SUCCESSFUL TREATMENT OF METASTATIC BRAIN TUMOR BY CYBERKNIFE: A CASE REPORT Cheng-Ta Hsieh, 1 Cheng-Fu Chang, 1 Ming-Ying Liu, 1 Li-Ping Chang, 2 Dueng-Yuan Hueng, 3 Steven D. Chang, 4 and Da-Tong Ju 1 1 Department of Neurological Surgery, 2 Department of Radiation Oncology, 3 Keelung Civilian Administration Division and Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; and 4 Department of Neurosurgery, Stanford University Medical Center, Stanford, California, USA. Stereotactic radiosurgery plays an important role in management of metastatic brain tumors, especially when the tumor has recurred after treatment with previous whole brain radiotherapy. Most metastatic brain tumors less than 1 cm 3 show a complete response after stereotactic radiosurgery. However, there are few reports of a dramatic change in the complete response of large metastatic brain tumors. Here, we report a case of adenocarcinoma of lung that had metastasized to the brain. Because the recurrence of the metastatic brain tumor measured approximately 3 cm in diameter, the tumor was previously treated with two prior craniotomies followed by whole brain radiation to the resection cavity. The tumor subsequently recurred and was treated with stereotactic radiosurgery (CyberKnife). A dramatic response was noted 3 months after radiosurgery with complete disappearance of the recurrent tumor. Key Words: brain metastases, CyberKnife, stereotactic radiosurgery (Kaohsiung J Med Sci 2010;26:144 9) Metastatic brain tumors are the most common intracranial neoplasm in adults with approximately 40 50% of cases secondary to lung cancer [1]. Many treatment modalities including surgery, whole brain radiotherapy (WBRT) and chemotherapy have been used to maximize survival time, provide local control, and improve neurological function [2]. However, the management of patients with recurrent metastatic brain tumors treated by prior surgery and WBRT remains a challenge for clinical physicians. Surgical intervention has been the primary treatment opinion for this condition before the development of stereotactic radiosurgery (SRS). SRS has been proven efficacious in the 144 Received: Apr 27, 2009 Accepted: Jun 17, 2009 Address correspondence and reprint requests to: Dr Da-Tong Ju, Department of Neurological Surgery, Tri-Service General Hospital, 325 Section 2, Cheng-Kung Road, Neihu District, Taipei, Taiwan. E-mail: nogor@mail2000.com.tw management of metastatic brain tumor, especially when the tumor has recurred after previous WBRT. SRS combines the principles of stereotactic localization, with multiple radiation beam trajectories, to deliver a high dose of radiation to the treatment site and minimize exposure to normal tissue [3]. The method was first developed in 1951 by Leksell [3], who used a stereotactic frame to focus radiation from a cobalt source through a series of collimators on a brain lesion. During the past several decades, this noninvasive technique, combined with new advances in radiosurgery, has proven to be effective in the ablation of intracranial lesions. The CyberKnife is a new image-guided frameless and real-time robotic SRS system that is capable of delivering a highly precise radiation beam using tomography [4]. The greater tumor control rate in smaller metastatic brain tumors measuring less than 1 cm 3 has already been demonstrated using this technique [5 7]. However, the complete response of larger metastatic Kaohsiung J Med Sci March 2010 Vol 26 No 3 2010 Elsevier. All rights reserved.
