Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2012  |  Volume : 8  |  Issue : 3  |  Page : 411-416

Clinical outcomes of reirradiation of brain metastases from small cell lung cancer with Cyberknife stereotactic radiosurgery


1 Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2 Department of Radiation Oncology and Otolaryngology, Head and Neck Surgery, University of Pittsburgh School of Medicine, Pittsburgh, USA
3 Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, USA

Date of Web Publication17-Nov-2012

Correspondence Address:
Dwight E Heron
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA
USA
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.103522

Rights and Permissions
 > Abstract 

Purpose: To analyze outcomes of reirradiation with stereotactic radiosurgery (SRS) for patients with brain metastases from small cell lung cancer (SCLC).
Materials and Methods: We reviewed the clinical outcomes of 27 patients with brain metastases from SCLC treated with CyberKnife® robotic radiosurgery (Accuray Inc., Sunnyvale, CA). Kaplan-Meier analyses were used to estimate local control (LC), intracranial control (IC), and overall survival (OS). The Graded Prognostic Assessment (GPA) prognostic index was determined with a Cox Regression analysis to model predictors of outcome.
Results: The median follow-up from SRS was 12 months (2-24 months). Nine patients (32.1%) had Graded Prognostic Assessment (GPA) scores 0-1 and 19 patients (67.9%) had GPA scores 1.5-2.5. 19 patients (70%) received whole brain radiation therapy (WBRT) and 8 patients (30%) received prophylactic cranial irradiation (PCI). The median SRS dose was 20.5 Gy (15-24 Gy) in 1 fraction. Actuarial LC at 6 months and 12 months was 76.5% and 76.5%, respectively. New metastases outside the treated area developed in 60% of assessable patients at a median 3.5 months; 78% received previous WBRT. The median OS was 3 months from SRS with actuarial 6-month and 12-month rates of 25% and 3.6%, respectively. On multivariate analysis no factors were associated with LC, IC, or OS.
Conclusions: SRS for reirradiation of brain metastases from SCLC is safe and achieves local tumor control in the majority of patients. Despite SRS, these patients are at high risk of distant brain failure.

Keywords: Brain metastases, radiosurgery, small cell lung cancer


How to cite this article:
Olson AC, Wegner RE, Rwigema JM, Heron DE, Burton SA, Mintz AH. Clinical outcomes of reirradiation of brain metastases from small cell lung cancer with Cyberknife stereotactic radiosurgery. J Can Res Ther 2012;8:411-6

How to cite this URL:
Olson AC, Wegner RE, Rwigema JM, Heron DE, Burton SA, Mintz AH. Clinical outcomes of reirradiation of brain metastases from small cell lung cancer with Cyberknife stereotactic radiosurgery. J Can Res Ther [serial online] 2012 [cited 2019 Mar 22];8:411-6. Available from: http://www.cancerjournal.net/text.asp?2012/8/3/411/103522


 > Introduction Top


Lung cancer is the most common cause of cancer mortality worldwide in both men and women. [1] Furthermore, lung cancer is the most common source of brain metastasis. [2] Small cell lung cancer (SCLC) accounts for 10-15% of all lung cancers and occurs predominantly in smokers. [3] Although only 10% of patients with SCLC will have brain metastases at diagnosis, the cumulative incidence at 2 years is approximately 50%. [4],[5],[6] For this reason, many patients with SCLC receive prophylactic cranial irradiation (PCI), which appears to reduce the incidence of delayed brain metastases and lengthen overall survival. [7],[8] Treatment options for brain metastases include surgical resection, whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), or a combination of these options. [9],[10],[11],[12],[13] Despite these treatments, many patients will have progression of their intracranial disease and require additional local therapy. There are few reports in the literature on the experience and efficacy of SRS in the management of brain metastases from SCLC. [14],[15] The aim of this study was to analyze clinical outcomes of reirradiation with CyberKnife® based SRS of SCLC patients with brain metastases.


 > Materials and Methods Top


Patient characteristics

We retrospectively reviewed 27 patients with brain metastases from a histologically proven primary SCLC treated with the CyberKnife® robotic radiosurgical system (Accuray Inc., Sunnyvale, CA, USA). The median patient age was 67 years (range: 51-86). 14 patients (52%) were male and 13 patients (48%) were female. The median Karnofsky performance status (KPS) at time of treatment was 80 (60-100). Twenty-three (85%) had active systemic disease at the time of SRS. The median total number of metastases per patient was 2 (1-6). Sixteen patients were asymptomatic at time of brain metastasis diagnosis, 5 had headaches, 1 had ataxia, 1 had generalized confusion, 3 had seizures, and 1 had unilateral weakness (some patients had multiple symptoms).

