescription de l’hormonothérapie alors que 61 % ne considèrent que l’évaluation cardiovasculaire pour définir le type d’hormonothérapie. Les agonistes de la LHRH sont la forme la plus prescrite chez les patients atteints de cancer de risque intermédiaire favorable (70 %) ou défavorable (98 %). Le poids (80 %), le profil métabolique (70 %) et l’évaluation cardiovasculaire (77 %) des patients sont pris en compte pour le suivi des patients sous hormonothérapie. 

Conclusion 

À notre connaissance, PROACT est la première enquête sur les critères pratiques de la prescription de l’hormonothérapie dans le cancer de la prostate de risque intermédiaire. L’enquête montre que trois-quarts des centres français identifient les sous groupes de patients atteints de cancer de risque intermédiaire pour adapter le traitement. L’évaluation cardiovasculaire est prise en compte pour décider de l’indication, du type et de la durée de l’hormonothérapie.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{biomedicines8120548,

title = {Targeting Stereotactic Body Radiotherapy on Metabolic PET- and Immuno-PET-Positive Vertebral Metastases},

author = {Baptiste Pichon and Caroline Rousseau and Audrey Blanc-Lapierre and Gregory Delpon and Ludovic Ferrer and Vincent Libois and Matthieu Le Turnier and Cédric Lenoble and Caroline Bodet-Milin and David M. Goldenberg and Françoise Kraeber-Bodere and Stéphane Supiot},

url = {https://www.mdpi.com/2227-9059/8/12/548},

doi = {10.3390/biomedicines8120548},

issn = {2227-9059},

year  = {2020},

date = {2020-11-28},

urldate = {2020-01-01},

journal = {Biomedicines},

volume = {8},

number = {12},

abstract = {(1) Background: Stereotactic body radiotherapy (SBRT) for vertebral metastases (VM) allows the delivery of high radiation doses to tumors while sparing the spinal cord. We report a new approach to clinical target volume (CTV) delineation based on anti-carcinoembryonic antigen (CEA) positron emission tomography (pretargeted immuno-PET; “iPET”) in patients with metastatic breast cancer (BC) or medullary thyroid cancer (MTC). (2) Methods: All patients underwent iPET, spine magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) using 18F-deoxyglucose (FDG) for BC or 18F-dihydroxy-phenylalanine (F-DOPA) for MTC. Vertebrae locations and vertebral segments of lesions were recorded and the impact on CTV delineation was evaluated. (3) Results: Forty-six VM eligible for SBRT following iPET were evaluated in eight patients (five BC, three MTC). Eighty-one vertebral segments were detected using MRI, 26 with FDG or F-DOPA PET/CT, and 70 using iPET. iPET was able to detect more lesions than MRI for vertebral bodies (44 vs. 34). iPET-based delineation modified MRI-based CTV in 70% (32/46) of cases. (4) Conclusion: iPET allows a precise mapping of affected VM segments, and adds complementary information to MRI in the definition of candidate volumes for VM SBRT. iPET may facilitate determining target volumes for treatment with stereotactic body radiotherapy in metastatic vertebral disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SARGOS2020S17,

title = {A Phase III Randomized Trial Comparing Adjuvant versus Early Salvage Radiotherapy, Both Combined with Short-term Androgen Deprivation Therapy, following a Radical Prostatectomy: Initial Results of the GETUG-AFU 17 Study [NCT00667069]},

author = {P Sargos and S Chabaud and I Latorzeff and N Magne and A Benyoucef and S Supiot and D Pasquier and S Abdiche and O Gilliot and P Graff and M Silva and P Bergerot and P Baumann and Y Belkacemi and D Azria and S Nenan and PM Richaud},

url = {https://www.sciencedirect.com/science/article/pii/S0360301620335197},

doi = {https://doi.org/10.1016/j.ijrobp.2020.07.2100},

issn = {0360-3016},

year  = {2020},

date = {2020-11-01},

urldate = {2020-01-01},

journal = {International Journal of Radiation Oncology*Biology*Physics},

volume = {108},

number = {3, Supplement},

pages = {S17-S18},

note = {Proceedings of the American Society for Radiation Oncology},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SARGOS2020733,

title = {GETUG-AFU 17 : étude de phase III randomisée comparant la radiothérapie adjuvante à la radiothérapie de rattrapage précoce, combinées à l’hormonothérapie courte, pour les patients présentant un cancer de la prostate traité par prostatectomie radicale},

author = {P Sargos and S Chabaud and I Latorzeff and N Magné and A Benyoucef and S Supiot and D Pasquier and S Abdiche and O Gilliot and P Graff-Cailleaud and M Silva and P Bergerot and P Baumann and Y Belkacemi and D Azria and M Brihou and M Soulié and P Richaud},

url = {https://www.sciencedirect.com/science/article/pii/S1166708720303079},

doi = {https://doi.org/10.1016/j.purol.2020.07.071},

issn = {1166-7087},

year  = {2020},

date = {2020-11-01},

urldate = {2020-01-01},

journal = {Progrès en Urologie},

volume = {30},

number = {13},

pages = {733-734},

abstract = {Objectifs 

La radiothérapie adjuvante (aRT) réduit le risque de rechute biochimique chez les patients atteints d’un cancer de la prostate traités par une prostatectomie radicale (RP). L’étude GETUG-AFU 17 a comparé l’efficacité et la toxicité de l’aRT par rapport à la radiothérapie de rattrapage précoce (sRT), associée à un traitement hormonal. 

