套细胞淋巴瘤的临床病理分析合并文献复习

目的：探讨套细胞淋巴瘤的组织学特征及免疫组化特点。方法对4例套细胞淋巴瘤的临床资料、病理形态学进行分析,并结合文献对其诊断及鉴别诊断进行探讨。结果套细胞淋巴瘤3例,男女比例为1：3,年龄44-69岁,平均年龄57岁,套细胞淋巴瘤免疫分型均为B淋巴细胞型,并伴有细胞周期D1的高度表达。结论套细胞淋巴瘤,发生率比较低,预后较差,细胞学形态特征及免疫组化特点对套细胞淋巴瘤的诊断具有重要价值。     

37例套细胞淋巴瘤患者临床病理特征及预后分析

目的 探讨套细胞淋巴瘤(MCL)的临床特征、病理特点、预后因素,旨在提高对MCL的认识.方法 回顾性分析了37例MCL患者的临床特征、病理特点、治疗过程及预后因素.结果 37例MCL占同期我院收治的非霍奇金淋巴瘤的6.00%(37/617),中位年龄61(41~78)岁,发病高峰年龄段为50~70岁,男女比例为4.28GA6FA1.发病首发部位:多以浅表淋巴结肿大最为常见(75.68%),结外受累见于骨髓(45.94%)、脾脏(21.62%)、胃肠道(5.41%)等.初次就诊时处于Ⅱ期6例(16.22%)、Ⅲ期8例(21.62%)、Ⅳ期23例(62.16%),3组患者总生存时间分别为49.50、41.60、17.74个月,比较差异有统计学意义(P<0.05).全组MIPI评分高危、中危、低危分别为16例(43.24%)、10例(27.03%)、11例(29.73%),3组患者总生存时间分别为45.43、42.4、21.32个月,比较差异有统计学意义(P<0.05).全组中骨髓受累17例(45.95%),未受累20例(54.05%),未受累组预后较受累组好(总生存时间65.32个月vs 22.12个月,P=0.010).全组中,母细胞型14例(37.84%),经典型23例(62.16%),经典型组预后较母细胞型组好(总生存时间38个月vs 18个月,P=0.028).核分裂相<20/10 HPF 24例(64.86%),≥20/10 HPF 13例,核分裂相<20/10 HPF组预后较≥20/10 HPF组好(总生存时间50.34个月vs 21.12个月,P=0.040).结节型生长组23例(62.16%),弥漫型生长组14例(37.84%),2种生长方式对预后无明显影响(总生存时间28.33个月vs 40.46个月,P=0.850).全组病例共有36例行CD5检测,阳性35例(97.22%),阴性1例(2.78%);30例行CD10检测,阳性1例(3.33%),阴性29例(96.67%);22例行CD23检测,阳性5例(22.73%),阴性17例(77.37%);37例均行CyclinD1检测,阳性35例(94.59%),阴性2例(5.41%);20例行Ki-67检测,Ki-67≥50%组12例(60.00%),Ki-67<50%组8例(40.00%),Ki-67<50%组预后较Ki-67≥50.00%组好(总生存时间11.15个月vs 31.62个月,P=0.001).白细胞计数、淋巴细胞计数、乳酸脱氢酶水平、B症状等因素对生存预后无明显影响(P>0.05).随访89(5~89)个月,随访率100.00%,生存超过2 a的共12例(32.43%),超过3 a的7例(18.92%).结论 MCL以全身浅表淋巴结肿大为常见首发症状,就诊时多已处于Ⅲ~Ⅳ期;CD5(+)、CyclinD(+)、CD10(-)、CD23(-)是常见的免疫学特征;分期晚、MIPI评分为高危、骨髓受累、母细胞变型、核分裂相≥20/10 HPF、Ki-67≥50%是预后不良因素;2 a生存率较低,预后较其他B细胞淋巴瘤相对差.     

