Whole Brain Radiotherapy Research Articles

Palliative whole brain radiation therapy: an international state of practice.

Improvements in radiation delivery and systemic therapies have resulted in few remaining indications for palliative whole brain radiation therapy (WBRT). Most centers preferentially use stereotactic radiotherapy (SRT) and reserve WBRT for those with >15 lesions, leptomeningeal presentation, rapidly progressive disease, or limited estimated survival. Despite regional differences among preferred dose, fractionation, and treatment technique, we predict survival post-WBRT will remain poor-indicating appropriate application of WBRT in this era of SRT and improved systemic therapies. A multi-center, international retrospective analysis of patients receiving WBRT in 2022 was performed. Primary end point was survival after WBRT. De-identified data were analyzed centrally. Patients receiving WBRT as part of a curative regimen, prophylactically, or as bridging therapy were excluded. The collected data consisted of patient parameters including prescription dose and fractionation, use of neurocognitive sparing techniques and survival after WBRT. Survival was calculated via the Kaplan-Meier method. Of 29,943 international RT prescriptions written at ten participating centers in 2022, 462 (1.5%) were for palliative WBRT. Participating centers were in the United States (n=138), the United Kingdom (n=111), Hong Kong (n=72), Italy (n=49), Belgium (n=45), Germany (n=27), Ghana (n=15), and Cyprus (n=5). Twenty-six different dose regimens were used. The most common prescriptions were for 3,000 cGy over 10 fractions (45.0%) and 2,000 cGy over 5 fractions (43.5%) with significant regional preferences (P<0.001). Prior SRT was delivered in 32 patients (6.7%), hippocampal avoidance (HA) was used in 44 patients (9.5%), and memantine was prescribed in 93 patients (20.1%). Survival ranged from 0 days to still surviving at 402 days post-treatment. The global median overall survival (OS) was 84 days after WBRT [95% confidence interval (CI): 68.0-104.0]. Actuarial survival at 7 days, 1 month, 3 months, and 6 months were 95%, 78%, 48%, and 32%, respectively. Twenty-seven patients (5.8%) were unable to complete their prescribed WBRT. This moment-in-time analysis confirms that patients with poor expected survival are being appropriately selected for WBRT-illustrating the dwindling indications for WBRT-and demonstrates the variance in global practice. Since poor survival precludes patients from deriving benefit, memantine and HA are best suited in carefully selected cases.

Is reduced-dose whole-brain radiotherapy also feasible in primary CNS lymphoma for curative or salvage purpose?

Recently, reduced-dose whole-brain radiotherapy (WBRT) has been used to treat primary central nervous system lymphoma (PCNSL). However, whether reduced-dose WBRT is also an acceptable option for curative or salvage purposes has not yet been reported. We analyzed the clinical outcomes of patients with PCNSL who received radiotherapy for curative or salvage purposes and compared the clinical outcomes according to the WBRT dose. A total of 66 patients were divided into two groups: those treated with 30Gy (2Gy per fraction) or less WBRT (low-dose WBRT, n = 34) and those treated with more than 30Gy WBRT (high-dose WBRT, n = 32). The median WBRT dose was 25.2 and 49.6Gy in low-dose and high-dose WBRT groups, respectively. The median total radiotherapy dose, including the boost dose, was 50Gy (range, 36.0-55.8Gy). The 3-year overall survival and progression-free survival were 77.8% and 29.8%, respectively. Intracranial relapse occurred in 31 patients (47.0%) at a median of 27 months after RT. Overall survival and progression-free survival did not differ between the two groups. The 3-year intracranial disease control rate did not differ between the two groups (35.2% vs. 41.6%, p = 0.300). Grade 3 or higher neurological toxicities were observed in six patients, of whom five were in the high-dose WBRT group. Reduced-dose WBRT in curative and salvage treatments for PCNSL had no significant negative effect on the intracranial disease control rate or survival. Therefore, without impaired efficacy, use of reduced-dose WBRT appears promising for reduction of neurotoxicity.

Impact of Locoregional Therapies for Brain Lesions on Survival in Patients With Non-small Cell Lung Cancer With Multiple Extrathoracic Metastases.

