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.     

150例早期霍奇金淋巴瘤的综合治疗

目的 对比单纯化疗、单纯放疗与综合治疗对早期霍奇金淋巴瘤(HL)的疗效.方法 回顾性分析150例Ⅰ期或Ⅱ期(早期)HL患者的临床资料,按照初次治疗方式分为单纯化疗组(22例)、单纯放疗组(18例)、化疗联合放疗的综合治疗组(109例)和手术组(1例).化疗方案以ABVD和MOPP为主,放疗方式主要包括受累野放疗、扩大野放疗和次全淋巴结照射.结果 结节硬化型、混合细胞型、淋巴细胞为主型、淋巴细胞消减型和结节性淋巴细胞为主型HL分别为84、39、23、3和1例.全组有72例患者资料完整,可判断预后,其中以欧洲癌症研究和治疗组织及德国霍奇金淋巴瘤研究组标准判断为0分者分别占36.1%和29.2%.全组完全缓解33例,部分缓解109例,疾病稳定5例,疾病进展3例.全组中位随访71.5个月,6年治疗失败率为18.8%,7年总生存率为89.3%.单因素分析显示,综合治疗的疗效显著优于单纯化疗,结节硬化型和混合细胞型的治疗失败风险明显低于淋巴细胞为主型(均P＜0.05).多因素分析显示,治疗方式可以显著影响预后,单纯化疗发生治疗失败的风险是综合治疗的2.52倍(P=0.004).单因素和多因素分析均未发现总生存时间的影响因素.综合治疗组的急性不良反应发生率较单纯化疗组或单纯放疗组高,主要表现为白细胞减低、胃肠道反应和脱发.结论 对于早期HL,综合治疗可降低治疗失败风险,但不良反应较重.     

霍奇金淋巴瘤的受累野照射

最近几十年,放射治疗在霍奇金淋巴瘤治疗中的作用发生了很大的变化.在20世纪60～70年代,扩大野照射可以有效地治愈大部分早期和中期HL.最近10年,化疗加受累野照射已成为Ⅰ～Ⅱ期HL的主要治疗手段,对于Ⅲ～Ⅳ期化疗后的患者,受累野照射应用于大肿块或残存病灶.本文描述受累野的定义、设计和常见受侵部位的射野边界.     

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.     

霍奇金淋巴瘤治疗进展:第54届美国血液学会年会深度报道

 【摘要】　目前,早期霍奇金淋巴瘤（HL）可通过化疗联合受累野放疗或单纯化疗的方式被治愈,但对放疗在早期HL治疗中的必要性仍有争议。而复发、难治HL的治疗仍存在着巨大挑战,除了大剂量化疗序贯自体造血干细胞移植外,尚缺乏有效的治疗手段。安全有效的新型药物如brentuximab vedotin的应用将有助于改善这类患者的生存预后。中期PET（PET-i）检查对早期和晚期HL患者都具有重要预后价值,尤其是在化疗2个周期后行PET检查,但依据PET-i结果而改变治疗方法除临床试验外并不被推荐。     

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。     

国际淋巴瘤放射治疗协作组(ILROG)现代放射治疗靶区勾画及剂量指南——HL

放疗是HL最有效的LC治疗手段和重要的治疗组成部分。这些指南用来指导现代综合治疗条件下放疗在HL中的应用。结合现代影像的三维治疗计划和先进的治疗技术,能减少照射体积和照射剂量。最初使用的EF和IF技术,是基于淋巴结站的大体积治疗方式,目前已被仅以最初可检测到的淋巴结(和结外侵犯)范围为基础的有限的照射野所取代。这种照射技术基于增强CT、PET-CT、MRI或结合运用。ICRU定义了GTV、CTV、ITV和PTV概念。更新的治疗技术包括IMRT、呼吸门控、IGRT和4D图像应用,可以显著降低正常组织损伤风险且同时可达到对原发肿瘤控制的主要目的。能够获得理想治疗前影像患者,可以采用高度适形的受累淋巴结放疗(INRT)。受累部位放疗(ISRT)这个新概念作为标准的适形治疗方式被提出,通常在最佳的影像不可获得的情况下使用。越来越多证据表明过去应用的放疗剂量在综合治疗时代比疾病控制所需剂量高。现有数据支持在早期HL中应用INRT和更低放疗剂量。尽管INRT的应用尚未在正式的研究中得到验证,其应用比ISRT更加保守谨慎,原因为欠理想的影像信息和合适的靶区设计以达到可靠的肿瘤LC。目前使用更小照射野治疗的目标是减少治疗体积和剂量,同时维持治疗有效性并使急性和晚期并发症最小化。这篇综述是ILROG督导委员会关于HL放疗现代治疗手段的共识,概括了对HL在可以达到有效LC的同时减少治疗体积的新概念,即ISRT。     

