早期霍奇金淋巴瘤化疗后受累野照射对疗效和长期毒副作用的影响

 扩大野放疗可以治愈早期霍奇金淋巴瘤（HL）。为了减少远期毒副作用,近10～20年来开展了系列综合治疗的随机对照研究。对于早期经典HL,化疗和放疗综合治疗较单纯放疗或单纯化疗均可明显改善长期无瘤生存率。目前已有部分研究证实受累野照射和较低照射剂量可以明显降低长期并发症,早期HL的标准治疗是短疗程化疗加受累野放疗。     

Ⅰ期和Ⅱ期原发于头颈部非霍奇金淋巴瘤预后因素分析

目的:分析影响Ⅰ期和Ⅱ期原发于头颈部非霍奇金淋巴瘤预后因素,寻求合理的治疗方案.方法:1994年6月至2000年6月共收治Ⅰ期和Ⅱ期原发于头颈部非霍奇金淋巴瘤54例,分别采用单纯放疗,放疗+化疗和单纯化疗.放疗多采用局部野或局部扩大野照射,原发部位DT50Gy～55Gy,邻近一站淋巴结区预防剂量DT45Gy.化疗用CHOP方案,化疗4～6周期.结果:全组5年生存率为64%,其中Ⅰ期为75%,Ⅱ期为47%(P＜0.05).低度恶性、中度恶性、高度恶性患者5年生存率分别为70%、54%、39%,其中低度恶性组5年生存率明显高于高度恶性组(P＜0.05).放疗+化疗组5年生存率69%,明显高于其它二组(P＜0.05).单纯放疗及放疗+化疗治疗后局部控制率达92%,明显高于单纯化疗组(P＜0.05).单纯化疗组治疗后局部复发率较高,达37.5%.结论:临床分期、病理类型及治疗方法是影响其预后的主要因素.单纯化疗组治疗后局部复发率较高,提示放疗在早期非霍奇金淋巴瘤治疗中还是占有比较重要的地位,不能用单纯化疗取代放疗,有计划的放疗+化疗是提高局部控制率和生存率的关键.     

早期霍奇金淋巴瘤的综合治疗

霍奇金淋巴瘤(HL)已成为一种可以治愈的疾病,目前研究的重点在于不增加疾病死亡率的前提下,降低治疗引起的并发症.最近10～15年,开展了Ⅰ～Ⅱ期HL综合治疗的系列随机研究,比较综合治疗和单纯放疗或单纯化疗的疗效,并研究综合治疗时的最佳化疗方案和化疗周期数、照射靶区大小和照射剂量.综合治疗和单纯放疗或单纯化疗比较,显著改善了早期HL无病生存率10%～15%,但未提高总生存率.预后好:早期HL行单纯放疗或2～4周期ABVD方案化疗加受累野照射;预后不良:早期HL行4～6周期ABVD化疗加受累野照射.     

成年人早期霍奇金淋巴瘤的治疗并发症

 目的 探讨降低早期霍奇金淋巴瘤（HL）治疗并发症的方法。方法 对212例初治的早期HL成年人患者进行回顾性分析,其中136例接受单纯放射治疗（RT组）,76例接受放射治疗+化疗综合治疗（RT+CT组）。结果 全组有61例（28.8 %）出现治疗并发症,共75例次。RT组和RT+CT组的并发症发生率分别为33.8 %和38.2 %（P＞0.05）。全组共有51例患者死亡,其中76.5 %死于HL未控或复发、13.7 ％死于第二原发肿瘤、7.8 ％死于放射性心包炎。结论 早期HL经过放疗和（或）化疗可取得满意疗效,合理地设计照射野,并严格控制照射剂量和化疗周期能有效地降低治疗所造成的各种并发症。     

结节性淋巴细胞为主型霍奇金淋巴瘤七例

目的 探讨结节性淋巴细胞为主型霍奇金淋巴瘤(NLPHL)临床病理特征及治疗.方法 经病理免疫组织化学证实为NLPHL患者7例.6例患者接受化疗和受累野放疗的综合治疗;1例仅接受单纯化疗.结果 3年局部控制率和总生存率分别为100%和86%.1例患者死于化疗后肺部感染.结论 NLPHL预后良好,综合治疗耐受好,不良反应少,但应注意治疗后不良反应的处理.     

