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.

Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of 1–3 cerebral metastases: Results of the EORTC 22952–26001 study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2008-2008 ◽  
Author(s):  
R. P. Mueller ◽  
R. Soffietti ◽  
M. U. Abaciouglu ◽  
S. Villa ◽  
F. Fauchon ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Systemic Disease ◽  
Local Treatment ◽  
Whole Brain Radiotherapy ◽  
Functional Independence ◽  
Phase Iii ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Primary Tumors ◽  
Brain Irradiation

2008 Background: The EORTC Radiotherapy and Brain Tumor Groups conducted a phase III trial to define the role of adjuvant whole brain irradiation (WBRT) after local treatment (surgery or radiosurgery) for brain metastases. It was hypothetized that WBRT would increase the duration of functional independence by reducing the number of intracranial relapses. Methods: Pts eligible for radiosurgery (RS) had 1–3 metastases of solid tumors (SCLC excluded) ≤ 3.0 cm in diameter (≤ 2.5 cm for 2–3 lesions). In case of surgery (S), a complete resection was mandatory. Only pts with no or stable systemic disease or with asymptomatic synchronous primary tumors, and with WHO PS 0–2 were allowed. Pts were randomized for adjuvant WBRT or observation (OBS). Primary endpoint was survival with functional independence measured by the time to WHO PS deterioration to > 3. Analysis is by intent-to-treat (Logrank, two-sided α = 0.05). Results: From 1996–2007, 359 pts were recruited. 160 surgical pts had resection of one (96%) or two (4%) metastases, and 185 (of 199 scheduled pts) had RS (marginal dose 20Gy, target dose 25Gy) of one (67%), two (23%), or three (10%) lesions. Adjuvant whole brain irradiation (30Gy/10 fractions) was given to 166/180 pts. (92%) randomized for WBRT and to 4/179 pts (2%) in the OBS arm. Median time to WHO PS > 3 was 9.8 months (95% CI 8.0 - 11.7) in the OBS arm and 9.8 months (95% CI 7.8 - 12.6) in the WBRT arm (p > 0.5). It was only significantly influenced by initial WHO PS and initial systemic disease status (p < 0.01). Overall survival was 10.9 months (95% CI 9.2 - 14.6) in both arms (p > 0.5). Cumulative incidence of intracranial progression at 6 and 24 months was 39.7% (95% CI 32.5 - 46.8) and 54.0% (95% CI 46.7 - 61.3) of the OBS pts, but only 15.2% (95% CI 9.9 - 20.5) and 31.4% (95% CI 24.5 - 38.2) of the WBRT pts (p < 0.0001). Intracranial progression was a cause of the death in 77/179 pts (43%) of the OBS group and in only 45/180 pts (25%) of the WBRT group. Conclusions: After radiosurgery or surgery of 1–3 brain metastases, adjuvant WBRT reduces the frequency of intracranial relapses and neurologic deaths but fails to prolong the time period of functional independence and overall survial time. Updated results will be presented at the Meeting. No significant financial relationships to disclose.

scholarly journals Effects of Surgery With Salvage Stereotactic Radiosurgery Versus Surgery With Whole-Brain Radiation Therapy in Patients With One to Four Brain Metastases (JCOG0504): A Phase III, Noninferiority, Randomized Controlled Trial

2018 ◽  
Vol 36 (33) ◽  
pp. 3282-3289 ◽  
Author(s):  
Takamasa Kayama ◽  
Shinya Sato ◽  
Kaori Sakurada ◽  
Junki Mizusawa ◽  
Ryo Nishikawa ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Cognitive Dysfunction ◽  
Controlled Trial ◽  
Performance Status ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Whole Brain