早期霍奇金病综合治疗中受累野照射的临床疗效

目的 评价Ⅰ、Ⅱ期霍奇金病（HD）患者综合治疗时受累野照射的疗效和毒副作用,并与扩大野照射进行比较。方法 早期HD 88例,根据Ann Arbor分期,ⅠA期12例（13．7％）,ⅡA期56例（63．6％）,ⅡB期20例（22．7％）。全部患者接受化疗和放疗综合治疗,先化疗后放疗患者83例,先放疗后化疗患者5例。化疗多采用ABVD或ABVD／MOPP方案;受累野照射42例,扩大野照射46例。结果 全组有6例膈上原发HD治疗后复发,受累野组和扩大野组各3例。扩大野组有1例照射野内复发,受累野组有1例在邻近照射部位的腋窝复发,其余4例患者均表现为结外器官或膈下淋巴结受侵。全组患者1、2、3年总生存率分别为100．0％、98．6％和96．3％,受累野组患者分别为100．0％、97．1％和97．1％,扩大野组患者分别为100．0％、100．0％和95．8％,两组生存率差异无统计学意义（P=0．86）。受累野组1、2、3年无进展生存率分别为97．6％、94．8％和91．7％,扩大野组分别为97．8％、93．2％和93．2％,两组无进展生存率差异无统计学意义（P=0．65）。发生Ⅰ度和Ⅱ度白细胞减少症者,受累野组3例（7．2％）,扩大野组9例（19．5％,P=0．089）。结论 Ⅰ、Ⅱ期HD患者进行综合治疗时,采用受累野照射可获得与扩大野照射相同的疗效,且能减少并发症的发生。     

41例霍奇金淋巴瘤综合治疗的疗效观察

目的:对霍奇金淋巴瘤(HL)患者综合治疗的方案、疗效、不良反应进行总结,为今后选择治疗策略提供借鉴和指导.方法:41例HL患者化疗后接受两种不同剂量及设野的放疗,并对疗效及不良反应进行随访.结果:采用ABVD、MOEP/ABV、COEP/BACOP、CHOP及MOPP化疗方案的单周期有效率分别为85.5%、75.7%、70.4%、69.8%、65.7%;接受受累野照射或扩大野照射的两组CR率分别为82.3%和83.3%;放疗后出现局部纤维化15例,心电图明显异常8例,心包、胸腔积液4例,第二癌1例.综合治疗5年总生存率(OS)91.2%,3年总生存率94.9%.结论:ABVD仍为HL的首选化疗方案;30Gy＜DT≤40Gy剂量纽与40Gy＜DT≤55Gy剂量组间远期疗效无显著统计学差异,但低剂量组不良反应明显小于另一组.     

霍奇金淋巴瘤治疗进展

霍奇金淋巴瘤（Hodgkin lymphoma,HL）是起源于淋巴造血组织的恶性肿瘤。随着化疗药物和放射技术的进步,尤其是化、放疗综合治疗的应用,早期HL的5年生存率超过90%。晚期HL的5年无失败生存率为60%～70%。对于早期HL而言,治愈率已经很高,研究方向是在保持现有疗效的基础上,减少化疗周期数、降低放射剂量、缩小照射范围,以降低远期毒性,改善患者的生存状态。对于早期预后不良和晚期HL,复发率仍然很高,近年来国际上研究的方向是寻求合理、个体化的放、化疗综合治疗模式,探索新药和新的化疗方案,以期进一步提高患者的生存率,改善生活质量。此外,一些新的靶向药物如抗CD30单抗的复合物,去组蛋白乙酰化抑制剂等也进入了临床前和临床研究,有望进一步提高疗效。     

Treatment of early-stage nonbulky Hodgkin lymphoma

PURPOSE OF REVIEW: Excellent results have been achieved in the treatment of early-stage Hodgkin lymphoma for more than 30 years with radiation therapy alone or the combined modalities of radiotherapy and chemotherapy. A major concern has been the long-term toxicity of treatment, most of which is attributable to radiotherapy. Recent trials that attempt to decrease acute and long-term toxicity are reviewed. RECENT FINDINGS: To address the problem of late treatment morbidity, randomized trials of combined-modality therapy have been conducted demonstrating that the number of chemotherapy cycles and the extent and doses of radiotherapy can be reduced. Several studies, including three randomized trials of chemotherapy alone vs. combined-modality therapy, suggest that chemotherapy alone is a reasonable option for the treatment of nonbulky early-stage Hodgkin lymphoma. Positron emission tomography after one or two cycles of chemotherapy has been found to be highly predictive of treatment outcome for Hodgkin lymphoma. Combination chemotherapy alone including gemcitabine, a highly active drug with a favorable toxicity profile, with positron emission tomography early during treatment is under evaluation. SUMMARY: Less toxic regimens with the aid of positron emission tomography may reduce the short-term and long-term toxicities of treatment of early-stage nonbulky Hodgkin lymphoma.     

