[Role of tractography in stereotactic radiosurgery and brain stereotactic radiotherapy]. / Intérêt de la tractographie pour la radiochirurgie et la radiothérapie stéréotaxique cérébrale.

Hypofractionated stereotactic radiotherapy and stereotactic radiosurgery are major therapeutic weapons in the brain, whether for tumor, vascular or functional treatments. They tend increasingly to democratize and to become standard treatments. However, human brain anatomy is very complex and not limited to the currently described organs at risk. Diffusion tensor imaging (DTI) tractography is a simple tool that enables to identify reproducibly big white matter fiber tracts. Not only does tractography allow a redefinition of organs at risk in the brain, but it would also allow the identification of new targets, such as the ventral intermediate nucleus (Vim) within the thalamus for treatment of movement disorders. We present here a review of the role of tractography and the anatomy, function and currently described dose-effect relationships of white matter fiber tracts with a major functional impact: the pyramidal tract for motor ability, the optic radiation for vision and the arcuate fasciculus for language.

Toxicity and time lapse between immunotherapy and stereotactic radiotherapy of brain metastases.

PURPOSE: Stereotactic radiotherapy (SRT) is the standard treatment for brain metastases of non-small-cell lung cancer (NSCLC) and melanoma, mostly in combination with immunotherapy. The objective was to retrospectively evaluate the influence of the time-lapse between immunotherapy and stereotactic radiotherapy on toxicity. PATIENTS AND METHODS: From 2016 to 2019, 59 patients treated with SRT for 103 brain metastases of NSCLC (60%) and melanoma (40%) in combination with concomitant immunotherapy (≤30 days) were included. The prescribed dose was 20Gy/1f or 33Gy/3f at the isocentre and 14Gy or 23.1Gy (70%) respectively at the PTV envelope (PTV=GTV+2mm). The mean tumour diameter was 14mm (4-52mm). The immunotherapies used were anti-PD1 and anti-PDL1. The 103 metastases were classified into 3 groups according to the time-lapse between instatement of immunotherapy and instatement of SRT for the patient concerned: 7 (7%) in group A (≤7 days), 38 (37%) in group B (7 to 14 days) and 58 (56%) in group C (14 to 30 days). RESULTS: The mean follow-up was 10.1 months. The median overall survival was 11.5 months for NSCLC and 12.5 months for melanoma. The percentage of local control (LC) at one year was 65.1% (93.6% for NSCLC and 26.5% for melanoma). The time-lapse between immunotherapy and SRT was not a significant predictor of LC (P=0.86), while the histology was (P<0.001). The proportion of grade≥3 toxicities was 5.1%, and that of radionecrosis was 9.7% (among these patients, 80% were non-symptomatic): 0%, 13.1% and 8.6% for groups A, B and C respectively. The time-lapse between immunotherapy and SRT was not a significant predictor of toxicity. Only tumour volume was a significant predictive factor (P=0.03). CONCLUSION: The time lapse between immunotherapy and SRT does not influence brain toxicity. The tumour volume remains the main factor.

Hypofractionated stereotactic radiotherapy for large brain metastases: Optimizing the dosimetric parameters.

PURPOSE: Stereotactic radiotherapy plays a major role in the treatment of brain metastases (BM). We aimed to compare the dosimetric results of four plans for hypofractionated stereotactic radiotherapy (HFSRT) for large brain metastases. MATERIAL AND METHODS: Ten patients treated with upfront NovalisTx® non-coplanar multiple dynamic conformal arcs (DCA) HFSRT for≥25mm diameter single BM were included. Three other volumetric modulated arc therapy (VMAT) treatment plans were evaluated: with coplanar arcs (Eclipse®, Varian, VMATcEclipse®), with coplanar and non-coplanar arcs (VMATncEclipse®), and with non-coplanar arcs (Elements Cranial SRS®, Brainlab, VMATncElements®). The marginal dose prescribed for the PTV was 23.1Gy (isodose 70%) in three fractions. The mean GTV was 27mm3. RESULTS: Better conformity indices were found with all VMAT techniques compared to DCA (1.05 vs 1.28, P<0.05). Better gradient indices were found with VMATncElements® and DCA (2.43 vs 3.02, P<0.001). High-dose delivery in healthy brain was lower with all VMAT techniques compared to DCA (5.6 to 6.3 cc vs 9.4 cc, P<0.001). Low-dose delivery (V5Gy) was lower with VMATncEclipse® or VMATncElements® than with DCA (81 or 94 cc vs 110 cc, P=0.02). CONCLUSIONS: NovalisTx® VMAT HFSRT for≥25mm diameter brain metastases provides the best dosimetric compromise in terms of target coverage, sparing of healthy brain tissue and low-dose delivery compared to DCA.

