大剂量甲氨蝶呤化疗的脑脊液浓度监测

为了监测大剂量甲氨喋呤（ＨＤＭＴＸ）化疗时脑脊液中药物浓度的动态变化,采用高效液相色谱法对１２例患者２０例次静脉点滴ＨＤＭＴＸ（每次１．５～３．０ｇ）后的脑脊液和血浆中ＭＴＸ浓度同时进行监测,并以２例常规ＭＴＸ用量（每次６０ｍｇ）的脑脊液监测浓度做对比。结果显示,滴注ＭＴＸ后０,６,１２,２４,３６ｈ的脑脊液ＭＴＸ平均浓度分别为３．３７×１０－６,６．８３×１０－７,１．６８×１０－７,２．９９×１０－８,０．４０×１０－８ｍｏｌ／Ｌ,血浆ＭＴＸ平均浓度分别为８．７０×１０－５,２．７９×１０－５,２．６７×１０－６,７．０７×１０－７,６．６５×１０－８ｍｏｌ／Ｌ。２例常规ＭＴＸ用量者的脑脊液ＭＴＸ浓度未测出。结果表明ＨＤＭＴＸ化疗时,脑脊液ＭＴＸ浓度是血浆ＭＴＸ浓度的（４．５７±１．６０）％,２者呈线性关系。并提示ＭＴＸ透过血脑屏障的机理可能为被动转运。     

后程适形放射治疗联合ＮＰ方案同步化疗治疗Ⅲ期非小细胞肺癌

目的　观察三维适形放射治疗联合长春瑞滨（ＮＶＢ）加顺铂（ＤＤＰ）同步化疗治疗Ⅲ期非小细胞肺癌（ＮＳＣＬＣ）的疗效及耐受性。方法　５０例Ⅲ期ＮＳＣＬＣ患者随机分为同步放化疗组和单放组,每组各２５例。单放组采用６ＭＶ或１５ＭＶＸ线常规外放疗ＤＴ４０Ｇｙ,后采用三维适形放疗２.５～３Ｇｙ／ｆ,１ｆ／ｄ,至ＤＴ７０～７５Ｇｙ,同步放化疗组在放疗的第１～３天联合ＮＰ方案化疗（ＮＶＢ２５ｍｇ／ｍ^２,ｄ_１、ｄ_８,ＤＤＰ３０ｍｇ／ｍ^２,ｄ_１～ｄ_３）,２１天为１周期,放疗后再采用该方案化疗３～６个周期。结果　同步放化疗组与单放组的有效率（ＣＲ＋ＰＲ）分别为８４.０％和６４.０％（Ｐ＞０.０５）;１、２年生存率分别为７６.０％、３６.０％和６８.０％、２４.０％（Ｐ均＞０.０５）。主要毒副反应表现为骨髓抑制和消化道反应。结论　后程三维适形放射治疗联合ＮＰ方案同步化疗治疗Ⅲ期ＮＳＣＬＣ近期疗效好,且毒性反应可以耐受。     

诱导化疗结合交替放化疗治疗Ⅳ期未分化鼻咽癌

瑞士日内瓦ＢｅｎａｓｓｏＭ等在局部进展期未分化鼻咽癌（ＵＮＰＣ）的治疗研究中发现 ,同时进行放化疗和单纯放疗比较 ,在Ⅲ期试验中证明是获得更好疗效的唯一策略。在进行放化疗的同时增加有效的化疗能进一步提高未分化鼻咽癌的疗效。该研究对３０例未经治的Ｔ４ 和（或）Ｎ２～３未分化鼻咽癌 ,先行３个疗程的化疗 :表阿霉素９０ｍｇ／ｍ２ 第１天 ;顺铂４０ｍｇ／ｍ２,第１天和第２天 ;每３周１次。经过一个放疗和临床反应后接受３个疗程化疗 :顺铂每天２０ｍｇ／ｍ２,第１至４天 ;氟尿嘧啶每天２００ｍｇ／ｍ２,第１至４天 ,静脉注射…     

原发小细胞膀胱癌5例报告和文献复习

目的：报告５例小细胞膀胱癌治疗结果,复习相关文献,探讨小细胞膀胱癌临床特点,手术、化疗和放疗在小细胞膀胱癌治疗中的作用。方法：我院从１９７９～１９９９年收治５例小细胞膀胱癌患者,其中Ｔ１Ｎ０Ｍ０１例,接受双髂内动脉导管化疗;Ｔ２Ｎ０Ｍ０１例,行膀胱切除术加术后放疗;Ｔ３Ｎ０Ｍ０１例,仅行膀胱切除术;Ｔ４Ｎ０Ｍ０２例,１例经放疗、动脉导管化疗后行探查术,另１例术前放疗后膀胱切除术加术后全身化疗。结果     

