Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method

doi:10.1016/S0360-3016(01)01622-4

International Journal of Radiation OncologyBiologyPhysics

Volume 51, Issue 2, 1 October 2001, Pages 426-434

https://doi.org/10.1016/S0360-3016(01)01622-4 Get rights and content

Abstract

$Purpose:$ To estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class and treated with radiosurgery (RS) plus whole brain radiotherapy (WBRT).

$Methods and Materials:$ An analysis of the RS databases of 10 institutions identified patients with brain metastates treated with RS and WBRT. Patients were stratified into 1 of 3 RPA classes. Survival was evaluated using Kaplan-Meier estimates and proportional hazard regression analysis. A comparison of survival by class was carried out with the RTOG results in similar patients receiving WBRT alone.

$Results:$ Five hundred two patients were eligible (261 men and 241 women, median age 59 years, range 26–83). The overall median survival was 10.7 months. A higher Karnofsky performance status (p = 0.0001), a controlled primary (median survival = 11.6 vs. 8.8 months, p = 0.0023), absence of extracranial metastases (median survival 13.4 vs. 9.1 months, p = 0.0001), and lower RPA class (median survival 16.1 months for class I vs. 10.3 months for class II vs. 8.7 months for class III, p = 0.000007) predicted for improved survival. Gender, age, primary site, radiosurgery technique, and institution were not prognostic. The addition of RS boosted results in median survival (16.1, 10.3, and 8.7 months for classes I, II, and III, respectively) compared with the median survival (7.1, 4.2, and 2.3 months, p <0.05) observed in the RTOG RPA analysis for patients treated with WBRT alone.

$Conclusion:$ In the absence of randomized data, these results suggest that RS may improve survival in patients with BM. The improvement in survival does not appear to be restricted by class for well-selected patients.

Introduction

The median survival of patients with brain metastases is <6 months and has not changed in >20 years. Very few advances have altered this grim statistic. Two contemporary trials that compared whole brain radiotherapy (WBRT) with surgical resection plus WBRT for patients with single brain metastases showed that surgical resection yielded clinically and statistically significant improved survival 1, 2, validating the hypothesis that aggressive local treatment for selected patients can improve survival.

Radiosurgery (RS) is an effective method for achieving sustained local control in selected patients with brain metastases. In contrast to surgery, RS is less restricted by location, number of brain metastases, performance status, or general medical condition. Retrospective studies suggest that RS improves control of intracranial metastases 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and yields a survival advantage 5, 7, 8, 9, 10, 11, 12, 13, 14, 15. However, in the absence of a large body of randomized data, it is not clear whether this survival benefit is due to the treatment itself or to selection of patients with known favorable prognostic factors. Recently, Gaspar et al. (16) performed a recursive partitioning analysis (RPA) using databases from three Radiation Therapy Oncology Group (RTOG) trials and proposed 3 prognostic classes: class I, Karnofsky performance status (KPS) >70, age <65 years, controlled primary tumor site, and no extracranial metastases; class III, KPS <70; and class II, all others. This stratification organizes a heterogeneous group of patients with brain metastases into prognostically homogeneous groups, allowing for comparison of different treatment modalities among patients with comparable prognostic variables.

We report a retrospective review using data from 10 institutions to estimate the survival difference, if any, for patients with newly diagnosed brain metastases undergoing RS in addition to WBRT. To allow comparison with prior RTOG results, patients were stratified using the RPA classification derived from the RTOG experience (16). The survival in each group was compared with the equivalent RTOG classes involving patients who underwent WBRT without RS.

