Radioterapia estereotáxica extracraniana em câncer de pulmão: atualização

Abreu, Carlos Eduardo Cintra Vita; Ferreira, Paula Pratti Rodrigues; Moraes, Fabio Ynoe de; Neves Jr, Wellington Furtado Pimenta; Gadia, Rafael; Carvalho, Heloisa de Andrade

doi:10.1590/S1806-37132015000000034

Carlos Eduardo Cintra Vita Abreu

Departamento de Radioterapia, Hospital Sírio-Libanês, São Paulo (SP) Brasil.

Paula Pratti Rodrigues Ferreira

Departamento de Radioterapia, Hospital Sírio-Libanês, São Paulo (SP) Brasil.

Fabio Ynoe de Moraes

Departamento de Radioterapia, Hospital Sírio-Libanês, São Paulo (SP) Brasil.

Wellington Furtado Pimenta Neves Jr

Departamento de Radioterapia, Hospital Sírio-Libanês, São Paulo (SP) Brasil.

Rafael Gadia

Departamento de Radioterapia, Hospital Sírio-Libanês, Brasília (DF) Brasil.

Heloisa de Andrade Carvalho

Departamento de Radioterapia, Hospital Sírio-Libanês, São Paulo (SP) Brasil.

Serviço de Radioterapia, Departamento de Radiologia e Oncologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil.

Endereço para correspondência: Heloisa de Andrade Carvalho. Rua Dona Adma Jafet, 91, CEP 01308-050, São Paulo, SP, Brasil. Tel.: 55 11 3394-5367. E-mail: heloisa.carvalho@hc.fm.usp.br

Figuras (2)
Tabelas (4)

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Figura 1
Processo do tratamento com stereotactic body radiation therapy e os principais aspectos de cada etapa. IGRT: image-guided radiotherapy. Adaptada de Radiation Therapy Oncology Group.¹⁶16 . Radiation Therapy Oncology Group [Internet]. Philadelphia: RTOG. 2011 Feb 9 - RTOG 0236 Protocol Information, A phase II trial of stereotactic body radiation therapy (SBRT) in the treatment of patients with medically inoperable stage I/II non-small cell lung cancer; 2009 Sep 9 [cited 2014 Sep 25]; [about 2 screens]. Available from: http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0236
http://www.rtog.org/ClinicalTrials/Proto...

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Figura 2
Definição de zona central: região dentro de um raio de 2 cm (interna à linha pontilhada) ao redor da árvore brônquica principal. Adaptada de Radiation Therapy Oncology Group. ¹⁶16 . Radiation Therapy Oncology Group [Internet]. Philadelphia: RTOG. 2011 Feb 9 - RTOG 0236 Protocol Information, A phase II trial of stereotactic body radiation therapy (SBRT) in the treatment of patients with medically inoperable stage I/II non-small cell lung cancer; 2009 Sep 9 [cited 2014 Sep 25]; [about 2 screens]. Available from: http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0236
http://www.rtog.org/ClinicalTrials/Proto...

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Tabela 1
Séries reportando resultados clínicos em lesões pulmonares periféricas tratadas com stereotactic body radiation therapy.

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Tabela 2
Resultados clínicos do uso de stereotactic body radiation therapy em lesões centrais.

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Tabela 3
Toxicidade relacionada à stereotactic body radiation therapy em lesões centrais em números absolutos de pacientes.

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Tabela 4
Esquemas de stereotactic body radiation therapy utilizados no tratamento de lesões centrais em estudos que não apresentaram toxicidade grau 3 ou 4.