鼻咽癌放疗后的MRI表现

目的：探讨ＭＲＩ在评价ＮＰＣ放疗后改变中的作用。方法;对４２例ＮＰＣ放疗后患者行ＭＲＩ检查,其中１５例为ＲＦ,２１例ＲＮＰＣ,３例ＲＦ及３例ＲＮＰＣ伴有局部淋巴结转移,病例经病一活检或针吸收细胞学检查或随访追踪证实。ＭＲＩ扫描使用０．５Ｔ超导型磁共振成像仪。常规ＳＥ序列Ｔ１,Ｔ２加权横断,冠状,矢状位成像,其中３４例加行Ｇｄ－ＤＴＰＡＴ１Ｗ增强扫描。     

肝癌单克隆抗体与氨甲喋呤交联物的制备及细胞毒的研究

在肝癌单克隆抗体Ｈｅｐａｍａ－１－人血清白蛋白－ＭＴＸ结合物的制备中，首先ＭＴＸ在二环己基碳二亚胺（Ｄｉｃｙｃｌｏｈｅｘｙｌｃａｒｂｏｄｉｍｉｄｅ，ＤＣＣ）作用下，与Ｎ－羟基琥珀酰亚胺（Ｎ－Ｈｙｄｒｏｘｙｓｕｃｃｉｎｉｍｉｄｅ，ＮＨＳ）反应，得到ＭＴＸ活性酯，中间载体ＨＳＡ与ＳＰＤＰ作用引入巯基，再与ＭＴＸ活性酯反应得到ＨＳ－ＨＳＡ－ＭＴＸ。然后与碘乙酰化单克隆抗体Ｈｅｐａｍａ－Ｉ反应，获得硫醚键连接的交联物。交联物中Ｈｅｐａｍａ－Ｉ：ＨＳＡ：ＭＴＸ克分子比为１１．６３０，对靶细胞ＢＥＬ－７４０５及对照细胞ＨｅＬａ的杀伤效率，以交联物按ＭＴＸ的克分子浓度计算，ＩＣ５０（５０％抑止率）分别为２．５×１０－８ｍｏｌ／Ｌ和６．４×１０－７ｍｏｌ／Ｌ。单独ＭＴＸ对上述二种细胞株不显示选择性杀伤，ＩＣ５０均为７．１×１０－８ｍｏｌ／Ｌ。     

THE HUMORAL ANTITUMOR RESPONSES INDUCED BY IL-4 GENE-MODIFIED TUMOR VACCINE

ＴＨＥＨＵＭＯＲＡＬＡＮＴＩＴＵＭＯＲＲＥＳＰＯＮＳＥＳＩＮＤＵＣＥＤＢＹＩＬ４ＧＥＮＥＭＯＤＩＦＩＥＤＴＵＭＯＲＶＡＣＣＩＮＥ１ＹｕＹｉｚｈｉ于益芝ＣａｏＸｕｅｔａｏ２曹雪涛ＺｈａｎｇＭｉｎｇｈｕｉ张明徽ＬｅｉＨｏｎｇ雷虹ＴａｏＱｕｎ陶群Ｄｅｐ...     

肺癌脑转移罕见类型一例报告

患者男性,５８岁,１９９４年９月确诊为右肺腺癌,Ｔ４Ｎ３Ｍ１Ⅳ期,双肺转移,双侧胸膜转移及双侧颈部淋巴结转移。经ＮＶＢ＋ＤＤＰ方案化疗７个周期,ＶＤＳ＋ＭＭＣ＋ＡＤＭ化疗２个周期和右肺放疗３５Ｇｙ,右肺中叶病灶基本消失,双肺野病灶明显缩小,胸水吸收,...     

影响鼻咽癌颈淋巴结复发多因素分析

目的探讨鼻咽癌放疗后颈淋巴结复发的原因。方法１９８７年１月～１９９２年１２月首次治疗鼻咽癌３２１例，颈部用＾６０Ｃ０加深部Ｘ线照射，ＤＴ５２～７８Ｇy/４０～８８d。应用Ｄaplan-Ｍiere方法和ＣＯＸ模型对放疗后３年颈部局控及影响局中复发因素作分析和评价。结果３年颈淋巴结复发率１５％，多因素ＣＯＸ模型显示影响局控率的有Ｎ分期、总疗程时间、生物有效剂量（ＢＥＤ）、化疗和肿瘤残留。在Ｎ１～２中总疗程时间≤６     

