Treatment of brain metastases in patients with non-small cell lung cancer (NSCLC) by stereotactic linac-based radiosurgery: prognostic factors
Introduction
Brain metastases are frequent in patients with non-small cell lung cancer (NSCLC) and are associated with a crucial decrease in prognosis and impairment of quality of life. The incidence of brain metastases in patients with NSCLC is approximately 25% [1]. The outcome of untreated patients is poor with a median survival rate of only 1 month after diagnosis. The use of steroids to decrease the tumor surrounding edema improves neurological dysfunction and prolongs the median survival to approximately 2 months [2]. Standard treatment of brain metastases from NSCLC is fractionated whole brain radiation therapy (WBRT). Neurological function could be improved with minimal morbidity and median survival is prolonged by WBRT alone of 3–5 months [3], [4]. The addition of a focal treatment to WBRT was investigated by a number of studies. Several reports suggest improved median survival after surgical resection of solitary brain metastases [4], [5] or radiosurgery [6] combined with WBRT compared with WBRT alone. However, no benefit could be seen in patients with active systemic disease [7].
Stereotactic radiosurgery (SRS) is a non-invasive alternative to surgical resection. It is a valuable tool especially in patients with surgically inaccessible metastases. In contrast to surgery, SRS could be offered to patients in poor medical conditions as well. It allows the precise focal delivery of a high single radiation dose to brain metastases and causes high rates of local control [8], [9]. SRS is effective and associated with few complications. Local control rates of 84–90% are reported in literature [8], [10], [11]. Postradiological complications include the onset of transient or symptomatic peritumoral edema or delayed intratumoral hemorrhage or necrosis which requires surgical resection in approximately 4% of patients [10].
The indication for SRS alone or in combination with WBRT remains unclear. However, WBRT requires at least 4–20 fractions meaning a treatment duration of 1 to 4 weeks and is usually delivered as 30 Gy in 2 weeks in patients with reduced performance status. It should be considered if time consuming treatment modalities like WBRT are appropriate in case of terminal cancer patients with only a short time to live and, therefore, are unlikely to develop new brain metastases.
In order to identify patients who benefit from palliative radiosurgery alone, we evaluate local control and outcome after linac-based radiosurgery and identify prognostic factors that may affect survival of patients with brain metastases of NSCLC.
Section snippets
Methods and materials
Between May 1984 and July 2000, 86 patients (60 males, 26 females) with histologically verified NSCLC were treated with SRS for a total of 110 brain metastases at our institution. Seventeen patients (20%) received conventional WBRT prior (11) or during (six) radiosurgery. Median total dose was 40 Gy with a median dose of 2 Gy per daily fraction. The eleven patients treated with WBRT prior to radiosurgery relapsed and received SRS in recurrent disease 12 months median (range 4–21 months) after
Survival of patients with NSCLC after radiosurgery
Median follow-up was 6 months (range 1 1/2–77 months) with 63 patients of 80 deceased during follow-up. Median actuarial survival was 4.5 months. The Kaplan–Meier-plot of survival and brain disease progression-free survival of the patients is seen in Fig. 1, Fig. 2. Median actuarial survival time was 8.3 months (95% confidence interval 5.5–18.4) in 43 patients with metachronous onset of brain metastases in comparison to 3.3 months (95% confidence interval 2.7–5.9) in 37 patients with
Discussion
Brain metastases are a direct cause of death in one-third to one-half of patients affected by lung cancer [14]. Palliation of neurologic symptoms is the aim in therapy for patients with brain metastases, thus, aiming at an improved quality of life. Either surgical resection or SRS as focal treatments are capable to achieve local control which results in an improvement or stabilization of neurological dysfunction [5], [11]. Our evaluation showed the effectiveness of high precision radiosurgery
Conclusion
With high response rate and short treatment time, linac-based SRS is an immediate method to effectively control brain metastases from NSCLC. We identified controlled primary tumor site, absence of extracranial metastases and metachronous onset of brain metastases as prognostic factors associated with longer survival. Patients with favorable prognostic factors for survival are under increased risk to develop additional brain metastases during long term follow-up. An ongoing EORTC study
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Cited by (47)
Lung cancer: Biology and treatment options
2015, Biochimica et Biophysica Acta - Reviews on CancerStereotactic radiosurgery in the treatment of brain metastases: The current evidence
2014, Cancer Treatment ReviewsCitation Excerpt :Local control rates after stereotactic radiosurgery in general were quite consistent: between 81%,100,101 85%,58 94%56 and 98%.102 Tumor control rates after Gamma Knife radiosurgery varied depending on the tumor volume: Between 94% for metastases between 0.5 and 2 cm3 and 85.7% for tumors between 8 and 14 cm,3 respectively64 with better result when minimum doses of ⩾18 Gy are applied.87 The median survival for patients with brain metastases from lung cancer treated with Gamma Knife ranged between 9 and 18 months.56,58,64,70,101–105
Evaluation of results of linac-based radiosurgery for brain metastases from primary lung cancer
2014, Reports of Practical Oncology and RadiotherapyCitation Excerpt :Death risk in patients treated with single radiosurgery was 2.9 times higher than in those treated with multiple radiosurgery. Mean survival in patients with brain metastases from lung cancer treated with radiosurgery, as reported in literature, ranges from 4.5 to 13.5 months.21–31 Those data apply to patients treated with both a gamma knife and accelerator.
Clinical outcomes of biological effective dose-based fractionated stereotactic radiation therapy for metastatic brain tumors from non-small cell lung cancer
2013, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :In our series, the MST was 17.1 months and the overall survival at 1 year was 63.3%. These results compare favorably with those of earlier studies on patients with brain metastases from lung cancer (13-20). Recent advances in drug therapy, especially molecular target drugs, may have played a role.
- 1
Present address: Strahlentherapie, Universitätsklinikum Heidelberg, INF 400, 69120 Heidelberg, Germany.
- 2
Present address: Abt. Klinische Forschungseinheit Strahlentherapeutische Onkologie, DKFZ, INF 280, 69120 Heidelberg, Germany.
- 3
Present address: Strahlentherapie, Universitätsklinikum Heidelberg, INF 400, 69120 Heidelberg, Germany.
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Present address: Abt. Klinische Forschungseinheit Strahlentherapeutische Onkologie, DKFZ, INF 280 69120 Heidelberg, Germany.