Prognostic and therapeutic factors of gliosarcoma from a multi-institutional series.

The aims of this multicentre retrospective study were to identify prognostic or therapeutic factors impacting on overall survival in patients with gliosarcoma. The analysis included all patients treated for gliosarcoma between 1998 and 2014 in seven French academic centres. Seventy-five patients with a median age of 60 years (range from 23 to 79 years) were treated with a combination of surgery (n = 66), radiotherapy (adjuvant for 64 patients and exclusive for 8 patients) and temozolomide based chemotherapy (n = 58). Median follow-up was 12 months (range from 2 to 71 months). Two-year overall survival (OS) and disease free survival rates were 12 % (95 % CI 4-20 %) and 2 % (95 % CI 0-6 %), respectively. The median OS was 13 months. Treatment at recurrence consisted of chemotherapy (n = 38) (bevazicumab for 18 patients, repeat temozolomide for 10 patients), salvage surgery (n = 8) and radiochemotherapy (n = 1). In univariate analysis, younger age, higher total dose of radiotherapy, longer time to recurrence and treatment at recurrence significantly increased OS. In multivariate analysis, high total dose of radiotherapy (HR = 0.97, p = 0.007) and treatment at recurrence (HR = 0.28, p < 0.001) were favourable prognostic factors of OS. Radiotherapy at a minimum dose of 54 Gy and salvage treatment increased OS of gliosarcoma. Unlike glioblastoma, in our analysis, TMZ based chemotherapy was not associated with an improvement in OS compared to patients who received radiation therapy only.

Radiotherapy of benign intracranial tumours.

We present the updated recommendations of the French Society for Radiation Oncology on benign intracranial tumours. Most of them are meningiomas, vestibular schwannomas, pituitary adenomas, craniopharyngiomas, and glomus tumours. Some grow very slowly, and can be observed without specific treatment, especially if they are asymptomatic. Symptomatic or growing tumours are treated by surgery, which is the reference treatment. When surgery is not possible, due to the location of the lesion, or general conditions, radiotherapy can be applied, as it is if there is a postoperative growing residual tumour, or a local relapse. Indications have to be discussed at a multidisciplinary panel, with precise evaluation of the benefit and risks of the treatments. The techniques to be used are the most modern ones, as multimodal imaging and image-guided radiation therapy. Stereotactic treatments, using fractionated or single doses depending on the size or the location of the tumours, are commonly realized, to avoid as much a possible the occurrence of late side effects.

[Clinical research in radiation oncology: how to move from the laboratory to the patient?] / Recherche clinique en oncologie radiothérapie : comment passer du laboratoire au patient ?

Translational research in radiation oncology is undergoing intense development. An increasingly rapid transfer is taking place from the laboratory to the patients, both in the selection of patients who can benefit from radiotherapy and in the development of innovative irradiation strategies or the development of combinations with drugs. Accelerating the passage of discoveries from the laboratory to the clinic represents the ideal of any translational research program but requires taking into account the multiple obstacles that can slow this progress. The ambition of the RadioTransNet network, a project to structure preclinical research in radiation oncology in France, is precisely to promote scientific and clinical interactions at the interface of radiotherapy and radiobiology, in its preclinical positioning, in order to identify priorities for strategic research dedicated to innovation in radiotherapy. The multidisciplinary radiotherapy teams with experts in biology, medicine, medical physics, mathematics and engineering sciences are able to meet these new challenges which will allow these advances to be made available to patients as quickly as possible.

Discontinuous stereotactic body radiotherapy schedule increases overall survival in early-stage non-small cell lung cancer.

OBJECTIVES: The duration of stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) may affect patient outcomes. We aimed to determine the impact of a continuous versus discontinuous SBRT schedule on local control (LC) and overall survival (OS) in NSCLC patients. MATERIALS AND METHODS: Consecutive NSCLC stage I patients (475) treated with SBRT in four centers were retrospectively analyzed. The delivered dose ranged from 48 to 75 Gy in 3-10 fractions. Based on the ratio between the treatment duration (TD) and number of fractions (n), patients were divided into two groups: continuous schedule (CS) (TD ≤ 1.6n; 239 patients) and discontinuous schedule (DS) (TD > 1.6n; 236 patients). LC and OS were compared using Cox regression analyses after propensity score matching (216 pairs). RESULTS: The median follow-up period was 41 months. Multivariate analysis showed that the DS (hazard ratio (HR): 0.42; 95 % confidence interval (CI): 0.22-0.78) and number of fractions (HR: 1.24; 95 % CI: 1.07-1.43) were significantly associated with LC. The DS (HR: 0.67; 95 % CI: 0.51-0.89), age (HR: 1.02; 95 % CI: 1-1.03), WHO performance status (HR: 2.27; 95 % CI: 1.39-3.7), and T stage (HR: 1.4; 95 % CI: 1.03-1.87) were significantly associated with OS. The 3-year LC and OS were 92 % and 64 % and 81 % and 53 % for DS and CS treatments, respectively (p < 0.01). Cox analysis confirmed that the discontinuous SBRT schedule significantly increased LC and OS. CONCLUSION: DS is associated with significantly improved LC and OS in early-stage NSCLC patients treated with SBRT.