套细胞淋巴瘤

<正>套细胞淋巴瘤(mantle cell lymphoma,MCL)是2001年WHO淋巴造血组织肿瘤新分类中的一种独立的B细胞非霍奇金淋巴瘤[1],占非霍奇金淋巴瘤的5%~10%。它来源于初级淋巴滤泡未成熟生发中心前CD5+的B细胞或次级淋巴滤泡套区细胞。好发于中老年人。大多诊断时处于Ⅲ~Ⅳ期,有广     

98例套细胞淋巴瘤临床特点及预后分析

  目的  探讨套细胞淋巴瘤（mantle cell lymphoma，MCL）患者的临床特点、不同治疗方案的疗效及预后分析。   方法  回顾性分析2005年1月至2013年12月北京大学肿瘤医院收治的98例MCL患者资料，结合临床特征和治疗方案进行相关预后分析。   结果  98例患者中位发病年龄61岁，男女比例2.9:l，Ann Arbor分期Ⅲ~Ⅳ期患者为85例，占86.8%。骨髓累及者46例（46.9%）。消化道为最常见的结外侵犯器官，共25例患者（25.5%）出现消化道侵犯。53例患者接受R-CHOP方案一线治疗，预期3年生存率为61.4%；14例患者接受自体造血干细胞移植（ASCT）治疗，预期5年生存率为92.3%，其总生存期显著高于使用R-CHOP方案治疗的患者（75.5个月vs. 43.6个月，P=0.039）。年龄>60岁、血沉高于正常、LDH高于正常、B症状、Ki-67≥25%、病理存在母细胞或大B细胞转化均提示预后不佳（P < 0.05）。   结论  MCL以晚期多见，常伴有骨髓及结外病变，单纯R-CHOP方案不能获得满意疗效，ASCT治疗MCL的疗效好于常规化疗，且安全性较高。年轻患者应该选择作为一线巩固治疗。      

41例套细胞淋巴瘤患者临床特征及预后分析

背景与目的:套细胞淋巴瘤(mantle cell lymphoma,MCL)现今尚无有效的治愈方法,预后差.本回顾分析了我院有完整临床及治疗资料的MCL,分析MCL在非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)中的构成比、临床特点、治疗及预后因素.方法:回顾分析1996年1月-2009年12月在本院就诊的41例MCL患者临床资料及预后因素.结果:MCL在本院NHL中所占构成比为2.1％.男性多于女性(7.4:1),41例患者中位发病年龄57岁,分期晚,Ⅲ～Ⅳ期占75.6％,国际预后指数(International Prognostic Index,IPI)≥3分占41.4％,结外侵犯多见,消化道侵犯高达33％,骨髓侵犯达21.4％,Ⅰ～Ⅱ期10例,Ⅲ期16例,Ⅳ期15例,2例Ⅰ期患者接受手术治疗后未进一步治疗,1例晚期患者放弃治疗,3例局限期患者接受单纯放疗,35例患者接受化疗,其中CHOP方案19例,EPOCH方案10例,COP方案2例,BACOP方案3例,Hyper-CVAD方案1例,使用化疗加利妥昔单抗的有4例,大多化疗周期数为4～6个.全组首次治疗后达完全缓解者12例,部分缓解者占25例,稳定3例,进展1例.随访时间12～210个月中位随访时间为39个月,失访1例,随访满2年的病例38例,随访满3年的32例,27例进展,13例死亡.全组2、3年总生存率分别为92.68％、78.20％.2、3和5年无进展生存率分别为62.88％、35.56％和28.86％,中位无进展时间为28个月.预后分析显示分期、近期疗效,对无进展生存有影响,而年龄＞60岁、骨髓侵犯、IPI评分对无进展生存无显著影响,年龄＞60岁、临床分期、IPI评分对总生存期无显著影响,近期疗效及骨髓侵犯对总生存期有影响.结论:MCL治疗完全缓解率低,无疾病进展时间短,预后不佳,对部分患者应行个体化治疗.     

