Radiotherapy For Brain Metastases Research Articles

Radiotherapy of brain metastases from breast cancer: Treatment results and prognostic factors.

Brain metastases (BM) from breast cancer are associated with high morbidity and a poor prognosis. The aim of this study was to analyse the role of radiotherapy in treatment of BM from breast cancer in the context of modern local therapy modalities, current systemic treatment options and prognostic factors. A retrospective analysis of 86 consecutive female patients treated with radiotherapy for BM from breast cancer between 2000 and 2010 was conducted. Patient and treatment characteristics were registered and survival data calculated. All patients received whole-brain radiotherapy (WBRT) with a median dose of 36 Gy, and 19 patients were treated with an additional boost; this included fractionated schemes (median dose, 18 Gy) and radiosurgery (5 and 17 Gy). The median overall survival time from the start of WBRT was 4.1 months in the present cohort. Patients receiving a boost survived 19.7 months in comparison to 3.1 months for patients treated with WBRT alone (P<0.001). Other factors that improved overall survival, based on a univariate analysis, were dose of WBRT and number of BM. There was no statistical evidence for the influence of the human epidermal growth factor receptor 2 status on survival in the current study. The administration of boost treatment following WBRT was also identified as a significant factor influencing survival on multivariate analysis (P=0.030). In conclusion, radiotherapy affects the survival time of patients with BM from breast cancer. In particular, the implementation of boost treatment following WBRT in selected patients seems to extend survival time.

Methods and results of local treatment of brain metastases in patients with breast cancer.

This article presents methods and results of surgical treatment and radiation therapy of brain metastases in breast cancer patients (brain metastases from breast cancer BMF-BC). Based on the literature data, it was shown that patients with single BMF-BC, aged less than 65 years, with Karnofsky score (KPS) of 70 or more and with cured or controlled extracranial disease are the best candidates to surgical treatment. Irrespective of the extracranial disease control status, there are indications for surgery in patients with symptomatic mass effect (tumour diameter larger than 3 cm) and patients with obstructive hydrocephalus from their BMF-BC. Stereotactic radiosurgery (SRS) has some advantages over surgery, with similar effectiveness: it may be used in the treatment of lesions inaccessible to surgery, the number of lesion is not a limiting factor if each lesion is small (< 3) and adequate doses can be delivered, it is not contraindicated in patients with active extracranial disease, it does not interfere with ongoing systemic treatment, and it does not require general anaesthesia or hospitalisation. A disadvantage of SRS, as compared to whole brain radiotherapy (WBRT), in patients with BMF-BC is the possibility of subsequent development of new lesion in the non-irradiated field. Thus the majority of the BMF-BC patients are not good candidates to surgery or SRS; WBRT alone or combined with a systemic treatment still plays a major role in the treatment of these patients.

Methods and results of locoregional treatment of brain metastases in patients with non-small cell lung cancer.

This article presents methods and results of surgery and radiotherapy of brain metastases from non-small cell lung cancer (BMF-NSCLC). Patients with single BMF-NSCLC, with Karnofsky score ≥ 70 and controlled extracranial disease are the best candidates for surgery. Stereotactic radiosurgery (SRS) is recommended in patients with 1–3 BMF-NSCLC below 3–3.5 cm, with minor neurological symptoms, located in parts of the brain not accessible to surgery, with controlled extracranial disease. Whole brain radiotherapy (WBRT) following SRS reduces the risk of local relapse; in selected patients median survival reaches more than 10 months. Whole brain radiotherapy alone is a treatment in patients with multiple metastases, poor performance status, uncontrolled extracranial disease, disqualified from surgery or SRS with median survival 3 to 6 months. There is no doubt that there are patients with BMF-NSCLC who should receive only the best supportive care. There is a debate in the literature on how to select these patients.

Expert Recommendations for First-Line Management of Metastatic Renal Cell Carcinoma in Special Subpopulations.

