新辅助化疗加保肢手术治疗肢体骨肉瘤

目的评价新辅助化疗加保肢手术治疗肢体骨肉瘤的临床疗效。方法选择1994年6月至2002年6月新辅助化疗加保肢手术治疗肢体骨肉瘤17例。达到广泛切除者11例，仅达边缘切除者6例；15例接受过术前化疗的病例切除标本均做多病理切片的坏死率评估。结果17例中无瘤生存超过5年的共有9例(52．9％)，其中截肢术2例(17．6％)，肢体功能评分结果，优7例、良2例、可3例、差5例，优良率为69．9％。结论新辅助化疗加保肢手术是治疗肢体骨肉瘤患者理想的治疗方法，术前有效化疗是保肢术成功的关键。     

Prognostic significance of serum alkaline phosphatase in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: recent experience at Rizzoli Institute.

In 560 patients with high-grade osteosarcoma of the extremity treated with 5 different protocols of neoadjuvant chemotherapy at a single institution between 1983 and 1995, the pre-treatment serum alkaline phosphatase (SAP) was examined to evaluate whether the enzyme levels had a clinical value in predicting the course of the disease. SAP was normal in 302 (54%) patients and high in 258 (46%). High levels of SAP was observed significantly and independently more frequently in male patients over 14-years-old, and in tumours larger than 150 ml and of osteoblastic subtypes. The 5-year event-free survival (EFS) and overall survival (OS) for all patients were respectively 60 and 68%. With multivariate analysis only two factors were independently correlated with the 5-year EFS: SAP levels (p=0.002) and the grade of chemotherapy-induced necrosis (p=0.0001). The authors conclude that in planning randomized clinical trials of neoadjuvant treatment for osteosarcoma, patients should be stratified according to SAP levels, and that when tailoring the aggressiveness of postoperative chemotherapy to the risk of relapse, in addition to the histologic response to preoperative treatment, the SAP levels should also be considered.     

新辅助化疗结合保肢手术治疗骨肉瘤的临床研究

目的:探讨新辅助化疗结合保肢手术治疗骨肉瘤临床效果。方法:选取2010年5月-2013年5月47例采用新辅助化疗结合保肢手术治疗的骨肉瘤患者为观察组,同期仅实施保肢手术治疗的骨肉瘤患者47例作为对照组,观察比较两组患者治疗后临床效果。结果:观察组患者临床疗效明显高于对照组,组间差异有统计学意义（P<0.05）;两组优良率及总有效率比较,观察组均明显优于对照组,组间比较差异有统计学意义（P<0.05）;治疗后6个月、1年、3年时间随访两组患者的复发、转移、死亡率,对照组均明显高于观察组,差异有统计学意义（P<0.05）。结论:新辅助化疗结合保肢手术治疗骨肉瘤近远期临床效果显著。     

Treatment and outcome of recurrent osteosarcoma: experience at Rizzoli in 235 patients initially treated with neoadjuvant chemotherapy

The pattern of relapse, treatment and final outcome of 235 patients with osteosarcoma of the extremity who relapsed after neoadjuvant treatments performed between 1986 and 1998 at a single institution is reported. The 235 relapses were treated by surgery, surgery plus second line chemotherapy, and only second line chemotherapy or radiotherapy. The 5-year post-relapse-event-free-survival (PREFS) was 27.6% and the post-relapse-overall-survival (PROS) 28.7%. All 69 patients who are presently alive and free of disease were treated by surgery, alone or combined with chemotherapy. None of patients treated only by chemotherapy or radiotherapy survived. We conclude that it is possible to obtain prolonged survival and cure in about 1/4 of relapsing osteosarcoma patients with aggressive treatments. The complete removal of the recurrence is essential for outcome, while the role of the association of second-line chemotherapy remains to be defined.     

新辅助动脉灌注化疗在肢体骨肉瘤保肢治疗中的应用

目的:探讨新辅助动脉灌注化疗联合保肢手术在肢体骨肉瘤中的应用价值。方法:对38例肢体骨肉瘤患者采用多柔比星(ADM)50mg/m2、顺铂(DDP)70mg/m2和长春新碱(VCR)1.4mg/m2新辅助动脉灌注化疗联合保肢手术,比较同等剂量单纯静脉新辅助化疗联合保肢手术39例患者的临床疗效和组织学疗效。结果:动脉灌注化疗组临床有效率为79.0%,组织学有效率为92.1%;对照组临床有效率为56.4%,组织学有效率为69.2%。前者优于后者差异有统计学意义,P&lt;0.05。结论:ADM、DDP和VCR新辅助动脉灌注化疗联合保肢手术是肢体骨肉瘤的有效方法,极具临床应用前景。     

Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases

PURPOSE: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. PATIENTS AND METHODS: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. RESULTS: Two patients received palliative treatment because their osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. CONCLUSION: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.01).     

Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 year experience at Rizzoli Institute, Italy

Around 1148 patients with non-metastatic osteosarcoma of the extremity were treated in a single institution between 1972 and 1999 with 4 different protocol of adjuvant and 7 different protocols of neoadjuvant chemotherapy. The rate of limb salvage increased from 20% to 71%. The 5-year event-free survival (EFS) and overall survival (OS) were 57% and 66%, respectively. The 10-year EFS and OS were 52% and 57%, respectively, and the results significantly correlated with serum alkaline phosphatase levels; the type of chemotherapy (adjuvant vs neoadjuvant); and with histologic response to pre-operative treatment. Aggressive chemotherapy and surgery could cure about the 60% of patients with osteosarcoma of the extremity. However, since local or systemic relapses, myocardiopathies and a second malignancy are possible even 5 or more years since the beginning of treatment, a long-term follow-up is recommended.     