Méthodes 

Cette étude multicentrique, de phase III, randomisée et contrôlée, a été réalisée dans 46 centres français. Les patients devaient être âgés de plus de 18 ans, avec un statut Eastern Cooperative Oncology Group ≤1, une maladie classée pT3-4 et marges positives, pNx ou pN0, avec PSA postopératoire ≤0,1ng/mL. Les patients ont été randomisés (par minimisation ; 1 : 1) après RP, entre aRT ou observation avec sRT, combiné avec 6 mois de triptoréline. Le critère principal était la survie sans événement (EFS). Les critères d’évaluation secondaires étaient la survie globale (SG), la survie sans métastase (MFS), l’incidence des toxicités aiguës et tardives (CTCAE v3.0) et la qualité de vie (QoL) (échelles QLQ-C30 et PR-25). Cet essai est enregistré sous le numéro ClinicalTrials.gov NCT00667069. 

Résultats Entre le 7 mars 2008 et le 23 juin 2016, 424 patients ont été inclus. Nous avions prévu d’inclure 718 patients. Les inclusions ont été interrompues prématurément en raison de taux d’événements étonnamment bas. Les caractéristiques initiales des patients et de leur tumeur étaient bien équilibrées entre les bras. Le suivi médian était de 75, 3 mois (IQR : 50–100). Lors de l’analyse, 115/212 patients (54 %) du bras sRT avaient commencé le traitement. Avec 58 événements, l’EFS à 5 ans était de 92 % (IC95 % : 86–95) dans le bras aRT et de 90 % (IC95 % : 85–94) dans le bras sRT (HR=0,81 [IC95 % : 0,48–1,36] ; test du log-rank p=0,42). Le taux de SG à 5 ans était de 96 % (IC95 % : 92–98) dans le bras aRT et de 99 % (IC95 % : 96–100) dans le bras sRT (HR=1,60 [IC95 % : 0,71–3,60] ; p=0,25). Les toxicités génito-urinaires de grade ≥2 étaient plus importantes dans le bras aRT (27 % vs 7 % ; p<0,0001). La dysfonction érectile de grade ≥2 était majorée dans le bras aRT (p<0,0001). Les changements dans tous les domaines du QLQ-C30 étaient similaires dans les deux bras (p=0,11). 

Conclusion 

L’étude GETUG-AFU 17 n’a montré aucun bénéfice en EFS pour l’aRT par rapport à la sRT. L’aRT a augmenté le risque de toxicité génito-urinaire et de dysfonction érectile. Une stratégie de sRT précoce pourrait épargner aux hommes la RT et la toxicité associée.},

note = {114e congrès français d’urologie},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{HUIJSKENS2020S251,

title = {OC-0454: Current radiotherapy practice for children with metastases from solid tumors: SIOPE survey analysis},

author = {S Huijskens and P Kroon and C Demiroz Abakay and B Timmermann and J Giralt and M Gaze and S Harrabi and G Scarzello and A Alexopoulou and L Padovani and A Escande and L Gandola and S Supiot and M Chojnacka and J Bokun and A Napieralska and B Rombi and JH Maduro and S Bolle and A Mussano and H Mandeville and L Claude and E Seravalli and GO Janssens},

url = {https://www.sciencedirect.com/science/article/pii/S016781402100476X},

doi = {https://doi.org/10.1016/S0167-8140(21)00476-X},

issn = {0167-8140},

year  = {2020},

date = {2020-11-01},

urldate = {2020-01-01},

journal = {Radiotherapy and Oncology},

volume = {152},

pages = {S251-S253},

note = {ESTRO 2020 - Online Congress, 28 November to 1 December 2020},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SUPIOT2020S105,

title = {OC-0210: Salvage radiotherapy in oligorecurrent pelvic node relapses of prostate cancer : a phase 2 trial},

author = {S Supiot and D Pasquier and X Buthaud and N Magne and V Becckendorf and G Crehange and P Pommier and G Loos and A Hasbini and I Latorzeff and M Silva and F Denis and L Campion and L Vaugier and A Blanc-Lapierre},