Ⅰ期和Ⅱ期原发于头颈部非霍奇金淋巴瘤预后因素分析

目的:分析影响Ⅰ期和Ⅱ期原发于头颈部非霍奇金淋巴瘤预后因素,寻求合理的治疗方案。方法:1994年6月至2000年6月共收治Ⅰ期和Ⅱ期原发于头颈部非霍奇金淋巴瘤54例,分别采用单纯放疗,放疗 化疗和单纯化疗。放疗多采用局部野或局部扩大野照射,原发部位DT50Gy~55Gy,邻近一站淋巴结区预防剂量DT45Gy。化疗用CHOP方案,化疗4~6周期。结果:全组5年生存率为64%,其中Ⅰ期为75%,Ⅱ期为47%(P<0.05)。低度恶性、中度恶性、高度恶性患者5年生存率分别为70%、54%、39%,其中低度恶性组5年生存率明显高于高度恶性组(P<0.05)。放疗 化疗组5年生存率69%,明显高于其它二组(P<0.05)。单纯放疗及放疗 化疗治疗后局部控制率达92%,明显高于单纯化疗组(P<0.05)。单纯化疗组治疗后局部复发率较高,达37.5%。结论:临床分期、病理类型及治疗方法是影响其预后的主要因素。单纯化疗组治疗后局部复发率较高,提示放疗在早期非霍奇金淋巴瘤治疗中还是占有比较重要的地位,不能用单纯化疗取代放疗,有计划的放疗 化疗是提高局部控制率和生存率的关键。     

霍奇金淋巴瘤的治疗共识及临床研究进展

霍奇金淋巴瘤（HL）起源于淋巴造血组织,是治疗效果较好、治愈率较高的恶性肿瘤之一.目前,早期HL可通过化疗联合受累野放疗或单纯化疗的方式治愈,但复发、难治性HL患者仍缺乏有效治疗手段.近年来随着个体化分层治疗、靶向药物brentuximab vedotin、PET-CT检查等新型策略的应用,HL的预后评价及治疗研究均取得了新进展.     

局限期霍奇金淋巴瘤的治疗及放疗原则:第54届美国血液学会年会报道

 局限期霍奇金淋巴瘤（HL）的治疗多数首选联合治疗,也有部分学者认为对于无大肿块的Ⅰ、Ⅱ期预后良好HL单纯ABVD方案化疗是可以接受的;单纯放疗目前主要被用于Ⅰ期或局限Ⅱ期结节性淋巴细胞为主型HL患者。今后通过缓解速度进行调整治疗的个体化治疗可能会使更多的患者获益。     

结节性淋巴细胞为主型霍奇金淋巴瘤七例

 目的　探讨结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）临床病理特征及治疗。方法　经病理免疫组织化学证实为NLPHL患者7例。6例患者接受化疗和受累野放疗的综合治疗；1例仅接受单纯化疗。结果　3年局部控制率和总生存率分别为100 %和86 %。1例患者死于化疗后肺部感染。结论　NLPHL预后良好，综合治疗耐受好，不良反应少，但应注意治疗后不良反应的处理。     

原发骨非霍奇金淋巴瘤临床分析

目的:探讨原发骨非霍奇金淋巴瘤的临床特点、诊断、治疗及预后.方法:选择1970年11月～2003年2月我院收治的21例原发于骨的非霍奇金淋巴瘤,其中Ⅰ期14例(66.7%),Ⅱ期2例(9.5%),Ⅳ期5例(23.8%).弥漫性大B细胞型12例(57.1%),混合细胞型4例(19.0%),小淋巴细胞型1例(4.8%),T细胞型1例(4.8%),未分型3例(14.3%).采用单纯放疗6例(28.6%),放疗和化疗综合治疗15例(71.4%).结果:中位随访86个月,2例(95%)局部复发,9例(42.9%)出现远处受侵,3年、5年、10年无进展生存率分别为56.7%、38.9%、29.1%;3年、5年、10年总生存率分别为69.1%、42.2%、42.2%.结论:原发于骨的非霍奇金淋巴瘤首选放疗和化疗的综合治疗;放疗剂量推荐45Gy～46Gy.     

Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease.

