Publications by authors named "Stéphane Supiot"

98 Publications

Cytokine release syndrome and tumor lysis syndrome in a multiple myeloma patient treated with palliative radiotherapy: A case report and review of the literature.

Clin Transl Radiat Oncol 2022 Jan 12;32:24-28. Epub 2021 Nov 12.

Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, Nantes, St-Herblain, France.

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.
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http://dx.doi.org/10.1016/j.ctro.2021.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591462PMC
January 2022

Interaction Between Modern Radiotherapy and Immunotherapy for Metastatic Prostate Cancer.

Front Oncol 2021 14;11:744679. Epub 2021 Sep 14.

Institut de Cancérologie de l'Ouest, Nantes, France.

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.
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http://dx.doi.org/10.3389/fonc.2021.744679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477651PMC
September 2021

Stereotactic Re-Irradiation for Local Recurrence after Radical Prostatectomy and Radiation Therapy: A Retrospective Multicenter Study.

Cancers (Basel) 2021 Aug 27;13(17). Epub 2021 Aug 27.

Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, Boulevard J. Monod, 44800 St-Herblain, France.

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.
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http://dx.doi.org/10.3390/cancers13174339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430661PMC
August 2021

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.

Eur Urol 2021 10 8;80(4):405-414. Epub 2021 Jul 8.

Department of Biostatistics, Institut de Cancérologie de l'Ouest, Boulevard J. Monod, Nantes, St-Herblain, France.

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.
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http://dx.doi.org/10.1016/j.eururo.2021.06.010DOI Listing
October 2021

Late Gastrointestinal Tolerance After Prostate Radiotherapy: Is the Anal Canal the Culprit? A Narrative Critical Review.

Front Oncol 2021 16;11:666962. Epub 2021 Jun 16.

Department of Radiation Oncology, Centre Eugene Marquis, Rennes, France.

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.
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http://dx.doi.org/10.3389/fonc.2021.666962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242201PMC
June 2021

Recommendations for planning and delivery of radical radiotherapy for localized urothelial carcinoma of the bladder.

Radiother Oncol 2021 08 10;161:95-114. Epub 2021 Jun 10.

Department of Radiotherapy, Institut Bergonié, Bordeaux, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.radonc.2021.06.011DOI Listing
August 2021

A Monte Carlo Determination of Dose and Range Uncertainties for Preclinical Studies with a Proton Beam.

Cancers (Basel) 2021 Apr 15;13(8). Epub 2021 Apr 15.

Institut de Cancérologie de l'Ouest, 44800 Saint-Herblain, France.

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.
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http://dx.doi.org/10.3390/cancers13081889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071150PMC
April 2021

Radical radiotherapy for paediatric solid tumour metastases: An overview of current European protocols and outcomes of a SIOPE multicenter survey.

Eur J Cancer 2021 03 16;145:121-131. Epub 2021 Jan 16.

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands; Princess Máxima Center for Paediatric Oncology, Utrecht, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.ejca.2020.12.004DOI Listing
March 2021

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

Bull Cancer 2021 Jan 24;108(1):125-128. Epub 2020 Dec 24.

Institut de cancérologie de l'Ouest, Nantes, St-Herblain, France; Université de Nantes, Nantes, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2020.10.015DOI Listing
January 2021

[Innovation in radiotherapy in 2021].

Bull Cancer 2021 Jan 7;108(1):42-49. Epub 2020 Dec 7.

Département de radiothérapie, Institut de cancérologie de l'Ouest René-Gauducheau, boulevard Jacques-Monod, 44805 Saint-Herblain, France; Centre de Recherche en Cancéro-Immunologie Nantes/Angers (CRCINA, UMR 892 Inserm), Institut de Recherche en Santé de l'Université de Nantes, Nantes cedex 1, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2020.10.005DOI Listing
January 2021

Targeting Stereotactic Body Radiotherapy on Metabolic PET- and Immuno-PET-Positive Vertebral Metastases.

Biomedicines 2020 Nov 28;8(12). Epub 2020 Nov 28.

Department of Radiotherapy and Nuclear Medicine Institut de Cancérologie de l'Ouest (ICO), F-44800 Saint-Herblain, France.

(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 F-deoxyglucose (FDG) for BC or F-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.
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http://dx.doi.org/10.3390/biomedicines8120548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760481PMC
November 2020

Prostate Bed Delineation Guidelines for Postoperative Radiation Therapy: On Behalf Of The Francophone Group of Urological Radiation Therapy.