The treatment of brain metastases in patients with non-small cell lung cancer (NSCLC) typically involves surgery, irradiation, and chemotherapy (single or combination therapy). However, the impact of these therapies on the survival of patients with NSCLC with multiple extrathoracic metastases has not yet been determined. Therefore, in the present study, we examined the prognostic effect of multimodal treatment for brain metastases in patients with NSCLC with multiple extrathoracic metastases in the absence of driver mutations. Patients with NSCLC with multiple extrathoracic metastases (including at least one brain metastasis), who visited Saitama Medical Center, Saitama Medical University from January 1, 2010 to December 31, 2016, were enrolled in this study; follow-up was conducted until December 31, 2021. A total of 56 patients were enrolled, including 12 and 44 patients with single and multiple brain metastases, respectively. The median overall survival (OS) for all patients was 4.9 months, and did not differ significantly between patients with single and multiple brain metastases (3.0 vs. 4.9 months, respectively). The selection of locoregional treatment for brain metastases did not depend on Karnofsky performance status (p=0.0862). Among patients with multiple brain metastases, the OS for those who underwent craniotomy followed by whole brain radiation therapy (WBRT), those who received only WBRT, and those treated without locoregional therapy was 47.7, 3.9, and 15.9 months, respectively (p=0.00382). Surgical resection followed by radiation therapy is an effective treatment option for brain metastases in patients with multiple metastases. However, WBRT alone did not improve prognosis.

Treatment and survival of patients with small cell lung cancer and brain metastasis.

To elucidate treatment patterns and their outcomes in patients with small cell lung cancer (SCLC) and brain metastasis (BM). In this retrospective study, patients with SCLC and BM were stratified by treatment modality into three groups: those treated with systemic therapy only, those treated with stereotactic radiosurgery (SRS) and systemic therapy, and those treated with whole-brain radiotherapy (WBRT) and systemic therapy. The primary outcomes were overall survival (OS) and time to central nervous system progression (TTCP). The analysis included 149 patients. After BM diagnosis, 48 patients (32.2%) received systemic therapy alone, 33 received SRS with systemic therapy, and 68 received WBRT with systemic therapy. The median OS and TTCP were 7.2 months and 8.7 months, respectively. Patients receiving WBRT with systemic therapy exhibited better intracranial control, but not better OS, than did the other patients. Key prognostic factors affecting OS were age, BM lesion count, chemotherapy, and immunotherapy. Notably, the Eastern Cooperative Oncology Group performance status and BM lesion count significantly influenced intracranial control in patients treated with SRS and systemic therapy. Although WBRT combined with systemic therapy offer better intracranial control in patients with SCLC and BM, this approach is not superior to the other approaches in terms of OS benefits. Emerging systemic therapies, such as immunotherapy, may be used as alternative or adjunctive treatments for specific patient populations. Further studies are warranted to refine treatment selection.

Pharmacological restoration of NAD+/NADH prevents chronic neurodegeneration and neuropsychiatric impairment after whole-brain radiotherapy.

Pharmacological restoration of NAD+/NADH prevents chronic neurodegeneration and neuropsychiatric impairment after whole-brain radiotherapy.

Therapeutic strategies for HER2-positive breast cancer with central nervous system involvement: a literature review and future perspectives.

Brain metastases (BMs) are present in approximately 55% of patients with HER2-positive breast cancer (HER2+ BC). The introduction of anti-HER2 agents has radically changed the prognosis of these patients by prolonging overall survival. In this review, we describe the biology of central nervous system (CNS) spreading in patients with HER2+ BC. We also provide a literature review of current treatment strategies of brain metastatic BC, focusing on HER2+ disease, and future perspectives. Treatment of symptomatic BMs includes traditionally neurosurgery and/or radiotherapy, depending on the number of metastases, performance status and systemic disease control. Local treatments, such as surgical excision of BM and stereotactic radiosurgery (SRS), when feasible, are preferred over whole-brain radiotherapy, because of related cognitive impairment. These treatments can lead to a local control of the disease, however, systemic relapses can affect the prognosis of these patients. Recently, new anti-HER2 agents have demonstrated to be effective on BMs, thereby leading to improved survival outcomes with an acceptable quality of life. Despite the clinical benefit of these approaches, BMs still represent a cause of death and effective therapeutic strategies are needed. Different targeted agents have demonstrated significant efficacy with tolerable safety profiles in HER2+ BC patients with BM, and have already been approved for clinical use in this setting. A better understanding of the molecular mechanisms underlying the onset of BMs could suggest novel targeted approaches in order to prevent CNS localization or delay progression to CNS in HER-2 metastatic patients.

Treatment modalities and survival outcomes in prostate cancer parenchymal brain metastasis.

