Indication and perspectives of radiation therapy in the setting of de-novo metastatic prostate cancer.

Prostate cancer is the most common cancer and the third leading cause of cancer mortality in men. Each year, approximately 10% of prostate cancers are diagnosed metastatic at initial presentation. The standard treatment option for de-novo metastatic prostate cancer is androgen deprivation therapy with novel hormonal agent or with chemotherapy. Recently, PEACE-1 trial highlighted the benefit of triplet therapy resulting in the combination of androgen deprivation therapy combined with docetaxel and abiraterone. Radiotherapy can be proposed in a curative intent or to treat local symptomatic disease. Nowadays, radiotherapy of the primary disease is only recommended for de novo low-burden/low-volume metastatic prostate cancer, as defined in the CHAARTED criteria. However, studies on stereotactic radiotherapy on oligometastases have shown that this therapeutic approach is feasible and well tolerated. Prospective research currently focuses on the benefit of intensification by combining treatment of the metastatic sites and the primary all together. The contribution of metabolic imaging to better define the target volumes and specify the oligometastatic character allows a better selection of patients. This article aims to define indications of radiotherapy and perspectives of this therapeutic option for de-novo metastatic prostate cancer.

[Understanding/acceptance of radiotherapy: An ethical dilemma resolved by an ethics of care]. / Compréhension/acceptation de la radiothérapie : un dilemme éthique résolu par une éthique de la considération et de la sollicitude.

PURPOSE: Ethical questions are poorly investigated specifically in radiation oncology. The objective of the study was to identify and understand the main ethical issue in radiation oncology. MATERIALS AND METHODS: A quantitative analysis was based on the answers to a questionnaire of 200 professionals from 22 radiation oncology departments. The questionnaire mainly aimed to characterize the main ethical issue. A monocentric qualitative analysis was based on semi-structured interviews focused on the main identified ethical issue, carried out with eight technologists, and 20 patients undergoing radiotherapy. RESULTS: The main ethical issue was the understanding and/or acceptance of the treatment by the patients (71 %), which frequently arises (more than once a month) (52 %), and corresponds to an ethical tension between the principles of respect for autonomy and beneficence (the good as viewed by the patient) as defined by Beauchamp and Childress. The technologists, wish the patient to be fully involved in his treatment, with the even possibility of refusing it. However, excluding paternalism and autonomic relentlessness, the technologists have the feeling of acting for the good of the patients by treating them with radiation, even if the patients are not always aware of it, because they are within a situation of vulnerability. If the hierarchy of principles is a compromise alternative, this problem is finally well resolved by the effective implementation of an ethic of consideration and solicitude, restoring the patient capabilities, i.e. the maximum development of his potentialities in his situation of vulnerability. Beyond the legal dimension, patient information is crucial and must consider the specific temporality of the patient. CONCLUSION: The main ethical issue in radiation oncology is the understanding and/or acceptance of the treatment involving the development of an ethic of consideration and solicitude.

[Intermediate-risk prostate cancer treated with exclusive external irradiation: Focus on anatomical sites of recurrence in two French trials]. / Cancer de la prostate de risque intermédiaire traité par irradiation externe exclusive : focus sur les sites anatomiques de récidive dans deux essais français.

PURPOSE: Retrospective description of anatomical sites of relapse based on (18F)-choline PET-CT, (68Ga)-prostatic specific-membrane antigen PET-CT, bone scan, and prostate magnetic resonance imaging (MRI) data. MATERIALS AND METHODS: From two French prospective cohorts, patients treated with exclusive radiotherapy for an intermediate-risk cancer were identified during their follow-ups. They were included if they presented a rising of the prostate-specific antigen (PSA) associated with the realization of an imaging showing the sites of recurrences. RESULTS: Two hundred and sixty-three patients were included. After a median follow-up of 76 months (interquartile range [IQR] 67-95), 65 patients had biochemical recurrence and positive imaging. The median nadir PSA was 0.6ng/mL and the median PSA at recurrence was 3.4ng/mL. A single lesion was found in 48% of cases, 2 to 4 lesions in 43% of cases and more than 4 lesions in 9% of cases. The sites of relapse identified were prostate (37/65), prostate only (19/65), seminal vesicles (9/65) Pelvic nodes (35/65), extrapelvic nodes (15/65) and bone (13/65). CONCLUSIONS: The majority of relapses presented as a single lesion localized in the pelvis.

