肺癌脑转移瘤不同放射治疗方法的疗效分析
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摘要
目的：探讨不同放射治疗方法对肺癌脑转移瘤的疗效。方法：164例有病理学证实的肺癌脑转移瘤患者分为4组：单纯全脑放疗组(WBRT)32例、全脑放疗加立体定向放射外科组(WBRT+SRS)51例，全脑放疗加立体定向放射治疗组(WBRT+SRT)40例，单纯立体定向放射治疗组(SRT)41例。单纯全脑放疗组，1.8Gy～2.0Gy／次，总剂量3600cGy～4000cGy／18次～20次；全脑放疗加立体定向放射外科组，立体定向放射外科前或后行全脑放疗，立体定向放射外科单次1200～1600cGy(周边剂量)，全脑放疗3200cGy～3600cGy／16次～18次；全脑放疗加立体定向放射治疗组，单次靶区平均周边剂量300cGy～500cGy，总量2500～4000cGy。单纯立体定向放射治疗组，单次靶区平均周边剂量300cGy～500cGy，总量2500～6000cGy。其中鳞癌59例，腺癌82例，小细胞未分化癌23例。全组患者加或不加全身静脉化疗。结果：各组的局部控制率分别为46.9％，78.9％，87.5％，78％，中位生存期分别为5.0，12.0，12.0，10.0个月；局部无进展生存期分别为4.0，9.56，9.5，8.5个月；颅脑无新病灶生存期分别为4.0，10.5，9.0，8.5个月。单纯全脑放疗组死于脑转移的占62.5％，与其他3组相比有显著性差异(P=0.000)。而全脑放疗加立体定向放射外科组的晚期放射反应的发生率为23.5，较其它组高。结论：肺癌单发脑转移瘤患者的最佳治疗方式是单纯立体定向放射治疗。全脑放疗加立体定向放射治疗(WBRT+SRT)在提高多发脑转移瘤的生存率以及减少并发症方面优于其他治疗方法。
Purpose: To evaluate the effects of various radiotherapeutic models for brainmetastasis from lung cancer. Methods: One hundred and sixty-four lung cancerpatients with brain metastasis pathologically proved were divided into fourgroups: 32 cases were whole brain radiotherapy (WBRY)alone, 51 cases werestereotactic radiosurgery(SRS) combined with WBRT, 40cases were stereotacticradiotherapy(SRT) combined with WBRT. 41 cases were stereotacticradiosurgery(SRS) alone. The dose fraction of whole brain radiotherapy was3600cGy～4000cGy in 18 to 20 fractions, 180cGy～200cGy perfraction. Stereotactic radiosurgery(SRS)were combined with whole brainradiotherapy (WBRY)before or behind , In stereotactic radiosurgery(SRS),singletumor target dose ranged from 1200cGy to 1600cGy, and the dose fraction ofwhole brain radiotherapy was 3200cGy～3600cGy in 16 to 18 fractions. Instereotactic radiotherapy(SRT)group,single tumor target dose ranged from 300cGy to500cGy with total dose 2500cGy to 6000cGy. Results: The response rates in fourgroups were 46.9%,78.9%,87.5%,78%,;median survival were 5.0,12.0, 12.0,10.0months respectively;the median of progression free survival(PFS) was4.0,9.56,9.5,8.5 months;the median survival willout new brain metastasis was4.0,10.5,9.0,8.5 months respeclively.There were 62.5% patients in WBRT alone failed due to brain metastasis, the significant difference to the other 3 groups wasfound (P=0.000). The long term complication rate in stereotactic radiosurgery(SRS)combined with WBRT group was 23.5%, the difference was statisticlly significantcompared with other 3 groups. Conclusion: SRS alone is the optional treatment forsingle brain metastasis. For multi-metastasis of brain, the effect of SRT combinedwith WBRT is better than that of other treatrments, not only in improving survival,butalso in reducing complication.