Prostate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes. We retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan-Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups. At the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate-specific antigen (PSA) was 2.2 (0.1-26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6-100.9). The median (IQR) primary Gleason score was 8 (7-9) and over a median (IQR) follow-up time of 2.2 (1.2-16.5) months, 76.5% (n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log-rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16-0.86, p = 0.022). In our single-institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.

Radiosurgery for Brain Metastases: Challenges in Imaging Interpretation after Treatment.

Stereotactic radiosurgery (SRS) has transformed the management of brain metastases by achieving local tumor control, reducing toxicity, and minimizing the need for whole-brain radiation therapy (WBRT). This review specifically investigates radiation-induced changes in patients treated for metastasis, highlighting the crucial role of magnetic resonance imaging (MRI) in the evaluation of treatment response, both at very early and late stages. The primary objective of the review is to evaluate the most effective imaging techniques for assessing radiation-induced changes and distinguishing them from tumor growth. The limitations of conventional imaging methods, which rely on size measurements, dimensional criteria, and contrast enhancement patterns, are critically evaluated. In addition, it has been investigated the potential of advanced imaging modalities to offer a more precise and comprehensive evaluation of treatment response. Finally, an overview of the relevant literature concerning the interpretation of brain changes in patients undergoing immunotherapies is provided.

Physical Activity Attenuates Brain Irradiation-Associated Skeletal Muscle Damage in the Rat

Background: Radiotherapy for brain tumors increases patient survival. Nonetheless, side effects are increasingly reported such as cognitive deficits and fatigue. The etiology of fatigue remains poorly described. Our hypothesis is that the abscopal effects of radiotherapy on skeletal muscle may be involved in fatigue. The present study aims to assess the impact of brain irradiation on skeletal muscles, its relationships with fatigue and to analyze whether physical activity could counteract brain radiation-induced side effects. Methods: Adult Wistar rats were randomly distributed between 4 groups: control (CTL), irradiated (IR), non-irradiated with physical activity (PA) and irradiated with physical activity (IR+PA). Irradiated rats were exposed to a whole-brain irradiation (WBI) of 30 Gy (3×10 Gy). Rats subjected to PA underwent sessions of running on a treadmill, 3 times/week during 6 months. The effects of WBI on muscles were evaluated by complementary approaches: behavioral tests (fatigue, locomotion activity), magnetic resonance imaging (MRI) and histological analyses. Results: Irradiated rats displayed a significant fatigue and a reduced locomotor activity at short term compared to the CTL group which were attenuated with PA at 6 months after whole-brain irradiation. The IR rat's gastrocnemius mass decreased compared to CTL rats which was reversed by physical activity at 14 days after WBI. Multiparametric MRI imaging of the skeletal muscle highlighted an alteration of the fiber organization in IR rats as demonstrated by a significant decrease of the mean diffusivity in the gastrocnemius at short term. Alteration of fibers was confirmed by histological analyses: the number of type I fibers was decreased while that of type IIa fibers was increased in irradiated animals but not in IR+PA group. Conclusions: The data show that whole-brain irradiation induces skeletal muscle damage which are attenuated by PA. This muscle damage may explain, at least in part, the fatigue of patients treated with radiotherapy.

Selecting the Appropriate Radiation Therapy Technique for Extensive Brain Metastases from Tens to Hundreds: Should the Latest Technique Always Be the Best Option?

Brain metastases (BMs) are one of the most common metastatic lesions in adult cancer patients and the most common intracranial neoplasms in adult patients. Especially for multiple BMs, historically, whole-brain radiotherapy (WBRT) has been performed as the mainstay of therapy, which improves neurological symptoms and median survival. However, WBRT could negatively impact the patient's quality of life due to late complications. Owing to these complications, attempts have been made to use the latest radiotherapy (LRT) such as stereotactic radiosurgery (SRS) and intensity-modulated radiotherapy (IMRT) to treat BMs. However, for the extensive BMs (ranging from tens to hundreds), there are currently no prospective studies comparing WBRT with LRT such as IMRT or SRS. For extensive brain metastases, LRT cannot be the best option. Instead, upfront WBRT should be considered given its advantages and disadvantages, rather than LRT. We hope that faster and more reliable LRT for extensive BMs will be applicable for clinical practice without any clinical concerns in the near future.

