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Objectives: Stereotactic radiotherapy (SRT) for brain metastases (BM) allows very good local control (LC). However, approximately 20%-30% of these lesions will recur. The objective of this retrospective study was to evaluate the impact of dosimetric parameters on LC in cerebral SRT., Methods: Patients treated with SRT for 1-3 BM between January 2015 and December 2018 were retrospectively included. A total of 349 patients with 538 lesions were included. The median gross tumour volume (GTV) was 2 cm3 (IQR, 0-7). The median biological effective dose with α/β = 10 (BED10) was 60 Gy (IQR, 32-82). The median prescription isodose was 71% (IQR, 70-80). Correlations with LC were examined using the Cox regression model., Results: The median follow-up period was 55 months (min-max, 7-85). Median overall survival was 17.8 months (IQR, 15.2-21.9). There were 95 recurrences and LC at 1 and 2 years was 87.1% (95% CI, 84-90) and 78.1% (95% CI, 73.9-82.4), respectively. Univariate analysis showed that systemic treatment, dose to 2% and 50% of the planning target volume (PTV), BED10 > 50 Gy, and low PTV and GTV volume were significantly correlated with better LC. In the multivariate analysis, GTV volume, isodose, and BED10 were significantly associated with LC., Conclusion: These results show the importance of a BED10 > 50 Gy associated with a prescription isodose <80% to optimize LC during SRT for BM., Advances in Knowledge: Isodose, BED, and GTV volume were significantly associated with LC. A low isodose improves LC without increasing the risk of radionecrosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Radiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations. The aim is to describe delineation guidelines for meningioma radiotherapy as an adjuvant or definitive treatment with intensity-modulated radiation therapy and stereotactic radiation therapy techniques. This guideline is based on a consensus endorsed by a multidisciplinary group of brain tumor experts, members of the Association of French-speaking Neuro-oncologists (ANOCEF)., Materials and Methods: A 3-step procedure was used. First, the steering group carried out a comprehensive review to identify divergent issues on meningiomas target volume delineation. Second, an 84-item web-questionnaire has been developed to precisely define meningioma target volume delineation in the most common clinical situations. Third, experts members of the ANOCEF were requested to answer. The first two rounds were completed online. A third round was carried out by videoconference to allow experts to debate and discuss the remaining uncertain questions. All questions remained in a consensus., Results: Limits of the target volume were defined using visible landmarks on computed tomography and magnetic resonance imaging, considering the pathways of tumor extension. The purpose was to develop clear and precise recommendations on meningiomas target volumes., Conclusion: New recommendations for meningiomas delineation based on simple anatomic boundaries are proposed by the ANOCEF. Improvement in uniformity in target volume definition is expected., (© 2023. The Author(s).)

Purpose: Differentiating brain metastasis recurrence from radiation necrosis can be challenging during MRI follow-up after stereotactic radiotherapy. [ 18 F]-FDG is the most available PET tracer, but standard images performed 30 to 60 minutes postinjection provide insufficient accuracy. We compared the diagnostic performance and interobserver agreement of [ 18 F]-FDG PET with delayed images (4-5 hours postinjection) with the ones provided by standard and dual-time-point imaging., Methods: Consecutive patients referred for brain [ 18 F]-FDG PET after inconclusive MRI were retrospectively