Estudo	Número de pacientes	Dose	Lesão central ou periférica	Controle local	Complicações
Onishi et al.²¹21 . Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, et al. Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study. J Thorac Oncol. 2007;2(7 Suppl 3):S94-100. http://dx.doi.org/10.1097/JTO.0b013e318074de34 http://dx.doi.org/10.1097/JTO.0b013e3180...	257	1-14 frações (30-84 Gy)	Ambas	84% (5 anos) BED ≥ 100 Gy	≥ grau 3: 5,4% pulmonar; 1,0% esofágica; 1,2% dermatite
Nagata et al.²²22 . Nagata Y, Hiraoka M, Shibata T, Onishi H, Kokubo M, Karasawa K, et al. Stereotactic Body Radiation Therapy For T1N0M0 Non-small Cell Lung Cancer: First Report for Inoperable Population of a Phase II Trial by Japan Clinical Oncology Group (JCOG 0403). Int J Radiat Oncol Biol Phys. 2012;84(Suppl):S46. http://dx.doi.org/10.1016/j.ijrobp.2012.07.330 http://dx.doi.org/10.1016/j.ijrobp.2012....	104	4 × 12 Gy	Ambas	69% sobrevida livre de progressão em 3 anos	Grau 3: 9% dispneia; 7% pneumonite; 2% dor intercostal; 1% tosse Grau 4: 1% dispneia
Baumann et al.²³23 . Baumann P, Nyman J, Lax I, Friesland S, Hoyer M, Rehn Ericsson S, et al. Factors important for efficacy of stereotactic body radiotherapy of medically inoperable stage I lung cancer. A retrospective analysis of patients treated in the Nordic countries. Acta Oncol. 2006;45(7):787-95. http://dx.doi.org/10.1080/02841860600904862 http://dx.doi.org/10.1080/02841860600904...	57	3 × 15 Gy	Periférica	92% (3 anos)	Grau 3: 28%; e grau 4: 1,7%
Senthi et al.²⁴24 . Senthi S, Lagerwaard FJ, Haasbeek CJ, Slotman BJ, Senan S. Patterns of disease recurrence after stereotactic ablative radiotherapy for early stage non-small-cell lung cancer: a retrospective analysis. Lancet Oncol. 2012;13(8):802-9. http://dx.doi.org/10.1016/S1470-2045(12)70242-5 http://dx.doi.org/10.1016/S1470-2045(12)...	676	3-8 frações (54-60 Gy)	Ambas	89% (5 anos)	-
Timmerman et al.¹⁸18 . Timmerman R, McGarry R, Yiannoutsos C, Papiez L, Tudor K, DeLuca J, et al. Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol. 2006;24(30):4833-9. http://dx.doi.org/10.1200/JCO.2006.07.5937 http://dx.doi.org/10.1200/JCO.2006.07.59...	70	3 × 20-22 Gy	Ambas	95% (2 anos)	6% pneumonite; 3% de fratura de costela
Brown et al.²⁵25 . Brown WT, Wu X, Fayad F, Fowler JF, Amendola BE, García S, et al. CyberKnife radiosurgery for stage I lung cancer: results at 36 months. Clin Lung Cancer. 2007;8(8):488-92. http://dx.doi.org/10.3816/CLC.2007.n.033 http://dx.doi.org/10.3816/CLC.2007.n.033...	59	1-5 frações (15,0-67,5 Gy)	Ambas	90% de sobrevida livre de doença	Grau 3: 7% pneumonite
Van der Voort et al.²⁶26 . Van der Voort van Zyp NC, Prévost J-B, Hoogeman MS, Praag J, van der Holt B, Levendag PC, et al. Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: clinical outcome. Radiother Oncol. 2009;91(3):296-300. http://dx.doi.org/10.1016/j.radonc.2009.02.011 http://dx.doi.org/10.1016/j.radonc.2009....	70	3 × 12-15 Gy	Periférica	96% (2 anos se 60 Gy)	10% toxicidade tardia

