Seymour John F, Pro Barbara, Fuller Lillian M, Manning John T, Hagemeister Fredrick B, Romaguera Jorge, Rodriguez Maria A, Ha Chul S, Smith Terry L, Ayala Ana, Hess Mark, Cox James D, Cabanillas Fernando, McLaughlin Peter
Department of Haematology, The Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia.
J Clin Oncol. 2003 Jun 1;21(11):2115-22. doi: 10.1200/JCO.2003.07.111.
Standard therapy for patients with stage I-II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients.
A total of 102 eligible patients with stage I-II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT.
The patients' median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease (>/= 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P =.02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta2-microglobulin was associated with shorter survival (P <.0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields.
With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.
I-II期惰性淋巴瘤患者的标准治疗方法是累及野放射治疗(IF-XRT),40%至50%的患者可实现10年无病生存,其中许多患者可治愈。我们研究了联合治疗方式增加此类患者无病生存的可能性。
1984年至1992年共纳入102例符合条件的I-II期低度淋巴瘤患者(国际工作分类标准)。治疗包括10个周期的风险适应性化疗(环磷酰胺、长春新碱、泼尼松、博来霉素[COP-Bleo],部分患者加用阿霉素[CHOP-Bleo])和30至40 Gy的IF-XRT。
患者的中位年龄为56岁(范围28至77岁),83%为滤泡组织学,24%有大包块病变(≥5 cm),52%为II期。无治疗相关死亡,99%的患者达到完全缓解。中位随访10年,10年治疗失败时间和总生存率分别为76%和82%。对于滤泡性淋巴瘤患者,这些数字分别为72%和80%。滤泡性淋巴瘤患者中与治疗失败相关的唯一因素是分期修正的国际预后指数评分(P = 0.02)。17例弥漫性小淋巴细胞或黏膜相关淋巴组织组织学患者均未复发。血清β2-微球蛋白升高与生存期缩短相关(P < 0.0001)。复发后10年生存率为46%。有2例骨髓发育异常及12例其他新发恶性肿瘤,包括4例发生在放射野内。
随着随访时间延长,风险适应性COP-/CHOP-Bleo联合IF放疗的联合治疗方式比之前单独使用IF-XRT报道的疾病控制率和生存率更高。正在进行的一项随机试验正在进一步探讨这一明显改善。