Multiple Brain Metastases Research Articles

131P - Upfront whole brain radiotherapy for multiple brain metastases in patients with EGFR-mutant lung adenocarcinoma

Purpose: This study aimed to evaluate the efficacy of upfront whole-brain radiotherapy (WBRT) in EGFR-mutant lung adenocarcinoma patients with multiple brain metastases (BM). Methods: In this study, 195 patients with EGFR mutations who had multiple BM at preliminary diagnosis were included and retrospectively reviewed. Patients were admitted to receive the following treatments in a multi-disciplinary setting: upfront WBRT followed by EGFR-TKI, concurrent EGFR-TKI and WBRT and upfront EGFR-TKI followed by WBRT. A disease-specific graded prognostic assessment (DS-GPA) was performed for all the patients. The treatment response and overall survival (OS) were assessed as well. Results: The median OS of these patients was 27 months. Objective response rate (ORR) was significantly better in upfront WBRT group than other two groups (P=0.004). Moreover, patients who received upfront WBRT (n=67) had longer OS than the concomitant group (36 vs 25 months; P=0.006) and the upfront EGFR-TKI group (36 vs 25 months; P<0.0001). The prognosis of patients with different DS-GPA scores significantly differed (P<0.0001). In concomitant group and upfront EGFR-TKIs group, patients with higher DS-GPA scores of 2-3 had more favorable prognosis compared with those with lower DS-GPA scores of 0-1.5 (27 vs 25 months; P=0.023). Patients who received EGFR-TKIs concurrently with WBRT had longer OS than those received upfront EGFR-TKIs with high DS-GPA scores. (37 vs 17 months; P=0.023). Conclusion: The use of upfront WBRT for EGFR-mutated lung adenocarcinoma patients with multiple BM can improve ORR and OS. More importantly, patients with high DS-GPA scores are recommended to receive WBRT immediately after EGFR-TKIs therapy.

Upfront whole brain radiotherapy for multiple brain metastases in patients with EGFR-mutant lung adenocarcinoma.

Purpose: This study aimed to evaluate the efficacy of upfront whole-brain radiotherapy (WBRT) in EGFR-mutant lung adenocarcinoma patients with multiple brain metastases (BM).Methods: In this study, 195 patients with EGFR mutations who had multiple BM at preliminary diagnosis were included and retrospectively reviewed. Patients were admitted to receive the following treatments in a multi-disciplinary setting: upfront WBRT followed by EGFR-TKI, concurrent EGFR-TKI and WBRT and upfront EGFR-TKI followed by WBRT. A disease-specific graded prognostic assessment (DS-GPA) was performed for all the patients. The treatment response and overall survival (OS) were assessed as well.Results: The median OS of these patients was 27 months. Objective response rate (ORR) was significantly better in upfront WBRT group than other two groups (P=0.004). Moreover, patients who received upfront WBRT (n=67) had longer OS than the concomitant group (36 vs 25 months; P=0.006) and the upfront EGFR-TKI group (36 vs 25 months; P<0.0001). The prognosis of patients with different DS-GPA scores significantly differed (P<0.0001). In concomitant group and upfront EGFR-TKIs group, patients with higher DS-GPA scores of 2–3 had more favorable prognosis compared with those with lower DS-GPA scores of 0–1.5 (27 vs 25 months; P=0.023). Patients who received EGFR-TKIs concurrently with WBRT had longer OS than those received upfront EGFR-TKIs with high DS-GPA scores. (37 vs 17 months; P=0.023).Conclusion: The use of upfront WBRT for EGFR-mutated lung adenocarcinoma patients with multiple BM can improve ORR and OS. More importantly, patients with high DS-GPA scores are recommended to receive WBRT immediately after EGFR-TKIs therapy.