RADIORYTHMIC: Phase III, Opened, Randomized Study of Postoperative Radiotherapy Versus Surveillance in Stage IIb/III of Masaoka Koga Thymoma after Complete Surgical Resection.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway. PATIENTS AND METHODS: Three hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers. RESULTS: The first patient will be enrolled in January 2021, with results expected in 2028.

[Alpha-radioimmunotherapy: a review of recent developments]. / Le point sur les avancées récentes de la radio-immunothérapie alpha.

The use of heavy particles in the treatment of cancer is increasing remarkably, whether with external radiation or using a vector such as an antibody in radioimmunotherapy. Recent pre-clinical and clinical developments of alpha-radioimmunotherapy have provided more interesting information in parallel of the use of high Linear Energy Transfer (LET) external irradiation. This review aims at presenting recent advances of this therapeutic approach, and at detailing the biological specificities of this kind of radiation.

Stereotactic radiotherapy following surgery for brain metastasis: Predictive factors for local control and radionecrosis.

PURPOSE: To evaluate local control and adverse effects after postoperative hypofractionated stereotactic radiosurgery in patients with brain metastasis. METHODS: We reviewed patients who had hypofractionated stereotactic radiosurgery (7.7Gy×3 prescribed to the 70% isodose line, with 2mm planning target volume margin) following resection from March 2008 to January 2014. The primary endpoint was local failure defined as recurrence within the surgical cavity. Secondary endpoints were distant failure rates and the occurrence of radionecrosis. RESULTS: Out of 95 patients, 39.2% had metastatic lesions from a non-small cell lung cancer primary tumour. The median Graded Prognostic Assessment score was 3 (48% of patients). One-year local control rates were 84%. Factors associated with improved local control were no cavity enhancement on pre-radiation MRI (P<0.00001), planning target volume less than 12cm3 (P=0.005), Graded Prognostic Assessment score 2 or above (P=0.009). One-year distant cerebral control rates were 56%. Thirty-three percent of patients received whole brain radiation therapy. Histologically proven radionecrosis of brain tissue occurred in 7.2% of cases. The size of the preoperative lesion and the volume of healthy brain tissue receiving 21Gy (V21) were both predictive of the incidence of radionecrosis (P=0.010 and 0.036, respectively). CONCLUSION: Adjuvant hypofractionated stereotactic radiosurgery to the postoperative cavity in patients with brain metastases results in excellent local control in selected patients, helps delay the use of whole brain radiation, and is associated with a relatively low risk of radionecrosis.

[Risk of radionecrosis after hypofractionated stereotactic radiotherapy targeting the postoperative resection cavity of brain metastases]. / Risque de radionécrose après radiothérapie hypofractionnée en conditions stéréotaxiques du lit opératoire de métastases cérébrales.

PURPOSE: To investigate the factors that potentially lead to brain radionecrosis after hypofractionated stereotactic radiotherapy targeting the postoperative resection cavity of brain metastases. METHODS AND MATERIALS: A retrospective analysis conducted in two French centres, was performed in patients treated with trifractionated stereotactic radiotherapy (3×7.7Gy prescribed to the 70% isodose line) for resected brain metastases. Patients with previous whole-brain irradiation were excluded of the analysis. Radionecrosis was diagnosed according to a combination of criteria including clinical, serial imaging or, in some cases, histology. Univariate and multivariate analyses were performed to determine the predictive factors of radionecrosis including clinical and dosimetric variables such as volume of brain receiving a specific dose (V8Gy-V22Gy). RESULTS: One hundred eighty-one patients, with a total of 189 cavities were treated between March 2008 and February 2015. Thirty-five patients (18.5%) developed radionecrosis after a median follow-up of 15 months (range: 3-38 months) after hypofractionated stereotactic radiotherapy. One third of patients with radionecrosis were symptomatic. Multivariate analysis showed that infra-tentorial location was predictive of radionecrosis (hazard ratio [HR]: 2.97; 95% confidence interval [95% CI]: 1.47-6.01; P=0.0025). None V8Gy-V22Gy was associated with appearance of radionecrosis, even if V14Gy trended toward significance (P=0.059). CONCLUSION: Analysis of patients and treatment variables revealed that infratentorial location of brain metastases was predictive for radionecrosis after hypofractionated stereotactic radiotherapy for postoperative resection cavities.