Int J Radiat Oncol Biol Phys 2021 04 10;109(5):1243-1253. Epub 2020 Nov 10.

Radiation Oncology Department, Center Hospitalier Lyon Sud, Pierre Benite, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.010DOI Listing
April 2021

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

Radiother Oncol 2021 02 1;155:113-119. Epub 2020 Nov 1.

Dept. of Radiation Oncology, University Medical Center Utrecht, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.radonc.2020.10.032DOI Listing
February 2021

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.

Lancet Oncol 2020 10;21(10):1341-1352

Institut Bergonié, Bordeaux, France.

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.
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http://dx.doi.org/10.1016/S1470-2045(20)30454-XDOI Listing
October 2020

Report of a unique case of gemcitabine-induced radiation recall myelitis following spinal cord irradiation.

BJR Case Rep 2020 Sep 23;6(3):20190118. Epub 2020 Apr 23.

Department of Radiation Oncology, Institut de cancérologie de l'Ouest René-Gauducheau, boulevard Jacques-Monod, 44805 Saint-Herblain, France.

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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http://dx.doi.org/10.1259/bjrcr.20190118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465732PMC
September 2020

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.

Int J Radiat Oncol Biol Phys 2020 12 6;108(5):1204-1217. Epub 2020 Aug 6.

Department of Clinical Research and Innovation, Leon Berard Cancer center, Lyon, France.

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.
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http://dx.doi.org/10.1016/j.ijrobp.2020.07.2324DOI Listing
December 2020

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

Int J Radiat Oncol Biol Phys 2020 12 13;108(5):1189-1195. Epub 2020 Jul 13.

Univ Rennes, CLCC Eugène Marquis, INSERM, LTSI-UMR 1099, Rennes, France.

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.
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http://dx.doi.org/10.1016/j.ijrobp.2020.07.019DOI Listing
December 2020

[Oligorecurrent prostate cancer: current management and perspectives].

Bull Cancer 2020 Jun;107(5S):S35-S40

Service de radiothérapie, Institut de cancérologie de l'Ouest, boulevard Professeur-Jacques-Monod, 44800 Nantes Saint-Herblain, France. Electronic address:

Oligometastatic prostate cancer (PCa) is an intense area of research thanks to the development of novel PET tracers such as F-choline or Ga-PSMA. Several retrospective studies in patients with hormone-sensitive oligorecurrent PCa (usually up to 5 metastases with a controlled primary tumor) showed PSA response and a low toxicity profile of metastasis-directed therapies (MDT) such as Stereotactic Body Radiation Therapy (SBRT) or salvage lymph node dissection. More recently, randomized phase 2 studies showed that SBRT can delay the introduction of androgen deprivation, decrease biochemical relapses and increase overall survival. Regarding oligoprogressive metastatic castration-resistant PCa, limited data is however available. Based on these studies the European Association of Urology and the American Society of Radiotherapy EAU now recommend using MDT instead of observation. Several studies are undergoing in France and worldwide in order to confirm the exact role of MDT.
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http://dx.doi.org/10.1016/S0007-4551(20)30276-9DOI Listing
June 2020

microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation.

Mol Cancer 2020 03 23;19(1):63. Epub 2020 Mar 23.

CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France.

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.
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http://dx.doi.org/10.1186/s12943-020-01186-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087366PMC
March 2020

Haute Couture or Ready-to-Wear? Tailored Pelvic Radiotherapy for Prostate Cancer Based on Individualized Sentinel Lymph Node Detection.

Cancers (Basel) 2020 Apr 10;12(4). Epub 2020 Apr 10.

Radiation Oncology Department, Institut de Cancérologie de l'Ouest, 44805 Nantes Saint-Herblain, France.