肺癌脑转移的放射治疗

目的 分析放射治疗肺癌转移的疗效及与化疗比较。材料与方法 １９８０年１月到１９９６年１２月,对肺癌脑转移１２６例进行回顾性研究。化疗采用ＣＣＮＵ,ＢＣＮＵ,ＣＴＸ,ＭＴＸ,ＤＤＰ,ＶＰ－１６。放疗采用＾６０Ｃｏ或６ＭＶ－Ｘ直线加速器,全脑ＤＴ３０－４０Ｇｙ,并局部追加ＤＴ１０－２０Ｇｙ,局部放疗ＤＴ３５￣５５Ｇｙ。结果 全组１、２年生存率分别为１６．７％（２１／１２６）,３．２（４／１２６）,中位     

34例原发性中枢神经系统恶性淋巴瘤临床分析

目的：分析免疫功能正常的中国人原发性中枢神经系统淋巴瘤（PCNSL）的临床资料,探讨PCNSL的临床特征,评价大剂量甲氨蝶呤（HD-MTX）加全脑放疗（WBRT）治疗PCNSL的疗效.方法：回顾性分析34例经病理证实的PCNSL患者的临床资料以及治疗效果,Kaplan-Meier法分析患者生存期.结果：34例PCNSL患者中B细胞淋巴瘤31例（91.2%）,T细胞淋巴瘤3例（8.8%）;所有患者治疗后评价完全缓解率（CR）41.2%,2年生存率60.2%;病理类型和是否接受HD-MTX加放疗是影响PCNSL生存期的主要原因（P＜0.05）.结论：PCNSL以颅内高压为主要表现,B细胞亚型占绝对优势,具有独特的预后因素,HD-MTX联合放疗是PCNSL有效的治疗方法.     

原发性中枢神经系统淋巴瘤临床及预后分析

目的:总结原发性中枢神经系统淋巴瘤(PCNSL)的临床特点、诊治方案及临床疗效.方法:回顾收活的21例PCNSL患者,均为病理确诊的B细胞来源非霍奇金淋巴瘤,其中5例接受单纯放疗,16例接受放化疗.对病理学检查、影像学表现、治疗及预后进行总结分析.结果:PCNSL以中老年人多见,发病急,病程短,病情进展快.临床表现复杂,颅内高压为主要表现之一.CT、MR增强扫描病灶多呈均匀明显强化,可单发或多发.21例患者中位生存时间22个月,1、3和5年生存率分别为76.2％、28.6％和4.76％.放化疗疗效优于单纯放疗,P=0.029.结论:PCNSL临床表现多样,影像学缺乏特异性,极易误诊,确诊需要依靠病理学检查,其最佳治疗方案是三维立体定向穿刺活检加放疗、化疗的联合治疗.PCNSL侵袭性强,生存期短,其预后主要与发病年龄、多灶性和体力状况有关.     

High-dose methotrexate is beneficial in parenchymal brain masses of uncertain origin suspicious for primary CNS lymphoma

In patients with parenchymal brain masses of uncertain origin responsive to corticosteroids, primary CNS lymphoma (PCNSL) should be considered. PCNSL is a rare but aggressive brain tumor that is highly sensitive to high-dose methotrexate (HDMTX)-based chemotherapy. We report a series of six patients with brain masses without histologic confirmation suspicious for PCNSL based on clinical and radiomorphologic criteria after exclusion of some infectious conditions. All patients were treated with HDMTX. We observed two complete responses, two partial responses, and one stable disease. One patient had progressive disease and received rescue whole-brain irradiation. All patients were alive without disease progression 12-48 months after HDMTX start. No symptoms of late neurotoxicity have occurred so far. The response and survival data in this small series of patients are encouraging and suggest a benefit for patients with suspected PCNSL after initial treatment with HDMTX.     

原发性中枢神经系统淋巴瘤35例临床及预后分析

目的：探讨原发中枢神经系统淋巴瘤（PCNSL）临床特点、诊治方案及临床疗效。方法：总结2001年1月-2008年1月收治的35例PCNSL患者,均经病理证实为B细胞来源非霍奇金淋巴瘤并接受放疗,其中25例放疗后接受化疗。结合文献对原发性中枢神经系统淋巴瘤患者的临床特点、病理学检查、影像学表现、治疗及预后进行回顾性分析。结果：本病以中老年人多见,发病急,病程短,病情进展快。临床表现复杂,颅内高压为主要表现之一。CT、MRI增强扫描病灶多呈均匀明显强化,可单发或多发。35例患者中位生存时间23月,1年生存率74．3％,3年生存率25．7％,5年生存率5．71％。肿瘤全切及局部切除者,生存率未见明显统计学差异（P=0．053）,加化疗疗效优于不加化疗（P=0．012）。结论：PCNSL临床表现多样,影像学缺乏特异性,极易误诊,确诊需要依靠病理学检查,最佳治疗方案是手术加放疗、化疗的联合治疗。PCNSL侵袭性强,生存期短,其预后主要与发病年龄、多灶性、一般状态有关。     