included between 2015 and 2020 in 3 centers. Two independent nuclear medicine physicians interpreted standard (visually), delayed (visually), and dual-time-point (semiquantitatively) images, respectively. Adjudication was applied in case of discrepancy. The final diagnosis was confirmed histologically or after 6 months of MRI follow-up. Areas under the receiver operating characteristic curves were pairwise compared., Results: Forty-eight lesions from 46 patients were analyzed. Primary tumors were mostly located in the lungs (57%) and breast (23%). The median delay between radiotherapy and PET was 15.7 months. The final diagnosis was tumor recurrence in 24 of 48 lesions (50%), with histological confirmation in 19 of 48 lesions (40%). Delayed images provided a larger area under the receiver operating characteristic curve (0.88; 95% confidence interval [CI], 0.75-0.95) than both standard (0.69; 95% CI, 0.54-0.81; P = 0.0014) and dual-time-point imaging (0.77; 95% CI, 0.63-0.88; P = 0.045), respectively. Interobserver agreement was almost perfect with delayed images ( κ = 0.83), whereas it was moderate with both standard ( κ = 0.48) and dual-time-point images ( κ = 0.61)., Conclusions: [ 18 F]-FDG PET with delayed images is an accurate and reliable alternative to differentiate metastasis recurrence from radiation necrosis in case of inconclusive MRI after brain stereotactic radiotherapy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: As a result of progress in diagnosis and treatment, there is a growing prevalence of metastatic breast cancer (MBC) with isolated CNS metastases. This study describes the largest-to-date real-life cohort of this clinical setting and compares it to other clinical presentations., Methods: We retrospectively analysed the French Epidemiological Strategy and Medical Economics (ESME) MBC database including patients who initiated treatment for MBC between 2008 and 2016. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Descriptive statistics and multivariate Cox model were used., Results: Of 22,266 patients, 647 (2.9%) and 929 (4.2%) patients had isolated first-site CNS metastases or combined with extra-CNS metastases, with longer OS for the group with isolated CNS metastases (16.9 versus 13.9 months, adjusted HR = 1.69 (95% CI: 1.50-1.91), p  < 0.001). Among the 541 (2.4%) patients with isolated CNS metastases and no intrathecal therapy (excluding leptomeningeal metastases), HER2+ cases were preponderant over TN or HR+ /HER2- cases (41.6% versus 26.1% versus 28.5%, respectively, p  < 0.01). The treatment strategy consisted of a combination of local treatment and systemic therapy (49.2%), local treatment only (35.5%) or systemic therapy only (11.4%), or symptomatic therapy only (3.9%). Median PFS was 6.1 months (95% CI: 5.7-6.8). Median OS was 20.7 months (95% CI: 17.3-24.3), reaching 37.9 months (95% CI: 25.9-47.6) in the HR+ /HER2+ subgroup. Older age, TN subtype, MBC-free interval of 6-12 months, lower performance status, and WBRT were associated with poorer survival. Patients who received systemic therapy within 3 months from MBC diagnosis had longer OS (24.1 versus 16.1 months, p  = 0.031), but this was not significant on multivariate analysis [HR = 1.0 (95% CI: 0.7-1.3), p  = 0.806]., Conclusions: Patients with isolated CNS metastases at MBC diagnosis represent a distinct population for which the role of systemic therapy needs to be further investigated in prospective studies., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JSF reports consulting fees from Novartis, Pfizer, AstraZeneca, Lilly, Roche, Biocad, Daiichi, Tesaro, GSK, Pierre Fabre. TB reports honoraria from Novartis, Roche, Pfizer, AstraZeneca and Seattle Genetics. The other authors report no conflicts of interest., (© The Author(s), 2022.)

