Poor prognostic indicators for patients treated with radiosurgery for brain metastases.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 32-32 ◽  
Author(s):  
Michael A Garcia ◽  
Wendy Anderson ◽  
Shannon E. Fogh ◽  
Jean L. Nakamura ◽  
Philip Theodosopoulos ◽  
...  
Keyword(s):  
Brain Metastases ◽  
San Francisco ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Whole Brain Radiotherapy ◽  
Median Number ◽  
Prognostic Indicators ◽  
Imaging Data ◽  
Primary Tumors ◽  
Brain Radiotherapy

32 Background: Radiosurgery (SRS) is a standard palliative treatment for patients with limited number of brain metastases. Growing evidence supports the use of SRS for more extensive disease. As SRS is increasingly used in advanced cancer, we sought to identify predictors of survival after SRS to help better inform patients about prognosis. Methods: We reviewed patients treated with SRS for brain metastases at the University of California, San Francisco (UCSF) from Jan 2010-Dec 2013. Before SRS, all patients were screened for appropriateness of SRS at a multidisciplinary conference. Post-SRS overall survival (OS) was estimated by Kaplan-Meier method and compared by log-rank tests. Frequencies of death within 30 days of SRS were compared by chi-squared tests. Results: Demographic and imaging data was available for 326 SRS patients. At SRS consult, 90% patients were Karnofsky Performance Status (KPS) ≥ 70. Median number of brain metastases at consult was 2 (range 1-37). Median follow up was 13 months. Median OS after SRS was 11 months. Median OS was shorter for patients with KPS < 70 (4 months) compared to those with KPS ≥ 70 (12 months) (p < 0.001). Overall, frequency of death within 30 days of SRS was 5.4%. Within 30 days of SRS, 13% of patients with KPS < 70 died compared to 3.8% with KPS ≥ 70 (p = 0.03). Death within 30 days of SRS was more common among patients with uncontrolled (10%) versus controlled primary tumors (3%) (p = 0.02). Both uncontrolled primary tumor and KPS < 70% were associated with death within 30 days of SRS on multivariate analysis (p = 0.02 and p = 0.03, respectively). Patients with both KPS < 70 and uncontrolled primary tumors had frequency of death within 30 days of 29%. Factors not associated with death within 30 days were age, extracranial metastatic disease burden, histology, number of brain metastases, prior whole brain radiotherapy, SRS, or neurosurgery. Conclusions: Death within 30 days of SRS within the UCSF cohort is uncommon, likely due to multidisciplinary screening for patients expected to live long enough to benefit from SRS. Most patients who die within 30 days of SRS have both KPS < 70 and uncontrolled primary tumors. The potential for poor prognosis should be discussed with these patients during shared-decision making.

scholarly journals Adjuvant Whole-Brain Radiotherapy Versus Observation After Radiosurgery or Surgical Resection of One to Three Cerebral Metastases: Results of the EORTC 22952-26001 Study

2011 ◽  
Vol 29 (2) ◽  
pp. 134-141 ◽  
Author(s):  
Martin Kocher ◽  
Riccardo Soffietti ◽  
Ufuk Abacioglu ◽  
Salvador Villà ◽  
Francois Fauchon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Systemic Disease ◽  
Performance Status ◽  
Whole Brain Radiotherapy ◽  
Functional Independence ◽  
Phase Iii ◽  
Whole Brain ◽  
Primary Tumors ◽  
Brain Radiotherapy

Purpose This European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after surgery or radiosurgery of brain metastases. Patients and Methods Patients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2. Results Of 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm. Conclusion After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.

Prospective evaluation of the palliative effect of whole-brain radiotherapy in patients with brain metastases and poor performance status

2010 ◽  
Vol 49 (3) ◽  
pp. 382-388 ◽  
Author(s):  
Katarzyna Komosinska ◽  
Lucyna Kepka ◽  
Anna Niwinska ◽  
Lucyna Pietrzak ◽  
Marek Wierzchowski ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Performance Status ◽  
Whole Brain Radiotherapy ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Prospective Evaluation ◽  
Whole Brain ◽  
Brain Radiotherapy

Multidisciplinary Approach to Brain Metastasis from Melanoma: The Emerging Role of Systemic Therapies

2013 ◽  
pp. 393-398 ◽  
Author(s):  
Georgina V. Long ◽  
Kim A. Margolin
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Brain Radiotherapy ◽  
First Line Therapy ◽  
Melanoma Brain Metastases

