与骨肉瘤化疗相关的几个因素的研究进展

骨肉瘤是一种主要发生于青少年的恶性骨肿瘤。自７０年代初Ｊａｆｆｅ［１］首创大剂量氨甲喋呤及四氢叶酸钙解救（ＨＤＭＴＸＣＦ）治疗骨肉瘤以来,相继发现阿霉素、顺铂及异环磷酰胺等亦对骨肉瘤有确切的疗效。许多学者开展了多药联合的辅助化疗与新辅助化疗。在强力化疗与外科手术的综合治疗下,骨肉瘤的治疗效果不断改善,五年无瘤生存率（ＲＦＳ）已由过去的１５％上升到４０％～８０％,保肢率也明显提高。一、化疗药物（一）氨甲喋呤（ＭＴＸ）：最早公认的对骨肉瘤化疗有效的药物,目前几乎所有的化疗方案均采用ＨＤＭＴＸＣＦ,单…     

骨肉瘤保肢与截肢疗法(附31例分析)

作者对３１例分别接受保肢或截肢疗法的骨肉瘤患者的随访结果进行了总结和分析。３１例患者中，９例施行广泛切除，８例施行边缘切除，１４例施行截肢手术，部分患者接受了以大剂量氨甲喋呤、顺铂、阿霉素为主的化疗。结果表明，配合化疗的广泛性切除组，患者的生存率和保肢率明显高于边缘切除组和截肢组；接受假体置换并获长期生存的患者，假体使用寿命长，大多数功能满意。作者认为，在骨肉瘤的保肢疗法中，化疗与根治性广泛切除术均属十分重要。对于符合适应证的患者，在配合化疗的基础上行肿瘤广泛性切除保肢疗法，可提高患者的生存率及生活质量。     

骨肉瘤保肢与截肢疗法

作者对３１例分别接受保肢或截肢疗法从瘤患者的随访结果进行了总结和分析。３１例患者中,９例施行广泛切除,８例施行边缘切除,１４例施行截肢手术,部分患者接受了以大剂量氨甲喋呤顺铂、阿霉素为主的化疗。结果表明,配合化疗的广泛性切除组,患者的生存率和保肢率明显高于边缘切除组和截肢组,接受假体置换并获长期生存的患者,假体使用寿命长,大多数功能满意。作者认为,在骨肉瘤的保肢疗法中,化疗与根治性广泛切除术均属十     

顺铂、异环磷酰胺与阿霉素联合化疗治疗骨肉瘤的疗效观察

背景：随着现代肿瘤理论及诊治手段的发展,骨肉瘤的治疗目的不能仅满足于生存率的提高,更要提高患者的生活质量。治疗原则已转变为在肿瘤根治、追求生存的同时更多关注功能维持和心理健康。目的：观察顺铂（DDP）、异环磷酰胺（IFO）与阿霉素（ADM）联合化疗（DIA方案）治疗原发性骨肉瘤的疗效及对患者心理行为及生存质量的影响。方法：2004年1月至2011年11月应用DIA方案治疗51例骨肉瘤患者,男32例,女19例;年龄6～51岁,平均18岁;ⅡB期48例,Ⅲ期3例。对所有患者进行随访,计算5年无瘤生存率,对长期生存患者参照MSTS93评分标准进行患肢功能评价,采用90项自觉症状自评量表（SCL-90）和中文版医学结局研究简明调查表（SF-36）进行心理行为与生存质量评估。结果：全部获得随访,截至2013年1月,随访时间为2～104个月,中位随访时间为32个月,5年无瘤生存患者31例,无瘤生存率为60.7%。33例（31例无瘤生存,2例带瘤生存）长期生存患者的MSTS93评分为14～29分,平均20.6分,优良率为75.8%;SCL-90量表中人际关系、躯体化、焦虑、恐怖得分均高于常模（P〈0.05）;SF-36量表显示患者活力、总体健康、生理功能得分均较低。结论：DIA方案治疗原发性骨肉瘤切实可行,可使患者获得较高的长期生存率,但对患者心理行为和生存质量产生一定影响,提示我们需要加强骨肉瘤患者的心理支持,提高患者生存质量。     