The availability of agents targeting the vascular endothelial growth factor or mammalian target of rapamycin [mTOR] pathways has provided new treatment options for patients with metastatic renal cell carcinoma (RCC). Based on the results of pivotal randomized clinical trials, specific recommendations have been established for management of these patients in first- and second-line settings. However, certain subgroups of patients may be excluded or under-represented in clinical trials, including patients with poor performance status, brain metastases, and cardiac or renal comorbidities, elderly patients, and those with non-clear cell histology. For these subpopulations, management recommendations have emerged from expanded access programs (EAPs), small phase II studies, retrospective analysis of clinical data, and expert opinion. This paper describes recommendations from an expert panel for the treatment of metastatic RCC in these subpopulations. The efficacy of targeted agents appears to be inferior in these patient subgroups relative to the general RCC population. Tyrosine kinase inhibitors (TKIs) and mTOR inhibitors can be administered safely to elderly patients and those with poor performance status, although dose and schedule modifications are often needed, and close monitoring and management of adverse events is essential. In addition to local surgical treatment and radiotherapy for brain metastases, systemic treatment with a TKI should be offered as part of multidisciplinary care.While there are currently no data from randomized trials, sunitinib has the greatest body of evidence, and it should be considered the first choice in patients with a good prognosis. Patients with an acute cardiac event within the previous 6 months, New York Heart Association grade III heart failure, or uncontrolled high blood pressure should not be treated with TKIs. In patients with mild or moderate renal failure, there are no contraindications to TKI treatment. TKIs can be administered to patients undergoing dialysis, but other, less nephrotoxic agents and other alternatives should always be considered.In managing RCC among patients with non-clear cell histology, sunitinib seems to be more effective than everolimus for the papillary subtype, but there are no clear data to guide treatment for other subtypes. In conclusion, individualized treatment approaches are needed to manage RCC in subpopulations that are underrepresented in registration clinical trials.

Impact of EGFR mutations and KRAS amino acid substitution on the response to radiotherapy for brain metastasis of non-small-cell lung cancer.

Our study aimed to evaluate response rate (RR) to brain metastasis radiotherapy (RT), depending on the genomic status of non-small-cell lung cancer. We retrospectively reviewed 1971 non-small-cell lung cancer files of patients with EGFR and KRAS testing and focused on 157 patients who had undergone RT for brain metastasis. A total of 16 patients (10.2%) harbored EGFR mutations (mEGFR) and 45 patients (28.7%) KRAS (mKRAS). In univariate analysis, RR was significantly higher for mEGFR compared with wild-type EGFR/KRAS (odds ratio [OR]: 4.96; p = 0.05) or mKRAS (OR: 1.81; p = 0.03). In multivariate analysis, KRAS G12V or G12C status was associated with both poor RR (OR: 0.1; p < 0.0001) and overall survival (OR: 3.41; p < 0.0001). mEGFR are associated with higher RR to brain RT than wild-type EGFR/RAS or mKRAS.