Melanoma brain metastases are common, difficult to treat, and carry a poor prognosis. Until recently, systemic therapy was ineffective. Local therapy (including surgery, stereotactic radiotherapy, and whole brain radiotherapy) was considered the only option for a chance of disease control in the brain, and was highly dependent on the patient's performance status and age, number and size of brain metastases, and the presence of extracranial metastases. Since 2010, three drugs have demonstrated activity in progressing or “active” brain metastases including the anti-CTLA4 antibody ipilimumab (phase II study of 72 patients), and the BRAF inhibitors dabrafenib (phase II study of 172 patients, both previously treated and untreated brain metastases) and vemurafenib (a pilot study of 24 patients with heavily pretreated brain metastases). The challenge and unanswered question for clinicians is how to sequence all the available therapies, both local and systemic, to optimize the patient's quality of life and survival. This is an area of intense clinical research. The treatment of patients with melanoma brain metastases should be discussed by a multidisciplinary team of melanoma experts including a neurosurgeon, medical oncologist, and radiation oncologist. Important clinical features that help determine appropriate first line therapy include single compared with solitary brain metastasis, resectablity, BRAF mutation status of melanoma, rate of progression/performance status, and the presence of extracranial disease.

scholarly journals Management of lung cancer brain metastasis: An overview

2017 ◽  
Vol 03 (02) ◽  
pp. 121-127
Author(s):  
Himanshu Srivastava ◽  
Preety Negi ◽  
Pamela Alice Kingsley ◽  
Jaineet Sachdeva
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Brain Metastases ◽  
Receptor Gene ◽  
Performance Status ◽  
Whole Brain Radiotherapy ◽  
Combined Modality Treatment ◽  
Whole Brain ◽  
Anaplastic Lymphoma ◽  
Brain Radiotherapy

AbstractWith the improvements in systemic treatment for lung cancer, distant metastasis to sanctuary sites such as brain has become an increasingly more important issue. The management of these patients consists of supportive care and disease-directed treatment. Combined modality treatment (surgical resection or radiosurgery, followed by whole brain radiotherapy) of brain metastases has greatly improved the local control of disease in patients with single lesion, good functional performance status, and controlled extracranial disease as demonstrated in prospective randomized studies. For patients with multiple brain metastases, conventional fractionated whole brain radiotherapy continues to be a standard and efficacious treatment. At present, experience with the use of molecularly targeted tyrosine kinase inhibitors in nonsmall cell lung cancer patients with activating mutations in the epidermal growth factor receptor gene and anaplastic lymphoma kinase gene is growing. However, their effectiveness in patients with brain metastases is not well established. In the arena of targeted therapies, vascular endothelial growth factor pathway inhibitors such as bevacizumab have shown some activity in brain metastases. Further prospective studies are necessary to facilitate selection of patient subpopulation for targeted agents in future studies.

Palliative whole brain radiotherapy: Predictors of prescribing 5 versus 10 fractions.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 219-219
Author(s):  
Adele Duimering ◽  
Sarah Baker ◽  
Kim Paulson ◽  
Brock J Debenham ◽  
Sunita Ghosh ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Whole Brain Radiotherapy ◽  
Binary Logistic Regression ◽  
Optimal Dose ◽  
Dose Fractionation ◽  
Disease Extent ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Practice Methods

219 Background: The optimal dose for palliative whole brain radiotherapy (WBRT) continues to be debated. Common regimens include 20 Gy in five and 30 Gy in 10 fractions. We aimed to identify factors associated with WBRT dose schedules, hypothesizing that clinical prediction of survival (CPS) would influence prescribing practice. Methods: Demographic and clinicopathologic data were collected for consecutive patients with brain metastases receiving WBRT through a dedicated palliative radiation oncology clinic. At initial consultation, CPS were prospectively collected from treating radiation oncologists. Karnofsky performance status (KPS) and Mini-Mental Status Examination were available for 88.6% and 75.1%, respectively. Dose fractionation was collected and summary statistics calculated. Parameters were assessed for association with five fraction schedules using binary logistic regression, with odds ratios and 95% CI reported. Results: 193 patients underwent WBRT (N = 102 from 2010-2012; N = 91 from 2013-2014); 38/193 had 48 extracranial sites irradiated concurrently. 46.1% were male, mean age was 64.7 years (SD 11.6), and 63.7% had lung cancer. Median KPS was 70 (range 20-100) and median MMSE score was 27/30 (range 13-30). Median CPS and actual survival were 150 days (range 21-730d) and 96 days (range 11-1029d), respectively. 18.7% received WBRT within 30 days of death. 78.2% (151/193) and 17.6% (34/193) received five and 10 fractions, respectively; 8/193 were prescribed other schedules. On multivariate analysis, patients with KPS ≤ 70 were 5.93 times more likely to have received 5-fractions (95% CI 2.51-14.1; p < 0.0001). Those treated 2010-2012 were less likely to have received 5 fractions (OR 0.28; 95% CI 0.11-0.68; p = 0.005). CPS, age, gender, MMSE, histology, disease extent, and extracranial irradiation were not predictive of WBRT schedule. Conclusions: Patients treated with WBRT with KPS ≤70 and those treated more recently were more likely to receive five fractions. Oncologist CPS was not a statistically significant predictor of schedule in this cohort.