All patients had previously undergone cranial irradiation. Nineteen patients (70%) had received WBRT prior to SRS and 8 patients (30%) had received PCI prior to SRS. Brain metastases were identified on computed tomography (CT) or magnetic resonance imaging (MRI). Typically, tumors were contrast-enhancing lesions in the brain parenchyma with surrounding edema. The median SRS dose was 20.5 Gy (15-24 Gy) delivered in 1 fraction. All doses were prescribed to the 80% isodose line with a median tumor coverage of 95.3% (76.7-100%).The median tumor volume was 2.7 cc (0.14-30 cc). The median time from prior radiation therapy to SRS was 8 months (0.5-18 months).

Simulation and planning

Each patient was comfortably positioned on the CT simulation table and a custom mask was fabricated. A thin-slice high resolution CT with intravenous contrast was then obtained while the patient was immobilized. The acquired images were then transferred to the treatment planning workstation and fused with pre-treatment thin-slice (1.2mm) contrast-enhanced spoiled gradient recalled acquisition in steady state (SPGR) sequence MRI utilizing commercially available fusion software. The tumor volume and any surrounding critical structures were manually delineated by a team including a radiation oncologist, a medical physicist, and a neurosurgeon. The planning target volume (PTV) was defined as the contrast-enhancing tumor with no margin. Dose volume histograms were calculated for the target volume and nearby critical structures and were utilized to select the optimal treatment plan. An ideal SRS plan provided 95% of the prescription dose to the PTV while sparing surrounding organs at risk. If surrounding organs at risk were deemed to be at excess risk for toxicity, a plan with lower PTV coverage was accepted.

Follow-up

Follow up neurologic examination and MRI (or CT scanning if ineligible for MRI) was performed at 2 months after SRS, every 2-3 months for the 1 st year and at 3 to 6 monthly intervals thereafter. Imaging was performed to assess changes in tumor size, to identify the development of any new tumors, and to evaluate the risk of peritumoral reactive swelling. A significant change in tumor size was defined as either an increase or decrease of 2mm in the contrast enhancing dimensions in any single plane of the tumor. This definition is an institutional preference utilized in prior studies. [15] Local control was defined as persistent stable disease (SD), partially responding (PR) lesion, completely responding (CR) lesion, or progressive disease (PD) throughout the course of radiographic follow-up. CR was defined as a complete resolution of the lesion, SD as a post-treatment tumor size ±2 mm of the pre-treatment tumor volume, PR as a decrease in tumor size greater than 2 mm up to complete disappearance, and PD was defined as any increase in tumor measurement greater than 2 mm in any single plane. Distant failure was defined as the development of new brain metastases outside the original SRS treatment volume.

Statistical analysis

Survival time was computed from the time of SRS. Survival curves and median survival were calculated using the Kaplan-Meier method. [16] The Graded Prognostic Assessment (GPA) prognostic index was determined and included a multivariate Cox regression analysis to model predictors of outcome. [17] All statistical tests were carried out using SPSS Version 15.0 (SPSS, Chicago, IL). The project was reviewed and approved by the University of Pittsburgh institutional review board.


 > Results Top


The median follow-up from SRS in this patient population was 12 months (2-24 months). All patients had died by time of analysis. Eight died from progressive systemic disease and one patient's death was attributed to intracranial disease. The remaining 18 patients died from unknown or undocumented causes. The median OS was 16 months from primary diagnosis with actuarial 6-month and 12-month rates of 70% and 52%, respectively [Figure 1]. The median OS from the date of SRS was 3 months with actuarial 6-month and 12-month rates of 25% and 3.6%, respectively.
Figure 1: Overall survival (in months) from time of primary diagnosis in all 27 patients with brain metastases from small-cell lung cancer. The actuarial 6 months and 12 months overall survival rates were 70% and 52%, respectively

