Whole brain radiotherapy plus simultaneous in-field boost with image guided intensity-modulated radiotherapy for brain metastases of non-small cell lung cancer

Radiation Oncology

You Lu³  Zhenyu Ding¹  Renming Zhong⁴  Shichao Wang⁴  Lei Deng¹  Youling Gong¹  Yong Xu¹  Jianxin Xue¹  Jia Liu²  Lin Zhou¹ 

[1] Department of Thoracic Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China;Department of Oncology, Chengdu First People’s Hospital, Chengdu, Sichuan Province, China;State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Chengdu, Sichuan Province, China;Center of Radiation Physics, Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China

关键词: Non-small cell lung cancer;    Brain metastases;    Simultaneous in-field boost;    Whole brain radiotherapy;   

Others  :  803974
DOI  :  10.1186/1748-717X-9-117

 received in 2014-02-03, accepted in 2014-04-28,  发布年份 2014

【 摘 要 】

Background

Whole brain radiotherapy (WBRT) plus sequential focal radiation boost is a commonly used therapeutic strategy for patients with brain metastases. However, recent reports on WBRT plus simultaneous in-field boost (SIB) also showed promising outcomes. The objective of present study is to retrospectively evaluate the efficacy and toxicities of WBRT plus SIB with image guided intensity-modulated radiotherapy (IG-IMRT) for inoperable brain metastases of NSCLC.

Methods

Twenty-nine NSCLC patients with 87 inoperable brain metastases were included in this retrospective study. All patients received WBRT at a dose of 40 Gy/20 f, and SIB boost with IG-IMRT at a dose of 20 Gy/5 f concurrent with WBRT in the fourth week. Prior to each fraction of IG-IMRT boost, on-line positioning verification and correction were used to ensure that the set-up errors were within 2 mm by cone beam computed tomography in all patients.

Results

The one-year intracranial control rate, local brain failure rate, and distant brain failure rate were 62.9%, 13.8%, and 19.2%, respectively. The two-year intracranial control rate, local brain failure rate, and distant brain failure rate were 42.5%, 30.9%, and 36.4%, respectively. Both median intracranial progression-free survival and median survival were 10 months. Six-month, one-year, and two-year survival rates were 65.5%, 41.4%, and 13.8%, corresponding to 62.1%, 41.4%, and 10.3% of intracranial progression-free survival rates. Patients with Score Index for Radiosurgery in Brain Metastases (SIR) >5, number of intracranial lesions <3, and history of EGFR-TKI treatment had better survival. Three lesions (3.45%) demonstrated radiation necrosis after radiotherapy. Grades 2 and 3 cognitive impairment with grade 2 radiation leukoencephalopathy were observed in 4 (13.8%) and 4 (13.8%) patients. No dosimetric parameters were found to be associated with these late toxicities. Patients received EGFR-TKI treatment had higher incidence of grades 2–3 cognitive impairment with grade 2 leukoencephalopathy.

Conclusions

WBRT plus SIB with IG-IMRT is a tolerable and effective treatment for NSCLC patients with inoperable brain metastases. However, the results of present study need to be examined by the prospective investigations.