Cost-effectiveness of hypofractionated versus conventional radiotherapy in patients with intermediate-risk prostate cancer: An ancillary study of the PROstate fractionated irradiation trial - PROFIT.

PURPOSE: To evaluate the cost-effectiveness of moderate Hypofractionated Radiotherapy (H-RT) compared to Conventional Radiotherapy (C-RT) for intermediate-risk prostate caner (PCa). METHODS: A prospective randomized clinical trial including 222 patients from six French cancer centers was conducted as an ancillary study of the international PROstate Fractionated Irradiation Trial (PROFIT). We carried-out a cost-effectiveness analysis (CEA) from the payer's perspective, with a time horizon of 48 months. Patients assigned to the H-RT arm received 6000 cGy in 20 fractions over 4 weeks, or 7800 cGy in 39 fractions over 7 to 8 weeks in the C-RT arm. Patients completed quality of life (QoL) questionnaire: Expanded Prostate Cancer Index Composite (EPIC) at baseline, 24 and 48 months, which were mapped to obtain a EuroQol five-dimensional questionnaire (EQ-5D) equivalent to generate Quality Adjusted Life Years (QALY). We assessed differences in QALYs and costs between the two arms with Generalized Linear Models (GLMs). Costs, estimated in euro (€) 2020, were combined with QALYs to estimate the Incremental Cost-effectiveness ratio (ICER) with non-parametric bootstrap. RESULTS: Total costs per patien were lower in the H-RT arm compared to the C-RT arm €3,062 (95 % CI: 2,368 to 3,754) versus €4,285 (95 % CI: 3,355 to 5,215), (p < 0.05). QALY were marginally higher in the H-RT arm, however this difference was not significant: 0.044 (95 % CI: - 0.016 to 0.099). CONCLUSIONS: Treating localized prostate cancer with moderate H-RT could reduce national health insurance spending. Adopting such a treatment with an updated reimbursement tariff would result in improving resource allocation in RT management.

Prostate cancer brachytherapy: SFRO guidelines 2021.

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

External radiotherapy for prostatic cancers.

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.

[Dose optimization in 3D pulsed dose rate brachytherapy for patients with locally advanced cervical cancer: A French multicenter phase II trial]. / Optimisation de la curiethérapie utérovaginale de débit pulsé des cancers du col utérin localement évolués : résultats finaux du PHRC Tridicol.

PURPOSE: We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers. MATERIAL AND METHODS: Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy. RESULTS: The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications. CONCLUSION: HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer.

Best practice in brachytherapy.

The 2020 recommendations for good brachytherapy procedures ("Recorad") are updated based on the 2016 article. This new brachytherapy article took into account recent data published in the literature as well as international recommendations. The different brachytherapy steps are successively described from the treatment preparation (brachytherapy technique prescription; procedure and material, dedicated images for planification, dose distribution analysis and validation) to the end of the procedure as well as post-treatment surveillance.

Radiotherapy for penile cancers.

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

[Brachytherapy in France in 2020: State of the art and perspectives from the Groupe curiethérapie de la SFRO]. / Curiethérapie en France en 2020 : synthèse et perspectives du Groupe curiethérapie de la Société française de radiothérapie oncologique.

Because of its principle and its high proof level clinical results, brachytherapy represents a specific irradiation technique for the treatment of primary tumors as well as some local relapses in pre-irradiated area. After a glory period between the 80's and 90's, brachytherapy has progressively lost its attractiveness. In order to provide a practical solution to this deleterious situation, it is important that guardianships, health care payers, patient associations, specialist doctors and radiation oncologists understand the reasons leading to this harmful state as well as the risks concerned. A teaching judged insufficient, non-adapted value and an aging image of brachytherapy represent the three main reasons of this degradation and constitute the three most important challenges conditioning its maintain in the anticancer treatment arsenal. An adapted communication with radiation oncologists themselves but also with the other scientific societies remains crucial as well as with guardianship and patient associations. It is central that brachytherapy could be recognized in order to make it stronger and accessible for all the patients who could need it.