原发性中枢神经系统淋巴瘤35例临床及预后分析

目的:探讨原发中枢神经系统淋巴瘤(PCNSL)临床特点、诊治方案及临床疗效。方法:总结2001年1月-2008年1月收治的35例PCNSL患者,均经病理证实为B细胞来源非霍奇金淋巴瘤并接受放疗,其中25例放疗后接受化疗。结合文献对原发性中枢神经系统淋巴瘤患者的临床特点、病理学检查、影像学表现、治疗及预后进行回顾性分析。结果:本病以中老年人多见,发病急,病程短,病情进展快。临床表现复杂,颅内高压为主要表现之一。CT、MRI增强扫描病灶多呈均匀明显强化,可单发或多发。35例患者中位生存时间23月,1年生存率74.3%,3年生存率25.7%,5年生存率5.71%。肿瘤全切及局部切除者,生存率未见明显统计学差异(P=0.053),加化疗疗效优于不加化疗(P=0.012)。结论:PCNSL临床表现多样,影像学缺乏特异性,极易误诊,确诊需要依靠病理学检查,最佳治疗方案是手术加放疗、化疗的联合治疗。PCNSL侵袭性强,生存期短,其预后主要与发病年龄、多灶性、一般状态有关。     

Comparable outcomes of radiation therapy without high-dose methotrexate for patients with primary central nervous system lymphoma

BACKGROUND: The previous trials of radiotherapy conducted for primary central nervous system lymphoma (PCNSL) have not been successful. Therefore, we have investigated the clinical outcomes and the role of radiation therapy in the treatment of PCNSL. METHODS: Thirty-three consecutive patients with PCNSL treated with cranial radiotherapy (30-40 Gy whole brain plus 10-20 Gy boost) without administration of high-dose methotrexate were retrospectively analyzed. Nine patients received whole spinal irradiation (WSI) as an additional therapy. The median age of patients was 58 years (range: 28-78 years), and 70% showed a poor performance status (PS). RESULTS: The median survival time (MST) was 13 months, and the 5-year overall survival rate was 35%. The initial response and the number of tumors were significant prognostic factors, and WSI tended toward significance in a multivariate analysis. Four of five patients, who received prophylactic WSI, were 4-year survivors without a tumor relapse and none of them had tumor involvement in the vertebral canal. One patient developed radiation-induced brain necrosis, however, WSI did not seem to affect the late complications. CONCLUSIONS: We consider it important to reduce severe acute and late complications in patients qualified for receiving an aggressive therapy, and to explore the possible tolerable and curative treatment methods that can be used in order to improve the prognosis for PCNSL. Further modifications, including the application of WSI seem to be necessary in the management of PCNSL.     

首次复发?难治原发性中枢神经系统淋巴瘤预后影响因素分析

  目的  分析复发/难治原发性中枢神经系统淋巴瘤（primary central nervous system lymphoma,PCNSL）患者临床特点并探讨其影响预后的因素,为临床诊疗提供依据。  方法  选取复旦大学附属华山医院2006年10月至2015年8月确诊的64例复发/难治PCNSL患者的病例资料、治疗方案、实验室辅助检查指标进行回顾性分析。采用Cox回归多因素分析。  结果  单因素和多因素分析结果显示,首次无疾病进展生存期（progression-free survival of first time,PFS1）≤1年、Karnofsky评分（Karnofsky performance score,KPS） < 70分为影响复发/难治PCNSL预后的独立危险因素。PFS1≥1年患者中位第二次无疾病进展生存期（median progression-free survival of second time,mPFS2）和中位第二次总生存时间（median overall survival of second time,mOS2）分别为19个月和21个月,而PFS1 < 1年患者mPFS2和mOS2分别为10个月和14个月。复发/难治时KPS评分≥70分患者与KPS评分 < 70分患者mPFS2分别为40个月和10个月,mOS2分别为43个月和12个月。另外,单因素分析首次复发/难治PCNSL患者选用含有大剂量甲氨蝶呤（high-dose methotrexate,HD-MTX）化疗方案的mPFS2为18个月,而选用不含HD-MTX化疗方案的mPFS2为10个月,差异具有统计学意义。多因素分析结果显示,挽救方案为影响患者PFS的相关因素;单因素分析结果显示,挽救方案含有HD-MTX与不含有HD-MTX组的mOS2分别为23个月和12个月,差异无统计学意义,考虑与样本量较小有关。  结论  PFS1≤1年、KPS评分 < 70分是影响复发/难治PCNSL预后的独立危险因素。首次复发/难治PCNSL患者挽救治疗继续给予HD-MTX为基础的化疗方案可能会提高患者的远期疗效。      