Click here to view


Nine patients (33%) had GPA scores 0-1 and 18 patients (66%) had GPA scores 1.5-2.5. 15 patients (55%) had an available follow-up MRI. The treatment responses were 1 CR (6.3%), 6 PR (37.5%), 7 SD (43.7%) and 1 PD (7%) at a median time of 2 months. Actuarial local control at 6 months and 12 months was 76.5% and 76.5%, respectively [Figure 2]. New brain metastases outside of the treated area developed in 60% of assessable patients at a median interval of 3.5 months; 78% of these patients had received previous WBRT and the other 22% had prior PCI [Figure 3].
Figure 2: Local control from time of linear accelerator based radiosurgery reirradiation in all 27 patients with brain metastases from small cell lung cancer. Local control rates at 6 months and 12 months were both 75%

Click here to view
Figure 3: Distant intracranial control from time of linear accelerator based radiosurgery reirradiation in all 27 patients with brain metastases from small cell lung cancer. Distant intracranial control rates at 6 months
and 12 months were both 31.3%


Click here to view


On multivariate analysis, no factors were associated with LC and IC. There were also no factors that were associated with OS. There were no treatment-related toxicities and no patients required steroids post-SRS.


 > Discussion Top


Brain metastases are the most common type of intracranial tumor. [18] They frequently occur in SCLC and are found in approximately 10% of patients at the time of cancer diagnosis. More than 50% of patients will develop brain spread at 2 years. [4],[5],[6] Because of such a high incidence, PCI has been advocated to reduce the development of brain metastases and to lengthen overall survival in patients. [5],[6],[7],[8] Treatment options for patients with brain metastases from SCLC include surgical resection for selected patients, WBRT, repeat WBRT if the patient previously received PCI, and SRS. There are two case reports in the literature reporting the outcomes of 2 patients with controlled systemic SCLC and a solitary brain metastasis. Each patient had surgical resection followed by WBRT, resulting in excellent long-term control and survival. [19],[20] Results from studies including patients with a solitary brain metastasis from various primary histologies confirmed that the addition of WBRT to surgical resection improved local control and reduced the incidence of death from neurologic causes. [10],[21]

WBRT has been used for decades in patients with brain metastases and is thus very well-studied. The use of WBRT for patients with brain metastases from various primary cancers has been shown to improve existing neurologic symptoms and improve OS compared with corticosteroids and supportive care (median survival, 4-5 months). [22],[23],[24] Radiotherapy alone doubles the survival rate compared to steroids and supportive care alone. [25] The overall response rates to WBRT have varied from 50% to 85%. [26],[27],[28] There has been one prospective Phase II study examining outcomes in patients with brain-only failure from SCLC. [29] The study was small (n = 22) and none of the patients had received previous radiation. The response rate was 50% and neurologic symptoms remained stable or improved in 55% of the patients. The median duration of response was 5.4 months and the first site of relapse for the majority of the patients was the central nervous system. Median overall survival was 4.7 months in this cohort. Overall, compared with retrospective series, these results were somewhat inferior.

In more recent years, SRS has been shown to be an effective alternative therapy for patients with brain metastases. It is especially useful in patients with progression of disease following WBRT, for whom treatment-related neurotoxicity is a major concern. SRS allows for the delivery of a highly focused dose of radiation with rapid fall off and thereby reduces dose to the surrounding normal brain. This feature should potentially reduce the likelihood of developing late neurocognitive defects, an issue that becomes of increasing concern in long-term survivors. SRS has been very well studied in the setting of brain metastasis. However, SCLC patients are usually only a small fraction of the study population. In patients with brain metastases from various primary cancers, SRS has shown to be both efficacious and safe with local control rates of 65-95% and an adverse effect rate of 5-10%. [30],[31],[32],[33]