BMET-12SURVIVAL IN BREAST CANCER PATIENTS WITH BRAIN METASTASES AFTER GAMMA KNIFE STEREOTACTIC RADIOSURGERY

BACKGROUND: Recent studies have suggested a difference in outcome for breast cancer patients with brain metastases based on breast cancer subtype. These subtypes are defined as ER/PR+ and HER2- (luminal A), ER/PR+ and HER2+ (luminal B), ER/PR- and HER2- (triple-negative), and ER/PR- and HER2+ (HER2). The recently published modified Graded Prognostic Analysis (GPA) score for predicting overall survival (OS) in these patients includes subtype, number of CNS metastases, age, and performance status. We investigated whether this model was predictive of outcomes in these patients treated with Gamma Knife Stereotactic Radiosurgery (GKRS) at our institution and if any additional factors were predictive. METHODS: We reviewed all patients treated by GKRS for brain metastases from breast cancer at our institution from 2000 to 2014. Characteristics included subtype, age at breast cancer diagnosis, clinical stage, chemotherapy, age at diagnosis of brain metastases, Karnofsky Performance Status, years between breast cancer diagnosis and brain metastases, number of brain metastases, extracranial metastases, controlled primary tumor, type of treatment, and GPA score. OS was calculated using the Kaplan-Meier method and Cox regression analysis was performed to identify predictors. RESULTS: 61 patients were included. The majority of patients had luminal type. These patients were more likely to present with multiple metastases (p = 0.024). The median survival after treatment for the entire cohort was 16 months. We found no significant difference in survival based on subtype. According to GPA score, patients with the highest score had the best OS (p = 0.112). Multivariate analysis showed that stage II or III breast cancer at diagnosis, more than three brain metastases, and treatment with surgery and whole brain radiation for brain metastases were predictors for worse OS. CONCLUSION: In our cohort, breast cancer subtype is not a significant predictor for survival in these patients. The breast-cancer specific GPA was a good predictor of OS.

Local Control Following Postoperative Stereotactic Radiation Therapy for Brain Metastases

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiation therapy (FSRT) have emerged as viable alternatives to whole brain radiation therapy (WBRT) in patients with resected brain metastases. We performed a systematic review and quantitative analysis of the published experiences with adjuvant SRS and FSRT to determine local control (LC) rates and any relationship with dose-response, fractionation, and treatment delivery parameters. We identified published articles that reported local control rates following post-operative SRS or FSRT to the resection cavity in patients with brain metastases. For series in which uniform dosing schedules were used, biologically effective doses (BED) were calculated using the linear quadratic model and assuming an α/β ratio of 10 Gy. Local control data for the individual resection cavities treated in each study were extracted from actuarial survival curves and aggregated to form a single dataset. Kaplan-Meier curves for local control in the entire dataset and after grouping by treatment platform, fractionation, use of margin expansion, and BED were generated, and statistical comparisons were made using the log-rank test. Seventeen studies (1104 patients with 1155 resection cavities) met all inclusion criteria. Median dose for single fraction regimens was 14-20 Gy, while FSRT was used in 8 studies with regimens ranging from 9 Gy x 3 to 4 Gy x 10 (BED range of 41 Gy10 to 56 Gy10). One and two-year actuarial LC rates for the entire cohort were 83% and 75%, respectively. FSRT was associated with slightly higher one-year (87% v. 81%) and two-year (78% v. 73%) actuarial LC rates than SRS (p=0.049). For patients treated with SRS, use of Gamma Knife was associated with inferior LC compared to treatment with linear accelerator-based platforms (p=0.002). There was no association between use of a planning margin and LC. Most SRS series utilized a wide range of doses, so dose-response analysis could not be performed. In FSRT series, there was no significant association between BED and LC. The overall toxicity rate, which predominantly included radiation necrosis, was approximately 7% and not significantly different between treatment platforms or fractionation schemes. Adjuvant SRS and FSRT provide high rates of local control following resection of brain metastases. FSRT should be considered in cases where therapeutic doses cannot be safely delivered in a single fraction. Prospective trials are warranted to further characterize the optimal regimen and treatment parameters.

Local Control Following Fractionated Stereotactic Radiation Therapy for Brain Metastases

Local Control Following Fractionated Stereotactic Radiation Therapy for Brain Metastases

Efficacy of Stereotactic Radiation Therapy for Brain Metastases Using Dynamic Jaws Technology in the Helical Tomotherapy System: Planning and Clinical Studies

Efficacy of Stereotactic Radiation Therapy for Brain Metastases Using Dynamic Jaws Technology in the Helical Tomotherapy System: Planning and Clinical Studies

Update on the diagnosis and management of gestational trophoblastic disease.

Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow-up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histology type and regression rate. Low-risk GTN (FIGO Stages I-III: score 7 and Stage IV) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors.

Whole-brain radiation therapy for brain metastases: detrimental or beneficial?