Metastatic brain tumor treated by CyberKnife brain tumors after CyberKnife therapy has been rarely discussed [6]. We report a case of a 3 cm (in diameter) metastatic brain tumor that was initially treated by surgical intervention and WBRT. The tumor subsequently recurred and was treated with CyberKnife SRS with a dramatic response to the new therapy. CASE PRESENTATION A 56-year-old man presented with blurred vision, headache, and weakness in the left lower leg for 1 month prior to his hospital admission on June 6, 2005. On admission, a neurological examination revealed left hemianopsia and grade 4/5 decreased muscle strength in the left lower leg. Magnetic resonance imaging (MRI) demonstrated a 5.7 cm rim-enhancing lesion in the right parieto-occipital lobe and a 1.9 cm rim-enhancing lesion in the left temporal lobe, which were both highly suspicious for brain metastases. Because of the patient s progressive symptoms, he underwent craniotomy to remove the tumor in the parieto-occipital lobe on June 20, and a repeat craniotomy on July 4 was performed to remove the tumor in the left temporal lobe. The pathology reports confirmed the diagnosis of metastatic adenocarcinoma of the lung. WBRT (3,000 cgy/15 fractions) was administered from November 3 to November 23. A follow-up brain MRI scan on November 14 revealed a rim-enhancing cystic lesion measuring 4.6 cm in maximal diameter in the right parieto-occipital region compatible with recurrence and the patient underwent another craniotomy on November 28. However, on February 14, 2007, additional computed tomography and MRI showed a 3 cm (in diameter) recurrent tumor in the right occipital region (Figures 1A and 1B). Because the size of the tumor was so large and no obvious neurological deficits were present, SRS with A B C D Figure 1. (A) Pre-stereotactic radiosurgery (SRS) computed tomography of the brain shows a heterogeneously contrast-enhanced tumor mass approximately 3 cm in diameter, located in the right parieto-occipital lobe. (B) Pre-SRS T1-weighted axial images of magnetic resonance imaging show a contrast-enhanced tumor mass in the right parieto-occipital lobe. (C) Two months after CyberKnife SRS, computed tomography of the brain revealed a reduced tumor mass without obvious peritumoral edema. (D) Three months after CyberKnife SRS, T1-weighted axial images of magnetic resonance imaging revealed the disappearance of the tumor mass with complete response. Kaohsiung J Med Sci March 2010 Vol 26 No 3 145
C.T. Hsieh, C.F. Chang, M.Y. Liu, et al Figure 2. Planning of CyberKnife stereotactic radiosurgery. CyberKnife was indicated. On October 12, 2007 our patient received CyberKnife SRS with a marginal dose of 1,500 cgy delivered to the 80% isodose line. The treated tumor volume was 23,771 mm 3 with 98.1% tumor coverage. The conformity index was 1.43 and the modified conformity index was 1.46 (Figure 2). During regular follow-up, there were no side effects due to the radiation and the tumor shrunk within 2 months (Figure 1C) and had completely disappeared within 3 months (Figure 1D). DISCUSSION The exact incidence of metastatic brain tumors remains unknown but has been estimated at approximately 146 200,000 cases per year [2]. If left untreated, the median survival time is approximately 1 2 months [6]. Various treatments, including surgery, chemotherapy, WBRT or combined modalities, have been shown to prolong survival time and improve neurological outcome [2]. Factors such as the age, clinical performance status (Karnofsky score), systematic disease and the number, size, volume, and location of the tumor can predict the outcome after these therapies [8,9]. Although glucocorticoids and WBRT have been the mainstay of treatment for metastatic brain tumors, craniotomy for tumor resection has been the standard therapy for local control [10]. The median survival time in patients with metastatic brain tumors treated with additional WBRT remains limited to 3 6 months [11]. However, if the metastatic brain tumor Kaohsiung J Med Sci March 2010 Vol 26 No 3