[Type 1 neurofibromatosis: Onset of two tumors before the age of 5years]. / Neurofibromatose de type 1 : survenue de deux tumeurs avant l'âge de 5 ans.

Neurofibromatosis type 1 (NF1) is a frequent autosomal dominant genetic disorder that predisposes to the development of benign and malignant tumors. Mutation of the NF1 gene affects the RAS-MAPK signaling pathway and leads to a dysfunction in cell proliferation and induces tumor development. Epidemiology of cancer in children with NF1 is very different from the general pediatric population, which requires regular and specific monitoring. Neurofibroma is the most frequent benign tumor. It can be very invalidating depending on the size and location of the tumor. Currently, there is no specific treatment for these tumors. The most frequent malignancies in children with NF1 are leukemias, rhabdomyosarcomas, malignant peripheral nerve sheath tumors and gliomas. The treatment of these tumors should consider the risk of second cancers induced by radio- and chemotherapy. We report on the case of a 5-year-old boy with NF1 developing two tumors.

[Intensity modulated radiotherapy for head and neck cancer, dose constraint for normal tissue: Cochlea vestibular apparatus and brainstem]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures, dose de tolérance des tissus sains : appareil cochléovestibulaire et tronc cérébral.

Modern techniques such as intensity modulated radiation therapy (IMRT) have been proven to significantly decrease the dose delivered to the cochleovestibular apparatus, limiting consecutive toxicity especially for sensorineural hearing loss. However, recent data still report a 42% rate of radio-induced hypoacusia underscoring the need to protect the cochleovestibular apparatus. Due to the small size of the cochlea, a precise dose-volume analysis could not be performed, and recommendations only refer to the mean dose. Confusing factors such as age, concomitant chemotherapy, primary site and tumor stage should be taken into account at the time of treatment planning. (Non-coplanar) VMAT and tomotherapy have been proven better at sparing the cochlea in comparison with 3D CRT. Brainstem radio-induced injuries were poorly studied because of their infrequency and the difficulty of distinguishing between necrosis and tumor progression in the case of a primary tumor located at the base of skull. The following toxicities have been described: brainstem focal radionecrosis, cognitive disorders without dementia, cranial nerve injuries and sensori motor disability. Maximal dose to the brainstem should be kept to < 54Gy for conventional fractionation. This dose could be exceeded (no more than 10mL should receive more than 59Gy), provided this hot spot is located in the peripheral area of the organ.

[Prostate cancer brachytherapy]. / Curiethérapie des cancers de la prostate.

Prostate brachytherapy techniques are described, concerning both Iodine 125 high dose rate brachytherapy. The following parts are presented: brachytherapy indications, technical description, immediate postoperative management and post-treatment evaluation, and 4 to 6 weeks as well as long-term follow-up.

[Prostate cancer external beam radiotherapy]. / Radiothérapie externe des cancers prostatiques.

The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy.

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer.

PURPOSE: Intensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study (NCT02024035). PATIENTS AND METHOD: This prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1-T4, M0, N0-N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization. RESULTS: From the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching (P=0.0275). Cetuximab was not significantly associated with more grade 3 mucositis (P=0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities (P=1.000 and P=0.5731, respectively). There was no significant difference in local relapse-free survival (P=0.0920) or overall survival (P=0.4575) between patients treated with or without cetuximab. CONCLUSION: Patients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles.

[Prostate cancer: what treatment techniques for which tumors? Ethical and methodological issues]. / Cancers de prostate : quelles techniques de radiothérapie pour quelles tumeurs ? Enjeux éthiques et méthodologiques.