【 授权许可】

   
2014 Zhou et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Mujoomdar A, Austin JH, Malhotra R, Powell CA, Pearson GD, Shiau MC, Raftopoulos H: Clinical predictors of metastatic disease to the brain from non-small cell lung carcinoma: primary tumor size, cell type, and lymph node metastases. Radiology 2007, 242:882-888.
• [2]Khuntia D, Brown P, Li J: Mehta MP:Whole-brain radiotherapy in the management of brain metastasis. J Clin Oncol 2006, 24:1295-1304.
• [3]Flickinger JC, Kondziolka D, Pollock BE, Maitz AH: Lunsford LD:Complications from arteriovenous malformation radiosurgery: multivariate analysis and risk modeling. Int J Radiat Oncol Biol Phys 1997, 38:485-490.
• [4]Schlienger M, Nataf F, Huguet F, Pene F, Foulquier JN, Orthuon A, Roux FX, Touboul E: Hypofractionated stereotactic radiotherapy for brain metastases. Cancer Radiother 2010, 14:119-127.
• [5]Cardinale RM, Benedict SH, Wu Q, Zwicker RD, Gaballa HE, Mohan R: A comparison of three stereotactic radiotherapy techniques; ARCS vs. noncoplanar fixed fields vs. intensity modulation. Int J Radiat Oncol Biol Phys 1998, 42:431-436.
• [6]Ingrosso G, Miceli R, Fedele D, Ponti E, Benassi M, Barbarino R, Di Murro L, Giudice E, Santarelli F, Santoni R: Cone-beam computed tomography in hypofractionated stereotactic radiotherapy for brain metastases. Radiat Oncol 2012, 7:54. BioMed Central Full Text
• [7]Dincoglan F, Beyzadeoglu M, Sager O, Oysul K, Sirin S, Surenkok S, Gamsiz H, Uysal B, Demiral S, Dirican B: Image-guided positioning in intracranial non-invasive stereotactic radiosurgery for the treatment of brain metastasis. Tumori 2012, 98:630-635.
• [8]Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr: 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, 363:1665-1672.
• [9]Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G: Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 2006, 295:2483-2491.
• [10]Jiang XS, Xiao JP, Zhang Y, Xu YJ, Li XP, Chen XJ, Huang XD, Yi JL, Gao L, Li YX: Hypofractionated stereotactic radiotherapy for brain metastases larger than three centimeters. Radiat Oncol 2012, 7:36. BioMed Central Full Text
• [11]Serizawa T, Yamamoto M, Sato Y, Higuchi Y, Nagano O, Kawabe T, Matsuda S, Ono J, Saeki N, Hatano M, Hirai T: Gamma Knife surgery as sole treatment for multiple brain metastases: 2-center retrospective review of 1508 cases meeting the inclusion criteria of the JLGK0901 multi-institutional prospective study. J Neurosurg 2010, 113(Suppl):48-52.
• [12]Rodrigues G, Yartsev S, Yaremko B, Perera F, Dar AR, Hammond A, Lock M, Yu E, Ash R, Caudrelier JM, Khuntia D, Bailey L, Bauman G: Phase I trial of simultaneous in-field boost with helical tomotherapy for patients with one to three brain metastases. Int J Radiat Oncol Biol Phys 2011, 80:1128-1133.
• [13]Rodrigues G, Yartsev S, Tay K, Pond GR, Lagerwaard F, Bauman G: A phase II multi-institutional study assessing simultaneous in-field boost helical tomotherapy for 1–3 brain metastases. Radiation Oncology 2012, 7:42. BioMed Central Full Text
• [14]Rodrigues G, Eppinga W, Lagerwaard F, de Haan P, Haasbeek C, Perera F, Slotman B, Yaremko B, Yartsev S, Bauman G: A pooled analysis of arc-based image-guided simultaneous integrated boost radiation therapy for oligometastatic brain metastases. Radiotherapy and Oncology 2012, 102:180-186.
• [15]Gupta T, Basu A, Master Z, Jalali R, Munshi A, Sarin R: Planning and delivery of whole brain radiation therapy with simultaneous integrated boost to brain metastases and synchronous limited-field thoracic radiotherapy using helical tomotherapy: a preliminary experience. Technol Cancer Res Treat 2009, 8:15-22.
• [16]De Potter B, De Meerleer G, De Neve W, Boterberg T, Speleers B, Ost P: Hypofractionated frameless stereotactic intensity-modulated radiotherapy with whole brain radiotherapy for the treatment of 1–3 brain metastases. Neurol Sci 2013, 34:647-653.
• [17]Ma LH, Li G, Zhang HW, Wang ZY, Dang J, Zhang S, Yao L, Zhang XM: Hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy for patients with newly diagnosed brain metastases from non-small cell lung cancer. J Neurosurg 2012, 117(Suppl):49-56.