The published experience of treating brain metastases from SCLC with SRS is limited to four retrospective studies. The first, by Sheehan et al., reviewed the outcomes of 27 patients with brain metastases from SCLC. [14] All patients had undergone previous WBRT. The median number of tumors in that cohort was one (1-4) with a median volume of 5.4 cm 3 . The median survival from SRS was 4.5 months with a local control rate of 81% in patients with available follow-up imaging. Significant prognostic factors for survival that were identified in that patient population were performance status, tumor volume, and length of interval between primary lung cancer diagnosis and brain metastasis diagnosis. Only 3 patients (11%) in that study developed new intracranial lesions after SRS. The second retrospective series included 34 patients with brain metastases from SCLC. [34] No patients had received prior WBRT. The mean number of tumors treated was 1.9 and the mean volume was 0.93 ± 2.45 cm 3 . The local control rate at 1 year was 95% with a mean survival of 9.1 months. Significant predictors of poor survival were male gender, uncontrolled primary disease, and KPS <70. The mean time to development of new intracranial lesions was 6.9 months in that study. The third retrospective series, from Wegner et al., described the outcomes of 44 patients with brain metastases from SCLC. [15] Thirty patients (68%) had received prior PCI or WBRT. The actuarial local control rate at 6 and 12 months was 90% and 86% respectively with a median OS of 9 months. Significant predictors of increased OS were performance status and combined treatment involving WBRT and SRS within 4 weeks. Patients treated with a combined approach had a median OS of 14 months compared to 6 months if SRS was delivered alone. The final retrospective study, from Harris et al., analyzed 51 patients with SCLC and previous WBRT who were treated with SRS. [35] All patients had received prior radiation therapy; 17 patients (33%) received PCI and 34 patients (67%) received WBRT. The actuarial local control rate at 12 and 24 months were 54% and 40%, respectively with a median OS of 5.9 months. The status of extracranial disease at the time of salvage predicted for increased OS, as did the use of post-SRS chemotherapy. These findings support the use of SRS for this patient population with a particular benefit for those patients with no active extracranial disease, and support the increasing utilization of combined modality therapy for these patients. [Table 1] for a comparison of the four prior retrospective studies and the present analysis.
Table 1: C linical outcomes of small cell lung cancer patients treated with stereotactic radiosurgery

Click here to view


These data support the use of SRS for brain metastases from SCLC, which in the context of current clinical practice will most likely be used after failure of WBRT. This was indeed the case with our patient population, as 100% of patients had previously been treated with WBRT or PCI. Despite the use of SRS, many patients will still experience failure outside the treatment area. In our series, 62.5% of patients experienced distant brain metastases at a median interval of 3.5 months, highlighting the magnitude of this risk and perhaps the need of incorporating WBRT if possible. The use of additional WBRT, however, is often limited by a history of previous radiation, which in our series was present in 80% of patients with distant failure. In one outcomes report of 86 patients receiving reirradiation of brain metastases using repeat WBRT, Wong et al. described a 27% rate of complete resolution of neurologic symptoms, 43% rate of partial symptom resolution, and 29% with no response. [36] Median survival after reirradiation was relatively short at 4 months. Thus SRS is still an important tool when it comes to managing patients with brain metastases from SCLC.

The outcomes presented in the current study are relatively worse than the previously published series described above. This may be due to several factors. First, all our patients had received prior radiation therapy, whereas in some of the prior studies some patients had received SRS prior to other radiation therapy. Secondly, a high percentage of patients (85%) in our series also had active systemic disease, a known prognostic factor for decreased survival. Along those lines, a third of the patients in our study had relatively low GPA scores (0-1) which portends a poorer prognosis and outcome (GPA not reported in the other studies mentioned above), and all patients had a GPA score less than 2.5. The median OS in our study is similar to those patients with a GPA score less than 2.5 in Sperduto et al.'s original analysis. [37]

Chemotherapy is another treatment option for patients with brain metastases from SCLC given the systemic nature of the disease. Its efficacy in the treatment of brain metastases however, is limited by an inability to cross the blood brain barrier. There was a small phase II trial which compared WBRT (40 Gy in 20 fractions) with and without concurrent and adjuvant temozolomide for patients with brain metastases from various primaries. [28] The temozolomide group showed a significantly better response rate on follow-up imaging-96% with 38% of those responding experiencing a complete response. In the WBRT alone group only 67% of patients had an imaging response. Similarly, the patients receiving temozolomide were more likely to experience neurological improvement and less likely to require corticosteroids. In terms of OS, patients in the temozolomide arm had a slight survival advantage of 1.6 months, but given the small number of patients this did not reach significance. Unfortunately, in our series we were unable to get an accurate history of the chemotherapy the patients were receiving to determine if there was an effect.

Some of the weaknesses of the present study include its retrospective nature and the inherent biases present in such studies. In addition, our lack of data regarding the use of chemotherapy was a limitation of this study. The staging information as limited stage versus extensive stage was also unavailable for this analysis, which would be useful information and could potentially explain some of the outcomes differences seen in our study compared to previous analyses. Also, that 18 patients died of unknown causes may lead to misrepresentation of the survival data. Finally, only 55% of patients in our study had follow-up imaging available for review; although this likely due in part, to the poor prognosis in this particular group of patients (median OS from SRS: 3 months). This could lead to a misrepresentation of the true local and regional control rates.


 > Conclusions Top


SRS for reirradiation of brain metastases from SCLC is safe and achieves local tumor control in the majority of patients. Despite aggressive treatment with SRS, these patients still remain at a high risk of distant brain failure, highlighting the importance of WBRT in this patient population.

