Hoffman R, Sneed PK, McDermott MW, et al. Radiosurgery for brain metastases from primary lung carcinoma

Department of Radiation Oncology, University of California, San Francisco 94143-0226, USA.
The Cancer Journal (Impact Factor: 4.24). 01/2001; 7(2):121-31.
Source: PubMed


Brain metastases are a common problem in patients with lung cancer. This retrospective review was performed to describe the efficacy and toxicity of stereotactic radiosurgery for brain metastases from lung carcinoma and to evaluate prognostic factors for survival.
A retrospective review was performed of 113 patients with the diagnosis of lung carcinoma who underwent radiosurgery with or without whole-brain radiotherapy for management of newly diagnosed or recurrent, single, or multiple brain metastases from 1991 through 1998 at the University of California, San Francisco. Freedom from progression and survival were measured from the date of radiosurgery and estimated using the Kaplan-Meier method. Prognostic factors were evaluated with the log-rank test and Cox proportional hazards models.
The median patient age at the time of radiosurgery was 59 years (range, 37-82 years), and the median Karnofsky performance score was 90 (range, 50-100). The median survival time from radiosurgery was 12.0 months overall, 13.9 months for 41 patients treated with radiosurgery alone initially, 14.5 months for 19 patients treated with radiosurgery and whole-brain radiotherapy initially, and 10.0 months for 53 patients with recurrent brain metastases. Among newly diagnosed patients, multivariate analysis showed that improved survival was associated with absence of extracranial metastases and fewer brain metastases. Among patients with recurrent brain metastases, improved survival was associated with higher Karnofsky performance score, control of the primary tumor, and fewer metastases. Measured by lesion, 1-year local freedom from progression probabilities were 81% for radiosurgery alone, 86% for radiosurgery and whole-brain radiotherapy, and 65% for radiosurgery performed after recurrence. In patients with newly diagnosed brain metastases, there was a significantly greater risk of developing subsequent brain metastases and of worse overall brain freedom from progression after radiosurgery alone versus radiosurgery and whole-brain radiotherapy. One-year brain freedom from progression probabilities were 13% without salvage therapy and 62% with salvage therapy in the 41 patients treated initially with radiosurgery alone, versus 67% without salvage therapy and 89% with salvage therapy in the 19 patients treated initially with radiosurgery plus whole-brain radiotherapy.
Radiosurgery is an effective therapy for selected patients with newly diagnosed or recurrent brain metastases from lung carcinoma. Initial whole-brain radiotherapy with radiosurgery appears to improve brain control but not survival. Prospective, randomized trials are needed to further investigate the role of radiosurgery with and without whole-brain radiotherapy for brain metastases.