url = {https://www.sciencedirect.com/science/article/pii/S0167814021002346},

doi = {https://doi.org/10.1016/S0167-8140(21)00234-6},

issn = {0167-8140},

year  = {2020},

date = {2020-11-01},

urldate = {2020-01-01},

journal = {Radiotherapy and Oncology},

volume = {152},

pages = {S105},

note = {ESTRO 2020 - Online Congress, 28 November to 1 December 2020},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{MYLONA2020S829,

title = {PO-1535: Machine Learning and Oversampling techniques to predict urinary toxicity after prostate cancer RT},

author = {E Mylona and F Filias and M Ibrahim and S Supiot and N Magne and G Crehange and M Hatt and O Acosta and R De Crevoisier},

url = {https://www.sciencedirect.com/science/article/pii/S016781402101553X},

doi = {https://doi.org/10.1016/S0167-8140(21)01553-X},

issn = {0167-8140},

year  = {2020},

date = {2020-11-01},

urldate = {2020-01-01},

journal = {Radiotherapy and Oncology},

volume = {152},

pages = {S829},

note = {ESTRO 2020 - Online Congress, 28 November to 1 December 2020},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{2512c408dbd041e2a96bc992f35deff9,

title = {Current radiotherapy practice for children with metastases from solid tumors: SIOPE survey analysis},

author = {S Huijskens and P Kroon and C Demiroz Abakay and B Timmermann and J Giralt and M Gaze and S Harrabi and G Scarzello and A Alexopoulou and L Padovani and A Escande and L Gandola and S Supiot and M Chojnacka and J Bokun and A Napieralska and B Rombi and J H Maduro and S Bolle and A Mussano and H Mandeville and L Claude and E Seravalli and GO Janssens},

url = {https://www.sciencedirect.com/science/article/pii/S016781402100476X},

doi = {10.1016/S0167-8140(21)00476-X},

issn = {0167-8140},

year  = {2020},

date = {2020-11-01},

urldate = {2020-11-01},

journal = {Radiotherapy and Oncology},

volume = {152},

pages = {S251--S253},

publisher = {ELSEVIER IRELAND LTD},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SARGOS20201341,

title = {Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial},

author = {Paul Sargos and Sylvie Chabaud and Igor Latorzeff and Nicolas Magné and Ahmed Benyoucef and Stéphane Supiot and David Pasquier and Menouar Samir Abdiche and Olivier Gilliot and Pierre Graff-Cailleaud and Marlon Silva and Philippe Bergerot and Pierre Baumann and Yazid Belkacemi and David Azria and Meryem Brihoum and Michel Soulié and Pierre Richaud},

url = {https://www.sciencedirect.com/science/article/pii/S147020452030454X},

doi = {https://doi.org/10.1016/S1470-2045(20)30454-X},

issn = {1470-2045},

year  = {2020},

date = {2020-10-01},

urldate = {2020-01-01},

journal = {The Lancet Oncology},

volume = {21},

number = {10},

pages = {1341-1352},

abstract = {Summary 

Background 

Adjuvant radiotherapy reduces the risk of biochemical progression in prostate cancer patients after radical prostatectomy. We aimed to compare adjuvant versus early salvage radiotherapy after radical prostatectomy, combined with short-term hormonal therapy, in terms of oncological outcomes and tolerance. 

Methods 

GETUG-AFU 17 was a randomised, open-label, multicentre, phase 3 trial done at 46 French hospitals. Men aged at least 18 years who had an Eastern Cooperative Oncology Group performance status of 1 or less, localised adenocarcinoma of the prostate treated with radical prostatectomy, who had pathologically-staged pT3a, pT3b, or pT4a (with bladder neck invasion), pNx (without pelvic lymph nodes dissection), or pN0 (with negative lymph nodes dissection) disease, and who had positive surgical margins were eligible for inclusion in the study. Eligible patients were randomly assigned (1:1) to either immediate adjuvant radiotherapy or delayed salvage radiotherapy at the time of biochemical relapse. Random assignment, by minimisation, was done using web-based software and stratified by Gleason score, pT stage, and centre. All patients received 6 months of triptorelin (intramuscular injection every 3 months). The primary endpoint was event-free survival. Efficacy and safety analyses were done on the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT00667069. 