Estudo	Número de pacientes	Tumor	Dose	Controle local	Sobrevida
Haasbeek et al.³⁶36 . Haasbeek CJ, Lagerwaard FJ, Slotman BJ, Senan S. Outcomes of stereotactic ablative radiotherapy for centrally located early-stage lung cancer. J Thorac Oncol. 2011;6(12):2036-43. http://dx.doi.org/10.1097/JTO.0b013e31822e71d8 http://dx.doi.org/10.1097/JTO.0b013e3182...	63	CPCNP (T1-3N0M0)	60 Gy (8 fx)	92,6% (5 anos)	SLD: 71%; SG: 49,5% (5 anos)
Nuyttens et al.³⁷37 . Nuyttens JJ, van der Voort van Zyp NC, Praag J, Aluwini S, van Klaveren RJ, Verhoef C, et al. Outcome of four-dimensional stereotactic radiotherapy for centrally located lung tumors. Radiother Oncol. 2012;102(3):383-7. http://dx.doi.org/10.1016/j.radonc.2011.12.023 http://dx.doi.org/10.1016/j.radonc.2011....	56	CPCNP: 69,6%; metastático: 30,4%	45-60 Gy (5 fx); 48 Gy (6 fx)	76% (2 anos)	SCE: 80% (3 anos); SG: 60% (2 anos)
Rowe et al.³⁸38 . Rowe BP, Boffa DJ, Wilson LD, Kim AW, Detterbeck FC, Decker RH. Stereotactic body radiotherapy for central lung tumors. J Thorac Oncol. 2012;7(9):1394-9. http://dx.doi.org/10.1097/JTO.0b013e3182614bf3 http://dx.doi.org/10.1097/JTO.0b013e3182...	47	CPCNP: 59%; metastático: 41%	50 Gy (4 fx)^a	2 falhas locais	SLP: 24% (2 anos)
Oshiro et al.³⁹39 . Oshiro Y, Aruga T, Tsuboi K, Marino K, Hara R, Sanayama Y, et al. Stereotactic body radiotherapy for lung tumors at the pulmonary hilum. Strahlenther Onkol. 2010;186(5):274-9. http://dx.doi.org/10.1007/s00066-010-2072-y http://dx.doi.org/10.1007/s00066-010-207...	21	CPCNP recorrente ou metastático: 95%	25-39 Gy (1-10 fx)	60% (2 anos)	SG: 62,2% (2anos)
Unger et al.⁴⁰40 . Unger K, Ju A, Oermann E, Suy S, Yu X, Vahdat S, et al. CyberKnife for hilar lung tumors: report of clinical response and toxicity. J Hematol Oncol. 2010;3:39. http://dx.doi.org/10.1186/1756-8722-3-39 http://dx.doi.org/10.1186/1756-8722-3-39...	20	CPCNP metastático: 85%; lesões hilares/brônquio principal	30-40 Gy (5 fx)	63% (1 ano)	SG: 54% (1 ano)
Milano et al.⁴¹41 . Milano MT, Chen Y, Katz AW, Philip A, Schell MC, Okunieff P. Central thoracic lesions treated with hypofractionated stereotactic body radiotherapy. Radiother Oncol. 2009;91(3):301-6. http://dx.doi.org/10.1016/j.radonc.2009.03.005 http://dx.doi.org/10.1016/j.radonc.2009....	53	CPCNP: 66%; Metastático: 37%	20-55 Gy (1-18 fx)	73% (2 anos)	SG: 44% (2 anos); T1-2: 72%
Chang et al.⁴²42 . Chang JY, Balter PA, Dong L, Yang Q, Liao Z, Jeter M, et al. Stereotactic body radiation therapy in centrally and superiorly located stage I or isolated recurrent non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2008;72(4):967-71. http://dx.doi.org/10.1016/j.ijrobp.2008.08.001 http://dx.doi.org/10.1016/j.ijrobp.2008....	27	CPCNP T1-2: 48%; e recorrente: 52%	40-50 Gy (5 fx)	3 falhas (40 Gy)	-

Estudo	Óbitos	Toxicidade grau 3a
Estudo	Óbitos	Aguda	Tardia
Haasbeek et al.³⁶36 . Haasbeek CJ, Lagerwaard FJ, Slotman BJ, Senan S. Outcomes of stereotactic ablative radiotherapy for centrally located early-stage lung cancer. J Thorac Oncol. 2011;6(12):2036-43. http://dx.doi.org/10.1097/JTO.0b013e31822e71d8 http://dx.doi.org/10.1097/JTO.0b013e3182...	Cardíaco: 1; falência respiratória: 1	1	4
Nuyttens et al.³⁷37 . Nuyttens JJ, van der Voort van Zyp NC, Praag J, Aluwini S, van Klaveren RJ, Verhoef C, et al. Outcome of four-dimensional stereotactic radiotherapy for centrally located lung tumors. Radiother Oncol. 2012;102(3):383-7. http://dx.doi.org/10.1016/j.radonc.2011.12.023 http://dx.doi.org/10.1016/j.radonc.2011....	-	4	6
Rowe et al.³⁸38 . Rowe BP, Boffa DJ, Wilson LD, Kim AW, Detterbeck FC, Decker RH. Stereotactic body radiotherapy for central lung tumors. J Thorac Oncol. 2012;7(9):1394-9. http://dx.doi.org/10.1097/JTO.0b013e3182614bf3 http://dx.doi.org/10.1097/JTO.0b013e3182...	Necrose brônquio: 1	4
Oshiro et al.³⁹39 . Oshiro Y, Aruga T, Tsuboi K, Marino K, Hara R, Sanayama Y, et al. Stereotactic body radiotherapy for lung tumors at the pulmonary hilum. Strahlenther Onkol. 2010;186(5):274-9. http://dx.doi.org/10.1007/s00066-010-2072-y http://dx.doi.org/10.1007/s00066-010-207...	Hemoptise: 1	0	2
Unger et al.⁴⁰40 . Unger K, Ju A, Oermann E, Suy S, Yu X, Vahdat S, et al. CyberKnife for hilar lung tumors: report of clinical response and toxicity. J Hematol Oncol. 2010;3:39. http://dx.doi.org/10.1186/1756-8722-3-39 http://dx.doi.org/10.1186/1756-8722-3-39...	Fístula brônquica: 1	1	0
Milano et al.⁴¹41 . Milano MT, Chen Y, Katz AW, Philip A, Schell MC, Okunieff P. Central thoracic lesions treated with hypofractionated stereotactic body radiotherapy. Radiother Oncol. 2009;91(3):301-6. http://dx.doi.org/10.1016/j.radonc.2009.03.005 http://dx.doi.org/10.1016/j.radonc.2009....	Lesão brônquio/traqueia: 4	0	1
Chang et al.⁴²42 . Chang JY, Balter PA, Dong L, Yang Q, Liao Z, Jeter M, et al. Stereotactic body radiation therapy in centrally and superiorly located stage I or isolated recurrent non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2008;72(4):967-71. http://dx.doi.org/10.1016/j.ijrobp.2008.08.001 http://dx.doi.org/10.1016/j.ijrobp.2008....	-	1