413例骨肉瘤化疗、手术和预后的10年随访研究

目的对骨肉瘤的化疗、手术及预后进行随访研究,探讨骨肉瘤治疗中影响患者预后、生存及医生治疗决策的因素。方法回顾性调查1998年1月-2008年1月单一骨肿瘤治疗中心注册的413例骨肉瘤患者的病例资料,记录患者的基本情况、手术情况、化疗情况以及随访和预后情况,比较规范化疗和未规范化疗患者局部复发、肺转移率以及生存率的差异,分析骨肉瘤治疗中存在的问题。结果 413例患者中,随访〉5个月352例,失访率14.8%;随访〉12个月251例,失访率39.2%;随访〉60个月216例,失访率47.7%。321例行手术治疗,其中截肢手术165例,保肢手术156例。126例完成规范化疗,287例由于各种原因没有完成规范化疗或未进行化疗。不规范化疗患者肺转移发生率、5年总生存率及5年总无瘤生存率均低于规范化疗患者,差异具有统计学意义（P〈0.05）。结论骨肉瘤的临床治疗存在患者就诊迟、完成规范化疗比例小、保肢率低、失访率高等问题。重视并解决这些问题对骨肉瘤患者的预后有重要意义。     

进展期结肠癌术后腹腔低渗热灌注联合静脉化疗的临床研究

目的观察进展期结肠癌患者术后早期腹腔低渗热灌注（HIPEC）联合静脉化疗的临床治疗效果。方法将89例进展期结肠癌患者随机分为HIPEC联合全身化疗组44例（试验组）及单纯全身化疗组45例（对照组）。根治性结肠癌切除术后,试验组行HIPEC4次后,进行FOLFOX6静脉化疗方案。对照组则行单纯FOLFOX6化疗方案进行静脉化疗。对照观察分析两组的临床效果与预后。结果两组均无发生严重并发症。试验组KPS评分升高率为54.54%,对照组为40.00%,差异比较有统计学意义（P〈0.05） 试验组术后1、3、5年生存率分别为96.8%、72.3%、52.3%,对照组分别为95.7%、65.4%、43.0%,两组术后3、5年生存率比较,差异有统计学意义（P〈0.05）。结论HIPEC联合静脉化疗能较有效地提高结肠癌术后生存率和生存质量,是结肠癌综合治疗中较为合理的手术后辅助治疗方式。     

重组人血管内皮抑素联合化疗治疗进展期胃癌的初步研究

目的探讨应用重组人血管内皮抑素联合OLF方案化疗对进展期胃癌术后生活质量和生存期的影响。方法将68例进展期胃癌术后患者随机分为两组：化疗组34例,采用OLF方案,奥沙利铂130mg/m2d1,甲酰四氢叶酸200mg/m2d1-5,5-氟脲嘧啶400mg/m2d1-5,3周为1个周期;靶向治疗组34例,化疗方案同化疗组并于每周期化疗第1天开始给予恩度7.5mg/m2,静脉滴注,每日1次,连用14d为1个疗程,间歇7d,重复使用。结果两组1年生存率分别为79.4%、85.3%,差异无统计学意义（P〉0.05）;3年生存率分别为32.4%、52.3%,差异有统计学意义（P〈0.05）。两组生活质量改善率分别为61.8%（21/34）、82.4%（28/34）,差异有统计学意义（P〈0.05）。结论进展期胃癌术后应用重组人血管内皮抑素联合化疗可提高患者生活质量,延长生存时间。     

骨肉瘤新辅助化疗的探讨

目的 评价新辅助化疗治疗骨肉瘤的临床疗效。方法 新辅助化疗保肢术治疗骨肉瘤38例。术前超大剂量化疗2个疗程，第12周手术，术后化疗3－5个疗程，根据肿瘤坏死率测定调整术后化疗方案。手术方法：关节置换17例，同种异体骨移植9例，自体骨移植7例，肿瘤骨灭活再植2例，肿瘤切除3例。结果 肿瘤坏死率测定：＞90％，32例，＜90％4例；未2例。3年无瘤生存率71．1％，5年无瘤生存率65．8％。结论 新辅助化疗配合保肢术是治疗骨肉瘤的理想方法。     