The identification of the optimal radiation technique in prostate cancer is based on the results of dosimetric and clinical studies, although there are almost no randomized studies comparing different radiation techniques. The feasibility of the techniques depends also on the technical and human resources of the radiation department, on the cost of the treatment from the points of view of the society, the patient and the radiation oncologist, and finally on the choice of the patient. The slow evolution of prostate cancer leads to consider the biochemical failure as the main judgment criteria in the majority of the studies. A proper urinary radio-induced toxicity evaluation implies a long follow-up. Intensity-modulated radiotherapy (IMRT) combined with image-guided radiotherapy (IGRT) is recommended in case of high dose (≥76Gy) to the prostate, pelvic lymph nodes irradiation and hypofractionation schedules. For low-risk tumors, the aim of the treatment is to preserve quality of life, while limiting costs. Stereotactic body radiotherapy shows promising results, although the follow-up is still limited and phase III trials are ongoing. Focal radiation techniques are in the step of feasibility. For intermediate and high-risk tumors, the objective of the treatment is to increase the locoregional control, while limiting the toxicity. IMRT combined with IGRT leads to either a well-validated dose escalation strategy for intermediate risk tumors, or to a strategy of moderate hypofractionated schedules, which cannot be yet considered as a standard treatment. These combined radiation techniques allow finally large lymph node target volume irradiation and dose escalation potentially in the dominant intraprostatic lesion. The feasibility of simultaneous integrated boost approaches is demonstrated.

[Impact of dynamic IMRT and tomotherapy in pelvic cancers: a prospective dosimetric study with 51 patients]. / Apport de la RCMI rotationnelle et de la tomothérapie hélicoïdale dans les cancers pelviens : étude dosimétrique prospective sur 51 patients.

PURPOSE: To compare the dosimetric results of different techniques of dynamic intensity modulated radiation therapy (IMRT) in patients treated for a pelvic cancer with nodal irradiation. PATIENTS AND METHODS: Data of 51 patients included prospectively in the Artpelvis study were analyzed. Thirty-six patients were treated for a high-risk prostate cancer (13 with helical tomotherapy, and 23 with Rapid'Arc(®)) and 15 patients were treated for a localized anal cancer (nine with helical tomotherapy and six with Rapid'Arc(®)). Plan quality was assessed according to several different dosimetric indexes of coverage of planning target volume and sparing of organs at risk. RESULTS: Although some dosimetric differences were statistically significant, helical tomotherapy and Rapid'Arc provided very similar and highly conformal plans. Regarding organs at risk, Rapid'Arc(®) provided better pelvic bone sparing with a lower non-tumoral integral dose. CONCLUSION: In pelvis cancer with nodal irradiation, Rapid'Arc and helical tomotherapy provided very similar plans. The clinical evaluation of Artpelvis study will verify this equivalence hypothesis.

Immunonutrition improves functional capacities in head and neck and esophageal cancer patients undergoing radiochemotherapy: a randomized clinical trial.

BACKGROUND & AIMS: Malnutrition is frequent in head and neck (HN) and esophageal cancer patients and aggravated by radiochemotherapy (RCT), increasing morbi-mortality and treatment toxicity. Our goal was to investigate the effect of immunonutrition consisting of an arginine, omega-3 fatty acid, nucleotides-enriched diet on nutritional status, and functional capacity in HN or esophageal cancer patients undergoing RCT. METHODS: 37 patients were randomized in a double-blind clinical trial. 5 days before and until the end of RCT (5-7 weeks), they received either an Immunomodulating Enteral Nutrition (IEN) or an isonitrogenous, isoenergetic Standard Enteral Nutrition (SEN). Anthropometrical parameters, nutritional risk index (NRI), serum albumin, plasma antioxidant capacity, and functional capacity were recorded between the beginning and the end of RCT. RESULTS: A significant gain in total body weight (+2.1 ± 3.1 kg) was observed in IEN patients. Albuminemia and NRI were improved concomitantly in IEN malnourished patients. Plasma antioxidant capacity was improved (+100 ± 13 µM EqTrolox) in IEN patients. Functional capacity measured by WHO Performance Status and Karnofsky index was maintained in IEN patients but significantly reduced in SEN patients. CONCLUSIONS: These preliminary data show that immunonutrition could improve the nutritional status together with functional capacity in HN and esophageal cancer patients undergoing RCT. CLINICAL TRIAL REGISTRATION: This clinical trial promoted by the University Hospital Center of Clermont-Ferrand has been registered at ClinicalTrial.gov website under the following reference: NCT00333099.