Purpose: To evaluate the effects of various radiotherapeutic models for brainmetastasis from lung cancer. Methods: One hundred and sixty-four lung cancerpatients with brain metastasis pathologically proved were divided into fourgroups: 32 cases were whole brain radiotherapy (WBRY)alone, 51 cases werestereotactic radiosurgery(SRS) combined with WBRT, 40cases were stereotacticradiotherapy(SRT) combined with WBRT. 41 cases were stereotacticradiosurgery(SRS) alone. The dose fraction of whole brain radiotherapy was3600cGy～4000cGy in 18 to 20 fractions, 180cGy～200cGy perfraction. Stereotactic radiosurgery(SRS)were combined with whole brainradiotherapy (WBRY)before or behind , In stereotactic radiosurgery(SRS),singletumor target dose ranged from 1200cGy to 1600cGy, and the dose fraction ofwhole brain radiotherapy was 3200cGy～3600cGy in 16 to 18 fractions. Instereotactic radiotherapy(SRT)group,single tumor target dose ranged from 300cGy to500cGy with total dose 2500cGy to 6000cGy. Results: The response rates in fourgroups were 46.9%,78.9%,87.5%,78%,;median survival were 5.0,12.0, 12.0,10.0months respectively;the median of progression free survival(PFS) was4.0,9.56,9.5,8.5 months;the median survival willout new brain metastasis was4.0,10.5,9.0,8.5 months respeclively.There were 62.5% patients in WBRT alone failed due to brain metastasis, the significant difference to the other 3 groups wasfound (P=0.000). The long term complication rate in stereotactic radiosurgery(SRS)combined with WBRT group was 23.5%, the difference was statisticlly significantcompared with other 3 groups. Conclusion: SRS alone is the optional treatment forsingle brain metastasis. For multi-metastasis of brain, the effect of SRT combinedwith WBRT is better than that of other treatrments, not only in improving survival,butalso in reducing complication.
引文
1. Ohta Y,Oda M,sunezuka Y,et al.Results of recent therapy for non-small cell lung cancer with brain metastasis as the initial relapse [J]. Am J Clin Oncol,2002 , 25 (5):476-479.
2. Park YG, Choi JY, Chang JW,et al. Gamma knife radiosurgery for metastatic brain tumors [J]. Stereotact Funct Neurosurg, 2001, 76(3-4): 201-203.
3. Serizawa T,Ono J,lichi T,et al.Gamma knife radiosurgery for metastatic brain tumors from lung cancena comparison between small cell and non-small cell carcinoma [J]. J Neurosurg, 2002,97(5):484-488.
4. Mori Y,Kondziolka D,Lunsford LD,et al.Stereotactic radiosurgery for brain metastases from renal cell carcinoma [J] Cancer, 1998,83: 344-353.
5. Cappuzzo F.Medical treatment of brain metastases from lung cancer[J]. Suppl Tumori,2002,l(4):558-559.
6. Shirato H,Takmura A,Tomita M,et al.Stereotactic irradiation without whole brain irradiation for single brain metastasis [J ].lnt J Radiat Oncol Biol Phys, 1997 , 2:385-391.
7. Kellir K, Bunn PA Jr. Is it time to reevaluate our approach to the treatment of brain metastases in patients with non-small cell lung cancer? [J]. Lung Cancer,1998,2:85-91.
8. Patchell RA,Tibbs PA,Regine WF , et al. Postoperative radiotherapy in the treatment of single metastase to the brain:a randomized trial [J}. JAMA, 1998,280:1485 — 1489.
9. Granone P, Margaritora S, D'Andrilli A, et al. Non-small cell lung cancer with single brain metastasis: the role of surgical treatment [J]. Eur J Cardiothorac Surg,2001,20 (2):361-366.
10. Yuile PG,Tran MH .Survival with brain metastases following radiation therapy [J].Alustralas Radiol,2002,46(4):390-395.
1. Bartumeus F, Clavel P.Surgical treatment of brain.RevNeurol,2000,31 (12):1247—1249
2. Posner JB: Management of brain metastases. Rev Neurol (Paris) 1992, 148: 477-487
3. Sano K: Intracranial metastatic tumors. An overview. In Neuro-Oncology. Edited by Paoletti只 Takakura K, Walker MD, et al.: Dordrecht: Kluwer. 1991: 309-319.