Abstract: We report the case of a 75-year-old man with history of prostate cancer whose left intracavernous lesion was successfully characterized by 3 PETs performed successively with different tracers. This poorly characterized tumor was initially discovered on an MRI conducted to investigate an acute diplopia and slowly growing during follow-up. On 18F-FDG PET, the lesion showed no significant uptake, and no extracranial lesion was found nor did it have increased 68Ga-DOTATOC uptake. Finally, this tumor displayed a high 18F-choline uptake, and no extracranial lesion was revealed with this tracer. The diagnosis of schwannoma without malignancy criterion was proven by biopsy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS)., Materials and Methods: From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients., Results: The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p < 0.001), grade ≥2 dermatitis (2.8% vs. 0.7%, p < 0.001), and grade 2 hyperpigmentation (6.9% vs. 3.6%, p = 0.005) were more frequent in arm B than arm A. No acute lung or cardiac toxicity was observed. Smoking history, large breast size, and large breast CTV were strong predictive factors of grade ≥2 acute skin toxicities., Conclusions: The QA program showed deviations in breast and tumor bed delineation. The boost significantly increased acute skin toxicities., Competing Interests: Conflict of interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In 2021, the Ethics Commission of the SFRO has chosen the issue of the practice of palliative care in radiotherapy oncology. Radiation oncology plays a central role in the care of patients with cancer in palliative phase. But behind the broad name of palliative radiotherapy, we actually find a large variety of situations involving diverse ethical issues. Radiation oncologists have the delicate task to take into account multiple factors throughout a complex decision-making process. While the question of the therapeutic indication and the technical choice allowing it to be implemented remains central, reflection cannot be limited to these decision-making and technical aspects alone. It is also a question of being able to create the conditions for a singularity focused care and to build an authentic care relationship, beyond technicity. It is through this daily ethical work, in close collaboration with patients, and under essential conditions of multidisciplinarity and multiprofessionalism, that our fundamental role as caregiver can be deployed., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Aim: The aims of the present study were to describe treatment patterns and survival outcomes in patients with central nervous system metastases (CNSM) selected among metastatic breast cancer (MBC) patients included in a retrospective study from the Epidemiological Strategy and Medical Economics (ESME) MBC cohort., Methods: Neurological progression-free survival (NPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Significant contributors to NPFS were determined using a multivariate Cox proportional hazards model., Results: After a median follow-up of 42.8 months, of 16 701 patients included in the ESME MBC database, CNSM were diagnosed in 24.6% of patients. The most frequent treatments after diagnosis of CNSM were whole-brain radiotherapy (WBRT) (45.2%) and systemic treatment (59.3%). Median OS and NPFS were 7.9 months (95% CI: 7.2-8.4) and 5.5 months (95% CI: 5.2-5.8), respectively. In multivariate analysis, age >70 years (vs <50 years; HR = 1.40; 95% CI: 1.24-1.57), triple-negative tumours (vs HER2-/HR+; HR = 1.87; 95% CI: 1.71-2.06), HER2+/HR-tumours (vs HER2-/HR+; HR = 1.14; 95% CI: 1.02-1.27), ≥3 metastatic sites (vs < 3; HR = 1.32; 95% CI: 1.21-1.43) and ≥3 previous treatment lines (vs < 3; HR = 1.75; 95% CI: 1.56-1.96) were detrimental for NPFS. A time interval between selection and CNSM diagnosis superior to 18 months (vs <9 months; HR = 0.88; 95% CI: 0.78-0.98) was associated with longer NPFS., Conclusions: This study describes current treatment patterns of MBC patients in a "real life" setting. Despite advances in stereotactic radiation therapy, most of the patients still received WBRT. More research is warranted to identify patient subsets for tailored treatment strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Metastatic breast cancer (MBC) behaviour differs depending on hormone receptors (HR) and human epidermal growth factor receptor (HER2) statuses., Methods: The kinetics of central nervous system (CNS) metastases (CNS metastasis-free survival, CNSM-FS) and subsequent patient's prognosis (overall survival, OS) according to the molecular subtype were retrospectively assessed in 16703 MBC patients of the ESME nationwide multicentre MBC database (Kaplan-Meier method)., Results: CNS metastases occurred in 4118 patients (24.6%) (7.2% at MBC diagnosis and 17.5% later during follow-up). Tumours were HER2-/HR+ (45.3%), HER2+/HR+ (14.5%), HER2+/HR- (14.9%) and triple negative (25.4%). Median age at CNS metastasis diagnosis was 58.1 years (range: 22.8-92.0). The median CNSM-FS was 10.8 months (95% CI: 16.5-17.9) among patients who developed CNS metastases. Molecular subtype was independently associated with CNSM-FS (HR = 3.45, 95% CI: 3.18-3.75, triple-negative and HER2-/HR+ tumours). After a 30-month follow-up, median OS after CNS metastasis diagnosis was 7.9 months (95% CI: 7.2-8.4). OS was independently associated with subtypes: median OS was 18.9 months (HR = 0.57, 95% CI: 0.50-0.64) for HER2+/HR+ , 13.1 months (HR = 0.72, 95% CI: 0.65-0.81) for HER2+/HR-, 4.4 months (HR = 1.55, 95% CI: 1.42-1.69) for triple-negative and 7.1 months for HER2-/HR+ patients (p <0.0001)., Conclusions: Tumour molecular subtypes strongly impact incidence, kinetics and prognosis of CNS metastases in MBC patients., Clinical Trial Registration: NCT03275311.