• [18]Kwon AK, Dibiase SJ, Wang B, Hughes SL, Milcarek B, Zhu Y: Hypofractionated stereotactic radiotherapy for the treatment of brain metastases. Cancer 2009, 115:890-898.
• [19]Marchetti M, Milanesi I, Falcone C, De Santis M, Fumagalli L, Brait L, Bianchi L, Fariselli L: Hypofractionated stereotactic radiotherapy for oligometastases in the brain: a single-institution experience. Neurol Sci 2011, 32:393-399.
• [20]Giubilei C, Ingrosso G, D'Andrea M, Benassi M, Santoni R: Hypofractionated stereotactic radiotherapy in combination with whole brain radiotherapy for brain metastases. J Neurooncol 2009, 91:207-212.
• [21]Serizawa T, Higuchi Y, Nagano O, Hirai T, Ono J, Saeki N, Miyakawa A: Testing different brain metastasis grading systems in stereotactic radiosurgery: Radiation Therapy Oncology Group's RPA, SIR, BSBM, GPA, and modified RPA. J Neurosurg 2012, 117(Suppl):31-37.
• [22]Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M: Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 2012, 30:419-425.
• [23]Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R: Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 1997, 37:745-751.
• [24]Weltman E, Salvajoli JV, Brandt RA, de Morais Hanriot R, Prisco FE, Cruz JC, de Oliveira Borges SR, Wajsbrot DB: Radiosurgery for brain metastases: a score index for predicting prognosis. Int J Radiat Oncol Biol Phys 2000, 46:1155-1161.
• [25]Eichler AF, Kahle KT, Wang DL, Joshi VA, Willers H, Engelman JA, Lynch TJ, Sequist LV: EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro Oncol 2010, 12:1193-1199.
• [26]Gow CH, Chien CR, Chang YL, Chiu YH, Kuo SH, Shih JY, Chang YC, Yu CJ, Yang CH, Yang PC: Radiotherapy in lung adenocarcinoma with brain metastases: effects of activating epidermal growth factor receptor mutations on clinical response. Clinical Cancer Research 2008, 14:162-168.
• [27]Johung KL, Yao X, Li F, Yu JB, Gettinger SN, Goldberg S, Decker RH, Hess JA, Chiang VL, Contessa JN: A clinical model for identifying radiosensitive tumor genotypes in non-small cell lung cancer. Clin Cancer Res 2013, 19:5523-5532.
• [28]Porta R, Sanchez-Torres JM, Paz-Ares L, Massuti B, Reguart N, Mayo C, Lianes P, Queralt C, Guillem V, Salinas P, Catot S, Isla D, Pradas A, Gurpide A, de Castro J, Polo E, Puig T, Taron M, Colomer R, Rosell R: Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J 2011, 37:624-631.
• [29]Welsh JW, Komaki R, Amini A, Munsell MF, Unger W, Allen PK, Chang JY, Wefel JS, McGovern SL, Garland LL, Chen SS, Holt J, Liao Z, Brown P, Sulman E, Heymach JV, Kim ES, Stea B: Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer. J Clin Oncol 2013, 31:895-902.
• [30]Lind JS, Lagerwaard FJ, Smit EF, Senan S: Phase I study of concurrent whole brain radiotherapy and erlotinib for multiple brain metastases from non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2009, 74:1391-1396.
• [31]Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, Majem M, Lopez-Vivanco G, Isla D, Provencio M, Insa A, Massuti B, Gonzalez-Larriba JL, Paz-Ares L, Bover I, Garcia-Campelo R, Moreno MA, Catot S, Rolfo C, Reguart N, Palmero R, Sanchez JM, Bastus R, Mayo C, Bertran-Alamillo J, Molina MA, Sanchez JJ, Taron M: Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009, 361:958-967.
• [32]Burel-Vandenbos F, Ambrosetti D, Coutts M: Pedeutour F:EGFR mutation status in brain metastases of non-small cell lung carcinoma. J Neurooncol 2013, 111:1-10.
• [33]Wiggenraad R, Kanter AV-d, Kal HB, Taphoorn M, Vissers T, Struikmans H: Dose–effect relation in stereotactic radiotherapy for brain metastases. A systematic review. Radiotherapy and Oncology 2011, 98:292-297.
• [34]Narayana A, Chang J, Yenice K, Chan K, Lymberis S, Brennan C, Gutin PH: Hypofractionated stereotactic radiotherapy using intensity-modulated radiotherapy in patients with one or two brain metastases. Stereotact Funct Neurosurg 2007, 85:82-87.
• [35]Zeng YD, Zhang L, Liao H, Liang Y, Xu F, Liu JL, Dinglin XX, Chen LK: Gefitinib alone or with concomitant whole brain radiotherapy for patients with brain metastasis from non-small-cell lung cancer: a retrospective study. Asian Pac J Cancer Prev 2012, 13:909-914.