PURPOSE: The management of early-stage Hodgkin's disease in the United States is controversial. To evaluate whether staging laparotomy could be safely avoided in early-stage Hodgkin's disease and whether chemotherapy should be a part of the treatment of nonlaparotomy staged patients, a phase III intergroup trial was performed. PATIENTS AND METHODS: Three hundred forty-eight patients with clinical stage IA to IIA supradiaphragmatic Hodgkin's disease were randomized without staging laparotomy to treatment with either subtotal lymphoid irradiation (STLI) or combined-modality therapy (CMT) consisting of three cycles of doxorubicin and vinblastine followed by STLI. RESULTS: The study was closed at the second, planned, interim analysis because of a markedly superior failure-free survival (FFS) rate for patients on the CMT arm (94%) compared with the STLI arm (81%). With a median follow-up of 3.3 years, 10 patients have experienced relapse or died on the chemoradiotherapy arm, compared with 34 on the radiotherapy arm (P <.001). Few deaths have occurred on either arm (three deaths on CMT and seven deaths on STLI). Treatment was well tolerated, with only one death on each arm attributed to treatment. CONCLUSION: These results demonstrate that it is possible to obtain a high FFS rate in a large group of stage IA to IIA patients without performing staging laparotomy and that three cycles of chemotherapy plus STLI provide a superior FFS compared with STLI alone. Extended follow-up is necessary to assess freedom from second relapse, overall survival, late toxicities, patterns of treatment failure, and quality of life.     

Early stage infradiaphragmatic Hodgkin's disease: results of radiotherapy and review of the literature.

PURPOSE: To assess the impact of modality therapy on long-term outcome for infradiaphragmatic Hodgkin's disease (IDHD). METHODS AND MATERIALS: During the period 1965-1997, 847 patients with early stage Hodgkin's disease (HD) were evaluated and treated at our institution, 20 of them had IDHD (2.4%). Patients characteristics: stage I, nine patients (five pathological stage (PS), and four clinical stage (CS)) and stage II: 11 patients (six PS and five CS). Two modalities of treatment were used: combined modality (CMT), consisting of chemotherapy followed by extended field radiotherapy or radiotherapy alone (XRT). All patients with CS or PS II, except in one case, were treated with CMT. Overall, 12 patients were treated with CMT and the remaining eight patients were treated with XRT. RESULTS: The relapse rate after initial treatment was 30%. Ten-year disease free survival (DFS) and 10-year cause-specific survival were 60% and 92%, respectively. There was a non-significant trend to a better DFS for the CMT group of patients (76% vs. 35% for the whole series and 100% vs. 24% for stage I patients). The four relapsed patients in the XRT group were inguino-femoral PS I. In four out of the six patients who relapsed (66%) the failure was located solely in the supradiaphragmatic area, outside of the radiation fields. CONCLUSIONS: In our experience, inguino-femoral stage I patients have a high relapse rate after XRT; consequently, CMT consisting of chemotherapy plus involved field radiotherapy should be recommended for early stage HD confined below diaphragm.     

The impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity in early-stage Hodgkin's disease

A retrospective analysis of patients with supradiaphragmatic Stage I-II Hodgkin's disease was performed to assess the impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity. One hundred twenty patients were treated with radiotherapy (RT) alone; 38 received total nodal (including pelvic) irradiation (TNI), 63 received modified total nodal (excluding pelvic) irradiation (MTNI), and 19 received involved-field or mantle irradiation only (less than MTNI). Thirty-three patients received combined-modality therapy. In laparotomy-staged (PS) patients treated with RT alone, the overall treatment failure rate was 13% after TNI, 24% after MTNI, and 43% after less than MTNI. The pelvic failure rate in PS patients was 0% after TNI, 9% after MTNI, and 29% after less than MTNI. Cause-specific deaths in patients treated with RT alone occurred in 10% following less than MTNI, 13% following MTNI, and 10% following TNI. Cause-specific deaths due to pelvic failure in patients treated with RT alone occurred in 5% following IF and 6% following MTNI, and also occurred in 7% of patients receiving combined-modality therapy. The potential disadvantages of elective pelvic irradiation in early-stage Hodgkin's disease include compromise of future tolerance of chemotherapy in the event of treatment failure, and infertility. Gonadal function was assessed in 67 patients less than 35 years old at the time of treatment. Compromise of gonadal function was correlated with the lack of special testicular shielding during pelvic irradiation and chemotherapy in the male, and with no oophoropexy before pelvic irradiation in the female. Twelve of 26 patients with recurrence after either less than MTNI or MTNI, with or without chemotherapy, were alive and without evidence of disease at greater than 2 years after completing salvage therapy, compared with 7 of 11 patients with recurrence after TNI.     

Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.     

Stage III Hodgkin's disease--long-term results following chemotherapy, radiotherapy and combined modality therapy

215 patients with stage III Hodgkin's disease (HD) were treated at the Royal Marsden Hospital between 1963 and 1985 (median follow-up 9 years). The actuarial 5- and 10-year survival was 77 and 65%, respectively with 55 and 48% 5 and 10 year disease-free survival. Of 13 variables tested, age was the only independent prognostic indicator for survival on multivariate analysis. Patients aged under 40, 40-59 and over 60 years had a 10-year survival of 76, 41 and 8%, respectively (p much less than 0.001). Ninety-one patients were initially treated with combined chemotherapy and radiotherapy (combined modality therapy, CMT), 73 patients with radiotherapy (RT) and 51 patients with chemotherapy (CT) alone. Patients under 40 years treated with CMT achieved the best disease-free survival (10 year disease-free survival: CMT 68%; RT 38%; CT 45%). The observed survival advantage for CMT was not statistically significant. In patients aged greater than 40 there was no survival or disease-free survival advantage following CMT. Analysis of recurrence pattern confirmed that CMT improves initial disease control both at previously involved and uninvolved sites. Recurrences at previously uninvolved sites continued up to 6 years following CT, up to 8 years following CMT and up to 14 years after RT alone. These results indicate that only long-term follow-up gives the true picture of stage III HD.     

Localized extranodal lymphoma of the head and neck: retrospective analysis of a series of 107 patients from a single institution

PURPOSE: To retrospectively analyze the outcome and patterns of relapse in localized extranodal non-Hodgkin's lymphoma of the head and neck (HN-NHL) after radiotherapy alone or combined modality treatment. PATIENTS AND METHODS: A retrospective analysis of 107 patients with HN-NHL was performed. Relapse patterns, overall survival (OS) and relapse-free survival (RFS) were analyzed. Only stage I (n=50) and stage II (n=57) patients were included with either low-grade (n=21) or high-grade (n=86) lymphoma. Fifty-nine patients were treated with radiotherapy (RT) alone and 48 patients received combined-modality treatment (CMT) consisting of chemotherapy (CHOP or CHOP-like) followed by radiotherapy. The volumes of irradiation included local field (n=24), involved field (n=13) and extended field (n=70). The median age at diagnosis was 63 years (range, 17-86 years). RESULTS: The overall response rates (CR+PR) in the radiotherapy group and the combined modality group were 100% and 96%, respectively. With a median follow-up of 49.4 months, 29 of 59 patients after RT alone (37%) and 30 of 48 patients after CMT (62%) were disease-free. In the whole series the projected five-year OS and RFS were 58.7% and 61.8%. At univariate analysis of clinical variables with potential impact on survival including age, stage, histology, IPI score, single or combined treatment and volumes of irradiation, only age and, to a limited extent, type of treatment influenced OS (age < or =60 years 79%, >60 years 41%, P < 0.001; RT alone 54.9%, CMT 62.8%, P = 0.0487) and RFS (< or =60 years 75%, >60 years 50%, P < 0.001; RT alone 54%, CMT 71%, P = 0.039). Better OS and RFS rates were obtained in patients with stage II and high-grade disease treated with CMT (five-year OS and RFS 63% and 69%, respectively; the corresponding values for RT alone were 38% and 34%). The final model of the multivariate analysis retained only age (< or =60 years) as a significant prognostic factor for both RFS and OS (P < 0.001). In the whole series, the sites of relapse were mainly systemic (n = 32/40, 80%) and in-field relapses were rare (n = 3/40, 7.5%). CONCLUSION: HN-NHL is characterized by a high risk of relapse, particularly at distant sites. Older patients have a significantly worse prognosis. Radiotherapy offers a very good local control rate although combined modality treatment possibly produces better RFS and OS, especially for stage II and high-grade disease. Better systemic approaches are warranted for a more consistent impact on survival in this particular subset of extranodal lymphoma. However, radiotherapy alone may offer a feasible and effective modality for patients who cannot tolerate more aggressive treatments. Extended-field radiotherapy and the treatment of a larger number of uninvolved lymph nodal regions does not confer a RFS or OS advantage, either after RT alone or after CMT.     

