Is Karnofsky performance status correlate with better overall survival in palliative conformal whole brain radiotherapy? Our experience

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.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2010.30.1655 ◽

2011 ◽

Vol 29 (2) ◽

pp. 134-141 ◽

Cited By ~ 1103

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.

Download Full-text

Stereotactic radiosurgery for brain metastases from pelvic gynecological malignancies: oncologic outcomes, validation of prognostic scores, and dosimetric evaluation

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002906 ◽

2021 ◽

pp. ijgc-2021-002906

Author(s):

Eva Meixner ◽

Tanja Eichkorn ◽

Sinem Erdem ◽

Laila König ◽

Kristin Lang ◽

...

Keyword(s):

Overall Survival ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Recursive Partitioning ◽

Whole Brain Radiotherapy ◽

Prognostic Scores ◽

Gynecologic Malignancies ◽

Whole Brain ◽

Brain Radiotherapy ◽

Cerebral Control

IntroductionStereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for radiosurgery in women with primary pelvic gynecologic malignancies metastatic to the brain. The aim of the present study is to evaluate the feasibility, safety, outcomes, and impact of established prognostic scores.MethodsWe retrospectively identified 52 patients treated with radiotherapy for brain metastases between 2008 and 2021. Stereotactic radiosurgery was utilized in 31 patients for an overall number of 75 lesions; the remaining 21 patients received whole-brain radiotherapy. Kaplan-Meier survival analysis and the log-rank test were used to calculate and compare survival curves and univariate and multivariate Cox regression to assess the influence of cofactors on recurrence, local control, and prognosis.ResultsWith a median follow-up of 10.7 months, overall survival rates post radiosurgery were 65.3%, 51.3%, and 27.7% for 1, 2, and 5 years, respectively, which were significantly higher than post whole-brain radiotherapy (p=0.049). Five local failures (6.7%) were detected, resulting in 1 and 2 year local cerebral control rates of 97.4% and 94.0%, respectively. Univariate factors for prediction of superior overall survival were high performance status (p=0.030) and application of three prognostic scores, especially the Recursive Partitioning Analysis score (p=0.028). Uni- and multivariate analysis revealed that extracranial progression prior to radiosurgery was significant for inferior overall survival (p<0.0001). Radionecrosis was diagnosed in five women (16%); long-term neurotoxicity was significantly worse after whole-brain radiotherapy compared with radiosurgery (p=0.023).ConclusionStereotactic radiosurgery for brain metastases from pelvic gynecologic malignancies appears to be safe and well tolerated, achieving promising local cerebral control. Prognostic scores were shown to be transferable and radiosurgery should be recommended as primary intracranial treatment, especially in women with no prior extracranial progression and Recursive Partitioning Analysis class I.

Download Full-text

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

Acta Oncologica ◽

10.3109/02841860903352942 ◽

2010 ◽

Vol 49 (3) ◽

pp. 382-388 ◽

Cited By ~ 18

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

Download Full-text

NQPC-5 Does high-dose methotrexate-based chemotherapy for relapsed primary CNS lymphoma increase a risk of leukoencephalopathy with prior whole brain radiotherapy?

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab159.083 ◽

2021 ◽

Vol 3 (Supplement_6) ◽

pp. vi22-vi22

Author(s):

Keiichi Kobayashi ◽

Nobuyoshi Sasaki ◽

Kuniaki Saito ◽

Yuki Yamagishi ◽

Naomi Hanayama ◽

...

Keyword(s):

Performance Status ◽

Primary Cns Lymphoma ◽

Central Nervous System Lymphoma ◽

Whole Brain Radiotherapy ◽

Progression Free Survival ◽

Cns Lymphoma ◽

High Dose ◽

Whole Brain ◽

Brain Radiotherapy ◽

Study Results

Abstract Backgrounds: Standard care for primary central nervous system lymphoma (PCNSL) comprises high-dose (HD) methotrexate (MTX) -based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). HD-MTX administration following WBRT has been suggested to increase a risk of leukoencephalopathy. However, given that there are no other agents with efficacy similar to or better than MTX, patients with relapsed PCNSL may often be treated with regimens containing HD-MTX if the initial MTX treatment achieved a long-term complete remission. Here, we retrospectively analyzed prevalence and an extent of white mater damages in association with prior WBRT in patients with relapsed PCNSL treated with HD-MTX based therapy. Patients & methods: Among 79 patients with relapsed/refractory PCNSL in a total of 162 patients with newly-diagnosed PCNSL treated in our institution from April, 2000 to February, 2021, 35 patients were identified with evaluable KPS, MMSE, and Fazekas scale data at both baseline and follow-up periods. Of the 35 patients, 22 were treated with chemotherapy at a relapse (10 with prior WBRT, while 12 without WBRT), and were included in this preliminary study. Results: In the WBRT group (male/female: 5/5), median age was 65 years (range, 45–73), initial median KPS was 70 (40–90), and median WBRT dose was 27 Gy (23.4–40). Median progression-free survival (mPFS) was 11.8 months, and median overall survival (mOS) was not reached. In the non-WBRT group (M/F 8/4), median age 75 (62–84), initial mKPS 80 (50–90), mPFS 16.2 m, and mOS not reached. Initial KPS and MMSE score tended to be worse in WBRT group, presumably due to enrichment of patients with poorer performance status and more comorbidities. A decline in the Fazekas score was not associated with MMSE deterioration.Conclusions: The preliminary analysis was not informative enough, and further extensive imaging analysis will be exploited.