Ovarian metastasis from breast cancer in three Chinese females

Rationale:The biological behavior and clinical features of ovarian metastasis from breast cancer remain unclear; diagnosis and treatment of this condition are challenging.Patient concerns:We reported three cases of ovarian metastasis from breast cancer in Chinese women aged 44, 46, and 30 years. The prognosis was different in all three patients; however, no symptoms of ovarian metastasis were observed.Diagnosis:All three premenopausal patients were diagnosed with hormone receptor-positive breast cancer and two of them had axillary lymph node metastasis. All three women had multiple extra-ovarian metastases when ovarian metastasis was detected.Interventions:All patients received systemic antitumor therapy and underwent bilateral ovariectomy.Outcomes:Patient 1 had stable bone metastasis; patient 2 had stable lung metastasis and died of heart disease, and patient 3 had multiple brain metastases, which suggested poor outcomes.Lessons:It is important to screen for ovarian metastasis from breast cancer when evaluating suspicious ovarian masses detected via transvaginal ultrasound in patients with a breast cancer history. Therefore, we recommend simple laparoscopic bilateral oophorectomy not only for pathological diagnosis but also for metastatic tumor removal and therapeutic castration. In such cases, systemic therapy is essential because ovarian metastasis is often a component of systemic metastatic disease.

189O - EGFR-TKIs plus bevacizumab demonstrated survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with multiple brain metastases

189O - EGFR-TKIs plus bevacizumab demonstrated survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with multiple brain metastases

SP-0694 Radiosurgery alone in multiple brain metastases

SP-0694 Radiosurgery alone in multiple brain metastases

EP-1829 Clinical validation of knowledge-based planning for multiple brain metastases

EP-1829 Clinical validation of knowledge-based planning for multiple brain metastases

EP-1236 Volumetric assessment of cerebral edema after fractionated SRT for multiple brain metastases

EP-1236 Volumetric assessment of cerebral edema after fractionated SRT for multiple brain metastases

EP-1737 “End-to-end test” for setting up multiple brain metastases SRS

EP-1737 “End-to-end test” for setting up multiple brain metastases SRS

EP-1250 Outcomes of Multiple Brain Metastases Radiosurgery with Gantry-Based Linac

EP-1250 Outcomes of Multiple Brain Metastases Radiosurgery with Gantry-Based Linac

Cerebral metastases: do size, peritumoral edema, or multiplicity predict infiltration into brain parenchyma?

Brain metastases (BMs) are the most frequent malignancy of the central nervous system. Previous research suggested that some metastases show infiltrative behavior rather than sharp demarcation. We hypothesized that three magnetic resonance (MR) imaging parameters-(a) tumor size, (b) extent of peritumoral edema, and (c) presence of multiple BMs-are predictors of cellular invasion beyond the surgically identifiable tumor margins. We performed a post hoc analysis on prospectively collected data of patients with BMs. Biopsies beyond the resection margin and immunohistochemistry were performed to assess infiltration status. The three MR imaging parameters were dichotomized into diameters ≤ 30mm ("small") and > 30mm ("large"), amount of peritumoral edema "extended" and "limited," and "multiple BMs" and "single BMs," respectively. The association between infiltration status and imaging parameters was calculated using chi-square test. Biopsy beyond the resection margin was performed in 77 patients; 49 (63.6%) had supramarginal infiltration and 28 patients (36.4%) showed no infiltration. Histological evidence of tumor infiltration was found in 25/41 patients with smaller lesions (61%) and in 24/36 with larger lesions (66.7%, p = 0.64), in 28/44 patients with limited (63.6%) and in 21/33 patients with extended edema (63.6%, p = 1.0), in 28/45 patients (62.2%) with single BM and in 21/32 patients (65.6%) with multiple BMs (p = 0.81). Based on the post hoc analysis of our prospective trial data, we could not confirm the hypothesis that infiltration of brain parenchyma beyond the glial pseudocapsule is associated with the MR imaging parameters tumor size, extent of edema, or multiplicity of metastases.