Purpose Whereas whole-brain radiotherapy (WBRT) has been the standard treatment of brain metastases (BMs), stereotactic radiosurgery (SRS) is increasingly preferred to avoid cognitive dysfunction; however, it has not been clearly determined whether treatment with SRS is as effective as that with WBRT or WBRT plus SRS. We thus assessed the noninferiority of salvage SRS to WBRT in patients with BMs. Patients and Methods Patients age 20 to 79 years old with performance status scores of 0 to 2—and 3 if caused only by neurologic deficits—and with four or fewer surgically resected BMs with only one lesion > 3 cm in diameter were eligible. Patients were randomly assigned to WBRT or salvage SRS arms within 21 days of surgery. The primary end point was overall survival. A one-sided α of .05 was used. Results Between January 2006 and May 2014, 137 and 134 patients were enrolled in the WBRT and salvage SRS arms, respectively. Median overall survival was 15.6 months in both arms (hazard ratio, 1.05; 90% CI, 0.83 to 1.33; one-sided P for noninferiority = .027). Median intracranial progression-free survival of patients in the WBRT arm (10.4 months) was longer than that of patients in the salvage SRS arm (4.0 months). The proportions of patients whose Mini-Mental Status Examination and performance status scores that did not worsen at 12 months were similar in both arms; however, 16.4% of patients in the WBRT arm experienced grade 2 to 4 cognitive dysfunction after 91 days postenrollment, whereas only 7.7% of those in the SRS arm did ( P = .048). Conclusion Salvage SRS is noninferior to WBRT and can be established as a standard therapy for patients with four or fewer BMs.

scholarly journals A Dutch phase III randomized multicenter trial: whole brain radiotherapy vs. stereotactic radiotherapy for 4-10 brain metastases

2021 ◽  
Author(s):  
Dianne Hartgerink ◽  
Anna Bruynzeel ◽  
Danielle Eekers ◽  
Ans Swinnen ◽  
Coen Hurkmans ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Side Effects ◽  
Brain Metastases ◽  
Survival Rates ◽  
Whole Brain Radiotherapy ◽  
Phase Iii ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
One Year

Abstract Background The clinical value of whole brain radiotherapy (WBRT) for brain metastases (BM) is a matter of debate due to the significant side effects involved. Stereotactic radiosurgery (SRS) is an attractive alternative treatment option that may avoid these side effects and improve local tumor control. We initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS compared with WBRT in patients with multiple brain metastases. Methods Patients with 4 to 10 BM were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). The primary endpoint was the difference in quality of life (QOL) at three months post-treatment. Results The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions were 6 (range, 4-9) and the median total treatment volume was 13.0 cc 3 (range, 1.8-25.9 cc 3). QOL at three months decreased in the SRS group by 0.1 (SD=0.2), compared to 0.2 (SD=0.2) in the WBRT group (p=0.23). The actuarial one-year survival rates were 57% (SRS) and 31% (WBRT) (p=0.52). The actuarial one-year brain salvage-free survival rates were 50% (SRS) and 78% (WBRT) (p=0.22). Conclusion In patients with 4 to 10 BM, SRS alone resulted in one-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined.

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

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.

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

scholarly journals Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001

2020 ◽  
Vol 38 (10) ◽  
pp. 1019-1029 ◽  
Author(s):  
Paul D. Brown ◽  
Vinai Gondi ◽  
Stephanie Pugh ◽  
Wolfgang A. Tome ◽  
Jeffrey S. Wefel ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Phase Iii ◽  
Reliable Change Index ◽  
Whole Brain ◽  
Phase Iii Trial ◽  
Brain Radiotherapy ◽  
Hippocampal Avoidance ◽  
Patient Reported

PURPOSE Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [ P = .049] and 16.4% v 33.3% [ P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue ( P = .04), less difficulty with remembering things ( P = .01), and less difficulty with speaking ( P = .049) and using imputed data, less interference of neurologic symptoms in daily activities ( P = .008) and fewer cognitive symptoms ( P = .01). CONCLUSION HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.

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.

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

Neurosurgery ◽  
2018 ◽  
Vol 85 (2) ◽  
pp. 257-263 ◽  
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.

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