Long-Term Outcomes After Linac Radiosurgery for Benign Meningiomas.

AIMS: Although several studies on outcomes following stereotactic radiosurgery (SRS) for benign meningiomas have been reported, Linac-based SRS outcomes have not been as widely evaluated. The aim of this retrospective institutional single-centre study was to determine long-term outcomes of Linac-based SRS for benign intracranial meningiomas. MATERIALS AND METHODS: From July 1996 to May 2011, 60 patients with 69 benign meningiomas were included. All patients were treated with single-fraction Linac-based SRS with four to five non-coplanar arcs, dynamic or not. The marginal dose prescribed for the periphery was 16 Gy. Prognostic factors associated with local control, progression-free survival (PFS) and overall survival were tested. RESULTS: The median follow-up was 128 months. No patient was lost to follow-up. The values observed at 1, 5 and 10 years were, respectively, 100%, 98.4% and 92.6% for local control, 94.9%, 93.2% and 78% for PFS and 100%, 94.7% and 92.7% for overall survival. In univariate analysis, local control after SRS was significantly higher for skull base and parasagittal meningiomas compared with convexity meningiomas (P = 0.031). Multivariate analyses showed significantly longer PFS when the minimum dose delivered to the tumour was greater than 10 Gy (P = 0.0082). No grade 5 toxicity was reported. CONCLUSION: Our long-term results from a large sample size of benign meningiomas treated with Linac-based SRS confirmed excellent local control (>90%) and good safety, which is in line with published studies on Gamma Knife surgery. Above all, we showed significantly poorer PFS if the minimum dose to the tumour was under 10 Gy.

[Functional stereotactic radiosurgery: Indications and perspectives]. / Radiochirurgie fonctionnelle : indications et perspectives.

Stereotactic radiosurgery (SRS) is a non-invasive technique that enables to create brain focal lesions with a high precision and localization. Thus, functional brain disorders can be treated by SRS in case of pharmacoresistance or inoperability. To date, treatment of trigeminal neuralgia is the most described and known indication. Other indications will be developed in the future like movement disorders, refractory epilepsy, obsessive compulsive disorder and severe depression. We present here a review of actual and future indications of functional brain SRS with their level of evidence. All these SRS treatments have to be strictly conducted by trained teams with an excellent collaboration between radiation physicists, medical physicists, neurosurgeons, neurologists, psychiatrists and probably neuroradiologists.

[Radionecrosis following stereotactic radiotherapy of a 3-cm brain metastasis: Can we improve the dosimetric results?] / Radionécrose après radiothérapie stéréotaxique d'une métastase cérébrale de 3cm : la technique peut-elle améliorer les résultats dosimétriques ?

Stereotactic radiotherapy is a major issue in the management of brain metastases. Radionecrosis is a major concern, especially for large lesions. Optimizing dosimetric parameters is essential to allow optimal local control rate while minimizing potential toxicity. We report the case of a 30-mm brain metastases treated with stereotactic radiotherapy after initial whole brain radiotherapy, complicated with symptomatic radionecrosis. A dose of 24Gy in three fractions on the 80% isodose were delivered using a dynamic conformal arc technique (Novalis TX®). We realized a dosimetric comparison with: (i) optimization of initial conformal arc plan, (ii) volumetric modulated arctherapy with coplanar arcs and (iii) volumetric modulated arctherapy with coplanar and non-coplanar arcs. The optimal dose planning in terms of planning target volume coverage (99.2%) and normal brain sparing (V24Gy=0.4cm3, V18Gy=6.5cm3, V10Gy=25.4cm3, V5=83.9cm3) was obtained with volumetric modulated arctherapy with coplanar and non-coplanar arcs. Volumetric modulated arctherapy-based stereotactic irradiation with coplanar and non-coplonar arcs seems an interesting option for the treatment of large brain metastases to optimize dosimetric parameters.

Radiotherapy plus temozolomide in elderly patients with glioblastoma: a "real-life" report.