Favorable early-stage Hodgkin lymphoma

The category of favorable early-stage Hodgkin lymphoma (HL) includes patients with Ann Arbor stages I or II disease with no bulky disease or B symptoms. The precise definition of favorable versus unfavorable early-stage disease may vary among American and European cooperative groups. The overall 10-year survival rate of patients with favorable early-stage HL exceeds 90%. Indeed, effective treatments for this group of patients have been available for more than 4 decades. However, treatment strategies have radically changed over the past 15 years and focus now on maintaining the high cure rate while reducing the risk of treatment-related long-term morbidity. The optimal treatment is still evolving, and more recently, reduction in the total amount of chemotherapy and in radiation field and dose has shown excellent results. Combined modality therapy is the preferred treatment for patients with classical favorable early-stage HL (nodular sclerosis or mixed cellularity histology). Patients with early-stage lymphocyte predominance HL are highly curable using involved-field radiation therapy (IFRT) alone and do not require chemotherapy. Classical favorable HL is also curable with radiotherapy alone or with chemotherapy alone, but larger fields and higher-dose radiation or longer chemotherapy is required compared with combined modality. The freedom from treatment failure rate is significantly better with a combination of short chemotherapy and IFRT than with either chemotherapy or radiotherapy alone. Although combined modality is the standard preferred treatment for favorable disease, radiation therapy alone or chemotherapy alone could be considered under special circumstances or as part of an investigational protocol.     

Treatment of Hodgkin lymphoma: the past, present, and future

Significant advances in the biology and treatment of Hodgkin lymphoma (HL) have been accomplished over the past decades. In a landmark study, DeVita and colleagues showed that half of patients with advanced-stage HL experienced long-term disease-free survival following treatment with a four-drug chemotherapy regimen. Subsequent reports and randomized clinical trials conducted over the past 40 years have defined prognostic categories and refined the treatment options for patients with early-stage and advanced-stage HL. New treatment concepts and regimens have continued to increase the cure rate of HL, while other analyses have documented the acute and long-term morbid and potentially fatal side effects of HL therapy. Increased knowledge of HL biology has been gained, in particular, much has been learnt about the genetic and phenotypic characteristics of malignant cells and the varied oncogenic signaling pathways involved in HL. Continued translational research is needed to improve the long-term survival and to lessen the toxicities associated with therapy. Furthermore, continued clinical-trial involvement by oncologists and patients is imperative to further advance the field of HL.     

The important role of radiation therapy in early-stage diffuse large B-cell lymphoma: time to review the evidence once again

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma in the USA, and approximately one-third of patients present with early stage, localized disease. While significant controversy still exists regarding the appropriate management of these patients, the overwhelming evidence from a wide range of studies over the last 40 years points to the superior efficacy of combined-modality therapy for this disease. The current standard of care for the vast majority of early-stage DLBCL cases now involves a combination of chemotherapy, immunotherapy and consolidation radiotherapy. Using this multimodality approach, very high rates of local control can be achieved, which will translate into significant survival benefits for patients with localized disease. The use of intensive immunochemotherapy without radiation therapy requires formal testing and validation in a randomized clinical trial before it can be used as an alternative treatment regimen for early-stage DLBCL. In this article, we discuss the results of the key randomized trials, critical retrospective studies and recent clinical trials, which collectively address the important role of radiotherapy in the treatment of early-stage DLBCL.     

Thoracic radiotherapy for limited-stage small cell lung cancer: issues of timing,volumes, dose,and fractionation

Although meta-analysis of randomized trials comparing chemotherapy alone versus chemotherapy plus thoracic irradiation demonstrated that thoracic radiotherapy reduced mortality by 14%, this analysis probably underestimates the effect of optimally delivered thoracic irradiation integrated with appropriate chemotherapy. However, there remains much debate as to the optimal timing of the radiotherapy and the radiotherapy volume, dose, and fractionation. Theoretically, early use of radiotherapy should reduce the probability of chemotherapy and radiation resistance, accelerated repopulation, and metastatic events. Deferred or sequential radiotherapy potentially allows smaller radiotherapy fields. Of the seven randomized controlled trials examining timing, only those with early chemoradiation have 5-year survival rates in excess of 20%. The "chemoradiation package" can be defined as the time from the start of chemotherapy until the completion of radiotherapy. The best median survival and long-term survival rates have been observed in trials with a chemoradiation package time of less than 6 weeks. Protocols combining chemotherapy and radiotherapy must respect radiobiologic principles concerning the time factor derived from radiotherapy fractionation studies.     