Findings Between March 7, 2008, and June 23, 2016, 424 patients were enrolled. We planned to enrol 718 patients, with 359 in each study group. However, on May 20, 2016, the independent data monitoring committee recommended early termination of enrolment because of unexpectedly low event rates. At database lock on Dec 19, 2019, the overall median follow-up time from random assignment was 75 months (IQR 50–100), 74 months (47–100) in the adjuvant radiotherapy group and 78 months (52–101) in the salvage radiotherapy group. In the salvage radiotherapy group, 115 (54%) of 212 patients initiated study treatment after biochemical relapse. 205 (97%) of 212 patients started treatment in the adjuvant group. 5-year event-free survival was 92% (95% CI 86–95) in the adjuvant radiotherapy group and 90% (85–94) in the salvage radiotherapy group (HR 0·81, 95% CI 0·48–1·36; log-rank p=0·42). Acute grade 3 or worse toxic effects occurred in six (3%) of 212 patients in the adjuvant radiotherapy group and in four (2%) of 212 patients in the salvage radiotherapy group. Late grade 2 or worse genitourinary toxicities were reported in 125 (59%) of 212 patients in the adjuvant radiotherapy group and 46 (22%) of 212 patients in the salvage radiotherapy group. Late genitourinary adverse events of grade 2 or worse were reported in 58 (27%) of 212 patients in the adjuvant radiotherapy group versus 14 (7%) of 212 patients in the salvage radiotherapy group (p<0·0001). Late erectile dysfunction was grade 2 or worse in 60 (28%) of 212 in the adjuvant radiotherapy group and 17 (8%) of 212 in the salvage radiotherapy group (p<0·0001). 

Interpretation 

Although our analysis lacked statistical power, we found no benefit for event-free survival in patients assigned to adjuvant radiotherapy compared with patients assigned to salvage radiotherapy. Adjuvant radiotherapy increased the risk of genitourinary toxicity and erectile dysfunction. A policy of early salvage radiotherapy could spare men from overtreatment with radiotherapy and the associated adverse events. 

Funding 

French Health Ministry and Ipsen.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{JOUGLAR2020594,

title = {Faut-il moduler les contraintes de dose dans les organes à risque lors d’une irradiation en association avec un traitement anticancéreux systémique ?},

author = {E Jouglar and J Doyen and S Supiot},

url = {https://www.sciencedirect.com/science/article/pii/S1278321820301712},

doi = {https://doi.org/10.1016/j.canrad.2020.05.010},

issn = {1278-3218},

year  = {2020},

date = {2020-10-01},

urldate = {2020-01-01},

journal = {Cancer/Radiothérapie},

volume = {24},

number = {6},

pages = {594-601},

abstract = {Résumé 

Les stratégies thérapeutiques anticancéreuses associant une radiothérapie et un traitement systémique incluant chimiothérapie, hormonothérapie mais aussi plus récemment immunothérapie et thérapie ciblée sont de pratique courante. Pourtant les traitements combinés concomitants ou séquentiels sont souvent à l’origine d’une augmentation de la toxicité. Pour augmenter le bénéfice d’une combinaison thérapeutique, la question d’une modulation de la dose délivrée aux organes à risque se pose afin de diminuer les effets indésirables. Une revue de la littérature sur les toxicités limitantes en lien avec les stratégies associant radiothérapie et traitements systémiques a été menée. Cette étude a permis de caractériser quatre situations parmi lesquelles 1) des contre-indications de certaines associations en raison de toxicité inacceptable ou recommandations de prudence avec limitations des indications, de la dose prescrite ou l’application de contraintes aux organes à risque plus sévères, 2) des traitements combinés sans toxicité surajoutée ne plaidant pas en faveur d’une modulation des contraintes de dose habituelles, 3) des associations semblant augmenter le risque de toxicité en faveur d’une modulation de la dose aux organe à risque, 4) des traitements combinés avec données de tolérance limitées ou inconnues, raison pour laquelle l’association n’est recommandée que dans le cadre d’un essai thérapeutique. 

Therapeutic strategies combining irradiation and drugs including chemotherapy, hormonotherapy, but also more recently targeted therapy and immunotherapy are routinely used for cancer treatment. Nevertheless, combined treatments usually lead to a rise in toxicity. In order to increase the therapeutic ratio in favour of a multimodality treatment, adapting dose constraints to organs at risk may be the key to lower the risk of toxicity. A review of the literature was conducted, focusing on the toxicity in dose-limiting organs at risk when radiation therapy is associated with drugs. Four situations were differentiated, including : 1) some contraindicated combinations due to an inacceptable increased of toxicity, or recommendations of careful use with restricted indications, reduction in prescribed dose, or severe dose constraints to organs at risk, 2) combined treatments without increased toxicity with no arguments for adjusted dose constraints, 3) associations with higher risk of toxicity, for which dose constraints could be adapted, 4) combined therapies with limited tolerance data, prohibiting their use out of clinical trials.},

note = {31e Congrès national de la Société française de radiothérapie oncologique},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{CHARGARI2020602,

