局限期滤泡性淋巴瘤:放疗可治愈的淋巴瘤? 一项随机对照试验的结果更新

2011年lugano国际淋巴瘤会议（icml）关注早期淋巴瘤放疗篇 摘要027

中国肿瘤化疗  发布时间：16:46 2011-9-22武汉协和医院肿瘤中心刘红利

研究目标:  who分级为i/ii级的早期滤泡性淋巴瘤单用放射治疗可取得良好的疗效。但是最佳放疗野尚未确定：只照射受累区域常出现较高的放疗野外复发率，而扩大放疗野的毒性很大且存在可能导致继发性肿瘤的风险。基于此,本研究旨在探究滤泡性淋巴瘤的根据年龄调整的适当的放疗野(随机试验，rd)，并对标准放疗治疗老年患者的疗效进行评估（前瞻性观察实验，obs）。

方法：年龄不超过65岁的i/ii期或局限性iii期滤泡淋巴瘤患者随机分入两个治疗组：扩大放疗野组(ef)或全淋巴放疗组(tli)，基本剂量为30gy，瘤床加量10/14gy（根据肿瘤的大小来定）。年龄在66-75岁的患者接受扩大放疗野治疗，年龄大于75岁的患者只接受侵犯区域的放疗。

结果：共入组255例符合条件的患者。202例随机试验（rd）的患者被随机分入扩大放疗组或全淋巴放疗组。患者的中位年龄54岁(23-65)；53例观察试验（obs）的患者中位年龄 70岁 (64-84)，接受扩大放疗野治疗(79%)或受累区域放疗(21%)。对所有255例患者的合并分析最新结果显示，中位随访51个月的总生存为97%。5年无复发生存和无进展生存分别为60% 和59%，并在第六年后进入平台期。所有患者的完全缓解(cr)率为92%。所有患者中24%出现复发，复发间期的中位数为24个月。在随机试验（rd）中，两组患者的复发率出现差异，即将达到揭盲所需的差异值。所有255例患者中复发病例的复发部位与放疗范围相关：复发主要出现在新部位(占92%, 其中79% 为单发新病灶)，多为放疗野外复发(73%)，68%患者的复发部位出现在膈肌的对侧。复发大多为淋巴结内复发(76%)，骨髓侵犯 (8%)或结外复发 (10%)均较少。对65%的复发患者获取标本进行组织学分型，发现其中30%的患者在诊断后15个月 (7-96)转化为弥漫大b细胞淋巴瘤（dlbcl），这占所有复发患者的19%、所有入组病例的5%。36个月 (4-119)后，出现的继发性肿瘤包括实体瘤6例，肉瘤及急性粒细胞白血病（aml）各1例，疑诊的骨髓增生异常综合征（mds）2例。

结论：早期滤泡性淋巴瘤患者采用标准放疗可获得较高的完全缓解率和很好的生存结果，超过六年的复发很少见。然而，复发主要出现在新部位和放疗野外的淋巴结内病灶，提示了肿瘤的早期播散，需要寻找新的治疗策略。

 

‘‘focus on. . .’’ session: radiotherapy and early stage

 

027 follicular lymphoma: curability by radiotherapy in limited stage nodal disease? updated results of a randomized trial.

aims: follicular lymphoma who grade i or ii (fl) in early stage nodal disease can be treated effectively by radiotherapy alone. the extent of optimal target volumes remains controversial with a high rate of relapse (rls) out-field after involved field irradiation, but higher toxicity and potentially risks of secondary neoplasia after large field techniques. therefore, this study aimed to determine adequate age-adapted irradiation volumes in fl patients (pts) [randomized trial (rd)] and to evaluate standardized radiotherapy in elderly fl pts [prospective observation trial (obs)].

methods: in fl stage i-ii and limited stage iii disease, pts up to 65 years (ys) were randomized to extended field (ef) or total lymphatic irradiation (tli), basic dose 30
gy, boost 10/14 gy (lymphoma size dependent). pts aged 66-75 ys were treated with ef, pts > 75 ys with involved field (if) radiotherapy.

results: a total of qualified 255 pts were recruited. in the rd trial, 202 pts, median age 54 (23-65) ys, were randomized to ef or tni. in the obs trial 53 pts, median age 70
(64-84) ys, were treated with ef (79%) or if (21%). in the updated combined analysis of all 255 pts, overall survival is 97%, median observation period of 51 months. relapse- and progression-free survival are 60% and 59% at five years with a plateau after six years. complete remissions (cr) were obtained in 92% of all pts. rls occurred in 24% of all pts, median interval 24 months. in the rd pts, differences in rls rates and probabilities between treatment arms emerge and the required number for unblinding will shortly be reached.
first rls sites of all 255 pts were correlated with extent of radiotherapy: rls developed predominantly as new manifestations (92%, 79% new site alone), more often out-of field (73%), and were in 68% located on the opposing side of the diaphragm. rls was mostly entirely nodal (76%), rarely bone marrow (8%), orextranodal (10%).
in 65% of all rls, histology was obtained, revealing transition into secondary diffuse large b-cell lymphoma (dlbcl) in 30% of these pts (19% of all rls, 5% of all
study pts), 15 (7-96) months from diagnosis. second tumors were observed as solid tumors (n=6), sarcoma and aml (one case each) and possibly mds (n=2) after 36
(4-119) months.

conclusions: in early stage nodal fl, standardized rt induced high rates of cr with excellent survival, and relapse is rare beyond six years. however, the predominance of
relapse in new and out-of field nodal sites is suggestive of early occult dissemination, warranting consideration in new treatment concepts.