套细胞淋巴瘤的治疗进展

0引言套细胞淋巴瘤是一种特殊临床病理表现的B细胞型非霍奇金淋巴瘤,在1992年首次作为一种独立的类型被提出[1],占非霍奇金淋巴瘤的4%~6%。     

西部单中心51例套细胞淋巴瘤患者临床特征及预后因素分析

目的:研究套细胞淋巴瘤（MCL)患者的临床特点及预后相关因素,进一步全面评估病情,探索个体化治疗。方法:回顾性分析2012年1 月至2016年12 月经我院病理科确诊的51例MCL 患者的临床特点、住院20例患者的预后分层和不同化疗方案的近期及远期疗效,并进行随访观察。结果:20例住院治疗患者中,R-Hyper-CVAD组及R-CHOP样组的ORR（分别为100%、100%）均高于其未联合美罗华组（分别为50%、40%）;MIPI评分中,低危组ORR为75.0%,明显高于中危组（16.6%）;CD5-患者CR、PR均高于CD5+患者;Ki67≥30%患者CR率（20%）大于Ki67＜30%组（11%）,PR率则相反;Ki67＜30%患者3年OS明显高于Ki67≥30%患者,有统计学差异,而PFS无统计学差异;MIPI分组中,低危组3年OS明显高于中高危组,有统计学差异,PFS无统计学差异;美罗华组无论OS还是PFS均高于非美罗华组;Hyper-CVAD组与非Hyper-CVAD组OS、PFS均无统计学差异。结论:美罗华联合化疗治疗MCL的疗效是肯定的,绝大多数患者能够耐受减低剂量的Hyper-CVAD A及B方案化疗,但统计学显示与非Hyper-CVAD组无明显差异,可能与病例数偏少相关,需要更多大样本的循证医学的支持。     

套细胞淋巴瘤研究进展

在不同的分类系统中，套细胞淋巴瘤有许多不同名称。Ｋｉｅｌ分类将其命名为“中心细胞性淋巴瘤”；在美国，许多血液病理学家采用Ｂｅｒａｒｄ和Ｄｏｒｆｍａｎ的命名：即中间淋巴细胞性淋巴瘤；Ｗｅｉｓｅｎｂｕｒｇｅｒ将正常生发中心外套区扩大所形成的结节性肿瘤命名...     

血管免疫母细胞性T细胞淋巴瘤临床-病理-分子遗传学改变与预后相关性分析

目的 血管免疫母细胞性T细胞淋巴瘤(angioimmunoblatic T-cell lymphoma,AITL)是一种侵袭性淋巴瘤,本研究探讨AITL的临床病理特征、与EB病毒相关性及分子遗传学改变,并分析相关预后因素.方法 选取2003-01-03-2012-12-31新疆医科大学第一附属医院有详细临床病理资料的16例AITL患者石蜡样本,EnVision法进行CXCL13、PD-1、CD10和Bcl-6免疫标记;原位杂交技术检测肿瘤EB病毒编码mRNA表达情况;荧光原位杂交技术检测肿瘤组织中Bcl-2、Bcl-6和C-MYC基因异常情况,并对所有患者进行随访.结果 16例患者,男11例(68.8％),女5例(31.2％),男女比例2.2∶1.中位年龄65.5岁.75.0％(12/16)患者国际预后指标(international prognostic indicators,IPI)评分为中高危,56.3％(9/16)患者血清乳酸脱氢酶(lactic dehydrogenase,LDH)异常,20％(2/10)患者存在骨髓侵犯,81.3％(13/16)患者临床分期为ⅢB期及以上;免疫组织化学染色结果示,CXCL13、PD-1、CD10、Bcl-6阳性率分别为93.8％(15/16,95％CI为70％～100％)、75.0％(12/16,95％CI为48％～93％)、50.0％(8/16,95％CI为25％～75％)和81.3％(13/16,95％CI为54％～96％);AITL显示特征性的CD23和CD21滤泡树突状细胞网增生,阳性率均为87.5％(14/16,95％CI为62％～98％);原位杂交:EBER阳性率为56.3％(9/16,95％CI为30％～80％);FISH检测结果示,10例AITL患者Bcl-2/IgH、Bcl-6、C-myc检测均为阴性;术后电话随访,自病理确诊之日起开始计算生存期,15例患者有随访结果.随访1～84个月,全组中位生存期为17个月;其中5例在1年内死亡,1年生存率为66.7％(5/15),总共6例患者死亡,占全组的40.0％(6/15).单因素分析显示,年龄≥65岁、IPI评分高危组、LDH水平异常、临床病理分期ⅢB～Ⅳ期患者预后较差.结论 AITL好发于老年患者,具有高度侵袭性,预后差,CXCL13、PD-1、CD10、Bcl-6可作为一个免疫组化套餐,在该肿瘤的诊断具有重要作用,临床病理分期、IPI评分、LDH水平是影响预后的重要因素.     