BACKGROUND: The optimization of the management for elderly glioblastoma patients is crucial given the demographics of aging in many countries. We report the outcomes for a "real-life" patient cohort (i.e. unselected) comprising consecutive glioblastoma patients aged 70 years or more, treated with different radiotherapy +/- temozolomide regimens. METHODS: From 2003 to 2016, 104 patients ≥ 70 years of age, consecutively treated by radiotherapy for glioblastoma, were included in this study. All patients were diagnosed with IDH-wild type glioblastoma according to pathological criteria. RESULTS: Our patient cohort comprised 51 female patients (49%) and 53 male. The median cohort age was 75 years (70-88), and the median Karnofsky performance status (KPS) was 70 (30-100). Five (5%) patients underwent macroscopic complete resection, 9 (9%) had partial resection, and 90 (86%), a stereotactic biopsy. The MGMT promoter was methylated in 33/73 cases (45%). Fifty-two (50%), 38 (36%), and 14 (14%) patients were categorized with RPA scores of III, IV, and I-II. Thirty-three (32%) patients received normofractionated radiotherapy (60 Gy, 30 sessions) with temozolomide (Stupp), 37 (35%) received hypofractionated radiotherapy (median dose 40 Gy, 15 sessions) with temozolomide (HFRT + TMZ), and 34 (33%) HFRT alone. Patients receiving only HFRT were significantly older, with lower KPSs. The median overall survival (OS; all patients) was 5.2 months. OS rates at 12, 18, and 24 months, were 19%, 12%, and 5%, respectively, with no statistical differences between patients receiving Stupp or HFRT + TMZ (P = 0.22). In contrast, patients receiving HFRT alone manifested a significantly shorter survival time (3.9 months vs. 5.9 months, P = 0.018). In multivariate analyses, the prognostic factors for OS were: i) the type of surgery (HR: 0.47 [0.26-0.86], P = 0.014), ii) RPA class (HR: 2.15 [1.17-3.95], P = 0.014), and iii) temozolomide use irrespective of radiotherapy schedule (HR: 0.54 [0.33-0.88], P < 0.02). MGMT promoter methylation was neither a prognostic nor a predictive factor. CONCLUSIONS: These outcomes agree with the literature in terms of optimal surgery and the use of HFRT as a standard treatment for elderly GBM patients. Our study emphasizes the potential benefit of using temozolomide with radiotherapy in a real-life cohort of elderly GBM patients, irrespective of their MGMT status.

[Hypofractionated stereotactic body radiation therapy for adrenal metastases]. / Radiothérapie stéréotaxique hypofractionnée des métastases surrénaliennes.

Adrenal glands are a common site for metastatic spread since they represent the fourth metastatic site of solid tumors. Interest in local ablative treatments of oligometastases is growing since literature suggests better progression-free survival, quality of life and potentially overall survival in selected patients. Surgery remains the first treatment of adrenal oligometastases because results are good, with a long enough follow-up. However, stereotactic radiotherapy appears to be comparable to surgery and could be proposed to elderly, unfit, inoperable patients, or even to patients whose systemic treatment should not be suspended for too long. This article aims to present a review of published studies to date on stereotactic radiotherapy of adrenal metastases and to propose a treatment protocol.

[Stereotactic lung radiotherapy: Technical setting up on Novalis Tx® and single centre prospective study of the 100 first malignant pulmonary nodules treated at centre Jean-Perrin]. / Radiothérapie en conditions stéréotaxiques pulmonaire : mise en place de la technique sur accélérateur linéaire d'électrons Novalis Tx® et évaluation prospective monocentrique des 100 premiers nodules pulmonaires traités au centre Jean-Perrin.

