A. Ducassou

Radiosensibilisation induite par le vémurafénib

The recent use of vemurafenib, a specific inhibitor of BRAF, has led to a significant improvement in disease-free survival and overall survival of patients treated for a BRAF-mutated metastatic melanoma. This new class of drugs is not devoid of side effects, including skin effects. In particular, its association with concomitant radiotherapy should be taken into consideration, vemurafenib appearing to be radiosensitizer. The radiation oncologist must be aware of this potential toxicity, which is not uncommon in clinical practice.

Paediatric brain tumours: A review of radiotherapy, state of the art and challenges for the future regarding protontherapy and carbontherapy.

BACKGROUND AND PURPOSE Brain tumours are the most frequent solid tumours in children and the most frequent radiotherapy indications in paediatrics, with frequent late effects: cognitive, osseous, visual, auditory and hormonal. A better protection of healthy tissues by improved beam ballistics, with particle therapy, is expected to decrease significantly late effects without decreasing local control and survival. This article reviews the scientific literature to advocate indications of protontherapy and carbon ion therapy for childhood central nervous system cancer, and estimate the expected therapeutic benefits. MATERIALS AND METHODS A systematic review was performed on paediatric brain tumour treatments using Medline (from 1966 to March of 2014). To be included, clinical trials had to meet the following criteria: age of patients 18 years or younger, treated with radiation, and report of survival. Studies were also selected according to the evidence level. A secondary search of cited references found other studies about cognitive functions, quality of life, the comparison of photon and proton dosimetry showing potential dose escalation and/or sparing of organs at risk with protontherapy; and studies on dosimetric and technical issues related to protontherapy. RESULTS A total of 7051 primary references published were retrieved, among which 40 clinical studies and 60 papers about quality of life, dose distribution and dosimetry were analysed, as well as the ongoing clinical trials. These papers have been summarized and reported in a specific document made available to the participants of a final 1-day workshop. Tumours of the meningeal envelop and bony cranial structures were excluded from the analysis. Protontherapy allows outstanding ballistics to target the tumour area, while substantially decreasing radiation dose to the normal tissues. There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non-secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas. Carbon ion therapy is just emerging and may be studied for highly aggressive and radioresistant tumours, as an initial treatment for diffuse brainstem gliomas, and for relapse of high-grade gliomas. CONCLUSION Both protontherapy and carbon ion therapy are promising for paediatric brain tumours. The benefit of decreasing late effects without altering survival has been described for most paediatric brain tumours with protontherapy and is currently assessed in ongoing clinical trials with up-to-date proton devices. Unfortunately, in 2015, only a minority of paediatric patients in France can receive protontherapy due to the lack of equipment.

Long-term side effects of radiotherapy for pediatric localized neuroblastoma

Introduction: Neuroblastoma (NB) is the most frequent indication for extracranial pediatric radiotherapy. As long-term survival of high-risk localized NB has greatly improved, we reviewed treatment-related late toxicities in pediatric patients who received postoperative radiotherapy (RT) for localized NB within two French prospective clinical trials: NB90 and NB94. Patients and methods: From 1990–2000, 610 children were enrolled. Among these, 35 were treated with induction chemotherapy, surgery, and RT. The recommended RT dose was 24 Gy at ≤ 2 years, 34 Gy at > 2 years, ± a 5 Gy boost in both age groups. Results: The 22 patients still alive after 5 years were analyzed. The median follow-up time was 14 years (range 5–21 years). Late effects after therapy occurred in 73 % of patients (16/22), within the RT field for 50 % (11/22). The most frequent in-field effects were musculoskeletal abnormalities (n = 7) that occurred only with doses > 31 Gy/1.5 Gy fraction (p = 0.037). Other effects were endocrine in 3 patients and second malignancies in 2 patients. Four patients presented with multiple in-field late effects only with doses > 31 Gy. Conclusion: After a median follow-up of 14 years, late effects with multimodality treatment were frequent. The most frequent effects were musculoskeletal abnormalities and the threshold for their occurrence was 31 Gy.

Long-term side effects of radiotherapy for pediatric localized neuroblastoma : results from clinical trials NB90 and NB94.

Introduction: Neuroblastoma (NB) is the most frequent indication for extracranial pediatric radiotherapy. As long-term survival of high-risk localized NB has greatly improved, we reviewed treatment-related late toxicities in pediatric patients who received postoperative radiotherapy (RT) for localized NB within two French prospective clinical trials: NB90 and NB94. Patients and methods: From 1990–2000, 610 children were enrolled. Among these, 35 were treated with induction chemotherapy, surgery, and RT. The recommended RT dose was 24 Gy at ≤ 2 years, 34 Gy at > 2 years, ± a 5 Gy boost in both age groups. Results: The 22 patients still alive after 5 years were analyzed. The median follow-up time was 14 years (range 5–21 years). Late effects after therapy occurred in 73 % of patients (16/22), within the RT field for 50 % (11/22). The most frequent in-field effects were musculoskeletal abnormalities (n = 7) that occurred only with doses > 31 Gy/1.5 Gy fraction (p = 0.037). Other effects were endocrine in 3 patients and second malignancies in 2 patients. Four patients presented with multiple in-field late effects only with doses > 31 Gy. Conclusion: After a median follow-up of 14 years, late effects with multimodality treatment were frequent. The most frequent effects were musculoskeletal abnormalities and the threshold for their occurrence was 31 Gy.

Role of radiation therapy in the conservative management of sarcoma within an irradiated field.