套细胞淋巴瘤研究进展

套细胞淋巴瘤是2001年WHO淋巴造血组织肿瘤新分类中的一种独立的B细胞非霍奇金淋巴瘤。该肿瘤有其独特的分子遗传学、病理组织学特点，文章对其分子遗传学、病理特征以及治疗与预后作一综述。     

An overlapping case of in situ mantle cell neoplasia and leukemic non-nodal mantle cell lymphoma

In situ mantle cell neoplasia (isMCN) and leukemic non-nodal mantle cell lymphoma (nnMCL) are classified as an indolent subtype of mantle cell lymphoma (MCL). The tumor cells of isMCN are restricted to the inner layer of the lymphoid tissue mantle zone, exhibiting an in situ pattern histologically. On the other hand, nnMCL is distributed in the peripheral blood, bone marrow and sometimes the spleen, but lymphadenopathy or systemic organ involvement is rare. We report a case of isMCN in a submandibular lymph node resected from a 65-year-old Japanese male. The tumor cells were positive for cyclin D1 (CCND1) and SOX11 expression, and were restricted to the mantle zone area of the lymph node. However, tumor cells were also detected in the stomach mucosa, bone marrow tissue and peripheral blood, suggesting nnMCL. isMCN and nnMCL may have a partly overlapping disease spectrum, although the correlation between these two subtypes has not been well described. This present case demonstrated characteristics overlapping between isMCN and nnMCL.     

Clinicopathologic features of 112 cases with mantle cell lymphoma

Objective

This study aims to explore the clinicopathologic features of 112 patients with mantle cell lymphoma (MCL).

Methods

Data from 112 MCL cases were collected, and immunohistochemical assay was conducted. Fluorescence in situ hybridization (FISH) detected a break in the CCND1 gene. The t-test was used in the statistical analysis.

Results

All tumor cells in the 112 cases expressed B cell-related antigen, including 1 blastoid subtype and 1 polymorphic subtype. Among all cases, 106 expressed CD5 and 104 expressed cyclin D1. A break in the CCND1 gene was not found in 3 cases with CD5-MCL. IgH/CCND1 polyploid was observed in 2 classic cases.

Conclusion

MCL is a type of special immunophenotypic B-cell lymphoma. The prognoses of blastoid and polymorphic subtypes are poor. Special subtypes should be classified during diagnosis.KEYWORDS : Mantle cell lymphoma (MCL), immunohistochemistry, fluorescence in situ hybridization (FISH), prognosis     

Serum beta‐2 microglobulin as a prognostic biomarker in patients with mantle cell lymphoma

Although serum beta‐2 microglobulin (B2M) has been suggested as a prognostic factor for mantle cell lymphoma (MCL), additional data are necessary to confirm its role. Between November 2005 and July 2014, a total of 52 patients with MCL were identified from the database of Asan Medical Center, Seoul, Korea. Pretreatment serum B2M information was available in 50 patients (96%). Overall survival (OS) was compared according to the serum B2M level with a cut‐off value of 2.5 mg/L. The median MCL international prognostic index (MIPI) score was 5.84 (range 4.72–7.80), and the median biologic MIPI (MIPI‐b) score was 6.27 (4.93–8.47). Pretreatment serum B2M was elevated in 30 patients (60%) and was significantly related to advanced stage (p = 0.02) and high MIPI (p = 0.03) and MIPI‐b (p = 0.03) scores. With median follow‐up duration of 29.8 months (range 0.8–87.0 months), the median OS was 56.2 months [95% confidence interval (CI) 36.6‐75.9 months] in all patients, and serum B2M was significantly associated with OS (p = 0.001). In multivariate analyses adjusted for MIPI or MIPI‐b scores and rituximab, elevated serum B2M was significantly associated with poor OS (when adjusting MIPI, hazard ratio = 26.4, 95% CI 2.9–241.3, p = 0.004; when adjusting MIPI‐b, hazard ratio = 20.1, 95% CI 2.4–170.1, p = 0.006). Thus, pretreatment serum B2M may be an independent and significant prognostic factor in patients with MCL. Copyright © 2015 John Wiley & Sons, Ltd.     

Central nervous system involvement in mantle cell lymphoma.