Estudo	Número de lesões/Número de pacientes	Dose
Xia et al.⁴⁴44 . Xia T, Li H, Sun Q, Wang Y, Fan N, Yu Y, et al. Promising clinical outcome of stereotactic body radiation therapy for patients with inoperable Stage I/II non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2006;66(1):117-25. http://dx.doi.org/10.1016/j.ijrobp.2006.04.013 http://dx.doi.org/10.1016/j.ijrobp.2006....	9/43	50 Gy/10 fx
Guckenberger et al.⁴⁵45 . Guckenberger M, Wulf J, Mueller G, Krieger T, Baier K, Gabor M, et al. Dose-response relationship for image-guided stereotactic body radiotherapy of pulmonary tumors: relevance of 4D dose calculation. Int J Radiat Oncol Biol Phys. 2009;74(1):47-54. http://dx.doi.org/10.1016/j.ijrobp.2008.06.1939 http://dx.doi.org/10.1016/j.ijrobp.2008....	22/159	48 Gy/8 fx; 26,0-37,5 Gy/1-3 fx
Baba et al.⁴³43 . Baba F, Shibamoto Y, Ogino H, Murata R, Sugie C, Iwata H, et al. Clinical outcomes of stereotactic body radiotherapy for stage I non-small cell lung cancer using different doses depending on tumor size. Radiat Oncol. 2010;5:81. http://dx.doi.org/10.1186/1748-717X-5-81 http://dx.doi.org/10.1186/1748-717X-5-81...	29/124	44-52 Gy/4 fx
Olsen et al.⁴⁶46 . Olsen JR, Robinson CG, El Naqa I, Creach KM, Drzymala RE, Bloch C, et al. Dose-response for stereotactic body radiotherapy in early-stage non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;81(4):e299-303. http://dx.doi.org/10.1016/j.ijrobp.2011.01.038 http://dx.doi.org/10.1016/j.ijrobp.2011....	19/130	45-50 Gy/5 fx; 54 Gy/3 fx
Takeda et al.⁴⁷47 . Takeda A, Kunieda E, Ohashi T, Aoki Y, Koike N, Takeda T. Stereotactic body radiotherapy (SBRT) for oligometastatic lung tumors from colorectal cancer and other primary cancers in comparison with primary lung cancer. Radiother Oncol. 2011;101(2):255-9. http://dx.doi.org/10.1016/j.radonc.2011.05.033 http://dx.doi.org/10.1016/j.radonc.2011....	33/232	50 Gy/5 fx
Stephans et al.⁴⁸48 . Stephans KL, Djemil T, Reddy CA, Gajdos SM, Kolar M, Mason D, et al. A comparison of two stereotactic body radiation fractionation schedules for medically inoperable stage I non-small cell lung cancer: the Cleveland Clinic experience. J Thorac Oncol. 2009;4(8):976-82. http://dx.doi.org/10.1097/JTO.0b013e3181adf509 http://dx.doi.org/10.1097/JTO.0b013e3181...	7/94	50 Gy/5 fx; 60 Gy/3 fx
Janssen et al.⁴⁹49 . Janssen S, Dickgreber NJ, Koenig C, Bremer M, Werner M, Karstens JH, et al. Image-guided hypofractionated small volume radiotherapy of non-small cell lung cancer - feasibility and clinical outcome. Onkologie. 2012;35(7-8):408-12. http://dx.doi.org/10.1159/000340064 http://dx.doi.org/10.1159/000340064...	29/65	40-48 Gy/8 fx; 37,5 Gy/3 fx

[1] Endereço para correspondência: Heloisa de Andrade Carvalho. Rua Dona Adma Jafet, 91, CEP 01308-050, São Paulo, SP, Brasil. Tel.: 55 11 3394-5367. E-mail: heloisa.carvalho@hc.fm.usp.br

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