Download Full-text

Management of lung cancer brain metastasis: An overview

Asian Journal of Oncology ◽

10.4103/asjo.asjo_79_16 ◽

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.

Download Full-text

Clinical Outcomes of Upfront Stereotactic Radiosurgery Alone for Patients With 5 to 15 Brain Metastases

Neurosurgery ◽

10.1093/neuros/nyy276 ◽

2018 ◽

Vol 85 (2) ◽

pp. 257-263 ◽

Cited By ~ 8

Author(s):

Ryan T Hughes ◽

Emory R McTyre ◽

Michael LeCompte ◽

Christina K Cramer ◽

Michael T Munley ◽

...

Keyword(s):

Overall Survival ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Clinical Outcomes ◽

Whole Brain Radiotherapy ◽

Cox Proportional Hazards ◽

Whole Brain ◽

Brain Radiotherapy ◽

Increased Risk

Abstract BACKGROUND The role of primary stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) remains controversial. OBJECTIVE To compare the outcomes of patients treated with upfront SRS alone for 1, 2 to 4, and 5 to 15 BM and assess for predictors of clinical outcomes in the 5 to 15 BM group. METHODS A total of 478 patients treated with upfront SRS were stratified by number of lesions: 220 had 1 BM, 190 had 2 to 4 BM, and 68 patients had 5 to 15 BM. Overall survival and whole brain radiotherapy-free survival were estimated using the Kaplan–Meier method. The cumulative incidences of local failure and distant brain failure (DBF) were estimated using competing risks methodology. Clinicopathologic and dosimetric parameters were evaluated as predictors of survival and DBF in patients with 5 to 15 BM using Cox proportional hazards. RESULTS Median overall survival was 8.0, 6.3, and 4.7 mo for patients with 1, 2 to 4, and 5 to 15 BM, respectively (P = .14). One-year DBF was 27%, 44%, and 40%, respectively (P = .01). Salvage SRS and whole brain radiotherapy rates did not differ. Progressive extracranial disease and gastrointestinal primary were associated with poor survival while RCC primary was associated with increased risk of DBF. No evaluated dose-volume parameters predicted for death, neurologic death or toxicity. CONCLUSION SRS for 5 to 15 BM is well tolerated without evidence of an associated increase in toxicity, treatment failure, or salvage therapy. Further prospective, randomized studies are warranted to clarify the role of SRS for these patients.

Download Full-text

Resection and brain brachytherapy with permanent iodine-125 sources for brain metastasis

Journal of Neurosurgery ◽

10.3171/2016.4.jns152530 ◽

2016 ◽

Vol 126 (6) ◽

pp. 1749-1755 ◽

Cited By ~ 10

Author(s):

David R. Raleigh ◽

Zachary A. Seymour ◽

Bryan Tomlin ◽

Philip V. Theodosopoulos ◽

Mitchel S. Berger ◽

...

Keyword(s):

Overall Survival ◽

Brain Metastasis ◽

Brain Metastases ◽

Local Control ◽

Whole Brain Radiotherapy ◽

Cavity Volume ◽

Term Survival ◽

Whole Brain ◽

Brain Radiotherapy ◽

Iodine 125

OBJECTIVEStereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (125I) brachytherapy for brain metastases.METHODSA total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of 125I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models.RESULTSThe median age at surgery was 59 years (range 29.9–81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3 (range 0.21–76.2 cm3). Gross-total resection was achieved in 81% of the cases. The median number of 125I sources implanted per cavity was 28 (range 4–93), and the median activity was 0.73 mCi (range 0.34–1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0–22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02–13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05).CONCLUSIONSTherapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent 125I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients.▪ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV.

Download Full-text

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

BioMed Research International ◽

10.1155/2013/503421 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 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.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.26_suppl.32 ◽

2016 ◽

Vol 34 (26_suppl) ◽

pp. 32-32 ◽

Cited By ~ 1

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.

Download Full-text