PURPOSE To report on clinical outcome and toxicity profile after combined treatment that included radiation therapy (RT) in patients with localized sarcoma within an irradiated field. PATIENTS AND METHODS Individual clinical data from all consecutive patients diagnosed and treated for a localized SIF between January 2000 and October 2011 at the Institut Claudius Regaud, Toulouse, France, were retrospectively reviewed. Outcomes of patients with SIF who underwent adjuvant or definitive radiotherapy were compared with patients who did not receive further RT. RESULTS Of the 27 patients eligible for this study: surgery alone (S), surgery followed by RT (S + RT) or definitive RT (RT) was performed in 16, 8 and 2 cases respectively. The rate of unresectable, gross or microscopically positive margin disease among the 10 re-irradiated patients was significantly higher than the non re-irradiated group (90% vs. 12% p < 0.001). After a median follow-up of 3.8 years, there was a trend toward longer survival and better local control in the subgroup of patients who received adjuvant or definitive RT compared to the rest of the cohort with an acceptable toxicity profile. The 4-year relapse free survival rates of patients treated with and without RT were 53% and 27% respectively (p = 0.09). CONCLUSION SIF complete surgical resection is often difficult to achieve, enhancing the risk of relapse. RT should be discussed in case of unresectable tumor or after suboptimal surgery as part of intensified local management that has a curative intent.

Irradiation des sarcomes cardiaques de l’adulte

PURPOSE Primary cardiac sarcomas represent less than 10 yearly cases in France. Their median survival is approximately 18 months. The treatment consists of surgery when possible. The role of chemotherapy and radiation therapy is controversial, especially with respect to limiting cardiac radiation dose that is theoretically incompatible with the requirement of a tumoricidal dose for sarcoma. A recent series of 124 cases of the French Sarcoma Group suggested a benefit of radiation therapy on progression-free survival. PATIENTS AND METHODS The dosimetric data of 12 patients were analyzed. RESULTS There was variety in radiotherapy modalities and definition of target volumes, doses and techniques are evolving more conformal plans. Irradiation appeared feasible with conventional fractionation with respect to toxicities (although probably underestimated due to short follow-up and dismal prognosis) and previously demonstrated benefit of radiotherapy for primitive cardiac sarcomas. CONCLUSION A scheme of 45Gy in 1.8Gy per fraction to a preoperative volume with an additional dose of 14Gy in 7 fractions on areas at risk or residual disease and margins 1cm, may be proposed based on the preliminary data of this study. Intensity modulated radiotherapy with daily cone-beam CT-scanner should be evaluated.

Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors

PURPOSE To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. METHODS AND MATERIALS All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). RESULTS Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). CONCLUSIONS Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT after cytoreductive surgery and perioperative chemotherapy.

Time interval between surgery and start of adjuvant radiotherapy in patients with soft tissue sarcoma: A retrospective analysis of 1131 cases from the French Sarcoma Group

PURPOSE The aim of this study was to evaluate the impact of the time interval (TI) between surgery and adjuvant radiotherapy (RT) in soft tissue sarcoma (STS). METHODS AND MATERIALS Data from 1131 patients treated between 1990 and 2014 were retrospectively reviewed. Inclusion criteria were: limb or superficial trunk wall STS (R0 or R1 resection) and adjuvant RT. The impact of TI on 10-year local relapse-free survival (LRFS) and 10-year overall survival (OS) was analyzed using a Log-rank test and then Cox Model. RESULTS The median TI was 82days (range, 18-346). With a median follow-up of 235months (range, 2-296months), the 10-year LRFS was 57.5% (±2%) and the 10-year OS was 64.2% (±2%). With a TI of 19-39days, 40-79days, 80-119days, and ⩾120days, 10-year LRFSs were 65.3%, 55.5%, 56.9% and 61.2% (p=0.465), and 10-year OSs were 72.8%, 60.7%, 66.4% and 62.1% (p=0.347), respectively. After adjustment for the factors significantly (p⩽0.05) associated with LRFS and OS, TI did not alter LRFS (p=0.182) either OS (p=0.335). CONCLUSIONS In this retrospective STS database study, the TI between surgery and start of adjuvant RT did not seem to affect outcomes.

Radiothérapie des cancers de l’enfant

The purpose of this article is to describe the specificities of paediatric radiation oncology: cancer types, radiotherapy indications, techniques, organisation and reglementary framework.

Place de la radiothérapie dans le traitement conservateur des sarcomes en territoire irradié

PURPOSE To describe long-term outcome after combined-modality treatment including radiation therapy in patients with localized sarcoma within irradiated field. PATIENTS AND METHODS Individual clinical data from all consecutive patients diagnosed and treated for a localized sarcoma within irradiated field between January 2000 and October 2011 at the Institut Claudius-Regaud, Toulouse, France, were retrospectively reviewed. RESULTS Twenty-seven patients were eligible for this study. Ten patients were re-irradiated with a rate of unresectable, gross or microscopically positive margins disease significantly higher than the rest of the cohort (90% vs. 12%; P<0.001). After a median follow-up of 3.8 years, there is a non-significant trend toward longer 4-year relapse free survival in the subgroup of patients who received adjuvant or definitive radiation therapy compared to the rest of the cohort (53% vs. 27%; P=0.09) with an acceptable toxicity profile allowing conservative management. CONCLUSION The complete surgical resection sarcoma within irradiated field is often difficult to achieve enhancing the risk of relapse. Radiation therapy should be discussed when faced with an unresectable tumour or after suboptimal surgery as part of intensified local management with a curative intent.