Stereotactic radiosurgery is frequently used, either alone or together with whole-brain radiation therapy to treat brain metastases from solid tumors. Certain experts and radiation oncology groups have proposed replacing whole-brain radiation therapy with stereotactic radiosurgery alone for the management of brain metastases. Although randomized trials have favored adding whole-brain radiation therapy to stereotactic radiosurgery for most end points, a recent meta-analysis demonstrated a survival disadvantage for patients treated with whole-brain radiation therapy and stereotactic radiosurgery compared with patients treated with stereotactic radiosurgery alone. However the apparent detrimental effect of adding whole-brain radiation therapy to stereotactic radiosurgery reported in this meta-analysis may be the result of inhomogeneous distribution of the patients with respect to tumor histologies, molecular histologic subtypes, and extracranial tumor stages between the groups rather than a real effect. Unfortunately, soon after this meta-analysis was published, even as an abstract, use of whole-brain radiation therapy in managing brain metastases has become controversial among radiation oncologists. The American Society of Radiation Oncology recently recommended, in their “Choose Wisely” campaign, against routinely adding whole-brain radiation therapy to stereotactic radiosurgery to treat brain metastases. However, this situation creates conflict for radiation oncologists who believe that there are enough high level of evidence for the effectiveness of whole-brain radiation therapy in the treatment of brain metastases.

Stereotactic Radiosurgery for Metastases in Eloquent Central Brain Locations.

To examine stereotactic radiosurgery (SRS) following whole brain radiotherapy for metastases in eloquent, central brain locations: brainstem, thalamus, and basal ganglia. We conducted a retrospective review of patients with metastases in eloquent, central brain locations who were treated with SRS between January 2000 and April 2012. All patients had whole brain radiotherapy. Patients eligible for SRS had one to three brain metastases, metastasis size ≤4 cm, and Karnofsky performance status ≥70. Local progression-free survival and overall survival were calculated using the Kaplan-Meier method. For 24 patients, the median age was 50 years (range, 36-73). Metastases by location were: 11 brainstem, 9 thalamus, and 5 basal ganglia. The median metastasis size was 15 mm (range, 2-33) and the median SRS dose prescription was 15 Gy (range, 12-24). The median local progression-free survival was 13.7 months and median overall survival was 16.4 months. Compared with a cohort of 188 patients with noneloquent brain metastases receiving a median dose of 24 Gy, overall survival of 10.8 months was not significantly different (p=0.16). The only symptomatic complication was grade 2 headache in 8.3%. Asymptomatic adverse radiologic events were radionecrosis in two (8.3%), peritumoural edema in four (16.7%), and hemorrhage in one patient (4.2%). Lower SRS marginal doses do not appear to compromise survival in patients with eloquently located brain metastases compared with higher doses for other brain metastases, with minimal symptomatic complications.

OC-0059: Validated clinical model for survival prediction after stereotactic radiotherapy for brain metastases

OC-0059: Validated clinical model for survival prediction after stereotactic radiotherapy for brain metastases

Metastatic Malignant Phyllodes Tumor of the Breast: An Aggressive Disease-Analysis of 7 Cases.

Malignant phyllodes tumor (PT) of the breast behaves aggressively and the presentation of distant metastases is varied, ranging from synchronous or short interval commonly to a decade rarely. To assess the clinical and temporal pattern of distant metastases in malignant PTs. A retrospective analysis of patients with Phyllodes tumor of the breast from January, 2001 to November, 2014. There were a total of 167 patients with PT; 49 (29%) were malignant PT out of which 7 developed distant metastases. Detailed analysis of these 7 patients showed that mean age was 36.71years (range 28-53years). Three of the seven patients had additional local recurrences post lumpectomy. The procedure performed were wide local excision with muscle reconstruction (n = 1), lumpectomy (n = 1) and mastectomy (n = 5). The distant metastases were synchronous (n = 2) and other 5 had metastases developing within 2months to 13years. The sites for distant metastases included lung, brain, adrenal, para-aortic nodes and bone. Six patients received palliative chemotherapy (CT) and 2 also had radiation therapy for brain metastasis. Only 1 patient is alive and receiving CT and all others succumbed to the disease. Patients with malignant PT of the breast with distant metastases behave aggressively and have a dismal outcome with rare exceptions. They need multimodality therapy and close follow up. Newer targeted therapies may have a role to improve the outcome.

