Search

Purpose: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis., Materials and Methods: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation)., Conclusion and Recommendations: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting., (© 2024. The Author(s).)

The prognosis and prognostic factors of patients receiving whole-brain radiotherapy (WBRT) for leptomeningeal metastasis (LM) from lung adenocarcinoma have not been established. Particularly, the impact of EGFR mutations and ALK rearrangements on survival remains unclear. This retrospective study evaluated the prognosis and prognostic factors of patients receiving WBRT for LM. We evaluated overall survival (OS) from WBRT initiation and clinical variables in 80 consecutive patients receiving WBRT for LM from lung adenocarcinoma at our institution between June 2013 and June 2021. After a median follow-up of 5.2 (range 0.5-56.5) months, the median OS was 6.2 months (95% CI 4.4-12.4). Of the 80 patients, 51 were classified as EGFR/ALK mutant (EGFR: 44; ALK: 6; both: 1) and 29 as wild-type. The median OS was 10.4 (95% CI 5.9-20.9) versus 3.8 (95% CI 2.5-7.7) months in the EGFR/ALK-mutant versus wild-type patients (HR = 0.49, P = 0.0063). Multivariate analysis indicated that EGFR/ALK alterations (HR = 0.54, P = 0.021) and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (HR = 0.25, P < 0.001) were independent factors associated with favorable OS. Among the patients who underwent brain MRI before and after WBRT, intracranial progression-free survival was longer in the 26 EGFR/ALK-mutant than 13 wild-type patients (HR = 0.31, P = 0.0039). Although the prognosis of patients receiving WBRT for LM remains poor, EGFR/ALK alterations and good ECOG PS may positively impact OS in those eligible for WBRT., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

A 70-year old male with stage I large cell neuroendocrine carcinoma (LCNEC) of the lung underwent resection of a metachronous 5 cm brain metastasis and received postoperative hypofractionated stereotactic radiotherapy (hfSRT). Five sequential nodular leptomeningeal metastases up to 5.3 cm in diameter were diagnosed on MRI within 10 months and were treated with SRT. Currently the patient has no evidence of intracranial disease 24 months after last irradiation without chemotherapy or whole brain radiotherapy. This is the first report of sustained complete remission of multiple large leptomeningeal metastases achieved with hfSRT, highlighting this brain-sparing approach in selected patients with LCNEC lung cancer., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: Leptomeningeal metastasis (LM) is a rare but detrimental complication in patients with non-small cell lung cancer (NSCLC). Although whole brain radiotherapy (WBRT) is used to eliminating cancer cells or microscopic foci, it is becoming less favorable due to the concerns over neurocognitive toxicity. This study aimed to re-evaluate the role of WBRT in the setting of modern targeted therapy., Materials and Methods: From December 2014 to March 2019, 80 NSCLC patients with cytologically and/or radiologically proven LM diagnosis were retrospectively analyzed., Results: The median OS (mOS) after diagnosis of LM was 8.0 (95%CI: 4.4 to 11.6) months, and the one-year OS was 39.4%. The mOS for EGFR-mutated LM patients was 12.6 (3.0 to 22.2) months versus only 4.1 (2.8 to 5.4) for patients with wild-type EGFR (P < 0.001). Younger patients (< 53.5 yrs.) appeared to have a better OS than older patients (≥53.5 yrs.) (12.6 vs. 6.1, P = 0.041). No survival benefits were found in EGFR-mutated patients who received WBRT (P = 0.490). In contrast, mOS was significantly prolonged in wild-type EGFR patients with WBRT versus non-WBRT (mOS: 8.0 vs. 2.1, P = 0.002). Multivariate analysis indicated that WBRT (P = 0.025) and younger age (P = 0.048) were independent prognostic factors that predicted prolonged survival for wild-type EGFR LM patients from NSCLC., Conclusion: Our study demonstrated that WBRT has clear survival advantages for patients with wild-type EGFR, and molecular biological stratification of LM patients for WBRT is highly recommended.