4. Larson DA, Gutin PH, Leibel SA, et al.:Stereotactic irradiation of brain tumors.Cancer 1990, 65:792-799.
5. Black P, Alexander E Ⅲ, Loeffier JS: New treatments for metastatic brain tumors. in current techniques in neurosurgery. Current Medicine Publ, 1996: 151—156.
6．李先明．脑转移瘤的治疗进展．实用癌症杂志 1998；13(4)：318-319．
7. Sneed PK, Lamborn KR, Forster JM, et, al, Radiosurgery for brain metastases:is who brain radiosurgery necessary? Gutin PH int J Radiat Oncol Biol Phys,1999,43(3): 549—558
8．隋邦森．伽玛刀的适应症．功能性和立体定向外科杂志．1994；7(4)：51—53．
9. Patchell RA, Tibbs PA, Walsh JW et al.: A randomized trial of surgery in the treatment of single brain metastases to the brain. N Engl J Med 1990,322: 494-500
10. Smith KA: Metastatic brain tumors: gamma knife radiosurgery or microsurgical resection? BNI Q 1997, 13: 22-29.
11. Loeffier JS, Kooy HM, Wen PY et al.: The treatment of recurrent brain metastases with stereotactic radiosurgery. J Clin Oncol 1990, 8:576-582.
12. Peretti-Viton P, Margain D, Murayama N, et al.: Les metastases cerebrales.J Neuroradiol 1991, 18: 161—172.
13. Yokoi K, Kamiya V, 1latsuguma H, et al—Detection of brain metastasis in potentially operable non-small cell lung cancena comparison of CT and MRI. CHEST 1999;115:714 — 719.
14. Suzuki K, Yamamoto M, Hasegawa Y, et al. Magnetic resonance imaging and computed tomography in the diagnosis of brain metastases of lung cancer. Lung Cancer 2004;357 — 60.
15. Sze G, Johnson C,Kawamura Y, et al. Comparison of single- and triple dose contrast material in the ivlR screening of brain metastases. AJAR 1998,19:821 — 828.
16. Shehata MK, Young B, Reid B, et al. Stereotatic radiosurgery of 468 brain metastases≤2 cm:implications for SRS dose and whole brain radiation therapy. Int J Radiat Oncol Biol Phys 2004;59 (1):87-93
17. Aoyama H, Shirato H, Onimaru R, et al. Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skull.Int J Radiat Oncol Biol Phys a) 2003;56(3):793-800.
18. Varlotto JM, Flickinger JC, Niranjan A, et al. Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 2003:57 (2):452-64.
19. Gaspar L, Scott C, Rotman M, et al. Recursive partitioning analysis(RPA) of prognostic factors in three radiation therapy oncology group(RTOG) brain metastases trial.) Radiat Oncol Biol Phys 1997;37:745-51
20. Andrews DW, Scott CB, Sperduto PW, 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 RTOG9508 randomised trial.Lancet 2004:363:1665-72
21.Sneed PK, Suh JH, Goetsch SJ, et al.A multi — institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases. Int J Radiat Oncol Biol Phys, 2002;53 (3):519 — 26.
22. Jawahar A, Yr'illis BK, Smith DR, et al. Gamma Knife Radiosurgery for Brain Metastases:Do Patients Benefit from Adjuvant External-Beam Radiotherapy? An 18-Month Comparative Analysis.Sterotact Funct Neurosurg 2002;79:262 — 271
23.Chitapanarux I, Goss B, Vongtama R, et al. Prospective study of stereotactic radiosurgery without whole brain radiotherapy in patients with four or less brain metastases:incidence of intracranial progression and salvage radiotherapy. J Neurooncol, 2003:61:143-9
24.Regine fF, Huhn JL, Patchell RA, et al.Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases:results and implications. Int J Radiat Oncol Biol Phys, 2002;52 (2):333-8.
25.Lutterbach J, Cyron D, Henne K, et al.Radiosurgery followed by planned observation in patients with one to three brain metastases. Neurosurgery, 2003;52:1066-1074
26. Hasegawa T, Kondziolka D, Flickinger JC, et al.Brain metastases treated with radiosurgery alone:an alternative to whole brain radiotherapy? Neurosurgery 2003:52 (6): 1318-26
27. Chidel MA, Suh JH, Reddv C,4, et al.Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases. Int J Radiat Oncol Biol Phys 2000;47 (4):993-9.