Radiotherapy for brain metastases in southern Thailand: workload, treatment pattern and survival.

To study the patient load, treatment pattern, survival outcome and its predictors in patients with brain metastases treated by radiotherapy. Data for patients with brain metastases treated by radiotherapy between 2003 and 2007 were collected from medical records, the hospital information system database, and a population-based tumor registry database until death or at least 5 years after treatment and retrospectively reviewed. The number of treatments for brain metastases gradually increased from 48 in 2003 to 107 in 2007, with more than 70% from lung and breast cancers. The majority were treated with whole brain radiation of 30 Gy (3 Gy X 10 fractions) by cobalt-60 machine, using radiation alone. The overall median survival of the 418 patients was 3.9 months. Cohort analysis of relative survival after radiotherapy was as follows: 52% at 3 months, 18% at 1 year and 3% at 5 years in males; and 66% at 3 months, 26% at 1 year and 7% at 5 years in females. Multivariate analysis demonstrated that the patients treated with combined modalities had a better prognosis. Poor prognostic factors included primary cancer from the lung or gastrointestinal tract, emergency or urgent consultation, poor performance status (ECOG 3-4), and a hemoglobin level before treatment of less than 10 g/dl. This study identified an increasing trend of patient load with brain metastases. Possible over-treatment and under-treatment were demonstrated with a wide range of survival results. Practical prognostic scoring systems to assist in decision-making for optimal treatment of different patient groups is absolutely necessary; it is a key strategy for balancing good quality of care and patient load.

Statin use in cancer patients with brain metastases: a missed communication opportunity at the end of life.

Preventive care, referring to medical interventions with anticipated long-term benefits, is often inappropriately continued near the end of life. We examined the use of statin medications in patients with brain metastases receiving whole brain radiation therapy to determine the effect of short life expectancy and regular interaction with oncology providers on statin discontinuation. We propose reasons for the unnecessary continuation of preventive care and suggest that it is a frequently missed communication opportunity to discuss prognosis in a concrete manner. This is a retrospective study examining statin use in patients receiving whole brain radiotherapy for brain metastases. A total of 206 patients at two cancer centers were studied, and information on statin use and clinical characteristics was obtained from review of the medical record. Of the 206 patients, 53 (26 %) were on a statin at their initial radiation oncology consultation. Of these patients, 13 (25 %) had their statin discontinued by the time of their last follow-up visit, but 40 patients (75 %) were continued on their statin despite their limited life expectancy and low likelihood of benefit. The majority of patients who were on statins prior to starting palliative whole brain radiation therapy remained on a statin after completing treatment despite an estimated survival of months and regular visits with an oncologist. This represents a missed opportunity for doctors and patients to discuss the appropriateness of continuing preventive care as part of an important conversation about prognosis.

Considerations on the Management of EGF Receptor-TKIs For Brain Metastases In EGFR -Mutant Lung Carcinoma Patients

SUMMARY Approximately 20–30% of patients with NSCLC are present with brain metastases. The standard management for brain metastases is radiotherapy. Despite the administration of radiation therapy for brain metastases, the prognosis is still poor. The poor prognosis is related to the progression of extracranial lesions. Therefore, systemic therapy is important to improve survival of patients with brain metastases. EGF receptor-tyrosine kinase inhibitor (EGFR-TKI) is a standard treatment for advanced NSCLC patients with sensitive EGFR mutations and is also effective in controlling brain metastasis in such patients. Upfront EGFR-TKI therapy might be one of the treatment choices for EGFR-mutant NSCLC patients with asymptomatic brain metastases. However, it is unclear whether upfront EGFR-TKI or radiation therapy is more preferable. New EGFR-TKIs and combination with existing EGFR-TKIs and other drugs are being investigated for treatment options. Further investigations are required to determine the future direction for management of EGFR-mutant NSCLC patients with brain metastasis.