Decision analysis on alternative treatment strategies for favorable-prognosis, early-stage Hodgkin's disease.

PURPOSE: To compare the therapeutic outcomes of various treatment strategies in early-stage, favorable-prognosis Hodgkin's disease (HD) using methods of decision analysis. METHODS: We constructed a decision-analytic model to determine the life expectancy and quality-adjusted life expectancy for a hypothetical cohort of clinically or pathologically staged 25-year-old patients with early-stage, favorable-prognosis HD treated with varying degrees of initial therapy. Markov models were used to simulate the lifetime clinical course of patients, and baseline probability estimates were derived from published study results. RESULTS: Among patients with pathologic stage (PS) I to II, mantle and para-aortic (MPA) radiotherapy was favored over combined-modality therapy (CMT), mantle radiotherapy, and chemotherapy by 1.18, 1.33, and 1.55 years, respectively. For patients with clinical stage (CS) I to II, the treatment options of MPA-splenic radiotherapy, CMT, and chemotherapy yielded similar survival outcomes. Sensitivity analysis showed that the decision between CMT and MPA-splenic radiotherapy was highly influenced by the precise values of the estimates of treatment efficacy and long-term morbidity, the quality-of-life value assigned to the postsplenic irradiation state, and the time discount value used in the model. Probabilistic sensitivity analysis demonstrated that even if future studies doubled the precision of the estimates of the treatment-related variables, it would be impossible to demonstrate the superiority of one treatment over the other. CONCLUSION: Our model predicted that on average, MPA radiotherapy was clearly the preferred treatment for PS I to II patients. For CS I to II patients the treatment decision is a toss-up between MPA-splenic radiotherapy and CMT, emphasizing the importance of patient preference exploration and shared decision making between patient and physician when choosing between treatments.     

Prospective study of combined modality treatment or radiotherapy alone in the management of early-stage adult Hodgkin's disease

PURPOSE: To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients. METHODS AND MATERIALS: Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT. RESULTS: The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism. CONCLUSION: Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions.     

晚期霍奇金病128例临床总结分析

目的 探讨晚期霍奇金病的合理治疗方法。方法 对１２８例晚期霍奇金病的治疗结果进行了总结和分析。结果 总有效率９６．１％（１１２／１２７）,其中完全缓解（ＣＲ）率８．５％,化放疗组、单化疗组和单放疗组的ＣＲ率分别为６９．７％、５８．３％和１００％。全组１,３,５,１０年生存率分别为．４％、７０．３％、５６．８％和５２．４％。生存率分析显示,临床Ⅲ期,无全身症状、无巨块型、淋巴细胞为主型和结节经型、化     

Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group.

PURPOSE: We report results of a randomized trial comparing ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy alone with treatment that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma. PATIENTS AND METHODS: Patients with nonbulky clinical stage I to IIA Hodgkin's lymphoma were stratified into favorable and unfavorable risk cohorts. Patients allocated to radiation-containing therapy received subtotal nodal radiation if favorable risk or combined-modality therapy if unfavorable risk. Patients allocated to ABVD received four to six treatment cycles. RESULTS: We evaluated 399 patients. Median follow-up is 4.2 years. In comparison with ABVD alone, 5-year freedom from disease progression is superior in patients allocated to radiation therapy (P = .006; 93% v 87%); no differences in event-free survival (P = .06; 88% v 86%) or overall survival (P = .4; 94% v 96%) were detected. In a subset analyses comparing patients stratified into the unfavorable cohort, freedom from disease progression was superior in patients allocated to combined-modality treatment (P = .004; 95% v 88%); no difference in overall survival was detected (P = .3; 92% v 95%). Of 15 deaths observed, nine were attributed to causes other than Hodgkin's lymphoma or acute treatment-related toxicity. CONCLUSION: In patients with limited-stage Hodgkin's lymphoma, no difference in overall survival was detected between patients randomly assigned to receive treatment that includes radiation therapy or ABVD alone. Although 5-year freedom from disease progression was superior in patients receiving radiation therapy, this advantage is offset by deaths due to causes other than progressive Hodgkin's lymphoma or acute treatment-related toxicity.