Treatment Option For Brain Metastases Research Articles

Is stereotactic radiosurgery a rational treatment option for brain metastases from small cell lung cancer? A retrospective analysis of 70 consecutive patients.

BackgroundBecause of the high likelihood of multiple brain metastases (BM) from small cell lung cancer (SCLC), the role of focal treatment using stereotactic radiosurgery (SRS) has yet to be determined. We aimed to evaluate the efficacy and limitations of upfront and salvage SRS for patients with BM from SCLC.MethodsThis was a retrospective and observational study analyzing 70 consecutive patients with BM from SCLC who received SRS. The median age was 68 years, and the median Karnofsky performance status (KPS) was 90. Forty-six (66%) and 24 (34%) patients underwent SRS as the upfront and salvage treatment after prophylactic or therapeutic whole brain radiotherapy (WBRT), respectively. Overall survival (OS), neurological death-free survival, remote and local tumor recurrence rates were analyzed.ResultsNone of our patients were lost to follow-up and the median follow-up was 7.8 months. One-and 2-year OS rates were 43% and 15%, respectively. The median OS time was 7.8 months. One-and 2-year neurological death-free survival rates were 94% and 84%, respectively. In total, 219/292 tumors (75%) in 60 patients (86 %) with sufficient radiological follow-up data were evaluated. Six-and 12-month rates of remote BM relapse were 25% and 47%, respectively. Six-and 12-month rates of local control failure were 4% and 23%, respectively. Repeat SRS, salvage WBRT and microsurgery were subsequently required in 30, 8 and one patient, respectively. Symptomatic radiation injury, treated conservatively, developed in 3 patients.ConclusionsThe present study suggested SRS to be a potentially effective and minimally invasive treatment option for BM from SCLC either alone or after failed WBRT. Although repeat salvage treatment was needed in nearly half of patients to achieve control of distant BM, such continuation of radiotherapeutic management might contribute to reducing the rate of neurological death.

Radiation Therapy in the Management of Patients With Limited Brain Metastases

Brain metastases are the most common form of intracranial tumor in adults and an increasingly important cause of morbidity and mortality. Rising incidence is attributed to advanced radiographic imaging and prolonged survival due to improvements in cancer therapy (including systemic therapies) that are not as effective in treating intracranial disease. Standard treatment options for brain metastases include resection, whole-brain radiation therapy (WBRT), stereotactic radiosurgery, or a combination of these modalities. Most patients with brain metastases receive some form of radiation therapy during the course of their illness, and for the majority of them, the prognosis is poor and WBRT remains the standard. However, within this very diverse patient population, subgroups exist in which prolonged survival is possible. In recent years, several randomized controlled trials have clearly demonstrated the efficacy of stereotactic radiosurgery in well-selected patients. This, along with an increased recognition of the late neurocognitive effects of WBRT, has led many to question the role of upfront WBRT in patients with limited intracranial metastases. In this review, we summarize the evolving role of radiotherapy in the management of brain metastases and then discuss the issues related to neurotoxicity from radiation and future areas of investigation.

Gene silencing of c-Met leads to brain metastasis inhibitory effects

An unfortunate consequence of improvements in the treatments of advanced primary cancers is the concurrent increase of metastatic brain tumors. Despite of unfavorable clinical prognosis, radiation therapy is still the only viable treatment option for brain metastases. Expression of c-Met induces cell migration and invasion in many cancers, which are indispensable steps for metastasis. Accordingly, we examined the effects of gene silencing of c-Met on brain metastasis to evaluate the possibility of c-Met as a potential target. MDA-MB-435 cells were transfected with c-Met targeting short hairpin RNAs (shRNAs). Effects of c-Met shRNAs on the expression of epithelial mesenchymal transition (EMT) related proteins, in vitro migration, and in vivo brain metastasis were examined. Expression of mesenchymal markers and in vitro migration of MDA-MB-435 cells were significantly inhibited by introduction of c-Met shRNAs. When c-Met-silenced MDA-MB-435 cells were stereotactically implanted into the brains of immune-compromised mice or injected into the right internal carotid arteries, c-Met-silenced MDA-MB-435 cells produced significantly smaller tumor masses or survival time was significantly prolonged, respectively, compared with MDA-MB-435 cells transfected with control shRNA. The data reveal the novel function of c-Met in the process of brain metastasis and its potential as a preventive and/or therapeutic target in this disease.