Combined Treatment Modalities in Esophageal Cancer: Should chemotherapy be included?

The poor prognosis of esophageal carcinoma patients after treatment with local modalities (surgery/radiotherapy) is well known. The purpose of this review is to assess the question whether addition of chemotherapy to local treatment of squamous cell carcinoma of the esophagus has had any beneficial effect on treatment results. In the absence of a sufficient number of randomized trials addressing this issue, data mainly from single-arm studies are discussed. Compiled data from studies on preoperative chemotherapy, preoperative chemoradiation and chemoradiation without surgery suggest that addition of chemotherapy to local treatment (surgery/radiotherapy) might increase short-term survival (2 years) compared to local therapy alone. In the case of chemoradiation without surgery this conclusion is strengthened by results from randomized trials. In general lack of long-term follow-up data limits conclusion whether to recommend the inclusion of chemotherapy into treatment of esophageal cancer or not. Treatment results, however, from studies utilizing combination chemotherapy given concomitant with radiotherapy support the contention that well-designed randomized trials with long-term follow-up should be performed. Outside controlled trials, however, surgery or radiotherapy should still be regarded as standard treatment modalities.     

Concurrent chemoradiotherapy for inoperable stage III non-small-cell lung cancer

Chemoradiotherapy has become the standard treatment for patients with locally advanced non-small-cell lung cancer on the basis of several large randomized trials. Despite an increase in median survival from 10 months with radiotherapy alone to 16 to 17 months with concurrent chemoradiotherapy, long-term survival in this disease remains modest at best. With the advent of new biologic agents targeting specific cellular pathways associated with malignant progression, combined-modality therapy has the potential to target tumors selectively with less toxicity.     

Controversies in early-stage Hodgkin's disease

Early-stage Hodgkin's disease accounts for approximately 60% of all cases of the illness. Because of its excellent cure rate (80% to 90%) and high salvage rate, it is difficult to demonstrate survival advantages for different management options. Currently, there is no consensus as to the optimal staging and treatment strategy for early-stage Hodgkin's disease. With the increasing recognition of the late consequences of Hodgkin's disease therapy, the focus of recent clinical trials has been on exploring treatment modifications to reduce these late effects. Areas of controversy that are being explored include extent of staging work-up, radiation field size and dose (and as part of combined-modality therapy), optimal chemotherapy regimen, number of cycles of chemotherapy, and limited- vs extended-field radiation therapy and dose. In addition, several studies are investigating the feasibility of chemotherapy alone in early-stage patients. Along with the evaluation of modified treatments, long-term follow-up efforts should continue in patients who are cured in order to confirm the long-term safety of such therapies.     

A systematic overview of radiation therapy effects in Hodgkin's lymphoma

A systematic review of radiation therapy trials in several tumour types was carried out by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for Hodgkin's lymphoma (HL) is based on data from 12 randomized trials and 2 meta-analyses. Data from 3 prospective studies, 29 retrospective studies and 58 other articles were also used. In total, 58 scientific articles are included, involving 27,280 patients. The results were compared with those of a similar overview from 1996 including 38,362 patients. The conclusions reached can be summarized thus: Solid scientific documentation shows that in patients with HL more than 80% in the early stages and 60-70% of younger patients in advanced stages of disease are now cured by the development of radiotherapy and combination chemotherapy. Long-term follow-up shows that after 15 to 20 years the mortality from HL in early and intermediate stages is exceeded by other causes of death, mostly secondary malignancies and cardiac deaths, especially myocardial infarction. Convincing data show that radiotherapy plays a major role in the development of solid cancers and cardiovascular disease, but no randomized trials have been performed. During the past decade increasing awareness of fatal long-term sequelae has fundamentally changed treatment strategies in early and intermediate stages. A thorough long-term follow-up is essential to evaluate the effects of the modifications of the therapy. In early stages of disease extended field irradiation is now replaced by short periods of chemotherapy followed by limited radiotherapy to decrease late sequelae. This approach is strongly supported by early reports from randomized trials. Final results cannot be fully evaluated for many years. The optimal radiation dose and volume after chemotherapy are not defined or if irradiation is needed at all. Several studies are under way. In intermediate stages two recently reported randomized trials indicate that combined modality therapy is preferable and that involved field could replace extended field irradiation. It is still too early to draw any firm conclusions. In advanced stages, there is no evidence of any survival benefit from additional radiotherapy. The role of radiotherapy in the case of residual tumour and bulky disease still remains controversial. There is no scientific support for improved survival with radiotherapy in conjunction with high-dose chemotherapy with stem-cell support. Radiotherapy as salvage treatment might be an alternative in late limited nodal recurrence after initial chemotherapy. However, the body of knowledge is small. The role of radiotherapy in the treatment of HL is decreasing.