Risk factors of distant brain failure for patients with newly diagnosed brain metastases treated with stereotactic radiotherapy alone

Object This study was undertaken to analyze outcomes in patients with newly diagnosed brain metastases from non–small cell lung cancer (NSCLC) who were treated with hypofractionated stereotactic radiotherapy (HSRT) with or without whole-brain radiotherapy (WBRT). Methods One hundred seventy-one patients comprised the study population. Fifty-four patients received HSRT alone, and 117 patients received both HSRT and WBRT. The median survival time (MST) was determined using the Kaplan-Meier method. Recursive Partitioning Analysis (RPA) and Graded Prognostic Assessment (GPA) were also used to evaluate the results. Univariate and multivariate analyses were performed to determine significant prognostic factors for overall survival. Tumor control, radiation toxicity, and cause of death in the HSRT and HSRT+WBRT groups were evaluated. Results The MST for all patients was 13 months. According to the Kaplan-Meier method, the probability of survival at 1, 2, and 3 years was 51.2%, 21.7%, and 10.1%. The MSTs for RPA Classes I, II, and III were 19, 12, and 5 months, respectively; and the MSTs for GPA Scores 4, 3, 2, and 1 were 24, 14, 12, and 6 months, respectively. The MSTs in the HSRT+WBRT and HSRT groups were 13 and 9 months (p = 0.044), respectively, for all patients, 13 and 8 months (p = 0.031), respectively, for patients with multiple brain metastases, and 16 and 15 months (p = 0.261), respectively, for patients with a single brain metastasis. The multivariate analysis showed that HSRT+WBRT was a significant factor only for patients with multiple brain metastases (p = 0.010). The Kaplan-Meier–estimated tumor control rates at 3, 6, 9, and 12 months were 92.2%, 82.7%, 79.5%, and 68.3% in the HSRT+WBRT group and 73.5%, 58.4%, 51.0%, and 43.3% in the HSRT group, respectively, in all 165 patients (p = 0.001). The estimated tumor control rates at 3, 6, 9, and 12 months were 94.3%, 81.9%, 79.6%, and 76.7%, respectively, in the HSRT+WBRT group and 77.8%, 61.4%, 52.6%, and 48.2%, respectively, in the HSRT group in the 80 patients harboring a single metastasis (p = 0.009). The estimated tumor control rates at 3, 6, 9, and 12 months were 90.5%, 83.5%, 79.5%, and 60.9%, respectively, in the HSRT+WBRT group and 68.2%, 54.5%, 48.5%, and 36.4%, respectively, in the HSRT group in the 85 patients with multiple metastases (p = 0.010). The toxicity incidences of Grade 3 or worse were 6.0% (7 of 117 patients) in the HSRT+WBRT group and 1.9% (1 of 54 patients) in the HSRT group (p = 0.438). The differences in neurological death rates between the HSRT+WBRT group and the HSRT group were not statistically significant (34.4% vs 44.7%, p = 0.125, in all patients; 30.0% vs 52.0%, p = 0.114, in patients with a single metastasis; and 38.0% vs 36.4%, p = 0.397, in patients with multiple metastases). Conclusions The overall survival results in the present study were similar to those in other studies. Hypofractionated stereotactic radiotherapy provides an alternative method to traditional stereotactic radiosurgery. We suggest that WBRT should be combined with HSRT in patients with single or multiple newly diagnosed brain metastases from NSCLC.

Download Full-text

Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection

Radiation Oncology ◽

10.1186/s13014-016-0653-3 ◽

2016 ◽

Vol 11 (1) ◽

Cited By ~ 24

Author(s):

Pierina Navarria ◽

Federico Pessina ◽

Luca Cozzi ◽

Anna Maria Ascolese ◽

Fiorenza De Rose ◽

...

Keyword(s):

Brain Metastases ◽

Surgical Resection ◽

Stereotactic Radiotherapy ◽

Volumetric Modulated Arc Therapy ◽

Fractionated Stereotactic Radiotherapy ◽

Large Brain ◽

Arc Therapy ◽

Radiotherapy Alone

Download Full-text

A phase II study of radiosurgery and temozolomide for patients with one to four brain metastases

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.2048 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 2048-2048 ◽

Cited By ~ 2

Author(s):

J. B. Fiveash ◽

S. M. Sawrie ◽

B. L. Guthrie ◽

S. A. Spencer ◽

R. F. Meredith ◽

...

Keyword(s):

Brain Metastases ◽

Phase Ii ◽

Median Number ◽

Serious Adverse Events ◽

Whole Brain Radiation ◽

Brain Failure ◽

Actuarial Risk ◽

One Year ◽

Distant Brain Failure

2048 Background: To determine if temozolomide reduces the risk of distant brain failure (DBF, metachronous brain metastases) in patients with 1–4 brain metastases treated with radiosurgery without whole brain radiation therapy. Methods: Twenty-five patients with newly diagnosed brain metastases were enrolled in a single institution phase II trial of radiosurgery (15–24 Gy) and adjuvant temozolomide. Temozolomide was started within 14 days of radiosurgery and was administered 150–200 mg/m2 p.o. q day x 5 days in 28 day cycles. Temozolomide was continued for a total of 12 cycles unless the patient developed DBF, unacceptable toxicity, or systemic progression requiring other therapy. If more than 4 metastases were identified on the MRI performed on the day of radiosurgery, then the patient could still be treated on the clinical trial if all tumors could be treated with radiosurgery. In addition to clinical and radiographic follow-up, QOL was assessed utilizing the FACT-Br questionnaire. Results: Twenty-five patients were enrolled 2002–2005; three were not evaluable for determining DBF. Of the remaining twenty-two patients, tumor types included NSCLC (n=8), melanoma (n=7), other (n=7). Extracranial disease was present in ten (45%) patients. The median number of tumors was 3 (range 1–6). The median overall survival was 31 weeks. The median radiographic follow-up for patients that did not develop DBF was 33 weeks. Six patients developed DBF. The one year actuarial risk of DBF was 37%. Patients with melanoma had a higher risk of DBF than other patients (p<0.001, log-rank). Only 1/15 patients without melanoma vs. 5/7 patients with melanoma developed DBF. 15 serious adverse events (SAEs) occurred in 10 of the patients, but none of the SAEs were judged to be likely related to temozolomide. Among patients that experienced DBF, no significant differences were seen in QOL when pretreatment FACT-Br and time of distant brain failure FACT-Br scores were compared. Conclusions: Adjuvant temolozomide after radiosurgery is associated with a low risk of distant brain failure in non-melanoma patients. Larger clinical trials should examine the relative efficacy and QOL of WBRT and temozolomide in non-melanoma brain metastases patients. No significant financial relationships to disclose.

Download Full-text

Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF)

Neurosurgery ◽

10.1093/neuros/nyz428 ◽

2019 ◽

Vol 87 (4) ◽

pp. 664-671 ◽

Cited By ~ 2

Author(s):

Christopher P Cifarelli ◽

John A Vargo ◽

Wei Fang ◽

Roman Liscak ◽

Khumar Guseynova ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Gamma Knife ◽

Cell Lung Cancer ◽

Small Cell ◽

Local Failure ◽

Small Cell Lung ◽

Brain Failure ◽

Distant Brain Failure

Abstract BACKGROUND Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases. OBJECTIVE To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS). METHODS A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis. RESULTS Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P = .01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P = .005). CONCLUSION SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.

Download Full-text