title = {Traitement des effets tardifs après la radiothérapie : quoi de neuf ?},

author = {C Chargari and S Supiot and C Hennequin and A Chapel and J-M. Simon},

url = {https://www.sciencedirect.com/science/article/pii/S1278321820301773},

doi = {https://doi.org/10.1016/j.canrad.2020.06.007},

issn = {1278-3218},

year  = {2020},

date = {2020-10-01},

urldate = {2020-01-01},

journal = {Cancer/Radiothérapie},

volume = {24},

number = {6},

pages = {602-611},

abstract = {Résumé 

Les mécanismes des lésions radio-induites tardives sont la résultante de phénomènes multiples et complexes, avec de nombreux acteurs cellulaires et tissulaires intriqués. Le continuum biologique entre effets aigus et effets tardifs après irradiation sera décrit, avec en premier lieu une rupture d’homéostasie qui conduit à des redistributions cellulaires. De nouveaux éclairages sur la toxicité tardive seront enfin abordés. La radiosensibilité individuelle est un facteur primordial dans le développement de toxicité tardive, et les cliniciens ont un besoin urgent de disposer de tests prédictifs qui permettraient de proposer une radiothérapie réellement personnalisée. La mise au point est faite sur les différents tests fonctionnels et génétiques en cours de validation. La prise en charge des effets secondaires de la radiothérapie reste un problème fréquent pour l’oncologue radiothérapeute, et un point est fait sur les traitements qui peuvent être proposés dans certaines situations cliniques particulières. Enfin, une prise en charge innovante est développée pour les patients atteints d’effets secondaires importants après radiothérapie pelvienne, la greffe de cellules souches mésenchymateuses, avec la présentation du protocole « Prisme » actuellement ouvert au recrutement des patients. 

Mechanisms of late radio-induced lesions are the result of multiple and complex phenomena, with many entangled cellular and tissue factors. The biological continuum between acute and late radio-induced effects will be described, with firstly a break in homeostasis that leads to cellular redistributions. New insights into late toxicity will finally be addressed. Individual radiosensitivity is a primary factor for the development of late toxicity, and clinicians urgently need predictive tests to offer truly personalized radiation therapy. An update will be made on the various functional and genetic tests currently being validated. The management of radio-induced side effects remains a frequent issue for radiation oncologists, and an update will be made for certain specific clinical situations. Finally, an innovative management for patients with significant side effects after pelvic radiotherapy will be developed, involved mesenchymal stem cell transplantation, with the presentation of the “PRISME” protocol currently open to patients recruitment.},

note = {31e Congrès national de la Société française de radiothérapie oncologique},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DORE2020769,

title = {Prise en charge d’une tachycardie ventriculaire par radiothérapie en conditions stéréotaxiques : première expérience},

author = {M Doré and S Josset and E Mervoyer and J-B Gourraud and M Bonnin and P Cadot and S Chiavassa and G Kerdanet and J Lebreton and H Lorand and T Marsac and M Raimond and S Rousset and J-M Serfaty and G Delpon and S Supiot},

url = {https://www.sciencedirect.com/science/article/pii/S1278321820302031},

doi = {https://doi.org/10.1016/j.canrad.2020.08.004},

issn = {1278-3218},

year  = {2020},

date = {2020-10-01},

urldate = {2020-01-01},

journal = {Cancer/Radiothérapie},

volume = {24},

number = {6},

pages = {769-770},

abstract = {Introduction et but de l’étude 

Le traitement non invasif de la tachycardie ventriculaire par irradiation en conditions stéréotaxiques est une technique émergente. Nous présentons le premier cas pris en charge dans notre institut. 

Matériel et méthodes 

Il s’agit d’un homme de 68 ans pris en charge pour une hyperexcitabilité ventriculaire sévère à un mois d’un syndrome coronarien antérieur étendu, persistante malgré un traitement médical intense. L’ablation par radiofréquence a été récusée par la présence d’un thrombus intraventriculaire gauche. La pose d’un défibrillateur automatique implantable à double chambre a été réalisée. Devant la persistance d’accès de tachycardie ventriculaire soutenue devenant réfractaire aux chocs électriques internes, une de radiothérapie en conditions stéréotaxiques a été proposée. Après fabrication d’une contention thoracique thermoformée, une scanographie dosimétrique quadridimensionnelle et une scanographie en apnée expiratoire ont été réalisées. Les images ont été recalées avec celles de la coroscanographie diagnostique réalisée avant la pose du défibrillateur automatique implantable. La cible a été définie de manière consensuelle (radiothérapeute, cardiologue, radiologue) d’après les données morphologiques et électriques correspondant à deux volumes distincts en périphérie de la zone de myocarde infarcie et après identification de deux trajets de tachycardie ventriculaire antérieur et postérieur. Les mouvements respiratoires et cardiaques ont été pris en compte. Il a ensuite été appliqué une marge isotropique de 5mm afin de tenir compte des incertitudes de repositionnement, portant le volume cible prévisionnel à 75 cm3. La planification a utilisé une technique d’arcthérapie conformationnelle dynamique par photons de 6 MV du Novalis TrueBeam™. 