Risk factors to identify patients who may not benefit from whole brain irradiation for brain metastases - a single institution analysis

BackgroundRadiotherapy plays a major role in the management of brain metastases. This study aimed to identify the subset of patients with multiple brain metastases who may not benefit from whole brain irradiation (WBI) due to a short survival time regardless of treatment.MethodsWe analyzed a total of 339 patient records with brain metastases treated with whole brain radiotherapy from January 2009 to January 2016. External beam radiotherapy techniques were used to deliver 33 Gy in 11 fractions (4 fractions per week) to the whole brain. Eight clinical factors with a potential influence on survival were investigated using the Kaplan-Meier method. All factors with a P < 0.05 in univariate analysis were entered into multivariate analysis using Cox regression.ResultsIn the present series of 339 patients, median survival time was 2.5 months (M; range, 0–61 months). Four risk factors Karnofsky Performance Score (KPS) < 70, age > 70, > 3 of metastases intracranial, uncontrolled primary tumor) were identified that were significant and negatively correlated with median survival time. Patients with no risk factors had a median survival of 4.7 M; one risk factor, 2.5 M; two risk factors, 2.3 M; and 3–4 risk factors, 0.4 M (p < 0.00001).ConclusionsPatients with identified risk factors might have a negatively impacted overall survival after WBI. Accordingly, patients who will not benefit from WBI can be easily predicted if they have 3–4 of these risk factors.

Commentary: Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on Treatment Options for Adults With Multiple Metastatic Brain Tumors.

Target population These recommendations apply to adult patients newly diagnosed with multiple (more than 1) brain metastases. Question 1 In what circumstances should whole brain radiation therapy be recommended to improve tumor control and survival in patients with multiple brain metastases? Recommendation Level 2: It is recommended that whole brain radiation therapy can be added to stereotactic radiosurgery to improve local and distant control keeping in mind the potential for worsened neurocognitive outcomes and that there is unlikely to be a significant impact on overall survival. Question 2 In what circumstances should stereotactic radiosurgery be recommended to improve tumor control and survival in patients with multiple brain metastases? Recommendations Level 1: In patients with 2 to 3 brain metastases not amenable to surgery, the addition of stereotactic radiosurgery to whole brain radiation therapy is not recommended to improve survival beyond that obtained with whole brain radiation therapy alone. Level 3: The use of stereotactic radiosurgery alone is recommended to improve median overall survival for patients with more than 4 metastases having a cumulative volume Question 3 In what circumstances should surgery be recommended to improve tumor control and survival in patients with multiple brain metastases? Recommendation Level 3: In patients with multiple brain metastases, tumor resection is recommended in patients with lesions inducing symptoms from mass effect that can be reached without inducing new neurological deficit and who have control of their cancer outside the nervous system.The full guideline can be found at https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_6.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on Treatment Options for Adults With Multiple Metastatic Brain Tumors.

These recommendations apply to adult patients newly diagnosed with multiple (more than 1) brain metastases. In what circumstances should whole brain radiation therapy be recommended to improve tumor control and survival in patients with multiple brain metastases? Level 2: It is recommended that whole brain radiation therapy can be added to stereotactic radiosurgery to improve local and distant control keeping in mind the potential for worsened neurocognitive outcomes and that there is unlikely to be a significant impact on overall survival. In what circumstances should stereotactic radiosurgery be recommended to improve tumor control and survival in patients with multiple brain metastases? Level 1: In patients with 2 to 3 brain metastases not amenable to surgery, the addition of stereotactic radiosurgery to whole brain radiation therapy is not recommended to improve survival beyond that obtained with whole brain radiation therapy alone. Level 3: The use of stereotactic radiosurgery alone is recommended to improve median overall survival for patients with more than 4 metastases having a cumulative volume <7 cc. In what circumstances should surgery be recommended to improve tumor control and survival in patients with multiple brain metastases? Level 3: In patients with multiple brain metastases, tumor resection is recommended in patients with lesions inducing symptoms from mass effect that can be reached without inducing new neurological deficit and who have control of their cancer outside the nervous system.The full guideline can be found at https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_6.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Use of Stereotactic Radiosurgery in the Treatment of Adults With Metastatic Brain Tumors.