[Brain radiation necrosis after stereotactic radiotherapy of the resection cavity for intracranial metastases: analysis of the literature from four cases]. / Radionécrose cérébrale après irradiation en conditions stéréotaxiques des berges opératoires : analyse de la littérature à partir de quatre cas.

Stereotactic hypofractionated radiotherapy after resection of brain metastasis is an alternative to whole brain radiotherapy. A high dose per fraction is associated with a risk of radiation necrosis. We present four cases of confirmed histological radiation necrosis. Differentiating recurrent tumour from radiation necrosis in this scenario is challenging. An enhancing area in magnetic resonance imaging (MRI) with a "cut bell pepper" appearance may suggest radiation necrosis. Advanced imaging modalities such as perfusion MR imaging and positron emission tomography can be useful. Dosimetric predictors of the occurrence of radiation necrosis after stereotactic hypofractionated radiotherapy are poorly understood and require prospective studies on larger cohorts.

[Hypofractionated stereotactic radiotherapy of bone metastases]. / Radiothérapie stéréotaxique hypofractionnée des métastases osseuses.

Hypofractionated stereotactic radiotherapy can deliver high doses of bone metastases while sparing adjacent healthy tissue not only for a decompressive or analgesic purpose, but also to improve the local control of the irradiated region. Various phases I or II studies showed the feasibility of such an approach at the cost of limited toxicity, including during re-irradiation. Hypofractionated stereotactic radiotherapy to oligometastases may also improve the long-term control of metastatic disease.

[Postoperative brain radiotherapy: role of stereotactic radiotherapy]. / Radiothérapie cérébrale postopératoire : indication de l'irradiation en conditions stéréotaxiques.

The addition of whole-brain radiotherapy is a standard of care for patients with single, resectable intracranial metastasis. Stereotactic irradiation of the postoperative resection cavity seems to offer excellent local control rates and avoid the neurocognitive risks of whole-brain radiation therapy. The risk of remote intracranial recurrence imposes a strict surveillance imaging in order to proceed to a possible irradiation before a symptomatic stage. It must be validated in future randomized trials.

[Stereotactic radiotherapy for brain metastasis]. / Radiothérapie en conditions stéréotaxiques des métastases cérébrales.

Stereotactic radiosurgery is now well implanted in the radiotherapy treatment tools of brain metastasis. The dose can be delivered in one or multiple sessions. Results seem equivalent. CT scan and MRI imaging are required to delineate and calculate dosimetry. Doses are variable according to the size of the metastases, localization, pathology or equipment. Stabilization or reduction of tumour size is the rules after stereotactic treatment. Impact in terms of overall survival is more difficult to apprehend because of the general context of the disease. Many questions remain unresolved, such as the usefulness of whole brain irradiation, adaptation of the treatment schedule to tumour pathophysiology, role of stereotactic treatment after surgery of metastases, etc.

[Stereotactic radiotherapy for intracranial meningioma]. / Radiothérapie stéréotaxique des méningiomes intracrâniens.

Meningiomas are the most common non-malignant tumours of the brain. Gross-total resection remains the preferred treatment, if achievable without morbidity. Radiation therapy is advocated for inoperable, incompletely resected, or recurrent grade 1 tumours, if there is a progressive, symptomatic lesion, or in case of functional impairment. Postoperative radiation therapy is recommended for grade 2 or 3 lesions. Fractionated stereotactic radiotherapy and stereotactic radiosurgery are high precision techniques, allowing good sparing of surrounding tissues. Fractionated stereotactic radiotherapy and stereotactic radiosurgery give comparable results, with excellent 5-year tumour control rates of more than 90% for benign meningiomas. Toxicity is low and seems equivalent, despite a biased use of fractionated stereotactic radiotherapy for larger meningiomas, close to critical structures. Fractionated stereotactic radiotherapy seems to be of special interest in the treatment of cavernous sinus or optic pathways meningiomas. The different therapeutic modalities should be discussed by a multidisciplinary team.

[Medical devices needed for stereotactic radiosurgery and intracranial stereotactic radiotherapy]. / Équipements requis pour la mise en œuvre de la radiochirurgie et de la radiothérapie en conditions stéréotaxiques intracrânienne.

Since the previous special issue of Cancer Radiothérapie dedicated to radiosurgery in 1998, many important technological and computer developments have improved external beam radiotherapy treatment device performances. Whereas the Gamma Knife(®) was the gold standard for intracranial radiosurgery, new linear accelerator developments have led to new possibilities for the clinicians. This article describes quickly the different devices available for cranial radiosurgery or fractionated stereotactic radiotherapy.