保肢手术治疗肢体骨肉瘤的中长期疗效观察

目的 评价采用保肢和截肢术结合新辅助化疗治疗肢体骨肉瘤的临床疗效.方法 73例肢体骨肉瘤患者分为保肢组和截肢组,其中51例行保肢术,22例行截肢术.所有患者术前、术后均行化疗.两组以局部复发率、3年无瘤生存率和术后功能恢复评价为指标进行评价.术后6个月功能评价采用MSTS 93评分.结果 73例均获随访,时间7～64(37.50±15.51)个月.保肢组局部复发率为5.9%(3/51),3年无瘤生存率为72.5%(37/51),术后MSTS 93评分为17～30(23.21±3.66)分.截肢组局部复发率为4.5%(1/22),3年无瘤生存率为68.1%(15/22),术后MSTS 93评分为10～13(11.81±0.73)分.两组3年无瘤生存率与局部复发率差异无统计学意义(P＞0.05).结论 保肢和截肢术结合新辅助化疗是治疗肢体骨肉瘤理想的治疗方法.采用保肢术治疗同期骨肉瘤患者疗效优于截肢术.     

骨肉瘤治疗进展

骨肉瘤是儿童和青少年期最常见的恶性骨肿瘤。新辅助化疗及大剂量化疗的应用,可有效提高患者的5年生存率,并可促进保肢技术的发展。有研究对早期Rosen的新辅助化疗是否可提高骨肉瘤保肢率及5年生存率提出质疑,认为对无转移患者及时手术(保肢或截肢)、术后辅助化疗的预后与新辅助化疗无差异。研究显示多药耐药是骨肉瘤化疗失败的最主要原因。保肢手术已成为肢体骨肉瘤外科治疗的标准。瘤段骨灭活再植、异体骨移植、带血管腓骨移植、肿瘤型假体、同种异体骨复合型假体、可延长假体置换术等的出现,取代了传统截肢术。儿童骨肿瘤切除后的肢体重建是个难题,解决保肢术后肢体不等长是近年来儿童保肢治疗研究的热点。     

新辅助化疗结合保肢手术治疗合并病理性骨折的骨肉瘤

目的探讨应用新辅助化疗并结合保肢手术治疗合并病理性骨折的骨肉瘤治疗效果。方法对4例骨肉瘤合并病理性骨折患者术前使用阿霉素、顺铂、甲氨喋呤和长春新碱联合化疗2个循环后作化疗疗效评估,4例患者均施行肿瘤广泛切除、人工关节置换术。术后继续化疗3-4个循环。结果1例于术后5年6个月死于肺转移;其余3例患者术后至今已分别存活42、37和18个月,无感染,无假体松动,无肿瘤局部复发和远处转移。结论根据术前化疗疗效的评估,对化疗反应良好的合并病理性骨折的骨肉瘤患者采取保肢术,可获得良好的治疗效果。     

40~60岁肢体骨肉瘤病人的临床治疗效果与策略

目的 分析40~60岁肢体骨肉瘤病人的临床治疗疗效,总结预后相关因素并探讨治疗策略。方法 回顾性分析2002年4月至2015年10月国内7家骨肉瘤治疗中心收治的确诊为肢体骨肉瘤的62例病人的资料,其中男34例,女28例;年龄范围限定在40~60岁,平均年龄为50.4岁;收集病人一般情况、发病部位、术前穿刺、化疗情况、手术方式、复发转移及生存情况等。以上述因素为变量指标,应用Kaplan-meier法测算生存率,研究这些因素与3年、5年生存率之间的关系。结果 62例肢体骨肉瘤病人中发病于膝关节周围者50例,约占80.6%。62例病人均得到随访,随访12~115个月,平均随访时间为43个月;3年和5年总生存率为80.6％、56.5%;3年和5年无瘤生存率为41.9%、32.3%;5年总生存率：术前化疗组与未化疗组分别为51.5%、62.1%;术后化疗组与未化疗组分别为52.1%、71.4%;术前术后均化疗组与均未化疗组为51.6%,61.3%;保肢手术组和截肢手术组分别为57.1%、53.8%。术后无复发转移、单纯复发、肺转移、多发转移的病人3年生存率分别为89.7%、78.6%、50.0%、73.3%。结论 40~60岁肢体骨肉瘤病人,膝关节周围发病率高于年轻病人,且预后较差,其预后与术前穿刺明确诊断、术后复发转移情况密切相关,其临床治疗应当建立在充分切除肿瘤的基础之上,严格遵照Enneking外科分期,降低肿瘤的复发转移率,以期改善预后。     

Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities

Between September 1986 and December 1988, 125 patients with osteosarcoma of the extremities entered the second neoadjuvant study at the authors' institution. Patients received preoperatively two cycles of methotrexate (MTX) intravenously, followed by cisplatinum (CDP) intraarterially, plus adriamycin (ADM) intravenously. After surgery, the patients classified as "good responders" (more than 90% tumor necrosis) received ADM, MTX, and CDP, while the "poor responders" (less than 90% tumor necrosis) had a longer chemotherapy that included ifosfamide and etoposide (VP-16) in addition to MTX, ADM, and CDP. Limb salvage was possible in 85% of patients, 8% had an amputation, and 7% had a rotationplasty. The surgical margins were adequate (radical or wide) in 88% of cases and inadequate (marginal or intralesional) in 12%. At an average follow-up period of 28 months (range, 13 to 41), 109 patients (87%) remained continuously disease free, 15 (12%) relapsed with pulmonary metastases, and one patient (0.8%) had a local recurrence. Compared with the first neoadjuvant study at the authors' institution that used only MTX and CDP preoperatively, the percentage of limb salvages, "good responders," and continuously disease-free survival at two years was significantly higher in the second Rizzoli neoadjuvant study (85%, 74%, and 87% versus 77%, 52%, and 59%). Systemic toxicity because of chemotherapy was superimposable. A retrospective analysis of the real dose intensity for each patient demonstrated a correlation between the intensity of chemotherapy and prognosis.     

肢体原发成骨肉瘤综合治疗的远期结果

目的　对肢体原发成骨肉瘤综合治疗及非综合治疗的结果进行比较和评估。　方法　术前无远处转移的肢体成骨肉瘤患者 170例 ,年龄 6～ 5 2岁 ,平均年龄 2 1岁 ,男性 112例 ,女性 5 8例 ;肿瘤部位 :股骨远端 80例 ,胫骨近端 5 1例 ,股骨近端 7例 ,肱骨近端 10例 ,四肢其它部位 2 2例。施行术前化疗 手术切除肿瘤 术后化疗综合治疗 (综合治疗组 ) 10 4例 ,单纯手术切除肿瘤 (非综合治疗组 )6 6例 ;行保留肢体手术 94例 ,其中施行化疗者 71例 ,未行化疗者 2 3例 ;行截肢术 76例 ,其中行化疗者 33例 ,未行化疗者 43例。　结果　 5年生存率 :综合治疗组为 6 1% ,非综合治疗组为 2 8% ;10年生存率 :综合治疗组为 5 3% ,非综合治疗组为 2 6 % ;局部复发率 :综合治疗保肢组为 2 0 % ,截肢组为 3% ;非综合治疗保肢组为 44 % ,截肢组为 7% ;综合治疗组和非综合治疗组肺转移的发生率无明显差异。80例患者按照MSTS评分系统进行功能评定 ,其中保肢组 (5 6例 )平均分值为 71% ,截肢组 (2 4例 )平均分值为 5 3%。　结论　综合治疗可以提高骨肉瘤的存活率 ;肿瘤局部切除及重建手术可以为患者提供比较满意的肢体功能。     

Pathologic fracture in osteosarcoma : prognostic importance and treatment implications.