PURPOSE: Description of the treatment technique of stereotactic lung radiotherapy on Novalis Tx® and prospective study of the first 100 pulmonary nodules treated at centre Jean-Perrin (France). MATERIAL AND METHODS: From October 2012 to December 2015, 100 inoperable pulmonary nodules (62 stage I non-small-cell lung cancer and 38 metastases) of 90 patients with a mean age of 68.2 years (range: 46-89 years) were prospectively treated with dynamic arctherapy on Novalis Tx®. Mean gross tumour and planning target volumes were respectively 6.9 cm3 (range: 0.2-31.4 cm3) and 38.7 cm3 (range: 1.7-131 cm3), which correspond to diameters equal to 2.3cm and 4.2cm. Prescribed doses to the 80% isodose line were 54Gy in three fractions for peripheral non-small-cell lung cancer, 50Gy in five fractions for central non-small-cell lung cancer and 45Gy in three fractions for lung metastases. Clinical and radiological follow-up was done every three months with RECIST criteria for efficacy and NCI-CTCAE v4 scale for toxicity. Median follow-up was 12.5 months. RESULTS: Complete response was observed in 23.8% of cases. Local control rates were 100% and 90.7% respectively at 12 and 24 months, with 96% at 24 months for stage I non-small-cell lung cancer. Overall survival rates of patients with stage I non-small-cell lung cancer were 77.4% and 73.5% at 12 and 24 months (median overall survival was 32 months). Diffusing capacity of the lungs for carbon monoxide corrected for alveolar volume below 40% was significantly associated to a poor prognostic factor on univariate analysis (P=0.00013). At least three deaths were due to an acute respiratory failure, which correspond to about 4.8% of grade 5 radiation pneumonitis. Overall survival rate for metastatic patients were 95.2% and 59.5% respectively at 12 and 24 months (median overall survival was 25 months); 23.3% of grade 2 or less radiation pneumonitis, 7.8% of grade 2 or less radiation dermatitis, 2.2% of asymptomatic ribs fracture and 3.3% of chest pains were observed. CONCLUSION: Stereotactic lung radiotherapy is an effective treatment for inoperable stage I non-small-cell lung cancer and lung oligometastases of well informed and selected patients. Initial respiratory state, and especially the diffusing capacity of the lungs for carbon monoxide corrected for alveolar volume, seems to be important for tolerance.

[Non-small cell lung cancer irradiation in elderly]. / Radiothérapie des cancers bronchiques non à petites cellules des sujets âgés.

People over the age of 65 are often excluded from participation in oncological clinical trials. However, more than half of patients diagnosed with non-small-cell lung cancer are older than 65 years. Any therapeutic strategy must be discussed in multidisciplinary meetings after adapted geriatric assessment. Patients who benefit from the comprehensive geriatric assessment (CGA) of Balducci and Extermann are those whose G8 screening tool score is less than or equal to 14. Age itself does not contraindicate a curative therapeutic approach. Stereotactic radiotherapy is an alternative to surgery for early stages in elderly patients who are medically inoperable or who refuse surgery, because it significantly increases overall survival. Mostly sequential (rarely concomitant) chemoradiotherapy can be proposed to elderly patients with locally advanced stages in good general state of health. For the others, an exclusive palliative radiotherapy, a single or dual agent of chemotherapy, a targeted drug or best supportive care only may be discussed.

[Postoperative radiotherapy for non-small cell lung cancer: Efficacy, target volume, dose]. / Radiothérapie postopératoire des cancers bronchiques non à petites cellules: efficacité, volume cible, dose.

The rate of local failure of stage IIIA-N2 non-small cell lung cancer is 20 to 40%, even if they are managed with surgery and adjuvant chemotherapy. Postoperative radiotherapy improves local control, but its benefit on global survival remains to be demonstrated. Considered for many years as an adjuvant treatment option for pN2 cancers, it continues nevertheless to be deemed too toxic. What is the current status of postoperative radiotherapy? The Lung Adjuvant Radiotherapy Trial (Lung ART) phase III trial should give us a definitive, objective response on global survival, but inclusion of patients is difficult. The results are consequently delayed. The aim of this review is to show all the results about efficacy and tolerance of postoperative radiotherapy and to define the target volume and dose to prescribe.

[Surveillance after prostate cancer radiotherapy: Evaluation and management of toxicity and relapse]. / Suivi après radiothérapie des cancers de prostate : évaluation et prise en charge de la toxicité et de la récidive.

Prostate cancer is the most frequent cancer among European males with a high survival rate. The economic impact of treatments and follow-up are significant. The objectives of the follow-up after prostate radiotherapy is multiple: diagnosis and treatment of side-effects, early detection of biochemical recurrence, with the aim of proposing a second local treatment to improve quality of life or overall survival and feedback of the treatment results to better inform patients at the beginning of the disease. This article reports incidence of main side-effects (digestive, urinary and sexual) with their treatments and guidelines for clinical and biological follow-up with strategies of imaging studies and salvage treatments.