A Case of Adjuvant Treatment with Sorafenib after Radiotherapy for Brain Metastasis from Poorly Differentiated Thyroid Carcinoma

A Case of Adjuvant Treatment with Sorafenib after Radiotherapy for Brain Metastasis from Poorly Differentiated Thyroid Carcinoma

Radiosurgery and Stereotactic Radiotherapy for Brain Metastases According the New Prognostic Indexes: our Preliminary Experience

Purpose: This work is a retrospective analysis of our experience in the treatment of patients with BMs using SRS or SRT with Cyberknife ® (CK) system (Accuray Inc., Sunnyvale, California, USA). The aim is to evaluate the local control of disease and overall survival according to modern prognostic indices. Material and methods: From November 2012 to March 2014, we treated 116 patients, (178 brain metastases), with CK system, an image-guided frameless robotic SRS/SRT. We stratified the patients according to the Diagnosis- Specific GPA (DS-GPA) and we treated patients with a single fraction (10-24 Gy) in 72%, with two fractions (18-21 Gy) in 3%, with three fractions (18-24 Gy) in 23%, with five fractions (20-25Gy) in 2%. The dose was prescribed to 80% isodose line. All patients were evaluated with clinical and radiological follow-up using MRI every 2 months. We calculated the local tumor control rate according with RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Results: Percentage of complete remission, partial remission, stable disease, was: 38% in NSCLC (Non-smallcell lung carcinoma) (16% in classes with best score), 28% in Melanoma (all in classes with best score), 52% in breast (43% in classes with best score). We noted a similar result for partial remission and stable disease, particularly in Melanoma and Breast cancer, who have a higher percentage of PR (partial response) and SD (stable disease) of 33- 23%, and in Melanoma of 40-50% in classes with higher scores. Conclusions: we confirm the precious contribution of the DS-GPA in correct selection of patients with brain metastases, and encourage the use of special technologies in properly selected patients.

Epworth Sleepiness Scale- a novel tool to assess somnolence syndrome in patients receiving radiotherapy to the brain

Purpose: Radiation to brain causes early, early-delayed, and delayed side effects. There is paucity of literature regarding early-delayed effects like somnolence syndrome. Existing studies use general symptom assessment and visual analog scales. Epworth Sleepiness Scale (ESS) is a time tested tool to assess daytime sleepiness in various conditions. In this study, the ESS has been used to determine the occurrence of somnolence in patients receiving cranial radiotherapy for primary and metastatic brain tumors. Thus the ESS has been used in a novel setting in our study. The ESS is a simple to administer questionnaire and may be useful in grading the severity of somnolence. To our knowledge, this is the second study to determine post radiation somnolence using ESS. Methods: This prospective study was conducted in 23 patients with primary and metastatic brain tumor. Patient demographics and tumor type and grade was noted. Those with Karnofsky Performance Scale (KPS) less than 70 and with pre-existing sleep disorders were excluded. Radiotherapy regimen included palliative whole brain radiation for brain metastases and conformal adjuvant radiotherapy for primary brain tumors as per standard guidelines. All subjects included were administered ESS at baseline and weekly thereafter during and for 6 weeks after radiation. Results: All 23 patients (median age 50 years) completed the planned questionnaires until 6 weeks post radiation. Twenty (87%) patients had primary brain tumors whereas three (13%) patients had metastatic lesions in brain. Of the 23 patients, 14 patients (60.86%) had abnormal or increased daytime sleepiness; of which 3 had ESS scores greater than 16. Conclusion: Somnolence was noted in 60.86% of the patients, which is in accordance with existing literature. Epworth sleepiness scale is an effective tool to detect and quantify somnolence, However, it does not consider other symptoms of somnolence syndrome and hence should be combined with visual analog scale to get complete information.