 
 > References Top

1.Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.  Back to cited text no. 1
[PUBMED]    
2.Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 2004;22:2865-72.  Back to cited text no. 2
[PUBMED]    
3.Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: Analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006;24:4539-44.  Back to cited text no. 3
    
4.Hirsch FR, Paulson OB, Hansen HH, Vraa-Jensen L. Intracranial metastases in small cell carcinoma of the lung: Correlation of clinical and autopsy findings. Cancer 1982;50:2433-7.  Back to cited text no. 4
    
5.Arriagada R, Le Chevalier T, Borie F, Riviere A, Chomy P, Monnet I, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst 1995;87:183-90.  Back to cited text no. 5
    
6.Komaki R. Prophylactic cranial irradiation for small cell carcinoma of the lung. Cancer Treat Symp 1985;2:35-9.  Back to cited text no. 6
    
7.Auperin A, Arriagada R, Pignon JP, Le Pechoux C, Gregor A, Stephens RJ, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999;341:476-84.  Back to cited text no. 7
    
8.Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007;357:664-72.  Back to cited text no. 8
[PUBMED]    
9.Loeffler JS, Patchell RA, Sawaya R. Metastatic brain cancer. In: Devita HT, Hellman S, Rosenberg SA, editors. Cancer: Principles and Practice of Oncology. Philadelphia: JB Lippincott; 1997. p. 2523.  Back to cited text no. 9
    
10.Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322:494-500.  Back to cited text no. 10
[PUBMED]    
11.Vecht CJ, Haaxma-Reiche H, Noordijk EM, Padberg GW, Voormolen JH, Hoekstra FH, et al. Treatment of single brain metastasis: Radiotherapy alone or combined with neurosurgery?Ann Neurol 1993;33:583-90.  Back to cited text no. 11
[PUBMED]    
12.Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: A randomized trial. JAMA 1998;280:1485-9.  Back to cited text no. 12
[PUBMED]    
13.Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase III results of the RTOG 9508 randomised trial. Lancet 2004;363:1665-72.  Back to cited text no. 13
[PUBMED]    
14.Sheehan J, Kondziolka D, Flickinger J, Lunsford LD. Radiosurgery for patients with recurrent small cell lung carcinoma metastatic to the brain: Outcomes and prognostic factors. J Neurosurg 2005;102:247-54.  Back to cited text no. 14
    
15.Wegner RE, Olson AC, Kondziolka D, Niranjan A, Lunsford LD, Flickinger JC. Stereotactic radiosurgery for patients with brain metastases from small cell lung cancer. Int J Radiat Oncol Biol Phys 2011;81:e21-7.  Back to cited text no. 15
    
16.Kaplan EL, Meier P. Nonparametric estimation from incomplete estimations. J Am Stat Assoc 1958;53:457-481.  Back to cited text no. 16
    
17.Cox DR. Regression models and life tables. J R Stat Soc 1972;74:187-220.  Back to cited text no. 17
    
18.Walker AE, Robins M, Weinfeld FD. Epidemiology of brain tumors: The national survey of intracranial neoplasms. Neurology 1985;35:219-26.  Back to cited text no. 18
[PUBMED]    
19.Abratt RP, de Groot M, Willcox PA. Resection of a solitary brain metastasis in a patient with small cell lung cancer-long-term survival. Eur J Cancer 1995;31A:419.  Back to cited text no. 19
[PUBMED]    
20.Imai R, Hayakawa K, Sakurai H, Nakayama Y, Mitsuhashi N, Niibe H. Small cell lung cancer with a brain metastasis controlled for 5 years: A case report. Jpn J Clin Oncol 2001;31:116-8.  Back to cited text no. 20
    
21.Patchell RA, Cirrincione C, Thaler HT, Galicich JH, Kim JH, Posner JB. Single brain metastases: Surgery plus radiation or radiation alone. Neurology 1986;36:447-53.  Back to cited text no. 21
[PUBMED]    
22.Videtic GM, Adelstein DJ, Mekhail TM, Rice TW, Stevens GH, Lee SY, et al. Validation of the RTOG recursive partitioning analysis (RPA) classification for small-cell lung cancer-only brain metastases. Int J Radiat Oncol Biol Phys 2007;67:240-3.  Back to cited text no. 22
[PUBMED]    
23.Quan AL, Videtic GM, Suh JH. Brain metastases in small cell lung cancer. Oncology (Williston Park) 2004;18:961-72.discussion 974, 979-80, 987.  Back to cited text no. 23
    
