Recent progress in radiation therapy for primary gastrointestinal lymphoma

doi:10.3877/cma.j.issn.2095-3224.2016.02.02

Abstract

Abstract:

The gastrointestinal tract is the most common extranodal site of non-Hodgkin lymphoma. The gastrointestinal lymphoma represents a heterogeneous disease, where diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma are the most common subtypes. The role of radiotherapy varies in the treatment of lymphomas from different sites or with different subtypes. Conservative treatment using chemotherapy and/or radiotherapy produced favorable outcomes in gastric lymphoma. In gastric DLBCL, radiotherapy after chemotherapy improved locoregional control and survival, even for patients who achieved complete response after chemotherapy. In the era of rituximab, radiotherapy also improved locoregional control in patients with bulky disease. In gastric MALT lymphoma, radiotherapy alone could yield excellent outcomes for patients who are unresponsive to H. pylori eradication. However, surgery remains the mainstay of radical treatment for intestinal lymphoma, and radiotherapy is also a choice for indolent subtypes.

Key words: Gastrointestinal tract, Lymphoma, non-Hodgkin, Diffuse large B cell lymphoma, Mucosa-associated lymphoid tissue

Yexiong Li. Recent progress in radiation therapy for primary gastrointestinal lymphoma[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2016, 05(02): 114-120.

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Figures/Tables 3

References 62

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美罗华时代前，随机分组研究
研究	时间	例数	纳入条件	治疗		结果
SWOG 8736^[6,10]	1998	401	I期，或II期非大肿块，侵袭性NHL	CHOP3＋RT vs CHOP8		RT提高5 y PFS（77% vs 64%，P=0.03）和OS（92% vs 72%），但8.2年随访后无差别
ECOG 1484 ^[8]	2004	352	I~II期，侵袭性NHL	CR to CHOP*8：RT vs no RT		RT提高CR患者6 y DFS（73% vs 56%，P=0.05）
GELA LNH 93-1^[7]	2005	647	I~II期，≤60岁，无不良预后因素，侵袭性NHL	CHOP*3＋RT vs ACVBP		ACVBP方案提高5 y EFS（82% vs 74%，P<0.001）和OS（90% vs 82%，P=0.001）
GELA LNH 93-4 ^[9]	2007	576	I~II期，>60岁，无不良预后因素，侵袭性NHL	CHOP*4，RT vs no RT		5 y EFS（64% vs 61%，P=0.56）和OS（68% vs 72%，P=0.64）无差别
美罗华时代，放疗与不放疗单中心比较性研究
研究中心	时间	例数	纳入条件		治疗	多因素分析
MD Anderson^[11]	2010	469	I~II期（40.5%），III~IV期（59.5%） DLBCL		RCHOP*6~8，RT（30%）	RT提高PFS（HR：0.19，P<0.0001）and OS（HR：0.32，P<0.0001）
Seoul National University ^[13]	2015	198	I~II期，DLBCL		RCHOP*≥6（75.3%），RT（43%）	RT提高PFS（HR：0.23，P=0.021）and OS（HR：0.15，P=0.014）
Duke University^[4]	2012	79	III~IV期，DLBCL，化疗后CR		RCHOP*6，RT（48%）	RT提高LC（HR：8.0，P=0.014）和EFS（HR：4.3，P=0.01）
University of Chicago ^[5]	2013	110	III~IV期，DLBCL，化疗后CR		RCHOP*，RT（12.7%）	RT提高LC（HR：8.7，P=0.01）、PFS（HR：9.6，P=0.03）和OS（HR：5.9，P=0.08）
放疗与不放疗大数据库数据比较性研究
数据库	时间	例数	纳入条件	治疗		多因素分析
SEER^[15]	2008	13420	I~II期，DLBCL	化疗不详，RT（41%）		RT降低疾病特异死亡（HR：0.86，P=0.0001）和总死亡率（HR：0.89，P<0.0001）
NCCN^[16]	2014	841	I~II期（47.8%），III~IV期（52.2%），DLBCL	RCHOP*6~8（84%），RT（35%）		RT有提高FFS或OS倾向（特别对III~IV期）
NCDB^[14]	2015	59255	I~II，DLBCL	RT（39%）		RT提高生存（HR：0.66，P<0.001）
美罗华时代，前瞻性研究亚组分析
研究	时间	例数	纳入条件	治疗		多因素分析
Italian Lymphoma Study Group^[12]	2011	182	I~IV期	RCHOP*6，RT（22%）		RT提高EFS（HR：0.33 95% CI 0.11~0.97）
RICOVER-60^[17]	2014	164	≥7.5 cm/结外受累，I~IV期，DLBCL	RCHOP6＋R2，RT（ITT，29%；PP，35%）		RT提高EFS（HR：2.7，P=0.011），PFS（HR：4.4，P=0.001），OS（HR：4.3，P=0.02）
美罗华时代，随机分组研究
研究	时间	例数	纳入条件	治疗分组		多因素分析
UNFOLDER^[21]	2015	285	侵袭性B细胞NHL，≥7.5 cm/结外受累	R-CHOP14/21 vs RCHOP 14/21＋RT		中期分析显示RT提高EFS，故探究提前关闭
LYSA/GOELAMS 02- 03^[20]	2014	301	I~II期，<7 cm	R-CHOP4~6 vs RCHOP4~6 ＋RT		RT未提高EFS（91% vs 87%，P=0.13）and OS（95% vs 90%，P=0.32）