28. Noel G, Simon JM, Valery CA, et al. Radiosurgery for brain metastasis:impact of CTV on local control.Radiother Oncol 2003,68:15-21.
29.Nieder C, Nestle L, Walter K, et al. Dose/effect relationships for brain metastases. J Cancer Res Clin Oncol 1998;124:346-50.
30.Kondziolka D, Patel A, Lunsford LD, et al. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 1999:45 (2):427-3
31.Weltman E, Salvajoli JV, Oliveira VC, et al.Score index for stereotactic radiosurgery of brain metastases. J Radiosurg 1998; 1:89 ～ 95
32. Weltman E, Salvajoli JV, Brandt RA, et al. Radiosurgery for brain metastases:a score index for predicting prognosis. Int J Radiat Oncol Biol Phys 2000;46
2. Park YG, Choi JY, Chang JW,et al. Gamma knife radiosurgery for metastatic brain tumors [J]. Stereotact Funct Neurosurg, 2001, 76(3-4): 201-203.
3. Serizawa T,Ono J,lichi T,et al.Gamma knife radiosurgery for metastatic brain tumors from lung cancena comparison between small cell and non-small cell carcinoma [J]. J Neurosurg, 2002,97(5):484-488.
4. Mori Y,Kondziolka D,Lunsford LD,et al.Stereotactic radiosurgery for brain metastases from renal cell carcinoma [J] Cancer, 1998,83: 344-353.
5. Cappuzzo F.Medical treatment of brain metastases from lung cancer[J]. Suppl Tumori,2002,l(4):558-559.
6. Shirato H,Takmura A,Tomita M,et al.Stereotactic irradiation without whole brain irradiation for single brain metastasis [J ].lnt J Radiat Oncol Biol Phys, 1997 , 2:385-391.
7. Kellir K, Bunn PA Jr. Is it time to reevaluate our approach to the treatment of brain metastases in patients with non-small cell lung cancer? [J]. Lung Cancer,1998,2:85-91.
8. Patchell RA,Tibbs PA,Regine WF , et al. Postoperative radiotherapy in the treatment of single metastase to the brain:a randomized trial [J}. JAMA, 1998,280:1485 — 1489.
9. Granone P, Margaritora S, D'Andrilli A, et al. Non-small cell lung cancer with single brain metastasis: the role of surgical treatment [J]. Eur J Cardiothorac Surg,2001,20 (2):361-366.
10. Yuile PG,Tran MH .Survival with brain metastases following radiation therapy [J].Alustralas Radiol,2002,46(4):390-395.
1. Bartumeus F, Clavel P.Surgical treatment of brain.RevNeurol,2000,31 (12):1247—1249
2. Posner JB: Management of brain metastases. Rev Neurol (Paris) 1992, 148: 477-487
3. Sano K: Intracranial metastatic tumors. An overview. In Neuro-Oncology. Edited by Paoletti只 Takakura K, Walker MD, et al.: Dordrecht: Kluwer. 1991: 309-319.
4. Larson DA, Gutin PH, Leibel SA, et al.:Stereotactic irradiation of brain tumors.Cancer 1990, 65:792-799.
5. Black P, Alexander E Ⅲ, Loeffier JS: New treatments for metastatic brain tumors. in current techniques in neurosurgery. Current Medicine Publ, 1996: 151—156.
6．李先明．脑转移瘤的治疗进展．实用癌症杂志 1998；13(4)：318-319．
7. Sneed PK, Lamborn KR, Forster JM, et, al, Radiosurgery for brain metastases:is who brain radiosurgery necessary? Gutin PH int J Radiat Oncol Biol Phys,1999,43(3): 549—558
8．隋邦森．伽玛刀的适应症．功能性和立体定向外科杂志．1994；7(4)：51—53．
9. Patchell RA, Tibbs PA, Walsh JW et al.: A randomized trial of surgery in the treatment of single brain metastases to the brain. N Engl J Med 1990,322: 494-500
10. Smith KA: Metastatic brain tumors: gamma knife radiosurgery or microsurgical resection? BNI Q 1997, 13: 22-29.
11. Loeffier JS, Kooy HM, Wen PY et al.: The treatment of recurrent brain metastases with stereotactic radiosurgery. J Clin Oncol 1990, 8:576-582.