BACKGROUND: Extranodal involvement, including central nervous system (CNS), is a frequent event in patients with mantle cell lymphoma (MCL). However, the incidence, risk factors, and impact on outcome remain controversial. PATIENTS AND METHODS: Main clinical, biological, and evolutive features of 82 patients (60 males/22 females; median age: 61 years) diagnosed with MCL (blastoid, 26%) in a single institution were analyzed for risk of CNS involvement and prognosis. RESULTS: Most patients had advanced stage and intermediate or high-risk International Prognostic Index (IPI). Eleven patients eventually developed CNS involvement with an actuarial 5-year risk of 26% (95% confidence interval 10% to 42%). In one asymptomatic patient, cerebrospinal fluid infiltration was detected at staging maneuvers (1/62; 1.6%). The remaining 10 patients developed neurological symptoms during the course of the disease (median time from diagnosis, 25 months). Initial variables predicting CNS involvement were blastoid histology, high proliferative index measured by Ki-67 staining, high lactate dehydrogenase (LDH) and intermediate- or high-risk IPI. Histological subtype and serum LDH maintained significance in multivariate analysis. Treatment of CNS infiltration consisted of intrathecal chemotherapy (two cases), and intrathecal chemotherapy plus systemic treatment (seven cases). Median survival after CNS involvement was 4.8 months, patients with this complication having shorter survival than those with no CNS disease. CONCLUSION: This study confirms the high incidence of CNS involvement in MCL patients. Treatments aimed at preventing this complication are warranted.     

Proliferation predicts failure‐free survival in mantle cell lymphoma patients treated with rituximab plus hyperfractionated cyclophosphamide,vincristine, doxorubicin,and dexamethasone alternating with rituximab plus high‐dose methotrexate and cytarabine

BACKGROUND:

It has been demonstrated that the tumor proliferation index has prognostic significance in patients with mantle cell lymphoma (MCL). Patients in most of studies, however, have been treated with relatively traditional chemotherapy regimens. At the authors' institution, patients with MCL received an aggressive chemotherapy regimen: rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with rituximab plus high‐dose methotrexate and cytarabine (R‐hyper‐CVAD).

METHODS:

The authors assessed the proliferation rate of MCL using immunohistochemistry and an antibody specific for Ki‐67 in 71 untreated patients who subsequently received R‐hyper‐CVAD. The study group included 59 patients who had classic MCL and 12 patients who had the blastoid variant of MCL.

RESULTS:

For the entire study group and for the group of patients with classic MCL, a proliferation index of >20% Ki‐67‐positive cells was correlated significantly with shorter failure‐free survival. There was no correlation between the proliferation index and overall survival.

CONCLUSIONS:

The current results indicated that the proliferation index in patients with MCL predicted prognosis in those who uniformly received the R‐hyper‐CVAD chemotherapy regimen. Cancer 2009. © 2009 American Cancer Society.     

The clinical features, therapeutic responses, and prognosis of the patients with mantle cell lymphoma

Mantle cell lymphoma(MCL), a special type of non-Hodgkin’s lymphoma, is incurable through conventional treatment. This study aimed to analyze the clinical features, therapeutic responses, and prognosis of patients with MCL. Clinical data of 30 patients with MCL treated in our hospital between April 2006 and July 2011 were analyzed. Eighteen patients were treated with CHOP plus rituximab (R-CHOP) regimen, 12 underwent conventional chemotherapy. The median age of the 30 patients was 58 years, 23 were men, all patients had Cyclin D1 overexpression, 29 (96.7%) had advanced disease, 11 (36.7%) had bone marrow involvement, 9 (30.0%) had gastrointestinal involvement, and 15 (50.0%) had splenomegaly. The complete response(CR) rate and overall response rate(ORR) were significantly higher in patients undergoing R-CHOP immunochemotherapy than in those undergoing conventional chemotherapy (38.9% vs. 16.7%, P = 0.187; 72.2% vs. 41.4%, P = 0.098). The difference of 2-year overall survival rate between the two groups was not significant (P = 0.807) due to the short follow-up time. The 2-year progression-free survival (PFS) rate was higher in R-CHOP group than in conventional chemotherapy group (53% vs. 25%, P = 0.083), and was higher in patients with a lower mantle cell lymphoma international prognostic index (MIPI) (51% for MIPI 0-3, 33% for MIPI 4-5, and 0% for MIPI 6-11, P = 0.059). Most patients with MCL were elderly; in an advanced stage; showed a male predominance; and usually had bone marrow involvement, gastrointestinal involvement, or splenomegaly. R-CHOP regimen could improve the CR rate and ORR of MCL patients. MIPI can be a new prognostic index for predicting the prognosis of advanced MCL.     