美罗华时代前，随机分组研究
研究	时间	例数	纳入条件	治疗		结果
SWOG 8736^[6,10]	1998	401	I期，或II期非大肿块，侵袭性NHL	CHOP3＋RT vs CHOP8		RT提高5 y PFS（77% vs 64%，P=0.03）和OS（92% vs 72%），但8.2年随访后无差别
ECOG 1484 ^[8]	2004	352	I~II期，侵袭性NHL	CR to CHOP*8：RT vs no RT		RT提高CR患者6 y DFS（73% vs 56%，P=0.05）
GELA LNH 93-1^[7]	2005	647	I~II期，≤60岁，无不良预后因素，侵袭性NHL	CHOP*3＋RT vs ACVBP		ACVBP方案提高5 y EFS（82% vs 74%，P<0.001）和OS（90% vs 82%，P=0.001）
GELA LNH 93-4 ^[9]	2007	576	I~II期，>60岁，无不良预后因素，侵袭性NHL	CHOP*4，RT vs no RT		5 y EFS（64% vs 61%，P=0.56）和OS（68% vs 72%，P=0.64）无差别
美罗华时代，放疗与不放疗单中心比较性研究
研究中心	时间	例数	纳入条件		治疗	多因素分析
MD Anderson^[11]	2010	469	I~II期（40.5%），III~IV期（59.5%） DLBCL		RCHOP*6~8，RT（30%）	RT提高PFS（HR：0.19，P<0.0001）and OS（HR：0.32，P<0.0001）
Seoul National University ^[13]	2015	198	I~II期，DLBCL		RCHOP*≥6（75.3%），RT（43%）	RT提高PFS（HR：0.23，P=0.021）and OS（HR：0.15，P=0.014）
Duke University^[4]	2012	79	III~IV期，DLBCL，化疗后CR		RCHOP*6，RT（48%）	RT提高LC（HR：8.0，P=0.014）和EFS（HR：4.3，P=0.01）
University of Chicago ^[5]	2013	110	III~IV期，DLBCL，化疗后CR		RCHOP*，RT（12.7%）	RT提高LC（HR：8.7，P=0.01）、PFS（HR：9.6，P=0.03）和OS（HR：5.9，P=0.08）
放疗与不放疗大数据库数据比较性研究
数据库	时间	例数	纳入条件	治疗		多因素分析
SEER^[15]	2008	13420	I~II期，DLBCL	化疗不详，RT（41%）		RT降低疾病特异死亡（HR：0.86，P=0.0001）和总死亡率（HR：0.89，P<0.0001）
NCCN^[16]	2014	841	I~II期（47.8%），III~IV期（52.2%），DLBCL	RCHOP*6~8（84%），RT（35%）		RT有提高FFS或OS倾向（特别对III~IV期）
NCDB^[14]	2015	59255	I~II，DLBCL	RT（39%）		RT提高生存（HR：0.66，P<0.001）
美罗华时代，前瞻性研究亚组分析
研究	时间	例数	纳入条件	治疗		多因素分析
Italian Lymphoma Study Group^[12]	2011	182	I~IV期	RCHOP*6，RT（22%）		RT提高EFS（HR：0.33 95% CI 0.11~0.97）
RICOVER-60^[17]	2014	164	≥7.5 cm/结外受累，I~IV期，DLBCL	RCHOP6＋R2，RT（ITT，29%；PP，35%）		RT提高EFS（HR：2.7，P=0.011），PFS（HR：4.4，P=0.001），OS（HR：4.3，P=0.02）
美罗华时代，随机分组研究
研究	时间	例数	纳入条件	治疗分组		多因素分析
UNFOLDER^[21]	2015	285	侵袭性B细胞NHL，≥7.5 cm/结外受累	R-CHOP14/21 vs RCHOP 14/21＋RT		中期分析显示RT提高EFS，故探究提前关闭
LYSA/GOELAMS 02- 03^[20]	2014	301	I~II期，<7 cm	R-CHOP4~6 vs RCHOP4~6 ＋RT		RT未提高EFS（91% vs 87%，P=0.13）and OS（95% vs 90%，P=0.32）