Résultats et analyse statistique 

La prescription a été de 25Gy à la périphérie du volume cible prévisionnel. L’indice de conformation était de 2,0 et l’indice de gradient de 8,4. La dose moyenne au cœur était de 8,8Gy, et la dose maximale dans l’artère coronaire droite et la circonflexe était respectivement de 7,5Gy et 15,1Gy. Après désactivation du défibrillateur automatique implantable et mise en place d’une surveillance cardiaque, le repositionnement du patient a été ajusté à l’aide d’une tomographie conique et de la scopie, avec recalage sur l’extrémité de la sonde ventriculaire droite du défibrillateur automatique implantable. La tolérance immédiate a été correcte, en dehors de nausées de grade 2. Un sevrage progressif des antiarythmiques a pu être réalisé. Une hyperexcitabilité sous forme d’extrasystoles ventriculaires isolées a persisté, sans récidive de troubles ventriculaires soutenus. 

Conclusion 

Cette expérience confirme la faisabilité et l’efficacité à court terme du traitement de la tachycardie ventriculaire réfractaire par irradiation en conditions stéréotaxiques. Un travail est à mener pour une meilleure définition de la cible à partir d’imagerie morphologique et électrophysiologique additionnelles et sur une faisabilité en technique de traitement modulée en intensité (VMAT). L’objectif thérapeutique doit être démontré dans une étude de phase II.},

note = {31e Congrès national de la Société française de radiothérapie oncologique},

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}

@article{doi:10.1259/bjrcr.20190118,

title = {Report of a unique case of gemcitabine-induced radiation recall myelitis following spinal cord irradiation},

author = {Ingrid Masson and Stéphane Supiot and Isabelle Doutriaux-Dumoulin and François Thillays},

url = {https://doi.org/10.1259/bjrcr.20190118},

doi = {10.1259/bjrcr.20190118},

year  = {2020},

date = {2020-04-23},

urldate = {2020-04-23},

journal = {BJR|case reports},

volume = {6},

number = {3},

pages = {20190118},

abstract = {Radiation recall is a rare phenomenon, defined as an acute inflammatory reaction in a previously irradiated area, after administration of anti-tumor agents, including chemotherapy. It is most commonly reported to trigger skin reactions but internal organ involvement is possible, particularly with gemcitabine. We report here a unique case of a gemcitabine-induced radiation recall myelitis following spinal irradiation.A 53-year-old patient received analgesic irradiation of the seventh thoracic vertebra (T7) in the context of metastatic non-small cell lung cancer, at conventional radiotherapy dose and fractionation. She was subsequently treated with gemcitabine and developed myelitis whose chronology is compatible with a radiation recall reaction. Spinal MRI confirmed a T6–T7 spinal cord enhancement, with an associated spinal cord oedema. Corticosteroids and supportive care did not improve myelitis symptoms. The patient died within a year of the radiation recall, due to a metastatic progression of lung cancer.This is, to our knowledge, the first reported case of gemcitabine-induced radiation recall myelitis and only the third case involving the spinal cord. Radiation recall is a rare and poorly understood phenomenon and all cases should be reported.},

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pubstate = {published},

tppubtype = {article}

}

@article{pmid32267172,

title = {Radiotherapy-induced overexpression of exosomal miRNA-378a-3p in cancer cells limits natural killer cells cytotoxicity},

author = {Joséphine Briand and Delphine Garnier and Arulraj Nadaradjane and Karen Clément-Colmou and Vincent Potiron and Stéphane Supiot and Gwenola Bougras-Cartron and Jean-Sébastien Frenel and Dominique Heymann and François M Vallette and Pierre-François Cartron},

doi = {10.2217/epi-2019-0193},

issn = {1750-192X},

year  = {2020},

date = {2020-04-08},

urldate = {2020-01-01},

journal = {Epigenomics},

volume = {12},

number = {5},

pages = {397--408},

abstract = { We here hypothesized that tumor-derived exosomal miRNA (TexomiR) released from irradiated tumors may play a role in the tumor cells escape to natural killer (NK) cells.  Our study included the use of different cancer cell lines, blood biopsies of xenograph mice model and patients treated with radiotherapy.  The irradiation of cancer cells promotes the TET2-mediated demethylation of miR-378 promoter, miR-378a-3p overexpression and its loading in exosomes, inducing the decrease of granzyme-B (GZMB) secretion by NK cells. An inverse correlation between TexomiR-378a-3p and GZMB was observed in murine and human blood samples.  Our work identifies TexomiR-378a-3p as a molecular signature associated with the loss of NK cells cytotoxicity via the decrease of GZMB expression upon radiotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32293453,

title = {microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation},

author = {Maureen Labbé and Christianne Hoey and Jessica Ray and Vincent Potiron and Stéphane Supiot and Stanley K Liu and Delphine Fradin},