These recommendations apply to adult patients with new or recurrent solitary or multiple brain metastases from solid tumors as detailed in each section. Should patients with newly diagnosed metastatic brain tumors undergo stereotactic radiosurgery (SRS) compared with other treatment modalities? Level 3: SRS is recommended as an alternative to surgical resection in solitary metastases when surgical resection is likely to induce new neurological deficits, and tumor volume and location are not likely to be associated with radiation-induced injury to surrounding structures. Level 3: SRS should be considered as a valid adjunctive therapy to supportive palliative care for some patients with brain metastases when it might be reasonably expected to relieve focal symptoms and improve functional quality of life in the short term if this is consistent with the overall goals of the patient. What is the role of SRS after open surgical resection of brain metastasis? Level 3: After open surgical resection of a solitary brain metastasis, SRS should be used to decrease local recurrence rates. What is the role of SRS alone in the management of patients with 1 to 4 brain metastases? Level 3: For patients with solitary brain metastasis, SRS should be given to decrease the risk of local progression. Level 3: For patients with 2 to 4 brain metastases, SRS is recommended for local tumor control, instead of whole brain radiotherapy, when their cumulative volume is<7 mL. What is the role of SRS alone in the management of patients with more than 4 brain metastases? Level 3: The use of stereotactic radiosurgery alone is recommended to improve median overall survival for patients with more than 4 metastases having a cumulative volume<7 mL. The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_4.

Rapid effect of osimertinib re-challenge on brain metastases developing during salvage cytotoxic chemotherapy after osimertinib treatment failure: A case report.

We herein report a case of symptomatic brain metastases (BM) from lung adenocarcinoma in a 73-year-old female patient, which developed during salvage cytotoxic chemotherapy following failure of osimertinib treatment. The patient was proven to have a T790M mutation prior to osimertinib therapy, and achieved a clinical benefit from osimertinib for 3 years until the primary tumor progressed. Although active BM were not detected prior to initiating salvage cytotoxic chemotherapy, the patient developed numbness of the left hand, severe dizziness, and disturbance of behavior and thought after the 3-month course of the salvage cytotoxic chemotherapy. Brain magnetic resonance imaging revealed multiple BM with severe peritumoral brain edema. To avoid radiation-induced cognitive impairment, osimertinib re-challenge was undertaken. At 2 weeks after osimertinib initiation, the patient's neurological symptoms drastically improved. One month later, radiological evaluation revealed apparent shrinkage of the BM and subsiding brain edema, although the primary lung tumor remained stable. Therefore, osimertinib re-challenge may be a viable treatment option for BM developing during salvage cytotoxic chemotherapy.

Salvage Stereotactic Radiosurgery in Breast Cancer Patients with Multiple Brain Metastases

The overall survival rates for breast cancer are increasing due to controlled brain disease and improved systemic treatments. This study examined neurologic outcomes, tumor control, and survival data in breast cancer patients with multiple brain metastases and who required salvage stereotactic radiosurgery (SRS) for recurrent breast cancer brain metastases. The study included 231 patients with a primary diagnosis of breast cancer who underwent SRS for more than 1 brain metastases from May 1993 and July 2007. Survival analyses via univariate and multivariate Cox regression demonstrated interactions between survival and predictor values including Karnofsky Performance Scale, Recursive Partitioning Analysis Class, number of brain metastases, whole-brain radiotherapy (WBRT), immunotherapy, and chemotherapy. Of the 231 patients, the survival rate was 53% at 1 year and 26% at 5 years from initial SRS. Controlled systemic disease, adjuvant chemotherapy, and Recursive Partitioning Analysis class II were significant predictors of increased survival, while WBRT was a significant predictor of decreased survival. The median survival in patients who received WBRT after SRS was 11 months versus 23 months in those who did not. The local tumor control rate at initial follow-up was 95%. Of these, 40% of patients underwent additional brain SRS. Following salvage SRS, 8% of patients developed symptomatic adverse radiation events; however, the development of symptomatic adverse radiation events had no effect on patient survival. This report indicated that both initial and salvage SRS procedures in breast cancer patients with multiple brain metastases are effective for local control of intracranial disease while minimizing adverse radiation effects.

Robotic Radiosurgery for Brain Metastases Diagnosed With Either SPACE or MPRAGE Sequence (CYBER-SPACE)-A Single-Center Prospective Randomized Trial.