Section snippets

Patient selection

The patients analyzed in this study were pooled from the databases of 10 different institutions. The inclusion criteria were brain metastases treated with external beam WBRT and stereotactic RS boost to all visible lesions. The temporal interval between RS and WBRT was not restricted. The ineligibility criteria were prior WBRT, all visible brain metastases not treated with stereotactic RS, stereotactic RS without WBRT, surgical resection of brain metastases, and recurrent brain metastases. Age,

Results

The inclusion dates for this analysis were January 4, 1988 to May 21, 1998. A total of 973 patients were identified in the composite database; 502 were eligible for this analysis on the basis of the criteria previously outlined. Omission of WBRT (n = 242), surgical resection of brain metastases (n = 137), incomplete follow-up data (n = 39), not treating all brain metastases with RS (n = 22), and treatment after the cutoff date of June 1, 1998 (n = 13) accounted for most of the exclusions. The

Discussion

In the 1970s, the RTOG conducted randomized trials to determine the optimal dose and fractionation schedules for WBRT for brain metastases. The major conclusions from these randomized studies were that steroids provided no independent improvement in survival over WBRT. No survival improvement was observed with higher doses or prolonged courses of radiotherapy. The median survival was 15–18 weeks (18). The subsequent dose-escalation RTOG trials between the 1960s and 1990s failed to demonstrate

References (24)

E.M Noordijk et al.
The choice of treatment of single brain metastases should be based on extracranial tumor activity, and age
Int J Radiat Oncol Biol Phys
(1994)
V Sturm et al.
Stereotactic percutaneous single dose irradiation of brain metastases with a linear accelerator
Int J Radiat Oncol Biol Phys
(1987)
B.G Fuller et al.
Stereotaxic radiosurgery for brain metastasesThe importance of adjuvant whole brain irradiation
Int J Radiat Oncol Biol Phys
(1992)
M.P Mehta et al.
Defining the role of radiosurgery in the management of brain metastases
Int J Radiat Oncol Biol Phys
(1992)
J.C Flickinger et al.
A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis
Int J Radiat Oncol Biol Phys
(1994)
R.M Auchter et al.
A multi-institutional outcome, and prognostic factor analysis of radiosurgery for resectable single brain metastasis
Int J Radiat Oncol Biol Phys
(1996)
C.Y Shiau et al.
Radiosurgery for brain metastasesRelationship of dose and pattern of enhancement to local control
Int J Radiat Oncol Biol Phys
(1997)
D Kondziolka et al.
Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases
Int J Radiat Oncol Biol Phys
(1999)
L Gaspar et al.
Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials
Int J Radiat Oncol Biol Phys
(1997)
B Borgelt et al.
The palliation of brain metastasesFinal results of the first two studies by the Radiation Therapy Oncology Group
Int J Radiat Oncol Biol Phys
(1980)

T.L Phillips et al.

Results of a randomized comparison of radiotherapy and bromodeoxyuridine to radiotherapy alone for brain metastasesReport of RTOG trial 89-05

Int J Radiat Oncol Biol Phys

(1995)

M.P Mehta et al.

A cost-effective, and cost-utility analysis of radiosurgery vs. resection for single-brain metastases

Int J Radiat Oncol Biol Phys

(1997)

Cited by (238)