Prostate cancer (PCa) pelvic radiotherapy fields are defined by guidelines that do not consider individual variations in lymphatic drainage. We examined the feasibility of personalized sentinel lymph node (SLN)-based pelvic irradiation in PCa. Among a SLN study of 202 patients, we retrospectively selected 57 patients with a high risk of lymph node involvement. Each single SLN clinical target volume (CTV) was individually segmented and pelvic CTVs were contoured according to Radiation Therapy Oncology Group (RTOG) guidelines. We simulated a radiotherapy plan delivering 46 Gy and calculated the dose received by each SLN. Among a total of 332 abdominal SLNs, 305 pelvic SLNs (beyond the aortic bifurcation) were contoured (mean 5.4/patient). Based on standard guidelines, CTV missed 67 SLNs (22%), mostly at the common iliac level (40 SLNs). The mean distance between iliac vessels and the SLN was 11mm, and despite a 15mm margin around the iliac vessels, 9% of SLNs were not encompassed by the CTV. Moreover, 42 SLNs (63%) did not receive 95% of the prescribed dose. Despite a consensus on contouring guidelines, a significant proportion of SLNs were not included in the pelvic CTV and did not receive the prescribed dose. A tailored approach based on individual SLN detection would avoid underdosing pelvic lymph nodes that potentially contain tumor cells.
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http://dx.doi.org/10.3390/cancers12040944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226011PMC
April 2020

Radiotherapy-induced overexpression of exosomal miRNA-378a-3p in cancer cells limits natural killer cells cytotoxicity.

Epigenomics 2020 03 8;12(5):397-408. Epub 2020 Apr 8.

CRCINA, INSERM, Université de Nantes, Nantes 44000, France.

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.
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http://dx.doi.org/10.2217/epi-2019-0193DOI Listing
March 2020

Local dose analysis to predict acute and late urinary toxicities after prostate cancer radiotherapy: Assessment of cohort and method effects.

Radiother Oncol 2020 06 28;147:40-49. Epub 2020 Mar 28.

Univ Rennes, CLCC Eugène Marquis, INSERM, LTSI - UMR 1099, F-35000, Rennes, France.

Purpose: To perform bladder dose-surface map (DSM) analysis for (1) identifying symptom-related sub-surfaces (Ssurf) and evaluating their prediction capability of urinary toxicity, (2) comparing DSM with dose-volume map (DVM) (method effect), and (3) assessing the reproducibility of DSM (cohort effect).

Methods And Materials: Urinary toxicities were prospectively analyzed for 254 prostate cancer patients treated with IMRT/IGRT at 78/80 Gy. DSMs were generated by unfolding bladder surfaces in a 2D plane. Pixel-by-pixel analysis was performed to identify symptom-related Ssurf. Likewise, voxel-by-voxel DVM analysis was performed to identify sub-volumes (Svol). The prediction capability of Ssurf and Svol DVHs was assessed by logistic/Cox regression using the area under the ROC curve (AUC). The Ssurf localization and prediction capability were compared to (1) the Svol obtained by DVM analysis in the same cohort and (2) the Ssurf obtained from other DSM studies.

Results: Three Ssurf were identified in the bladder: posterior for acute retention (AUC = 0.64), posterior-superior for late retention (AUC = 0.68), and inferior-anterior-lateral for late dysuria (AUC = 0.73). Five Svol were identified: one in the urethra for acute incontinence and four in the posterior bladder part for acute and late retention, late dysuria, and hematuria. The overlap between Ssurf and Svol was moderate for acute retention, good for late retention, and bad for late dysuria, and AUCs ranged from 0.62 to 0.81. The prediction capabilities of Ssurf and Svol models were not significantly different. Among five symptoms comparable between cohorts, common Ssurf was found only for late dysuria, with a good spatial agreement.

Conclusion: Spatial agreement between methods is relatively good although DVM identified more sub-regions. Reproducibility of identified Ssurf between cohorts is low.
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http://dx.doi.org/10.1016/j.radonc.2020.02.028DOI Listing
June 2020

Can Comprehensive Geriatric Assessment Predict Tolerance of Radiotherapy for Localized Prostate Cancer in Men Aged 75 Years or Older?

Cancers (Basel) 2020 Mar 9;12(3). Epub 2020 Mar 9.

Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, 44800 Saint Herblain, France.

Curative radiotherapy for prostate cancer is common in the elderly. However, concerns about potential toxicity have inhibited access to radiotherapy for this population, for whom preserving quality of life (QoL) is crucial. The primary endpoint was to identify predictors of impaired QoL in men aged 75 years or older treated with curative intent radiotherapy with or without androgen deprivation therapy (ADT) for localized prostate cancer. We prospectively performed comprehensive geriatric assessment (CGA) and administered QoL questionnaires to 208 elderly (>75 years) patients prior to, plus two and six months after, radiotherapy (NCT02876237). The median age of the patients was 77 years (range 75-89). At the start of the study, comorbidities were highlighted in 65% of patients: 23% were depressed, 23% had cognitive impairment, and 16% had reduced independence. At six months, 9% of patients had a consistently decreased QoL (>20 points), and a further 16% had a more moderate reduction (10 to 20 points) in QoL. None of the parameters studied (tumor characteristic, treatment, or oncogeriatric parameters) were predictive of a reduced QoL following radiotherapy. Though co-existing geriatric impairment was common, QoL was maintained for 75% of patients six months after radiotherapy. CGA was poorly predictive of tolerance of prostatic radiotherapy. Geriatric assessments dedicated to quality of life following radiotherapy need to be developed.
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http://dx.doi.org/10.3390/cancers12030635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139355PMC
March 2020