Abstract C52: Gene silencing of c-met leads to brain metastasis inhibitory effects

Abstract An unfortunate consequence of improvements in the treatments of advanced primary cancers is the concurrent increase of metastatic brain tumors. Despite of unfavorable clinical prognosis, radiation therapy is still the only viable treatment option for brain metastases. Expression of c-Met induces cell migration and invasion in many cancers, which are indispensable steps for metastasis. Accordingly, we examined the effects of gene silencing of c-Met on brain metastasis to evaluate the possibility of c-Met as a potential target. MDA-MB-435 cells were transfected with c-Met targeting short hairpin RNAs (shRNAs). Effects of c-Met shRNAs on the expression of epithelial mesenchymal transition (EMT) related proteins, in vitro migration, and in vivo brain metastasis were examined. Expression of mesenchymal markers and in vitro migration of MDA-MB-435 cells were significantly inhibited by introduction of c-Met shRNAs. When c-Met-silenced MDA-MB-435 cells were stereotactically implanted into the brains of immune-compromised mice or injected into the right internal carotid arteries, c-Met-silenced MDA-MB-435 cells produced significantly smaller tumor masses or survival time was significantly prolonged, respectively, compared with MDA-MB-435 cells transfected with control shRNA. The data reveal the novel function of c-Met in the process of brain metastasis and its potential as a preventive and/or therapeutic target in this disease. Citation Format: Se Jeong Lee, Hye Won Lee, Mi Young Song, Kee Hang Lee, Young-Eun Lee, Kyeung Min Joo. Gene silencing of c-met leads to brain metastasis inhibitory effects. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C52.

Nearly Complete Response of Brain Metastases from HER2 Overexpressing Breast Cancer with Lapatinib and Capecitabine after Whole Brain Irradiation.

Trastuzumab treatment does not prevent intracranial seeding and is largely ineffective for established central nervous system metastasis in HER2 overexpressing breast cancer patients. Combination therapy of lapatinib and capecitabine may be an effective treatment option for brain metastasis of HER2-positive breast cancer. We report a patient with breast cancer overexpressing HER-2 where brain metastases were successfully treated with radiation and a combination of lapatinib and capecitabine.

New challenges and opportunities in the management of brain metastases in patients with ErbB2-positive metastatic breast cancer

The introduction of trastuzumab for the treatment of tumors that overexpress ErbB2 (also known as HER2) has contributed significantly to recent improvements in systemic therapy for advanced breast cancer. The advances in systemic therapy have highlighted an increasing prevalence of central nervous system involvement in patients with ErbB2-positive breast cancer and a consequent need for new treatment options for brain metastases. Just as ErbB2-targeted systemic therapy has given rise to this challenge, so too could targeted therapy represent an opportunity to meet it. This Review considers the potential for targeted therapy to facilitate effective management of brain metastases in patients with ErbB2-positive breast cancer, and discusses in particular the data currently available in this setting for lapatinib, an orally available small-molecule tyrosine kinase inhibitor of ErbB1 and ErbB2.

Radiosurgery in the treatment of brain metastases: critical review regarding complications

Stereotactic radiosurgery (SRS) has been described as an effective treatment option for brain metastases. In general, SRS has been indicated for the treatment of lesions smaller than 3 cm in maximum diameter and for lesions considered not surgically treatable, owing to the patient's clinical status or because the lesion was located in or near eloquent brain areas. In several studies, SRS has been associated with clinical and radiographic improvement of the lesions and has been compared with surgery as the modality of choice for brain metastases. Beyond the high rate of local disease control with SRS, the few complications that have been described occurred mainly in the acute post treatment period. Most publications have addressed the outcome and effectiveness of this treatment modality but have not critically analyzed long-term complications, steroid dependency, or results relating to specific brain locations. It is important to understand the radiobiologic effects of a well-demarcated high dose of radiation on the brain lesion, controlling the tumor growth and not causing significant alteration of the related brain region, especially in an area controlling eloquent function.