24.Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, 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;37:745-51.  Back to cited text no. 24
[PUBMED]    
25.Walker MD, Alexander E, Hunt WE, MacCarty CS, Mahaley MS, Mealey J, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. J Neurosurg 1978;49:333-43.  Back to cited text no. 25
    
26.Khuntia D, Brown P, Li J, Mehta MP. Whole-brain radiotherapy in the management of brain metastasis. J Clin Oncol 2006;24:1295-304.  Back to cited text no. 26
[PUBMED]    
27.Peacock KH, Lesser GJ. Current therapeutic approaches in patients with brain metastases. Curr Treat Options Oncol 2006;7:479-89.  Back to cited text no. 27
[PUBMED]    
28.Antonadou D, Paraskevaidis M, Sarris G, Coliarakis N, Economou I, Karageorgis P, et al. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol 2002;20:3644-50.  Back to cited text no. 28
[PUBMED]    
29.Postmus PE, Haaxma-Reiche H, Gregor A, Groen HJ, Lewinski T, Scolard T, et al. Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study. Radiother Oncol 1998;46:29-32.  Back to cited text no. 29
[PUBMED]    
30.Wen PY, Loeffler JS.Management of brain metastases. Oncology (Williston Park)1999;13:941-54, 957-61; discussion 961-2, 9.  Back to cited text no. 30
[PUBMED]    
31.Flickinger JC, Kondziolka D, Lunsford LD, Coffey RJ, Goodman ML, Shaw EG, et al. A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis. Int J Radiat Oncol Biol Phys 1994;28:797-802.  Back to cited text no. 31
[PUBMED]    
32.Alexander E 3 rd , Moriarty TM, Loeffler JS. Radiosurgery for metastases. J Neurooncol 1996;27:279-85.  Back to cited text no. 32
    
33.Pirzkall A, Debus J, Lohr F, Fuss M, Rhein B, Engenhart-Cabillic R, et al.Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases. J Clin Oncol 1998;16:3563-9.  Back to cited text no. 33
[PUBMED]    
34.Serizawa T, Ono J, Iichi T, Matsuda S, Sato M, Odaki M, et al. Gamma knife radiosurgery for metastatic brain tumors from lung cancer: A comparison between small cell and non-small cell carcinoma. J Neurosurg 2002;97:S484-8.  Back to cited text no. 34
[PUBMED]    
35.Harris S, Chan MD, Lovato JF, Ellis TL, Tatter SB, Bourland JD, et al.Gamma Knife stereotactic radiosurgery as salvage therapy after failure of whole-brain radiotherapy in patients with small-cell lung cancer. Int J Radiat Oncol Biol Phys 2012;83;e53-9.  Back to cited text no. 35
    
36.Wong WW, Schild SE, Sawyer TE, Shaw EG.Analysis of outcome in patients reirradiated for brain metastases. Int J Radiat Oncol Biol Phys 1996;34:585-90.  Back to cited text no. 36
[PUBMED]    
37.Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: An analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 2008;70:510-4.  Back to cited text no. 37
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]


This article has been cited by
1 Épithéliomas bronchiques à petites cellules et métastases cérébrales de leur traitement à leur prévention
P. Van Houtte,D. Devriendt,M. Roelandts
Revue des Maladies Respiratoires Actualités. 2014; 6(4): 525
[Pubmed] | [DOI]
2 Retreatment of Central Nervous System Tumours
B. Jones,W. Grant
Clinical Oncology. 2014;
[Pubmed] | [DOI]
3 Local recurrence and survival following stereotactic radiosurgery for brain metastases from small cell lung cancer
Paul Rava,Shirin Sioshansi,Thomas DiPetrillo,Rees Cosgrove,Christopher Melhus,Julian Wu,John Mignano,David E. Wazer,Jaroslaw T. Hepel
Practical Radiation Oncology. 2014;
[Pubmed] | [DOI]
4 Strahlentherapeutische Optionen bei Hirnmetastasen des kleinzelligen Lungenkarzinoms
D. Rades,S. Huttenlocher
Der Onkologe. 2013; 19(11): 950
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Materials and Me...>Results>Discussion>Conclusions>Article Figures>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed3182    
    Printed128    
    Emailed1    
    PDF Downloaded315    
    Comments [Add]    
    Cited by others 4    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]