BACKGROUND: The presence of a pathologic fracture in an osteosarcoma has been considered a poor prognostic factor and an indication for immediate amputation. The purpose of the present study was to determine, in the current era of neoadjuvant chemotherapy, whether a pathologic fracture in an osteosarcoma has prognostic importance and whether limb salvage can be safely performed in such patients without compromising clinical outcome. METHODS: In a cooperative effort of the Musculoskeletal Tumor Society, members from eight institutions provided retrospective data on fifty-two patients with osteosarcoma who had a pathologic fracture and on fifty-five patients with osteosarcoma who had not had a pathologic fracture and had been followed for at least two years or until disease recurrence, metastasis, or death. The two groups were matched for patient age and tumor location. Outcomes examined were survival and local recurrence. A subgroup analysis was performed to assess differences in outcome within the group with the pathologic fracture. RESULTS: The five-year estimated survival rates were 55% for the group with a pathologic fracture and 77% for the group without a fracture (p = 0.02). The rate of survival without a local recurrence at five years was 75% for the group with a fracture and 96% for the group without a fracture (p = 0.007). In the group with a fracture, seven (23%) of the thirty patients managed with limb salvage and four (18%) of the twenty-two managed with an amputation had a local recurrence (p = 0.75). Eleven (37%) of the thirty patients with a fracture who were managed with limb salvage and ten (45%) of the twenty-two patients with a fracture who were managed with an amputation died of the disease (p = 0.50). Five patients underwent open reduction and internal fixation followed by limb-salvage surgery. Two of them had a local recurrence and died at an average of eight months postoperatively. The remaining three patients were alive at an average of 6.1 years postoperatively. Local disease control and the survival of these patients were not significantly different from those for the thirty-three patients who were treated with nonoperative immobilization of the fracture followed by limb-salvage surgery. CONCLUSIONS: Patients with osteosarcoma who present with a pathologic fracture or sustain one during preoperative chemotherapy have an increased risk of local recurrence and a decreased rate of survival compared with patients who have not sustained a pathologic fracture. The performance of a limb-salvage procedure in carefully selected patients with a pathologic fracture does not significantly increase the risk of local recurrence or death. Factors predictive of improved outcome, such as the response to chemotherapy and union of the fracture, should be taken into account when limb salvage is being considered.     

ⅡB期肢体骨肉瘤189例综合治疗临床分析

目的 对肢体原发骨肉瘤综合治疗结果进行评估。方法术前无远处转移的肢体骨肉瘤患者189例,年龄4～39岁,平均年龄18岁,男性125例,女性64例;肿瘤部位：股骨下段86例,胫骨上段52例,股骨上段4例,肱骨上段19例,四肢其他部位28例,病理骨折22例。完成化疗方案的患者为规律化疗组116例,占61．4％;未完成化疗方案的患者为非规律化疗组73例,占38．6％。规律化疗组116例,依手术方法分为保肢组90例和截肢组26例;非规律化疗组73例中保肢组42例和截肢组31例。结果5年生存率：规律化疗组和非规律化疗组患者分别为78．5％和35．2％。局部复发率：规律化疗组保肢患者90例,复发15例（16．6％）,而非规律化疗组保肢患者42例,复发16例（38．1％）,差异有统计学意义（P〈0．01）,规律化疗组116例中,转移33例（28．4％）;而非规律化疗组73例中,转移48例（65．7％）,差异有统计学意义（P〈0．01）。56例股骨下端和胫骨上端的保肢患者按照MSTS评分系统进行功能评定,灭活再植36例,异体骨置换10例,人工关节置换10例,功能恢复达85％-86％,三类术式随访期内功能恢复状况差异无统计学意义（P〉0．05）。结论肺转移瘤是制约骨肉瘤患者生存率提高的重要因素;局部复发的发生与肿瘤的外科边界关系密切,恰当地选择外科边界可以提高保肢的安全性;规范的综合治疗应视为骨肉瘤治疗的首选,单纯外科治疗疗效有限,应辅以规律化疗。     

Dose response relationship of methotrexate in combination with cisplatin in murine bladder cancer

Methotrexate (MTX) has activity in transitional cell carcinoma (TCC) in man and some have suggested an advantage of high-dose methotrexate versus the standard dose in controlling tumor growth and prolonging survival. MBT-2, a poorly differentiated TCC induced by the carcinogen FANFT, is both grossly and histologically similar to human TCC and has been used as an animal model. One hundred twenty C3H/HE female mice were injected in the hind limb with 7.5 X 10(4) MBT-2 tumor cells. When palpable tumors developed in all animals, therapy was initiated. Animals were randomized into a control group and nine treatment groups as follows: cisplatin (DDP), MTX32 mg, MTX50 mg, MTX80 mg, DDP + MTX32, MTX50 + Leucovorin, MTX80 + Leucovorin, DDP + MTX50 + Leucovorin, DDP + MTX80 + Leucovorin. The combination of MTX50 mg with Leucovorin + DDP and DDP alone were the two most effective regimens in controlling tumor growth and prolonging survival. No statistically significant difference was observed between the group treated by high-dose MTX alone and those treated by low-dose MTX. No toxicity was observed even when high doses of MTX were used.