Diagnosis and management of central nervous system metastases from breast cancer.

The brain, cranial nerves, leptomeninges, spinal cord, and eye compose the central nervous system (CNS) and are at risk for the development of metastases from breast cancer. Such metastases are diagnosed on the basis of clinical suspicion and substantiated by neuroimaging, resection when indicated, and sampling of cerebrospinal fluid when leptomeningeal metastasis (LM) is suspected. Treatment is aimed at palliation of symptoms and preservation of neurologic function. Historically, conventional radiation therapy has been the mainstay of palliative treatment for brain, cranial nerve, spinal cord, and ocular metastases. However, additional treatment options for brain metastases have been brought about by technological advances in surgery to resect brain metastases, and stereotactic radiosurgery (SRS) to focally irradiate metastases, both of which have been substantiated by data from randomized trials. Ongoing research is aimed at refining criteria to select which patients with brain metastases should undergo surgery and SRS and how these focal therapies should be optimally integrated with whole-brain radiotherapy. Therapy for LM must carefully balance the potential risks and perceived benefits associated with CNS-directed therapies. Despite advances in neuroimaging, surgery, and radiation therapy, novel treatments are needed to improve the effectiveness of treatments for CNS metastases, especially LM, while reducing attendant neurotoxicity.

Treatment options for brain metastases in patients with non-small-cell lung cancer.

Brain metastases are a common complication for patients with non-small-cell lung cancer and a significant cause of morbidity and mortality. In the past, treatment of brain metastases and lung cancer focused on symptom palliation with whole-brain radiotherapy (WBRT) and steroids because of the grim outlook for patients. However, recent advances in technology and surgical techniques have created more options for the management of brain metastases, which include surgery, irradiation, stereotactic radiosurgery, and chemotherapy. These aggressive approaches have resulted in an improvement of neurologic outcomes and survival rates of patients with non-small-cell lung cancer. Central nervous system (CNS) metastases can be divided into three groups: solitary CNS metastases with controlled or controllable primary disease, oligometastatic disease (fewer than 3 metastases), and multiple metastases. For patients with solitary CNS metastases, long-term survival is possible. A radical treatment approach involving surgical resection or radiosurgery, followed by WBRT, is recommended. For patients with oligometastatic disease, surgical resection or radiosurgery is considered in selected cases and WBRT is indicated. For patients with multiple metastases, WBRT is recommended. For patients with oligometastatic disease and those with multiple metastases, recent evidence indicates that systemically effective chemotherapy may produce responses and can be instituted safely before radiotherapy. The treatment timing of chemotherapy and radiotherapy should be individualized.

Treatment options for brain metastases in patients with non-small cell lung cancer.

Brain metastases are a common complication for patients with non-small cell lung cancer and a significant cause of morbidity and mortality. In the past, treatment of brain metastases and lung cancer focused on symptom palliation with whole brain radiotherapy (WBRT) and steroids because of the grim outlook for patients. However, recent advances in technology and surgical techniques have created more options for the management of brain metastases, which include surgery, irradiation, stereotactic radiosurgery, and chemotherapy. These aggressive approaches have resulted in an improvement of neurologic outcomes and survival rates of patients with non-small cell lung cancer. Central nervous system (CNS) metastases can be divided into three groups: solitary CNS metastases with controlled or controllable primary disease, oligometastatic disease (fewer than three metastases), and multiple metastases. For patients with solitary CNS metastases, long-term survival is possible. A radical treatment approach involving surgical resection or radiosurgery, followed by WBRT, is recommended. For patients with oligometastatic disease, surgical resection or radiosurgery is considered in selected cases and WBRT is indicated. For patients with multiple metastases, WBRT is recommended. For patients with oligometastatic disease and patients with multiple metastases, recent evidence indicates that systemically effective chemotherapy may produce responses and can be instituted safely before radiotherapy. The treatment timing of chemotherapy and radiotherapy should be individualized.