Influence of Radiotherapy Fractionation Schedule on the Tumor Vascular Microenvironment in Prostate and Lung Cancer Models.

Cancers (Basel) 2020 Jan 2;12(1). Epub 2020 Jan 2.

Centre de Recherche en Cancérologie Immunologie Nantes Angers (CRCINA), Institut National de Santé et de la Recherche Médicale (INSERM) UMR U1232, Centre National de la Recherche Scientifique (CNRS) ERL 6001, Université de Nantes, 44007 Nantes, France.

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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http://dx.doi.org/10.3390/cancers12010121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017121PMC
January 2020

Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial.

Lancet Oncol 2019 12 16;20(12):1740-1749. Epub 2019 Oct 16.

Biostatistics Unit, Clinical Research and Innovation Department, Léon Bérard Cancer Centre, Lyon, France.

Background: Radiotherapy is the standard salvage treatment after radical prostatectomy. To date, the role of androgen deprivation therapy has not been formally shown. In this follow-up study, we aimed to update the results of the GETUG-AFU 16 trial, which assessed the efficacy of radiotherapy plus androgen suppression versus radiotherapy alone.

Methods: GETUG-AFU 16 was an open-label, multicentre, phase 3, randomised, controlled trial that enrolled men (aged ≥18 years) with Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed adenocarcinoma of the prostate (but no previous androgen suppression or pelvic radiotherapy), stage pT2, T3, or T4a (bladder neck involvement only) and pN0 or pNx according to the tumour, node, metastasis (TNM) staging system, whose prostate-specific antigen (PSA) concentration increased from 0·1 ng/mL to between 0·2 ng/mL and 2·0 ng/mL after radical prostatectomy, without evidence of clinical disease. Patients were assigned through central randomisation (1:1) to short-term androgen suppression (subcutaneous injection of 10·8 mg goserelin on the first day of irradiation and 3 months later) plus radiotherapy (3D conformal radiotherapy or intensity modulated radiotherapy of 66 Gy in 33 fractions, 5 days a week for 7 weeks) or radiotherapy alone. Randomisation was stratified using a permuted block method (block sizes of two and four) according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival in the intention-to-treat population. This post-hoc one-shot data collection done 4 years after last data cutoff included patients who were alive at the time of the primary analysis and updated long-term patient status by including dates for first local progression, metastatic disease diagnosis, or death (if any of these had occurred) or the date of the last tumour evaluation or last PSA measurement. Survival at 120 months was reported. Late serious adverse effects were assessed. This trial is registered on ClinicalTrials.gov, NCT00423475.

Findings: Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. At the time of data cutoff (March 12, 2019), the median follow-up was 112 months (IQR 102-123). The 120-month progression-free survival was 64% (95% CI 58-69) for patients treated with radiotherapy plus goserelin and 49% (43-54) for patients treated with radiotherapy alone (hazard ratio 0·54, 0·43-0·68; stratified log-rank test p<0·0001). Two cases of secondary cancer occurred since the primary analysis, but were not considered to be treatment related. No treatment-related deaths occurred.

Interpretation: The 120-month progression-free survival confirmed the results from the primary analysis. Salvage radiotherapy combined with short-term androgen suppression significantly reduced risk of biochemical or clinical progression and death compared with salvage radiotherapy alone. The results of the GETUG-AFU 16 trial confirm the efficacy of androgen suppression plus radiotherapy as salvage treatment in patients with increasing PSA concentration after radical prostatectomy for prostate cancer.

Funding: The French Health ministry, AstraZeneca, la Ligue Contre le Cancer, and La Ligue de Haute-Savoie.
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http://dx.doi.org/10.1016/S1470-2045(19)30486-3DOI Listing
December 2019

Advances in nasopharyngeal carcinoma.

Br J Radiol 2019 Oct;92(1102):20199004

Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, Nantes, St-Herblain, France.