doi = {10.1186/s12943-020-01186-6},

issn = {1476-4598},

year  = {2020},

date = {2020-03-23},

urldate = {2020-01-01},

journal = {Mol Cancer},

volume = {19},

number = {1},

pages = {63},

abstract = {As the most frequently diagnosed non-skin cancer in men and a leading cause of cancer-related death, understanding the molecular mechanisms that drive treatment resistance in prostate cancer poses a significant clinical need. Radiotherapy is one of the most widely used treatments for prostate cancer, along with surgery, hormone therapy, and chemotherapy. However, inherent radioresistance of tumor cells can reduce local control and ultimately lead to poor patient outcomes, such as recurrence, metastasis and death. The underlying mechanisms of radioresistance have not been fully elucidated, but it has been suggested that miRNAs play a critical role. miRNAs are small non-coding RNAs that regulate gene expression in every signaling pathway of the cell, with one miRNA often having multiple targets. By fine-tuning gene expression, miRNAs are important players in modulating DNA damage response, cell death, tumor aggression and the tumor microenvironment, and can ultimately affect a tumor's response to radiotherapy. Furthermore, much interest has focused on miRNAs found in biofluids and their potential utility in various clinical applications. In this review, we summarize the current knowledge on miRNA deregulation after irradiation and the associated functional outcomes, with a focus on prostate cancer. In addition, we discuss the utility of circulating miRNAs as non-invasive biomarkers to diagnose, predict response to treatment, and prognosticate patient outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31906502,

title = {Influence of Radiotherapy Fractionation Schedule on the Tumor Vascular Microenvironment in Prostate and Lung Cancer Models},

author = {Karen Clément-Colmou and Vincent Potiron and Manon Pietri and Maëva Guillonneau and Emmanuel Jouglar and Sophie Chiavassa and Grégory Delpon and François Paris and Stéphane Supiot},

doi = {10.3390/cancers12010121},

issn = {2072-6694},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Cancers (Basel)},

volume = {12},

number = {1},

abstract = {Background. The tumor vasculature acts as an interface for the primary tumor. It regulates oxygenation, nutrient delivery, and treatment efficacy including radiotherapy. The response of the tumor vasculature to different radiation doses has been disparately reported. Whereas high single doses can induce endothelial cell death, improved vascular functionality has also been described in a various dose range, and few attempts have been made to reconcile these findings. Therefore, we aimed at comparing the effects of different radiation fractionation regimens on the tumor vascular microenvironment.



METHODS: Lewis lung and prostate PC3 carcinoma-derived tumors were irradiated with regimens of 10 × 2 Gy, 6 × 4 Gy, 3 × 8 Gy or 2 × 12 Gy fractions. The tumor vasculature phenotype and function was evaluated by immunohistochemistry for endothelial cells (CD31), pericytes (desmin, α-SMA), hypoxia (pimonidazole) and perfusion (Hoechst 33342).



RESULTS: Radiotherapy increased vascular coverage similarly in all fractionation regimens in both models. Vessel density appeared unaffected. In PC3 tumors, hypoxia was decreased and perfusion was enhanced in proportion with the dose per fraction. In LLC tumors, no functional changes were observed at  = 15 days, but increased perfusion was noticed earlier ( = 9-11 days).



CONCLUSION: The vascular microenvironment response of prostate and lung cancers to radiotherapy consists of both tumor/dose-independent vascular maturation and tumor-dependent functional parameters.},

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pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1200/JCO.2020.38.6_suppl.93,

title = {Oligopelvis-GETUG P07: A multicenter phase II trial of combined salvage radiotherapy and hormone therapy in oligorecurrent pelvic node relapses of prostate cancer.},

author = {Stephane Supiot and David Pasquier and Xavier Buthaud and Nicolas Magné and Veronique Beckendorf and Paul Sargos and Gilles Crehange and Pascal Pommier and Genevieve Loos and Ali Hasbini and Igor Latorzeff and Marlon Silva and Fabrice Denis and Jean-Leon Lagrange and Loic Campion and Loig Vaugier and Audrey Blanc-Lapierre},

url = {https://doi.org/10.1200/JCO.2020.38.6_suppl.93},

doi = {10.1200/JCO.2020.38.6_suppl.93},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Journal of Clinical Oncology},