12. Peretti-Viton P, Margain D, Murayama N, et al.: Les metastases cerebrales.J Neuroradiol 1991, 18: 161—172.
13. Yokoi K, Kamiya V, 1latsuguma H, et al—Detection of brain metastasis in potentially operable non-small cell lung cancena comparison of CT and MRI. CHEST 1999;115:714 — 719.
14. Suzuki K, Yamamoto M, Hasegawa Y, et al. Magnetic resonance imaging and computed tomography in the diagnosis of brain metastases of lung cancer. Lung Cancer 2004;357 — 60.
15. Sze G, Johnson C,Kawamura Y, et al. Comparison of single- and triple dose contrast material in the ivlR screening of brain metastases. AJAR 1998,19:821 — 828.
16. Shehata MK, Young B, Reid B, et al. Stereotatic radiosurgery of 468 brain metastases≤2 cm:implications for SRS dose and whole brain radiation therapy. Int J Radiat Oncol Biol Phys 2004;59 (1):87-93
17. Aoyama H, Shirato H, Onimaru R, et al. Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skull.Int J Radiat Oncol Biol Phys a) 2003;56(3):793-800.
18. Varlotto JM, Flickinger JC, Niranjan A, et al. Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 2003:57 (2):452-64.
19. Gaspar L, Scott C, Rotman M, et al. Recursive partitioning analysis(RPA) of prognostic factors in three radiation therapy oncology group(RTOG) brain metastases trial.) Radiat Oncol Biol Phys 1997;37:745-51
20. Andrews DW, Scott CB, Sperduto PW, 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 RTOG9508 randomised trial.Lancet 2004:363:1665-72
21.Sneed PK, Suh JH, Goetsch SJ, et al.A multi — institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases. Int J Radiat Oncol Biol Phys, 2002;53 (3):519 — 26.
22. Jawahar A, Yr'illis BK, Smith DR, et al. Gamma Knife Radiosurgery for Brain Metastases:Do Patients Benefit from Adjuvant External-Beam Radiotherapy? An 18-Month Comparative Analysis.Sterotact Funct Neurosurg 2002;79:262 — 271
23.Chitapanarux I, Goss B, Vongtama R, et al. Prospective study of stereotactic radiosurgery without whole brain radiotherapy in patients with four or less brain metastases:incidence of intracranial progression and salvage radiotherapy. J Neurooncol, 2003:61:143-9
24.Regine fF, Huhn JL, Patchell RA, et al.Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases:results and implications. Int J Radiat Oncol Biol Phys, 2002;52 (2):333-8.
25.Lutterbach J, Cyron D, Henne K, et al.Radiosurgery followed by planned observation in patients with one to three brain metastases. Neurosurgery, 2003;52:1066-1074
26. Hasegawa T, Kondziolka D, Flickinger JC, et al.Brain metastases treated with radiosurgery alone:an alternative to whole brain radiotherapy? Neurosurgery 2003:52 (6): 1318-26
27. Chidel MA, Suh JH, Reddv C,4, et al.Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases. Int J Radiat Oncol Biol Phys 2000;47 (4):993-9.
28. Noel G, Simon JM, Valery CA, et al. Radiosurgery for brain metastasis:impact of CTV on local control.Radiother Oncol 2003,68:15-21.
29.Nieder C, Nestle L, Walter K, et al. Dose/effect relationships for brain metastases. J Cancer Res Clin Oncol 1998;124:346-50.
30.Kondziolka D, Patel A, Lunsford LD, et al. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 1999:45 (2):427-3
31.Weltman E, Salvajoli JV, Oliveira VC, et al.Score index for stereotactic radiosurgery of brain metastases. J Radiosurg 1998; 1:89 ～ 95
32. Weltman E, Salvajoli JV, Brandt RA, et al. Radiosurgery for brain metastases:a score index for predicting prognosis. Int J Radiat Oncol Biol Phys 2000;46