Pre-operative stereotactic radiosurgery for cerebral metastatic disease: A retrospective dose-volume study
2023, Radiotherapy and Oncology
Stereotactic radiosurgery (SRS) after maximal safe resection is an accepted treatment strategy for patients with cerebral metastatic disease. Despite its high conformality profile, the incidence of radionecrosis (RN) remains high. SRS delivered pre-operatively could be associated with a reduced incidence of RN. We sought to evaluate whether neoadjuvant SRS could reduce radiotherapy doses in a cohort of patients treated with post-operative SRS.
A cohort of 47 brain metastases (BM) treated at 2 academic institutions was retrospectively analyzed. Subjects underwent surgical extirpation of BMs and subsequent SRS to surgical bed. Post-operative volumetric and dosimetric data was collected from records or recreations of delivered plans; pre-operative data were derived from hypothetical radiotherapy courses and compared using Wilcoxon signed-rank tests.
Higher planned tumor volume post-operatively (median[IQR] 12.28 [6.54, 18.69]cc vs 10.20 [4.53, 21.70]cc respectively, p = 0.4150) was observed. The median prescribed radiotherapy dose (DRx) was 16 Gy pre-operatively and 24 Gy post-operatively (p < 0.0001). Further investigations revealed improved pre-operative conformity index (1.23[1.20, 1.29] vs 1.29[1.23, 1.39], p = 0.0098) and gradient index (2.72[2.59, 2.98] vs 2.94[2.69, 3.47], p = 0.0004). A significant difference was found in normal brain tissue exposed to 10 Gy (12.97[6.78, 25.54]cc vs 32.13[19.42, 48.40]cc, p < 0.0001), 12 Gy (9.31[4.56, 17.43]cc vs 23.80[14.74, 36.56]cc, p < 0.0001), and 14 Gy (5.62[3.23, 11.61]cc vs 17.47[9.00, 28.31]cc, p < 0.0001), favoring pre-operative SRS.
Neoadjuvant SRS is associated reduced DRx, better conformality profile and decreased radiation to normal tissue. These findings could support the use of neoadjuvant SRS for the treatment of BMs.
Advances in Radiotherapy for Brain Metastases
2023, Surgical Oncology Clinics of North America
Global management of brain metastasis from renal cell carcinoma
2022, Critical Reviews in Oncology/Hematology
During the last decade, major improvements have been made in the treatment of renal cell carcinoma (RCC) with the development and use of multiple tyrosine kinase inhibitors and immune checkpoint inhibitors. Brain metastases in RCC patients (BM-RCC) is associated with poor outcome and their management represents a challenge for clinicians. In most of case, brain metastases in this context require local intervention such as radiotherapy, stereotactic radiotherapy/stereotactic radiosurgery and whole brain radiation therapy. Despite efficacy in extracranial metastases, systemic therapies have modest antitumoral effect on cerebral lesions. In this review, we highlight the benefits and pitfalls of the available therapies in BM-RCC.
Initial Approach to Patients with a Newly Diagnosed Solitary Brain Metastasis
2020, Neurosurgery Clinics of North America
Identification and Management of Progressive Enhancement After Radiation Therapy for Brain Metastases: Results from a Neurosurgical Survey
2020, World Neurosurgery
There is a lack of consensus regarding diagnosis, timing, and method of intervention for progressive enhancement on surveillance imaging after stereotactic radiosurgery (SRS) treatment of brain metastases. We sought to characterize current practices among neurosurgeons in identifying and treating infield tumor recurrence (TR) or radiation necrosis (RN) after SRS for brain metastases.
A voluntary survey was distributed electronically to preidentified neurosurgeons. Results were analyzed using descriptive statistics and χ² analysis.
A total of 120 participants completed the survey from 72 U.S. and 17 international centers. Most (69.2%) agreed that growth over ≥2 surveillance scans spaced ≥90 days apart identified irreversible progression after SRS for brain metastases. Respondents were evenly divided on the need for tissue biopsy to distinguish between TR and RN. Preferred treatment modality and time frame to initiate treatment of suspected RN differed among neurosurgeons based on SRS case volume for brain metastases (P = 0.002 and P = 0.02, respectively). Neurosurgeons who used magnetic resonance–guided laser interstitial thermal therapy (LITT) for brain metastases were more likely to prefer LITT for suspected RN, whereas those with minimal LITT experience preferred steroids (P < 0.0001). Neurosurgeons in the United States were more likely to prefer LITT for RN (37.3%) compared with international counterparts (0%).
Our survey of practicing neurosurgeons highlights areas of controversy in distinguishing between TR and RN and preferred management of suspected RN.
Headache and Brain Tumor
2019, Neuroimaging Clinics of North America

View all citing articles on Scopus

View full text

Clinical investigation: brainRadiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method

Abstract

Introduction

Section snippets

Patient selection

Results

Discussion

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clinical investigation: brain
Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method