volume = {38},

number = {6_suppl},

pages = {93-93},

abstract = {Background: Oligorecurrent pelvic nodal relapse of prostatic cancer is a challenge for regional salvage treatments. We conducted OLIGOPELVIS – GETUG P07, a phase II trial of combined salvage radiotherapy and hormone therapy in oligorecurrent pelvic node relapses of prostate cancer (NCT02274779). Methods: OLIGOPELVIS–GETUG P07 was a prospective multi-center phase II trial investigating high-dose salvage pelvic irradiation with an additional dose to the fluorocholine-based positron-emission-tomography (FCH- PET)-positive pelvic lymph nodes (PLN), combined with six-month androgen blockade (LH-RH agonist or antagonist injections). The prescribed dose was 54 Gy in 1.8 Gy fractions with up to 66 Gy in 2.2 Gy fractions to the pathological PLN. Toxicity (CTCAE v4) and complete response rates (PSA < 0.20 ng/ml) were analyzed. The main objective was to assess biochemical-clinical failure defined by a cluster of events including PSA progression (≥25 % and ≥ 2 ng/ml above the nadir) or clinical evidence of local or metastatic progression or post- treatment initiation of hormonal therapy or prostate cancer-related death. We hypothesized that salvage treatment would achieve a 2-year relapse-free survival of 70 %. Results: Seventy-four patients were recruited in fifteen French radiation oncology departments between August 2014 and July 2016. Seven were excluded before treatment because of violation of the inclusion criteria. The intention-to-treat analysis therefore included sixty-seven patients. Half of them had received prior prostatic/prostate bed irradiation. Median age was 67.7. Grade 2+ two-year urinary and intestinal toxicity were 10% and 2% respectively. At 2 and 3 years, 73.1 and 45.9% of patients achieved a persisting complete response respectively. After a median follow-up of 34 months, the 2-year progression-free survival rate was 77.6%. Median progression-free survival was 40.1 months. Conclusions: Combined pelvic salvage radiotherapy and hormone therapy allowed for prolonged tumor control in oligorecurrent pelvic node relapses of prostate cancer with limited toxicity. Clinical trial information: NCT02274779.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1200/JCO.2020.38.6_suppl.331,

title = {Late toxicity and quality of life from GETUG-AFU 22 study.},

author = {Igor Latorzeff and Stephane Guerif and Sandra Pelissier and Emmanuel Meyer and Julien Fraisse and Stephane Supiot and Gilles Crehange and Edouard Lagneau and Philippe Ronchin and Ahmed Benyoucef and Ali Hasbini and Pascal Pommier and Guy De Laroche and Laurent Salomon and Paul Sargos},

url = {https://doi.org/10.1200/JCO.2020.38.6_suppl.331},

doi = {10.1200/JCO.2020.38.6_suppl.331},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Journal of Clinical Oncology},

volume = {38},

number = {6_suppl},

pages = {331-331},

abstract = {331Background: Radical prostatectomy (RP) is recommended as a standard treatment for localized prostate cancer. However no recommendations exist for pts with immediate detectable PSA after RP. Methods: Pts with localized prostate cancer, treated by RP (R0 or R1), with a PSA level post-RP ≥0.2 ng/mL and ≤2 ng/mL at randomization and N0 M0 on imaging were included. Pts were randomized (1:1) to radiotherapy (RT) alone (RT arm) or 6 months degarelix hormone therapy (HT) with RT (RT+HT arm). RT consisted of pelvic irradiation (46 Gy in 23 Fr) with a boost on the prostate bed (66 Gy in 33 Fr). The primary endpoint was event-free survival (EFS). Acute and late toxicities were evaluated as secondary endpoints and scored using CTCAE V4.0 scale. Quality of life (QOL) was assessed with QLQ-C30 and QLQ-PR25 questionnaires at 12 and 24 months. Late toxicity was reported at 24 months. Results: From Jan-2013 to Sept-2015, 125 pts were included (RT arm: 64 pts; RT+HT arm: 61). Median follow up is 38 months (31.4; 44). The baseline characteristics are well-balanced between two arms: median age was 66 yrs (50-77), all men having an ECOG ≤1 (ECOG 0 in 92%), a median Gleason score of 7 (3-9), a median PSA of 0.3 ng/mL (0.09-1.82) post-RP and 0.6 ng/mL (0.12-3.65) at randomization. All pts received 33 Fr of RT. In the RT+HT arm 98.4% of pts received the 6 months of HT planned. All pts were eligible for safety analysis. At 24 months, no difference in late genitourinary (GU) or gastrointestinal (GI)toxicity was observed between the two arms (p=0.145) Grade 3 late toxicities were reported for 15/125 pts (12%): 8/64 pts (6.5%) in the RT arm and 7/61 pts (5.5%) in RT+HT arm (NS) and no toxicity grade >3 was observed. Evaluation of QOL was assessable at 12 and 24 months of FU for 80%/89% pts and 59%/77% pts in RT/RT-HT arms respectively. At 12 months QLQ-PR25 HT related symptoms was significantly more important in the RT-HT arm (p=0.04). At 24 months no significant difference in QLQC-30 or QLQ-PR25 analysis was reported. Conclusions:, At 24 months in this phase II trial no significant difference in GI/GU toxicity and.QOL was observed between the two arms. GETUG-AFU 22 efficacy analysis is still pending. Clinical trial information: NCT01994239.},

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pubstate = {published},

tppubtype = {article}

}