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    • "This result confirms the efficacy of SRS alone, even for patients with 1-4 brain metastases1,2). Hoffman's group reported 10 month survival for patients with recurrent brain metastases after SRS10). Karlsson et al.13) presented no statistically significant relationship between number of brain metastases upon first treatment and total number of GKRS treatments. "
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    ABSTRACT: We compared the survival time between patients with multiple gamma knife radiosurgery (GKRS) and patients with a single GKRS plus whole brain radiation therapy (WBRT), in patients with multiple metachronous brain metastases from lung cancer. From May 2006 to July 2010, we analyzed 31 patients out of 112 patients who showed multiple metachronous brain metastases. 20 out of 31 patients underwent multiple GKRS (group A) and 11 patients underwent a single GKRS plus WBRT (group B). We compared the survival time between group A and B. Kaplan-Meier method and Cox proportional hazards were used to analyze relationship between survival and 1) the number of lesions in each patient, 2) the average volume of lesions in each patient, 3) the number of repeated GKRS, and 4) the interval of development of new lesions, respectively. Median survival time was 18 months (range 6-50 months) in group A and 6 months (range 3-18 months) in group B. Only the average volume of individual lesion (over 10 cc) was negatively related with survival time according to Kaplan-Meier method. Cox-proportional hazard ratio of each variable was 1.1559 for the number of lesions, 1.0005 for the average volume of lesions, 0.0894 for the numbers of repeated GKRS, and 0.5970 for the interval of development of new lesions. This study showed extended survival time in group A compared with group B. Our result supports that multiple GKRS is of value in extending the survival time in patients with multiple metachronous brain metastases, and that the number of the lesions and the frequency of development of new lesions are not an obstacle in treating patients with GKRS.
    Full-text · Article · Oct 2012 · Journal of Korean Neurosurgical Society
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    • "One RCT [38], one prospective cohort study (class II evidence) [35], and eight of 10 retrospective cohort studies (class II evidence) [40, 42–48] support equivalent survival results for single-dose SRS alone vs. WBRT + single-dose SRS, and one study restricted to breast cancer suggested a survival advantage for the single-dose SRS alone strategy [41]. Only one retrospective cohort study showed a survival result favoring WBRT + single-dose SRS, and this study was unusual in that it only included patients who had already survived >1 year since initial treatment [48]. "
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    ABSTRACT: QUESTION: Should patients with newly-diagnosed metastatic brain tumors undergo stereotactic radiosurgery (SRS) compared with other treatment modalities? Target population These recommendations apply to adults with newly diagnosed solid brain metastases amenable to SRS; lesions amenable to SRS are typically defined as measuring less than 3 cm in maximum diameter and producing minimal (less than 1 cm of midline shift) mass effect. Recommendations SRS plus WBRT vs. WBRT alone Level 1 Single-dose SRS along with WBRT leads to significantly longer patient survival compared with WBRT alone for patients with single metastatic brain tumors who have a KPS > or = 70.Level 1 Single-dose SRS along with WBRT is superior in terms of local tumor control and maintaining functional status when compared to WBRT alone for patients with 1-4 metastatic brain tumors who have a KPS > or =70.Level 2 Single-dose SRS along with WBRT may lead to significantly longer patient survival than WBRT alone for patients with 2-3 metastatic brain tumors.Level 3 There is class III evidence demonstrating that single-dose SRS along with WBRT is superior to WBRT alone for improving patient survival for patients with single or multiple brain metastases and a KPS<70 [corrected].Level 4 There is class III evidence demonstrating that single-dose SRS along with WBRT is superior to WBRT alone for improving patient survival for patients with single or multiple brain metastases and a KPS < 70. SRS plus WBRT vs. SRS alone Level 2 Single-dose SRS alone may provide an equivalent survival advantage for patients with brain metastases compared with WBRT + single-dose SRS. There is conflicting class I and II evidence regarding the risk of both local and distant recurrence when SRS is used in isolation, and class I evidence demonstrates a lower risk of distant recurrence with WBRT; thus, regular careful surveillance is warranted for patients treated with SRS alone in order to provide early identification of local and distant recurrences so that salvage therapy can be initiated at the soonest possible time. Surgical Resection plus WBRT vs. SRS +/- WBRT Level 2 Surgical resection plus WBRT, vs. SRS plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift). Level 3: Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. SRS alone vs. WBRT alone Level 3 While both single-dose SRS and WBRT are effective for treating patients with brain metastases, single-dose SRS alone appears to be superior to WBRT alone for patients with up to three metastatic brain tumors in terms of patient survival advantage.
    Full-text · Article · Dec 2009 · Journal of Neuro-Oncology
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    • "Time to progression was not reported. Of the other eight studies that addressed the role of SRS for recurrent disease in patients whose upfront treatment included WBRT, four specifically evaluated SRS treatment for recurrent/progressive brain metastases from particular primary tumor types–breast cancer (2 case series [12, 14]), small cell lung cancer (SCLC) (1 case series [22]) and lung cancer, predominantly NSCLC (1 case series [17]). See Table 3 for details. "
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    ABSTRACT: What evidence is available regarding the use of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), surgical resection or chemotherapy for the treatment of recurrent/progressive brain metastases? This recommendation applies to adults with recurrent/progressive brain metastases who have previously been treated with WBRT, surgical resection and/or radiosurgery. Recurrent/progressive brain metastases are defined as metastases that recur/progress anywhere in the brain (original and/or non-original sites) after initial therapy. Level 3 Since there is insufficient evidence to make definitive treatment recommendations in patients with recurrent/progressive brain metastases, treatment should be individualized based on a patient's functional status, extent of disease, volume/number of metastases, recurrence or progression at original versus non-original site, previous treatment and type of primary cancer, and enrollment in clinical trials is encouraged. In this context, the following can be recommended depending on a patient's specific condition: no further treatment (supportive care), re-irradiation (either WBRT and/or SRS), surgical excision or, to a lesser extent, chemotherapy. Question If WBRT is used in the setting of recurrent/progressive brain metastases, what impact does tumor histopathology have on treatment outcomes? No studies were identified that met the eligibility criteria for this question.
    Full-text · Article · Dec 2009 · Journal of Neuro-Oncology
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