Hypofractionated Stereotactic Radiotherapy (HFSRT) of the Resection Cavity vs. Whole-Brain Radiotherapy (WBRT) Following Brain Metastasis Resection – Results of the ESTRON Randomized Phase 2 Trial

Hypofractionated Stereotactic Radiotherapy (HFSRT) of the Resection Cavity vs. Whole-Brain Radiotherapy (WBRT) Following Brain Metastasis Resection – Results of the ESTRON Randomized Phase 2 Trial

Stereotactic Radiosurgery for 1-10 Brain Metastases Avoids Whole-Brain Radiotherapy - Results of the CYBER-SPACE Randomized Phase 2 Trial

Stereotactic Radiosurgery for 1-10 Brain Metastases Avoids Whole-Brain Radiotherapy - Results of the CYBER-SPACE Randomized Phase 2 Trial

Repeated Stereotactic Radiotherapy for Local Brain Metastases Failure or Distant Brain Recurrent: A Retrospective Study of 184 Patients.

The main advantages of stereotactic radiotherapy (SRT) are to delay whole-brain radiotherapy (WBRT) and to deliver ablative doses. Despite this efficacy, the risk of distant brain metastases (BM) one year after SRT ranges from 26% to 77% and 20 to 40% of patients required salvage treatment. The role and consequences of reirradiation remain unclear, particularly in terms of survival. The objective was to study overall survival (OS) and neurological death-free survival (NDFS) and to specify the prognostic factors of long-term survival. we retrospectively reviewed the data of patients treated between 2010 and 2020 with at least two courses of SRT without previous WBRT. In total, 184 patients were treated for 915 BMs with two-to-six SRT sessions. Additional SRT sessions were provided for local (5.6%) or distant (94.4%) BM recurrence. The median number of BMs treated per SRT was one with a median of four BMs in total. The mean time between the two SRT sessions was 8.9 months (95%CI 7.7-10.1) and there was no significant difference in the delay between the two sessions. The 6-, 12- and 24-month NDFS rates were 97%, 82% and 52%, respectively. The 6-, 12- and 24-month OS rates were 91%, 70% and 38%, respectively. OS was statistically related to the number of SRT sessions (HR = 0.48; p < 0.01), recursive partitioning analysis (HR = 1.84; p = 0.01), salvage WBRT (HR = 0.48; p = 0.01) and brain metastasis velocity (high: HR = 13.83; p < 0.01; intermediate: HR = 4.93; p < 0.01). Lung cancer and melanoma were associated with a lower NDFS compared to breast cancer. A low KPS, a low number of SRT sessions, synchronous extracerebral metastases, synchronous BMs, extracerebral progression at SRT1, a high BMV grade, no WBRT and local recurrence were also associated with a lower NDFS. A high KPS at SRT1 and low BMV grade are prognostic factors for better OS, regardless of the number of BM recurrence events.

Socio-economic disparities influence likelihood of post-operative radiation to resection cavities of metastatic brain tumors.

Irradiating the surgical bed of resected brain metastases improves local and distant disease control. Over time, stereotactic radiosurgery (SRS) has replaced whole brain radiotherapy (WBRT) as the treatment standard of care because it minimizes long-term damage to neuro-cognition. Despite this data and growing adoption, socio-economic disparities in clinical access can result in sub-standard care for some patient populations. We aimed to analyze the clinical and socio-economic characteristics of patients who did not receive radiation after surgical resection of brain metastasis. Our sample was obtained from Clinformatics® Data Mart Database and included all patients from 2004 to 2021 who did or did not receive radiation treatment within sixty days after resection of tumors metastatic to the brain. Regression analysis was done to identify factors responsible for loss to adjuvant radiation treatment. Of 8362 patients identified who had undergone craniotomy for resection of metastatic brain tumors, 3430 (41%) patients did not receive any radiation treatment. Compared to patients who did receive some form of radiation treatment (SRS or WBRT), patients who did not get any form of radiation were more likely to be older (p = 0.0189) and non-white (p = 0.008). Patients with Elixhauser Comorbidity Index ≥3 were less likely to receive radiation treatment (p < 0.01). Fewer patients with household income ≥ $75,000 did not receive radiation treatment (p < 0.01). Age, race, household income, and comorbidity status were associated with differential likelihood to receive post-operative radiation treatment.

A - 114 Long Term Cognitive Sequela of Intracranial Radiation Therapy in a Pediatric Cerebellar Medulloblastoma Survivor.