作者	例数	分期	治疗	随访（月）	CR（%）*	EFS（%）*	PFS（%）*	OS（%）*
Tanaka（2012）	95	I~IV	RCHOP*3＋30 Gy RT	35	9183	未报	92（3 y）	95（3 y）
Tanaka（2012）	95	I~IV	RCHOP*6	35	9183	未报	91（3 y）	91（3 y）
Mishima（2012）	40	I~IV	RCHOP3~4＋30 Gy RT/RCHOP6±30 Gy RT	43	87.5	未报	92.31	100
Sohn（2012）	93	I~IV	CHOP±RT±Surgery	48	98.1	86（3 y）	未报	94.7（3 y）
Sohn（2012）	93	I~IV	RCHOP±RT±Surgery	48	98.1	82（3 y）	未报	84.7（3 y）
Zhang（2012）	65	I~IV	CHOP±RT	68	82	72.3	未报	83.1
Zhang（2012）	65	I~IV	RCHOP±RT	68	95	89.8	未报	93.1
Li（2015）	71	I~II	RCHOP*3＋36Gy RT	52	未报	91.7（10 y）	未报	91.7（10 y）
Li（2015）	71	I~II	RCHOP*3	52	未报	77.1（10 y）	未报	77.8（10 y）

作者	例数	分期	治疗	随访（月）	CR（%）*	EFS（%）*	PFS（%）*	OS（%）*
Tanaka（2012）	95	I~IV	RCHOP*3＋30 Gy RT	35	9183	未报	92（3 y）	95（3 y）
Tanaka（2012）	95	I~IV	RCHOP*6	35	9183	未报	91（3 y）	91（3 y）
Mishima（2012）	40	I~IV	RCHOP3~4＋30 Gy RT/RCHOP6±30 Gy RT	43	87.5	未报	92.31	100
Sohn（2012）	93	I~IV	CHOP±RT±Surgery	48	98.1	86（3 y）	未报	94.7（3 y）
Sohn（2012）	93	I~IV	RCHOP±RT±Surgery	48	98.1	82（3 y）	未报	84.7（3 y）
Zhang（2012）	65	I~IV	CHOP±RT	68	82	72.3	未报	83.1
Zhang（2012）	65	I~IV	RCHOP±RT	68	95	89.8	未报	93.1
Li（2015）	71	I~II	RCHOP*3＋36Gy RT	52	未报	91.7（10 y）	未报	91.7（10 y）
Li（2015）	71	I~II	RCHOP*3	52	未报	77.1（10 y）	未报	77.8（10 y）

作者	例数	分期	随诊（月）	剂量（Gy）	照射野	技术	CR（%）	疗效（%）
作者	例数	分期	随诊（月）	剂量（Gy）	照射野	技术	CR（%）	LC	EFS	OS
Tsang（2003）	13	I~II	61	20~35	IFRT	2D	100	100	100	98
Burgers（1988）	24	I	48	20	WAR	2D	未报	未报	83	未报
Schechte（1998）	17	I~II	27	30	IFRT	2D	100	100	100	100
Fung（1999）	14	I~IV	88	40	IFRT	2D	89	100	100	93
Koch（2005）	143	I~II	42	30＋10补量	EFRT	未报	未报	未报	未报	93
Nokamura（2005）	10	I~II	32	30	IFRT	2D	80	100	80	90
Aviles（2005）	78	I~II	77	30＋10补量	WAR	2D	100	78	52（10 y）	75（10 y）
Tsai（2007）	21	I~II	61	30	IFRT	CRT	未报	90	81	94
Vrieling（2008）	56	I~II	72	20＋20补量	WAR	未报	96	93	93	94（10 y）
Yamashita（2009）	11	I~II	32	30	IFRT	CRT	100	100	93	98
Tomita（2009）	20	I~II	50	32	IFRT	2D/3CRT	100	100	82.2	96.6
Gobbi（2009）	5	I~II	70	30	IFRT	CRT	100	100	100	100
Goda（2010）	25	I~II	89	30	IFRT	未报	NM	100	99	94
Okada（2012）	22	I~II	74	30	IFRT	未报	100	100	84	91
Abe（2013）	34	I~II	90	30	IFRT	2D/CRT	97	97	100	97
Nam（2014）	34	I~II	48	30.6	IFRT	2D/CRT	100	97	100	90

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