Late relapse in primary central nervous system lymphoma: clonal persistence

Recurrence of primary central nervous system lymphoma (PCNSL) after initial diagnosis and treatment occurs within 2 years in most patients, and relapse after 5 years is rare. We evaluated late relapse in our PCNSL population. We identified 10 patients from our database of 378 patients (268 achieved a complete response and 230 had relapse) with PCNSL who had relapse ≥5 years after initial diagnosis. At initial diagnosis, their median age was 47 years; all patients had brain involvement and achieved a complete response to initial therapy (9 received high-dose methotrexate). Median time to first relapse was 7.4 years (range, 5.2-14.6 y). Eight patients had relapse in the brain, 1 had ocular relapse, and 1 had a systemic relapse. The histologic specimens at initial diagnosis and relapse were examined for clonal rearrangement in 3 patients; 1 had the identical clone at initial diagnosis and relapse 13.8 years later, and the other 2 were uninformative. All patients received salvage therapy (9 received systemic therapy and 1 received intraocular chemotherapy. Nine patients achieved a complete response to salvage therapy and 1 achieved a partial response. Four patients had relapse a second time. The median progression-free survival after first relapse was 31 months (range, 7.9-82.4). Late relapses accounted for 4% of all recurrences (10 of 230 patients) in our PCNSL population. Long-term persistence of the PCNSL clone was observed in one patient. Patients with late relapses have a good response to salvage therapy and prolonged survival.     

原发性中枢神经系统淋巴瘤的影像学特点及治疗

原发性中枢神经系统淋巴瘤是一种比较罕见的结外原发非霍奇金淋巴瘤（NHL）,其细胞来源多为弥漫大B淋巴细胞,淋巴细胞影像学表现为单发或多发的深部脑实质、脑室周围或脑膜等处的病变。其治疗尚无标准方案,目前多采用放化疗结合的综合治疗。化疗采用以大剂量MTX为主的方案,全脑放疗已被公认为治疗PCNSL的有效手段。但最佳的化疗方案组合、MTX最佳剂量及放疗剂量仍无定论。我们收治一例原发性中枢神经系统淋巴瘤,于外院行肿瘤切除术,术后予阿糖胞苷加大剂量MTX化疗6程后残留,现经多学科讨论后认为应予辅助放疗加替莫唑胺维持化疗。现患者已完成放疗,替莫唑胺维持化疗中。本文就此病例的影像特点及治疗进行讨论。     

Patterns of treatment in older adults with primary central nervous system lymphoma

BACKGROUND: The incidence of primary central nervous system lymphoma (PCNSL) has increased in recent decades and is highest in people aged >or=65 years. Radiotherapy (XRT) and systemic chemotherapy (CTX), alone or in combination, are reported to extend survival, but treatment-related toxicity is a particular concern in the elderly. The objective of the current study was to identify factors associated with the receipt and type of treatment in a population-based cohort of older PCNSL patients. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked with Medicare claims, the authors identified PCNSL cases in adults aged >or=65 years who were diagnosed between 1994 and 2002. Initial treatment was defined as XRT alone, CTX alone, combined CTX and XRT, or no treatment, based on Medicare claims in the 6 months after diagnosis. The authors assessed the effects of age, comorbidity, and sociodemographic characteristics on the odds of receiving treatment. RESULTS: Of 579 PCNSL patients, 464 (80%) received any treatment. XRT alone was the most common modality (46%), followed by combined therapy (33%) and CTX alone (22%). The type of treatment varied by age (P < .0001). The use of CTX alone or in combination with XRT decreased with increasing age, whereas the use of XRT alone increased with age. In adjusted analysis, younger age (P < .01) was found to be predictive of the receipt of any treatment. The use of CTX decreased with age (P < .0001). The median survival was 7 months (95% confidence interval, 6-8 months); no significant time trends were observed. CONCLUSIONS: Although the majority of older PCNSL patients received treatment, most did not receive optimal therapy. Age was found to have the greatest influence on treatment selection. Overall survival in elderly PCNSL patients appears to be poor.