This study aimed to evaluate the imaging findings and prognostic factors after whole-brain radiotherapy in patients with carcinomatous meningitis from breast cancer.A retrospective analysis of imaging data and prognostic factors was performed in patients treated with whole-brain radiotherapy or whole-brain/spine radiotherapy immediately after the first diagnosis of carcinomatous meningitis from breast cancer at our hospital from January 1, 2010 to December 31, 2018. Statistical significance was set at P < .05 (two-tailed).All patients (n = 31) were females with the mean age of 58.0 ± 11.0 years. The breast cancer subtypes were luminal (n = 14, 45.1%), human epidermal growth factor receptor 2 (HER2)-positive (n = 9, 29.0%), and triple-negative (n = 8, 26.0%) breast cancer. Brain metastasis and abnormal contrast enhancement in the sulci were observed in 21 (67.7%) and 24 (80.6%) patients, respectively. The median survival time after cancerous meningitis diagnosis was 62 (range, 6-657) days. Log-rank test showed significant differences in median survival time after cancerous meningitis diagnosis: 18.0 days for subjects treated with 30 Gy in < 10 fractions (n = 7) vs 78.5 days for subjects treated with 30 Gy in ≥10 fractions (n = 24) (P < .01) and 23.0 days for the triple-negative subtype vs 78.5 days for the other subtype (P < .01) groups. Univariate analysis using the Cox regression model showed significant differences in median survival time after cancerous meningitis diagnosis between the group treated with 30 Gy in <10 fractions and the group treated in ≥10 fractions (hazard ratio [HR] 0.08, 95% confidence interval [CI], 0.03-0.26; P < .01), and between the triple-negative subtype and the other subtypes (HR = 5.48; 95% CI, 1.88-16.0; P < .01) groups.Discontinuation of whole-brain radiotherapy and the presence of triple-negative breast cancer were indicators of poor prognosis.

We herein report a 66-year-old woman with advanced lung adenocarcinoma [programmed cell death and its ligand 1 (PD-L1) tumor proportion score 60%] lacking driver oncogenes in whom meningeal carcinomatosis, along with sudden onset dizziness, deafness, and consciousness disturbance, appeared after second-line chemotherapy. Whole-brain radiation therapy (WBRT) and Pembrolizumab were subsequently administered, and third-line chemotherapy with Pembrolizumab is now ongoing. At the time of writing, the patient has achieved a 23-month survival without disease progression. Our findings suggest that the combination of WBRT and an immune checkpoint inhibitor is effective for non-small-cell lung cancer patients lacking driver oncogenes who develop meningeal carcinomatosis.