Intracranial radiation therapy (IRT) for pediatric brain tumors is associated with late delayed brain injury due to cerebrovascular abnormality, white matter necrosis, demyelination, and gliosis which are irreversible. As a result, persistent cognitive deficits in adulthood emerge which are aggravated by younger age at diagnosis, higher radiation dose, whole brain radiation (WBR), and concurrent chemotherapy. The case is a childhood brain tumor survivor seen 18years post treatment who displayed cognitive deficits reflecting the cognitive sequela of WBR that overlapped with the anatomical distribution of white matter damage sustained. 23-year-old Black male with a history of childhood cerebellar medulloblastoma diagnosed at age 4, tumor resection, WBR, chemotherapy, more recent seizure disorder and medullary stroke, diabetes, and hypertension was seen for a neuropsychological evaluation due to memory complaints. His neuroimaging showed white matter hyperintensities in bilateral temporal and occipital lobes, bilateral cerebellar hemispheres, bilateral frontal lobes, medial posterior right cerebellar cyst, and 10 x 5mm cyst in the left temporal lobe. Results showed FSIQ = 59 and deficits in language, processing speed, visuospatial abilities, executive functioning, and verbal memory. His auditory working memory and visual memory were preserved. Based on his numerous adaptive limitations, moderate intellectual development disorder diagnosis was given. Deficits across several cognitive domains were consistent with multi-focal white matter lesions seen in patient's neuroimaging which reflect radiographic findings related to long-term sequela of previous intracranial radiation. A unique finding was relatively preserved visual memory as findings related to asymmetrical memory dysfunction in childhood medulloblastoma survivors are scarce.

LC3 Accelerated Brain-Lung Axis Abscopal Effects after Fractionated Whole-Brain Radiation by Promoting Motoneurons to Secrete Periostin.

The effect of autophagy on the radiation-induced bystander effect (RIBE) invivo is unclear. Here, the whole brains of microtubule-associated protein 1A/1B-light chain 3 (LC3) and C57BL/6 (B6) mice were irradiated once (10 Gy)(IR1), given 3 fractions in three weeks (IR3), or 6 fractions in six weeks (IR6). The median survival of LC3 mice was 56.5 days, and that of B6 mice was 65 days after IR6. LC3 mice showed more congestion and fibrosis in the lung after the IR3 and IR6 irradiation protocols than B6 mice. Quantitative proteomics of serum samples and lung RNA sequencing of the LC3 group showed that the common most clustered pathway of the IR3 group was the elastic fiber formation pathway, which contained Periostin (POSTN). POSTN in the motoneurons increased with increasing number of radiation fractions in LC3 mice. A 1 μg/g POSTN neutralizing antibody reduced the lung fibrosis of LC3 mice exposed to IR3 by one-third, and significantly prolonged the survival time of LC3 mice exposed to IR6. LDN-214117 and LRRK2-in-1 were the best two of sixteen transforming growth factor-beta1 (TGF-β) receptor and autophagy mediators to decrease Postn mRNA. These data led us to conclude that LC3 accelerated motoneuron secretion of POSTN and aggravated the RIBE in the lung after brain irradiation.

May we routinely spare hippocampal region in primary central nervous system lymphoma during whole brain radiotherapy?

PurposeOne of the main limiting factors of whole-brain radiation therapy (WBRT) for primary central nervous system lymphoma (PCNSL) is the impairment of neurocognitive functions (NCFs), which is mainly caused by radiation-induced injury to the hippocampus. With a view to preventing NCF impairment and personalizing treatment, we explored the feasibility of sparing the hippocampus during WBRT by correlating the sites of PCNSL lesions with the hippocampus.Methods and materialsPre-treatment MR images from patients who underwent WBRT between 2010 and January 2020—and post-radiotherapy images in cases of relapse—were imported into the Varian Eclipse treatment-planning system and registered with the simulation CT. We constructed three 3-dimensional envelopes around the hippocampus at distances of 5, 10 and 15 mm and also contoured primary lesions and recurrences.ResultsWe analyzed 43 patients with 66 primary lesions: 9/66 (13.6%) involved the hippocampus and 11/66 (16.7%) were located within 5 mm of it. Thirty-six lesions (54.5%) were situated more than 15 mm from the hippocampus, while 10/66 (15.2%) were between 5 and 15 mm from it. The most common location was in deep brain structures (31%). Thirty-five of the 66 lesions relapsed: in field in 14/35 (40%) and outfield in 21/35 (60%) in different sites. Globally, 16/35 recurrences (45.7%) were located in the hippocampus or within 5 mm of it.ConclusionThese data show that routinely sparing the hippocampus is not feasible. This approach could be considered in selected patients, when the lesion is more than 15 mm from the hippocampus.