Purpose: This study evaluates the peripheral dose (PD) delivered to healthy tissues for brain stereotactic radiotherapy treatments (SRT) performed with a CyberKnife M6™ Robotic Radiosurgery System and proposes a model to estimate PD before treatment., Method: PD was measured with thermoluminescent dosimeters. Measurements were performed to evaluate the influence of distance, collimator type (fixed or Iris™) and aperture size on PD for typical brain treatment plans simulated on an anthropomorphic phantom. A model to estimate PD was defined by fitting functions to these measurements. In vivo measurements were subsequently performed on 30 patients and compared to the model-predicted PD., Results: PD (in cGy) was about 0.06% of MU at 15cm for a 20mm fixed collimator and 0.04% of MU for the same aperture with Iris™ collimator. In vivo measurements showed an average thyroid dose of 55mGy (σ=18.8mGy). Computed dose for thyroid, breast, umbilicus and gonads showed on average a relative difference of 3.4% with the in vivo dose (σ=12.4%)., Conclusion: PD at the thyroid with Iris™ was about a third lower than with a fixed collimator in case of brain SRT. Despite uncertainties (use of anthropomorphic PD to estimate patient specific PD, surface PD to estimate OAR PD) the model allows PD to be estimated without in vivo measurements. This method could be used to optimise PD with different planning strategies., (Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Despite progress in the initial management of glioblastoma (GB), the vast majority of patients will experience recurrence within 2-3 years. The medical treatment of these recurrences is being modified by the use of antiangiogenic therapies. Twenty-four patients, who relapsed from GB after chemoradiation followed by adjuvant temozolomide in Rennes, were treated by conventional chemotherapy (nitrosourea) or by the combination of irinotecan and bevacizumab. In this retrospective analysis, overall survival from diagnosis of recurrence was significantly longer in patients treated with the combination of bevacizumab and irinotecan than with nitrosourea (5 months versus 11.5 months). The combination of irinotecan and bevacizumab appeared to provide clinical benefit to patients with recurrent GB.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

Background/aims: Dendritic cells (DCs), which play a critical role during immune response, could present alternative differentiation patterns depending on tissue microenvironment. Our aim was to examine the influence of hepatic microenvironment on human monocyte differentiation into DCs., Methods: Cytology, immunophenotyping, cytokine production and T-cell activation were analyzed in DCs differentiated from human monocytes co-cultured with rat liver epithelial cells (RLEC) or human cells from various tissue origins and compared to control DCs obtained on plastic with GM-CSF/IL-4., Results: RLEC environment promotes DC differentiation in the presence of IL-4 without GM-CSF. These DCs evidence similar expression of MHC-II, co-stimulatory and adhesion molecules than control DCs, but distinct lineage markers defining a CD11c+/CD14+/CD123+ DC subset. This phenotype is common to DCs from RLEC and human liver environment and differs from that obtained with skin or intestine environments. Functionally, they produce IL-10 but not IL-12p70 and favor IL-4/IL-10 secretion by T-cells rather than IFN-gamma., Conclusions: Our results confirm that tissue niches modulate DC differentiation and demonstrate that hepatic environment influences monocyte differentiation into a DC subset directing Th2 response, a key data for understanding the specialized immune response in liver. They also make RLEC co-culture system useful for studying liver DC functions.