scholarly journals RADI-21. STEREOTACTIC RADIOSURGERY FOR 10 OR MORE BRAIN METASTASES PROVIDES EXCELLENT RATES OF INTRACRANIAL DISEASE CONTROL WITH SUPERIOR HIPPOCAMPAL SPARING

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i25-i26
Author(s):  
Matthew Susko ◽  
Michael Garcia ◽  
Lijun Ma ◽  
Jean Nakamura ◽  
David Raleigh ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Radiation Effect ◽  
Whole Brain Radiotherapy ◽  
Median Number ◽  
Salvage Treatment ◽  
Single Institution ◽  
Brain Radiotherapy ◽  
Metastatic Lesions ◽  
Hippocampal Sparing

Abstract BACKGROUND: Recent evidence supports hippocampal sparing during whole brain radiotherapy (HS-WBRT) to improve neurocognitive outcomes in patients with brain metastases (BM). This study sought to quantify the hippocampal dosimetry and treatment efficacy of stereotactic radiosurgery (SRS) to 10 or greater BM to clarify the roles of SRS and WBRT. METHODS: Patients at a single institution treated with SRS to 10 or more BM without WBRT from 1999 to 2016 were retrospectively reviewed. Treatment-related outcomes including overall survival (OS), freedom from progression (FFP), freedom from new metastases (FFNM), and adverse radiation effect (ARE) were quantified. Hippocampal volumes were retrospectively delineated and dosimetry was evaluated in patients treated with upfront SRS. RESULTS: 143 patients with a total of 2198 lesions met criteria for inclusion with 75 patients treated with upfront SRS and 68 treated as salvage from prior WBRT. Median age was 57 (IQR: 46–65) and median KPS 80 (IQR: 70–90). Histologies included breast (n=52), lung (n=49), melanoma (n=30), and other (n=12). Median number of lesions per patient was 13 (IQR 11–17) with median total volume of treatment of 4.1 cc (IQR 2.0–9.9). 12-month FFP per lesion for upfront and salvage treatment was 96.8% (95% CI: 95.5–98.1) and 83.6% (95% CI: 79.9–87.5) respectively (p &lt; 0.001). 12-month FFNM for upfront and salvage FFSRS was 18.8% (95% CI: 10.9–32.3) versus 19.2% (95% CI: 9.7–37.8) respectively (p = 0.90). Mean hippocampal dose was 150 cGy (IQR 100–202). Symptomatic ARE was observed in 2% of patients or 1% of treated lesions. CONCLUSIONS: High rates of local control can be achieved when treating patients with greater than 10 BM with hippocampal doses that are dramatically lower than for HS-WBRT. Hippocampal sparing is readily achievable with expected rates of new metastatic lesions developing in treated patients with low rates of symptomatic ARE.

scholarly journals Heart Rate Variability Is Associated with Survival in Patients with Brain Metastasis: A Preliminary Report

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yu-Ming Wang ◽  
Hau-Tieng Wu ◽  
Eng-Yen Huang ◽  
Yu Ru Kou ◽  
Shu-Shya Hseu
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Brain Metastasis ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Univariate Analysis ◽  
Whole Brain Radiotherapy ◽  
Final Analysis ◽  
Brain Radiotherapy ◽  
Hazard Ratios

Impaired heart rate variability (HRV) has been demonstrated as a negative survival prognosticator in various diseases. We conducted this prospective study to evaluate how HRV affects brain metastasis (BM) patients. Fifty-one BM patients who had not undergone previous brain operation or radiotherapy (RT) were recruited from January 2010 to July 2012, and 40 patients were included in the final analysis. A 5-minute electrocardiogram was obtained before whole brain radiotherapy. Time domain indices of HRV were compared with other clinical factors on overall survival (OS). In the univariate analysis, Karnofsky performance status (KPS) <70 (P=0.002) and standard deviation of the normal-to-normal interval (SDNN) <10 ms (P=0.004) significantly predict poor survival. The multivariate analysis revealed that KPS <70 and SDNN <10 ms were independent negative prognosticators for survival in BM patients with hazard ratios of 2.657 and 2.204, respectively. In conclusion, HRV is associated with survival and may be a novel prognostic factor for BM patients.

scholarly journals Cesium-131 brachytherapy for recurrent brain metastases: durable salvage treatment for previously irradiated metastatic disease