Thirty-Year Experience of Radiotherapy for Primary Intraocular Lymphoma with and without Chemotherapy.

Primary intraocular lymphoma (PIOL) is a rare presentation of primary central nervous system lymphoma (PCNSL). We previously reported that ocular radiation therapy (RT) is an excellent option that can spare appropriate patients' upfront toxicity of whole brain radiotherapy (WBRT) and aggressive chemotherapy. A decade later, we expanded this series with almost double median follow up time. We identified all patients seen at our institution from 1990-2022 treated for PCNSL or who received RT to the orbits. Detailed chart review was completed for cases with isolated ocular involvement at presentation (PIOL) who received RT to unilateral or bilateral orbits. Patients with disease on MRI brain or CSF cytology were excluded. Analysis included Kaplan-Meier method, log-rank-test, and Wilcoxon rank sum test. Overall survival (OS) was measured from diagnosis. Freedom-from-recurrence (FFR) measured time from RT start to first recurrence identified on imaging (parenchymal), slit-lamp exam (ocular), or biopsy. A total of 75 patients were treated with RT to the orbits as part of management of PCNSL. 29 had PIOL with median follow up of 52 months from diagnosis. Of this subset, 22 (76%) received RT at our institution, median age at diagnosis was 65 (31-84) and 18 (62%) had bilateral disease. The majority were diagnosed by vitrectomy or vitreoretinal biopsy with B-cell lymphoma or unspecified lymphoma and 3 were clinically diagnosed. 17 patients received RT alone, 10 received RT after induction chemotherapy and 2 with induction and consolidation chemotherapy. Younger patients received chemotherapy (median age 60 vs 70, p = 0.03). RT dose ranged from 30 to 45 Gy, and 20 (69%) received 36 Gy, primarily with 1.8 Gy fractions. 22 (76%) received RT to bilateral orbits. 21 (72%) developed recurrence (Table 1), of which 6 (28.5%) recurred in a RT-treated eye and 11 (52.4%) isolated in the brain. 2 got salvage orbital RT and 4 got WBRT. Median OS was 5.4 years (95% CI 3.9, 7.6) and FFR was 8.4 months (95% CI 5.0, 25). There was no difference in OS (p = 0.4) or FFR (p = 0.3) between combined modality therapy versus RT alone. In this updated experience, we demonstrate that RT alone remains an effective option for isolated PIOL, especially for those at risk of poor toleration of chemotherapy. Systemic therapy or WBRT can be utilized at recurrence, which primarily occurs in the brain. Future comparisons are needed to compare orbital RT to intravitreal therapies, and to investigate how these methods can complement each other to further improve management.

Métastases du système nerveux central: Central nervous system metastases

Lung cancer is the leading provider of brain metastases (BMs). The prevalence of BMs varies depending on pathology and can occur in up to 50% of non-small cell lung cancers (NSCLC) and 80% of small cell lung cancers (SCLC) during follow-up. BMs prevalence is also higher in case of oncogenic addictions such as EGFR mutations or ALK rearrangements. Furthermore, BMs result in significant morbidity and mortality. They are directly responsible for death in 50% of cases.BMs evolution and response to treatments is heterogeneous, and can be different from the primary tumor. This is due to molecular differences between BMs and primary tumors related to the blood-brain barrier (BBB) but also to a very different tumor microenvironment.Depending on pathology, tumor mutation profile and PDL1 expression, systemic treatments may be based on immunotherapy alone, a combination of chemotherapy and immunotherapy, or targeted therapies. More and more data are available on intracranial response of systemic treatments, including data for new treatments in development. In addition to systemic treatments, local treatments such as surgery, whole brain radio therapy (WBRT) or stereotactic radiotherapy (SBRT) should be considered. Local treatment choice mainly depends on the number and volume of brain lesions. Because of fewer side effects, SBRT is becoming an increasingly important part of treatment. On the contrary, prophylactic cranial irradiation is limited to SCLCs with good response to chemotherapy.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

1610P A new updated prognostic index for patients with brain metastases (BM) treated with palliative whole brain radiotherapy (WBRT) in the era of precision oncology: METASNCore project

1610P A new updated prognostic index for patients with brain metastases (BM) treated with palliative whole brain radiotherapy (WBRT) in the era of precision oncology: METASNCore project