Leukemic involvement is a common feature in mantle cell lymphoma

BACKGROUND: The reported incidence of peripheral blood involvement in patients with mantle cell lymphoma (MCL) ranges from 13% to 77%. The aim of the study was to analyze the prevalence and the biologic and clinical significance of leukemic involvement in a series of patients with MCL. METHODS: Leukemic expression was assessed by conventional morphology and flow cytometry (FC) in 48 patients. In addition, comparative genomic hybridization (CGH) was performed in 27 patients. RESULTS: At diagnosis, 44 patients (92%) had evidence of leukemic expression by FC, including 8 patients (17%) without morphologically apparent leukemic involvement. Moreover, a lymphocyte count > or =5 x 10(9)/L was observed in 25 cases (52%). The most frequent imbalances detected by CGH were gains of 3q, 7p, 8q, 9q, 12q, and 13q, and losses of 13q, 1p, 9p, 11q, 10p, 17p, 6q, 8p, and 9q. Using a cutoff of 5 x 10(9)/L lymphocytes, cases with lymphocytosis more frequently presented with gains of 3q (P = .02), losses of 10p (P = .05), a low response rate (P = .04), and a short survival (P = .05). CONCLUSIONS: Leukemic expression at diagnosis detected by FC was found to be highly frequent in this series of patients with MCL. Although morphologically apparent leukemic expression was not associated with specific chromosomal alterations detected by CGH, a lymphocyte count > or =5 x 10(9)/L was correlated with particular genetic abnormalities and a poor outcome.     

Intensive therapy with peripheral stem cell transplantation in 16 patients with mantle cell lymphoma

Background: Despite improved detection of mantle cell lymphoma (MCL),results of its treatment with conventional therapies remain disappointing andthe survival rate poor. The role of high-dose chemotherapy has recently beeninvestigated but no potential benefit has been clearly established. We reporthere our experience with MCL patients treated with intensive chemotherapy andautologous stem cell transplantation (ASCT).Patients and methods: Of the 16 MCL patients who received high-dosechemotherapy and ASCT beginning in 1989, six were treated in first-line and10 in sensitive relapse. Twelve of 16 patients received regimens whichincluded total body irradiation. All patients received peripheral blood stemcells (PBSC) with the exception of one, who underwent bone marrowtransplantation.Results: Three patients died of toxic effects of treatment. Three monthsafter transplant, seven achieved complete responses (CR) and two partialresponses (PR), two were stable and two had progressed. With a medianfollow-up after transplant of 22 months, five of the six surviving patientswere without progression, and three were in CR. The median times forevent-free survival (EFS) and overall survival (OS) were, respectively, 249and 317 days. The expected three-year EFS and OS were 24%. The mediansurvival after diagnosis was only 29 months. None of the criteria appeared tobe significantly associated with a better outcome, but first-lineintensification and a short delay after initial diagnosis may be favorable.Conclusion: In this study we were not able to confirm the hypotheticalbenefit of high-dose chemotherapy and PBSC transplantation in mantle celllymphoma, even though this approach may be promising in a subgroup of patient.     

Radiotherapy in mantle cell lymphoma: A literature review

Mantle cell lymphoma (MCL) is a B-cell malignancy, comprising between 3% and 10% of all adult-onset non-Hodgkin lymphomas. MCL is considered incurable with current treatment modalities and most patients require multiple lines of treatment during their lifetime. MCL is very sensitive to radiotherapy (RT), even when delivered in low doses. In limited-stage MCL, RT can enable the de-escalation of systemic therapy. RT monotherapy is a valid option for frail patients. In advanced-stage disease, RT is very potent mode of palliation, even in heavily pretreated and chemo-resistant patients. Furthermore, it can provide a respite during which systemic treatment is unnecessary. In general, RT has a favorable toxicity profile and can be repeated as necessary for local relapse or distant disease. This effective, safe, and relatively inexpensive modality of therapy has been underutilized for patients with MCL. In this review, we will outline the use of RT for limited and advanced-stage disease and its potential application in combination with novel drugs.