2017 ◽  
Vol 126 (4) ◽  
pp. 1212-1219 ◽  
Author(s):  
A. Gabriella Wernicke ◽  
Andrew W. Smith ◽  
Shoshana Taube ◽  
Menachem Z. Yondorf ◽  
Bhupesh Parashar ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Total Activity ◽  
Median Number ◽  
Salvage Treatment ◽  
Cavity Surface ◽  
Tumor Diameter ◽  
Resection Cavity ◽  
Brain Radiotherapy ◽  
Resected Tumor

OBJECTIVE Managing patients whose intraparenchymal brain metastases recur after radiotherapy remains a challenge. Intraoperative cesium-131 (Cs-131) brachytherapy performed at the time of neurosurgical resection may represent an excellent salvage treatment option. The authors evaluated the outcomes of this novel treatment with permanent intraoperative Cs-131 brachytherapy. METHODS Thirteen patients with 15 metastases to the brain that recurred after stereotactic radiosurgery and/or whole brain radiotherapy were treated between 2010 and 2015. Stranded Cs-131 seeds were placed as a permanent volume implant. Prescription dose was 80 Gy at 5-mm depth from the resection cavity surface. The primary end point was resection cavity freedom from progression (FFP). Resection cavity freedom from progression (FFP), regional FFP, distant FFP, median survival, overall survival (OS), and toxicity were assessed. RESULTS The median duration of follow-up after salvage treatment was 5 months (range 0.5–18 months). The patients' median age was 64 years (range 51–74 years). The median resected tumor diameter was 2.9 cm (range 1.0–5.6 cm). The median number of seeds implanted was 19 (range 10–40), with a median activity per seed of 2.25 U (range 1.98–3.01 U) and median total activity of 39.6 U (range 20.0–95.2 U). The 1-year actuarial local FFP was 83.3%. The median OS was 7 months, and 1-year OS was 24.7%. Complications included infection (3), pseudomeningocele (1), seizure (1), and asymptomatic radionecrosis (RN) (1). CONCLUSIONS After failure of prior irradiation of brain metastases, re-irradiation with intraoperative Cs-131 brachytherapy implants provides durable local control and limits the risk of RN. The authors' initial experience demonstrates that this treatment approach is well tolerated and safe for patients with previously irradiated tumors after failure of more than 1 radiotherapy regimen and that it results in excellent response rates and minimal toxicity.

scholarly journals Consecutive single-institution case series of primary central nervous system lymphoma treated by R-MPV or high-dose methotrexate monotherapy

2020 ◽  
Vol 50 (9) ◽  
pp. 999-1008 ◽  
Author(s):  
Nobuyoshi Sasaki ◽  
Keiichi Kobayashi ◽  
Kuniaki Saito ◽  
Saki Shimizu ◽  
Kaori Suzuki ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Mini Mental State Examination ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Brain Radiotherapy ◽  
Dose Methotrexate

Abstract Objective The optimal regimen for use of high dose-methotrexate-based chemotherapy in primary central nervous system lymphoma is still under debate. We conducted a retrospective study to evaluate the treatment outcome of a combination immunochemotherapy consisting of rituximab, methotrexate, procarbazine and vincristine followed by with or without whole brain radiotherapy and consolidation cytarabine, in comparison with high dose-methotrexate monotherapy followed by full dose whole brain radiotherapy. Methods Newly diagnosed primary central nervous system lymphoma patients treated with either rituximab, methotrexate, procarbazine and vincristine or high dose-methotrexate in Kyorin University Hospital were identified, and the response rates and survival were compared. Toxicities, post-treatment transition of Mini-Mental State Examination, Karnofsky performance status score, Fazekas scale and prognostic factors were analysed in the rituximab, methotrexate, procarbazine and vincristine group. Results Ninety-five patients treated with rituximab, methotrexate, procarbazine and vincristine (n = 39) or high dose-methotrexate (n = 56) were analysed. The complete response/complete response unconfirmed rate was significantly higher in the rituximab, methotrexate, procarbazine and vincristine group (74.4 vs. 15.4%, P &lt; 0.001). Accordingly, both median progression-free survival and overall survival were significantly longer in the rituximab, methotrexate, procarbazine and vincristine group (median progression-free survival: unreached vs. 14.75 months, P &lt; 0.001) (median overall survival: unreached vs. 63.15 months, P = 0.005). Although the rate of grade 3/4 hematologic toxicities was high both during rituximab, methotrexate, procarbazine and vincristine and consolidation cytarabine, the rate of grade 3/4 infections was low, and no treatment related deaths were observed. Deterioration in Karnofsky performance status or Mini-Mental State Examination was rare, except on disease recurrence. Although whole brain radiotherapy was associated with Fazekas scale deterioration, its association with Karnofsky performance status or Mini-Mental State Examination deterioration was not significant. Conclusions Rituximab, methotrexate, procarbazine and vincristine was apparently promising in comparison with high dose-methotrexate monotherapy with manageable toxicity in this retrospective study, and further investigation is warranted.

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