Purpose: For brain metastases, surgical resection with postoperative stereotactic radiosurgery is an emerging standard of care. Postoperative cavity stereotactic radiosurgery is associated with a specific, underrecognized pattern of intracranial recurrence, herein termed nodular leptomeningeal disease (nLMD), which is distinct from classical leptomeningeal disease. We hypothesized that there is poor consensus regarding the definition of LMD, and that a formal, self-guided training module will improve interrater reliability (IRR) and validity in diagnosing LMD., Methods and Materials: Twenty-two physicians at 16 institutions, including 15 physicians with central nervous system expertise, completed a 2-phase survey that included magnetic resonance imaging and treatment information for 30 patients. In the "pretraining" phase, physicians labeled cases using 3 patterns of recurrence commonly reported in prospective studies: local recurrence (LR), distant parenchymal recurrence (DR), and LMD. After a self-directed training module, participating physicians completed the "posttraining" phase and relabeled the 30 cases using the 4 following labels: LR, DR, classical leptomeningeal disease, and nLMD., Results: IRR increased 34% after training (Fleiss' Kappa K = 0.41 to K = 0.55, P < .001). IRR increased most among non-central nervous system specialists (+58%, P < .001). Before training, IRR was lowest for LMD (K = 0.33). After training, IRR increased across all recurrence subgroups and increased most for LMD (+67%). After training, ≥27% of cases initially labeled LR or DR were later recognized as nLMD., Conclusions: This study highlights the large degree of inconsistency among clinicians in recognizing nLMD. Our findings demonstrate that a brief self-guided training module distinguishing nLMD can significantly improve IRR across all patterns of recurrence, and particularly in nLMD. To optimize outcomes reporting, prospective trials in brain metastases should incorporate central imaging review and investigator training., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Leptomeningeal disease (LMD) is an uncommon complication of advanced breast cancer. The prognosis is poor, and although radiotherapy (RT), systemic and intra-thecal (IT) chemotherapy are accepted treatment modalities, efficacy data are limited. This study was designed to evaluate potential predictors of survival in this patient group., Methods: Breast cancer patients with LMD diagnosed by MRI in a 10-year period (2004-2014) were identified from electronic patient records. PFS and OS estimates were calculated using Kaplan-Meier method, with planned sub-group analysis by treatment modality. Cox regression was employed to identify significant prognostic variables., Results: We identified 182 eligible patients; all female, median age at LMD diagnosis 52.5 years (range 23-80). Ninety patients (49.5%) were ER positive/HER2 negative; 48 (26.4%) were HER2 positive, and 27 (14.8%) were triple negative. HER2 status was unknown in 17 (9.3%). Initial management of LMD was most commonly whole or partial brain RT in 62 (34.1%), systemic therapy in 45 (24.7%) or supportive care alone in 37 (20.3%). Fourteen patients (7.7%) underwent IT chemotherapy, of whom two also received IT trastuzumab. From diagnosis of LMD, the median PFS was 3.9 months (95%CI 3.2-5.0) and median OS was 5.4 months (95%CI 4.2-6.6). Patients treated with systemic therapy had the longest OS (median 8.8 months, 95%CI 5.5-11.1), compared to RT; 6.1 months (95%CI 4.2-7.9 months), IT therapy; 2.9 months (95%CI 1.2-5.8) and supportive care; 1.7 months (95%CI 0.9-3.0). On multivariable analysis, triple negative histology, concomitant brain metastases, and LMD involving both the brain and spinal cord were associated with poor OS., Conclusions: Breast cancer patients with triple negative LMD, concomitant brain metastases or LMD affecting both the spine and brain have the poorest prognosis. Clinical trials to identify more effective treatments for these patients are urgently needed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

To assess the efficacy of whole-brain radiotherapy (WBRT) and prognostic factors in leptomeningeal carcinomatosis (LMC) of non-small-cell lung cancer (NSCLC) patients. WBRT records of 51 LMC patients confined to brain were reviewed. Eligible patients had squamous-cell carcinoma (SCC) or adenocarcinoma, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-3. The WBRT was either 20 or 30 Gray. The primary and secondary objectives were to determine overall survival (OS) and prognostic factors for improved treatment response, respectively. Median age was 53 years (range 39-68), 58.8 % had SCC, 74.5 % had ECOG PS 1-2, and 70.6 % had LMC accompanied by parenchymal brain metastases (BM). The median follow-up was 4.1 months (range 0.7-14.4); all patients died due to disease progression. Median OS was 3.9 months (95 % CI 3.3-4.5) with 6 and 12 month estimates of 19.6 and 5.9 %, respectively. Evaluation of prognostic factors revealed that patients with ECOG 1, longer time to LMC (TT-LMC) from NSCLC diagnosis (>11.3 months), and absence of parenchymal BM had significantly superior OS than those patients with ECOG 2 (p = 0.01) or 3 (p < 0.001), TT-LMC < 11.3 months (p = 0.001), and parenchymal BM (p = 0.012). Median OS of 3.9 months after WBRT appeared to confirm the poor prognosis of LMC. WBRT might be most effective for patients with favorable PS, longer TT-LMC, and no accompanying BM. Therefore, we identified ECOG PS 1, TT-LMC > 11.3 months, and no BM as independent prognosticators for better response to WBRT in NSCLC patients with LMC.