Metastatic brain tumor treated by CyberKnife recurs after WBRT, the next-step in management of these tumors remains a challenge for neurosurgeons because surgical intervention may be the only option. SRS uses multiple convergent beams to deliver a single large dose of radiation to a discrete target volume and is an alternative treatment for patients with metastatic brain tumors that are surgically unresectable or located in the eloquent brain areas [2,12]. Numerous studies have reported the effects of craniotomy alone compared with WBRT alone, SRS alone, and combined modalities for the management of metastatic brain tumors [2,10 13]. SRS has been proven an effective alternative and noninvasive treatment for metastatic brain tumors. In two series of non-small cell lung cancer with brain metastasis, SRS afforded effective local tumor control in approximately 84 94% of patients with a prolonged median survival time of approximately 15 months [12,14,15]. The CyberKnife is an image-guided frameless, realtime robotic radiosurgery system [4]. The benefits of the CyberKnife include more accurate target localization and better dose delivery for management of metastatic brain tumors [4 7]. To date, the local tumor control rate has been approximately 83%, which is comparable to other radiosurgery systems [16]. Shimamoto et al recently studied 48 patients with metastatic brain tumors, with the majority from lung primaries, treated with CyberKnife stereotactic irradiation. They demonstrated complete response to the CyberKnife with non-visualization of the previously enhancing lesions on subsequent imaging when the clinical target volume was less than 1 cm 3 [6]. This result suggests that smaller tumors have fewer propensities for progression and a lesser dose tolerance. Fractionated modality has been considered for the control of larger tumors. However, the complete response of larger metastatic brain tumors ( 1cm 3 ) has not yet been demonstrated. In our case, the recurrence of metastatic brain tumor following craniotomy with removal of the tumor and WBRT was observed during the follow-up neuroimaging studies. After CyberKnife radiosurgery with 1,500 cgy, the tumor, which initially measured 3 cm in diameter, completely resolved within 3 months. In conclusion, the image-guided SRS is especially useful for lesions that cannot be treated conventionally, such as lesions that have received the maximal radiation dose using conventional WBRT, or postoperative residual lesions. The complete response of metastatic tumors larger than 1 cm 3 can also be achieved within a few months after CyberKnife radiosurgery, as shown by our case study. ACKNOWLEDGMENTS The authors would like to thank the members of CyberKnife center of Tri-Service General Hospital, including physicist Jui-Pin Chen, therapists Maio-Jung Lin and Peng-Hsien Yang, and nurse Shiow-Hwa Hwang for their help with this study. REFERENCES 1. Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol 2005;75:5 14. 2. Eichler AF, Loeffler JS. Multidisciplinary management of brain metastases. Oncologist 2007;12:884 98. 3. Leksell L. The stereotactic method and radiosurgery of the brain. Acta Chir Scand 1951;102:316 9. 4. Gibbs IC. Frameless image-guided intracranial and extracranial radiosurgery using the Cyberknife robotic system. Cancer Radiother 2006;10:283 7. 5. Giller CA, Berger BD, Fink K, et al. A volumetric study of CyberKnife hypofractionated stereotactic radiotherapy as salvage for progressive malignant brain tumors: initial experience. Neurol Res 2007;29:563 8. 6. Shimamoto S, Inoue T, Shiomi H, et al. CyberKnife stereotactic irradiation for metastatic brain tumors. Radiat Med 2002;20:299 304. 7. Chang SD, Murphy M, Geis P, et al. Clinical experience with image-guided robotic radiosurgery (the Cyberknife) in the treatment of brain and spinal cord tumors. Neurol Med Chir (Tokyo) 1998;38:780 3. 8. Gaspar L, Scott C, Rotman M, 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. 9. Lagerwaard FJ, Levendag PC, Nowak PJ, et al. Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys 1999;43:795 803. 10. Smith ML, Lee JY. Stereotactic radiosurgery in the management of brain metastasis. Neurosurg Focus 2007; 22:E5. 11. Stafinski T, Jhangri GS, Yan E, et al. Effectiveness of stereotactic radiosurgery alone or in combination with WBRT compared with conventional surgery and/or WBRT for the treatment of one or more brain metastases: a systematic review and meta-analysis. Cancer Treat Rev 2006;32:203 13. Kaohsiung J Med Sci March 2010 Vol 26 No 3 147
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1 1 1 2 3 Steven D.Chang 4 1 1 2 3 4 1 cm 3 3 cm 2010;26:144 9 98 4 27 98 6 17 325 Kaohsiung J Med Sci March 2010 Vol 26 No 3 149