Stereotactic radiosurgery (SRS) of brain metastases (BM) is recommended in oligometastatic scenarios as a less toxic treatment alternative to whole-brain radiotherapy. Recent findings support SRS for patients with multiple (>3) BM. Furthermore, advances in MR imaging have facilitated the detection of very small BM, as advances in SRS technology have facilitated the highly conformal and simultaneous treatment of multiple target lesions. To compare efficacy and toxicity of repeated frameless robotic SRS of up to 10 simultaneous BM through a single-center prospective randomized trial. Two hundred patients will be randomized and receive imaging and treatment based on either the highly sensitive SPACE (sampling perfection with application optimized contrasts using different flip angle evolution) or the MPRAGE (magnetization-prepared rapid gradient-echo) magnetic resonance imaging sequence. If during follow-up new metastases are detected, treatment is repeated. The primary endpoint is reached when a patient develops more than 10 simultaneous new BM and is thus deemed unsuitable for further SRS. Overall survival will be assessed as secondary endpoint. Quality of life and neurocognition will be evaluated every 3 mo using CANTAB tests and EORTC (European Organisation for Research and Treatment of Cancer) questionnaires. We expect to show that repeated SRS based on sensitive imaging can delay intracranial dissemination while preserving neurocognitive function and quality of life. The present study is the first to prospectively assess the benefit of sensitive imaging and repeated stereotactic irradiation in the treatment of patients with multiple BM. It represents a novel approach, where in a palliative setting advanced technology in treatment and diagnostics is employed to improve tumor control while also reducing toxicity and preserving quality of life.

Brain Metastases from Ovarian Carcinoma: An Evaluation of Prognostic Factors and Treatment.

To review a series of patients with brain metastases from ovarian cancer at a single institution. To describe treatment modalities, their outcomes and to determine prognostic factors. Between January 1995 and December 2014, 25 patients with ovarian cancer brain metastases were treated at The Sheba Medical Center. The medical records were retrospectively reviewed to collect demographic, clinical, and imaging data as well as the information on the treatment modalities used and their outcomes. Mean patient age at the time of brain metastasis diagnosis was 62.7 years. The median interval between the diagnosis of primary cancer and brain metastasis was 42.3 months. Neurologic deficits, headache, and seizure were the most common symptoms. The brain was the only site of metastasis in 20% of the patients. Active ovarian cancer at the time of diagnosis of brain metastasis was observed in half of the patients with systemic disease. Multiple brain metastases were observed in 25% of the patients. We treated 11 patients with surgery plus radiation therapy protocols in various orders: surgery followed by complementary whole-brain radiation therapy (WBRT), surgery followed by stereotactic radiosurgery (SRS), and surgery followed by WBRT and then by adjuvant SRS. Five patients underwent surgery alone and nine patients were treated with radiation alone (WBRT, SRS, or both). Univariate analysis for predictors of survival demonstrated that age above 62.7 years at the time of central nervous system involvement was a significant risk factor and leptomeningeal disease was a poor prognostic factor in reference to supra-tentorial lesions. Multivariate analysis for predictors of survival, however, showed that multiple brain lesions (>4) were a poor prognostic factor, and multivariate analysis of the time to progression revealed that combined treatments of surgery and radiation resulted in longer median periods of progression-free survival than each modality alone. We conclude that the only significant predictors of survival or progression-free survival in our cohort were the number of brain metastases and the treatment modality.

Guidelines for Multiple Brain Metastases Radiosurgery.

Stereotactic radiosurgery (SRS) is an effective treatment for patients with multiple brain metastases. Three decades of increasingly powerful scientific studies have shown that SRS improves outcomes and reduces toxicity when it replaces whole-brain radiation therapy (WBRT). Expert opinion surveys of clinicians have reported that the total intracranial tumor volume rather than the number of brain metastases is related to outcomes. As a result, an increasing number of treating and referring physicians have replaced the reflex use of WBRT with SRS, unless the patient has miliary disease or carcinomatous meningitis. In the current era of immunotherapy and targeted therapies with potentially increased systemic disease survival, 10 or more tumors are routinely treated with SRS alone at most academic medical centers. In a single SRS session we routinely treat patients with cumulative tumor volumes of 25 cm3 even if they have ≥10 metastases.

First-line treatments for people with single or multiple brain metastases

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To compare the safety and efficacy of surgery, radiotherapy, and chemotherapy as first-line treatment for people with single or multiple brain metastases, either alone or in combination.