About 20% to 40% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases during the natural course of their disease. The prognosis for such patients is very poor with limited survival. In addition to the standard whole brain radiation therapy (WBRT), some studies have shown that chemotherapy drugs and/or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) can improve the outcome of these patients. Here, we report a stage IIIA patient who developed multiple brain metastases one year after operation. Oral gefitinib with concurrent WBRT were given as first-line therapy. Complete response and a 50-month progression-free survival (PFS) were obtained. Double dosage of gefitinib (500 mg per day) together with pemetrexed were given as the second-line therapy after the patient developed new brain lesions and leptomeningeal metastasis during the maintenance therapy of gefitinib. The PFS for the second-line therapy was six months. In total, the patient obtained an overall survival of 59 months since the first diagnosis of brain metastases. Mutational analysis showed a 15-nucleotide deletion and a missense mutation in exon 19 of the EGFR gene, and a missense mutation at codon 12 of the K-ras gene. These underlying genetic changes might partially explain the long-term survival of this patient after brain metastases when treated with concurrent or sequential therapies of EGFR-TKI, radiotherapy and chemotherapy.

Background: The purpose of the present study was to investigate outcome after whole brain radiotherapy (WBRT) alone as a palliative treatment without concomitant chemotherapy for intracranial leptomeningeal carcinomatosis (LMC)., Patients and Methods: Overall survival and treatment response were retrospectively analyzed in 27 consecutive patients with LMC from breast and lung cancer. All patients had evidence of intracranial manifestations of LMC. Seven potential prognostic factors were evaluated., Results: Median overall survival (OS) for the entire group was 8.1 weeks. OS rates after 6 and 12 months were 26% and 15%, respectively. Improvement of neurological deficits was observed in 3 patients. In 3 of 4 patients with follow-up MRI studies, a decreased size of contrast-enhanced lesions was observed. Prognostic factors for improved OS on univariate analysis were absence of cranial nerve dysfunction, Karnofsky Performance Score (KPS) > 60%, and time interval > 35 months between the initial diagnosis of malignant disease and development of LMC. On multivariate analysis, absence of cranial nerve dysfunction remained the only significant prognosticator for OS (median 3.7 vs. 19.4 weeks, p < 0.001)., Conclusion: WBRT alone is an effective palliative treatment for patients unfit/unsuitable for chemotherapy and low performance status suffering from intracranial LMC. However, prognostic factors should be considered in order to identify patients who are likely to benefit from WBRT.

A case of leptomeningeal carcinomatosis in a patient with known brain and lung metastases from renal cell cancer without previous systemic therapy is presented. Neoplastic meningitis (NM) developed 31 months after first diagnosis of simultaneous extra- and intracranial recurrence of kidney cancer and surgical resection of a cerebellar metastasis. In spite of local radiotherapy to the macroscopic NM lesions in the cervical and lumbar spine followed by initiation of sunitinib, the patient succumbed to his disease 4 months after the diagnosis of NM. The untreated lung metastases progressed very slowly during almost 3 years of observation. This case illustrates important issues around both biological behaviour and treatment approaches in metastatic renal cell cancer.

Purpose: To provide recommendations for palliative treatment of brain metastases (BM) and leptomeningeal carcinomatosis (LC) in breast cancer patients with specific emphasis on radiooncologic aspects., Methods: The breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) performed a comprehensive survey of the literature comprising national and international guidelines, lately published randomized trials, and relevant retrospective analyses. The search included publications between 1995-2008 (PubMed and Guidelines International Network [G-I-N]). Recommendations were devised according to the panel's interpretation of the evidence referring to the criteria of EBM., Results: Aim of any treatment of BM and LC is to alleviate symptoms and improve neurologic deficits. Close interdisciplinary cooperation facilitates rapid diagnosis and onset of therapy, tailored to the individual and clinical situation. Treatment decisions for BM should be based on the allocation to three prognostic groups defined by recursive partitioning analysis (RPA). Karnofsky Performance Score (KPS) is the strongest prognostic parameter. Together with the extent of the disease, KPS determines whether excision or radiosurgery/stereotactic radiotherapy is feasible and if exclusive or additional whole-brain radiotherapy (WBRT) is indicated. With adequate therapy, survival may be up to 3 years. For LC, treatment is mostly indicated for patients with positive cytology or in case of strongly indicative signs and symptoms. Radiotherapy (WBRT and involved-field irradiation of bulky spinal lesions) and chemotherapy (systemically or intrathecally applied methotrexate, thiotepa and cytarabine) are both effective and may prolong survival from several weeks to 4-6 months., Conclusion: Radiotherapy is an effective tool for palliative treatment of BM and LC.