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http://dx.doi.org/10.1259/bjr.20199004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774607PMC
October 2019

Feasibility of Dose Escalation in Patients With Intracranial Pediatric Ependymoma.

Front Oncol 2019 21;9:531. Epub 2019 Jun 21.

ToNIC, Toulouse NeuroImaging Center, Universite de Toulouse, Inserm, Toulouse, France.

Pediatric ependymoma carries a dismal prognosis, mainly owing to local relapse within RT fields. The current prospective European approach is to increase the radiation dose with a sequential hypofractionated stereotactic boost. In this study, we assessed the possibility of using a simultaneous integrated boost (SIB), comparing VMAT vs. IMPT dose delivery. The cohort included 101 patients. The dose to planning target volume (PTV59.4) was 59.4/1.8 Gy, and the dose to SIB volume (PTV67.6) was 67.6/2.05 Gy. Gross tumor volume (GTV) was defined as the tumor bed plus residual tumor, clinical target volume (CTV59.4) was GTV + 5 mm, and PTV59.4 was CTV59.4 + 3 mm. PTV67.6 was GTV+ 3 mm. After treatment plan optimization, quality indices and doses to target volume and organs at risk (OARs) were extracted and compared with the standard radiation doses that were actually delivered (median = 59.4 Gy [50.4 59.4]). In most cases, the proton treatment resulted in higher quality indices ( < 0.001). Compared with the doses that were initially delivered, mean, and maximum doses to some OARs were no higher with SIB VMAT, and significantly lower with protons ( < 0.001). In the case of posterior fossa tumor, there was a lower dose to the brainstem with protons, in terms of V59 Gy, mean, and near-maximum (D2%) doses. Dose escalation with intensity-modulated proton or photon SIB is feasible in some patients. This approach could be considered for children with unresectable residue or post-operative FLAIR abnormalities, particularly if they have supratentorial tumors. It should not be considered for infratentorial tumors encasing the brainstem or extending to the medulla.
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http://dx.doi.org/10.3389/fonc.2019.00531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598548PMC
June 2019

Tumor vasculature remodeling by radiation therapy increases doxorubicin distribution and efficacy.

Cancer Lett 2019 08 9;457:1-9. Epub 2019 May 9.

CRCINA, INSERM, Université de Nantes, Université D'Angers, Nantes, France; Institut de Cancérologie de L'Ouest René Gauducheau, Saint-Herblain, France. Electronic address:

The tumor microenvironment regulates cancer initiation, progression and response to treatment. In particular, the immature tumor vasculature may impede drugs from reaching tumor cells at a lethal concentration. We and others have shown that radiation therapy (RT) induces pericyte recruitment, resembling vascular normalization. Here, we asked whether radiation-induced vascular remodeling translates into improved tissue distribution and efficacy of chemotherapy. First, RT induced vascular remodeling, accompanied by decreased hypoxia and/or increased Hoechst perfusion in prostate PC3 and LNCaP and Lewis lung carcinoma. These results were independent of the RT regimen, respectively 10 × 2 Gy and 2 × 12 Gy, suggesting a common effect. Next, using doxorubicin as a fluorescent reporter, we observed that RT improves intra-tumoral chemotherapy distribution. These effects were not hindered by anti-angiogenic sunitinib. Moreover, sub-optimal doses of doxorubicin had almost no effect alone, but significantly delayed tumor growth after RT. These data demonstrate that RT favors the efficacy of chemotherapy by improving tissue distribution, and could be an alternative chemosensitizing strategy.
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http://dx.doi.org/10.1016/j.canlet.2019.05.005DOI Listing
August 2019

Reoxygenation during radiotherapy in intermediate-risk prostate cancer.

Radiother Oncol 2019 04 12;133:16-19. Epub 2019 Jan 12.

Laboratoire de Traitement de l'Information Médicale (LATIM), INSERM, UMR 1101, Université de Bretagne Occidentale, IBSAM, faculté de médecine, 29238 Brest CEDEX, France.

Hypoxia is a major risk factor of prostate cancer radioresistance. We evaluated hypoxia non-invasively, using F-Misonidazole PET/CT prior to radiotherapy and after a dose of 20 Gy in intermediate-risk prostate cancer patients. Decreased hypoxic volumes were observed in all patients, suggesting that radiotherapy induces early prostate tumor reoxygenation.
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http://dx.doi.org/10.1016/j.radonc.2018.12.022DOI Listing
April 2019
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