新辅助化疗联合保肢手术治疗骨肉瘤的近期疗效观察

目的探讨新辅助化疗联合保肢手术治疗骨肉瘤的临床疗效。方法 40例四肢骨肉瘤患者随机分为试验组和对照组,试验组患者采用新辅助化疗联合保肢手术治疗,对照组患者采用截肢手术治疗。两组患者手术后均给予化疗,同时对比分析两组患者的临床疗效。结果试验组和对照组分别有3例和11例患者出现复发和(或)转移(P<0.05)。两组患者的术后1年和2年生存率差异无统计学意义,但试验组患者的术后3年生存率高于对照组(P<0.05)。两组患者的临床疗效优良率比较,试验组优于对照组(P<0.05)。试验组患者肢体功能评分为(23.5±4.6)分,而对照组为(11.8±3.1)分,两组比较,差异有统计学意义(P<0.05)。结论新辅助化疗联合保肢手术治疗骨肉瘤能够保证患者的生存率,其局部复发率和转移率与截肢手术一致,同时保存了患者肢体,提高了患者的生活质量,值得临床推广。     

Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution

BACKGROUND: The evaluation variables influencing systemic and local recurrence and final outcome are extremely important in defining risk-adapted treatments for patients with nonmetastatic osteosarcoma of the extremity. METHODS: A homogeneous group of 789 patients treated at a single institution between March 1983 and March 1999 with different protocols of neoadjuvant chemotherapy, with a minimum followup of 5 years, were retrospectively evaluated in relation to gender, age, serum levels of alkaline phosphatase, tumor site and size of the pathologic fracture, type of surgery, protocol of chemotherapy, surgical margins, and histologic response to preoperative treatment. RESULTS: The 5-year event-free survival (EFS) and overall survival rates were 60.1% and 67.5%, respectively. Upon univariate analysis, EFS was significantly related to the age of patients, serum value of alkaline phosphatase, tumor volume, histologic subtype, type of surgery, surgical margins, histologic response to preoperative treatment, and chemotherapy protocol. Local recurrences (4.8%) were significantly correlated with surgical margins. The 5-year post-recurrence EFS survival was 17% and was significantly lower for patients who had a local recurrence and metastases than for those with metastases only. Patients who had a recurrence only in the lung had a post-recurrence survival rate significantly better than others, correlated with the number of metastatic nodules and the length of the disease-free interval. CONCLUSIONS: Upon multivariate analysis, age < or = 14 years, high serum levels of alkaline phosphatase, tumor volume > 200 mL, a two-drug regimen chemotherapy, inadequate surgical margins, and poor histologic response to treatment maintained independent prognostic values on the outcome of nonmetastatic osteosarcoma of the extremities. These factors must be considered when deciding risk-adapted treatments for osteosarcoma patients.     

肢体骨肉瘤的保肢治疗

化疗在骨肉瘤治疗中地位的确立，提高了骨肉瘤患者5年生存率，促进了保肢技术的发展，瘤段灭活再植、异体骨、复合人工关节、肿瘤型假体等替代了截肢，但目前还没有一个完美的方案，儿童保肢还面临着巨大的挑战。     

Reproductive functions in female patients treated with adjuvant and neoadjuvant chemotherapy for localized osteosarcoma of the extremity

BACKGROUND: The side effects of chemotherapy on ovarian and reproductive functions in female patients who received adjuvant and/or neoadjuvant treatment for localized osteosarcoma of the extremities at our institution in the last 21 years (1974-1995) were assessed. METHODS: Ninety-two patients with a mean actual age of 26 (14-51) were interviewed. They had been followed 3 to 16 years after treatment (mean: 9.6 yrs). Twenty-four of them had received chemotherapy before puberty and 68 after puberty. RESULTS: Amenorrhea during chemotherapy occurred in 69% of postpuberal patients but only in 2 patients aged 39 and 43, respectively, was permanent. After the end of treatment, the patients' menstrual activity started again, and only a slight number of cases showed increases of menstrual irregularities. Twenty-two patients married after treatment; 20 patients started a pregnancy at a mean age of 27. Of these 20 patients, 3 had voluntary abortions and 17 succeeded. At the time of article submission, three were pregnant, 14 had 19 full term pregnancies, and no birth defects nor congenital anomalies were registered in their 19 full term newborns. CONCLUSIONS: In this group of female patients, chemotherapy seemed to alter neither their reproductive function nor the health of their newborns.     

Relationship between dose-intensity of treatment and outcome for patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy.

One hundred and forty-four patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy at the authors' institution between 1986 and 1989 were retrospectively analyzed to evaluate the relationship between the dose-intensity of chemotherapy actually received (RDI) and the prognosis. Preoperative chemotherapy consisted of high-dose methotrexate i.v., cisplatin i.a., and doxorubicin i.v. After surgery "good responder" patients (90% or more tumor necrosis) had a 31-weeks of chemotherapy with the same drugs, while "poor responder" patients (less than 90% tumor necrosis) received a 40 weeks treatment with ifosfamide and etoposide added to the three drugs used preoperatively. Due to delays and dose-reductions, only 17 patients (12%) received the treatment exactly as scheduled by the protocol, 66 (46%) received a dose-intensity between 90 and 99%, and 61 (42%) a dose-intensity between 63 and 89%. At a follow-up ranging between 10 and 13 years, 97 patients (67%) remained continuously free of disease, 45 relapsed, and two died of doxorubicin-induced cardiopathy. The continuous disease-free survival (CDFS) was not related to patients' gender and age, tumor histology, site and size, serum value of alkaline phosphatase, type of surgery and histologic response to chemotherapy. According to the RDI, CDFS resulted significantly higher for those 81 patients who received 90% or more of the scheduled dose-intensity than for those 61 who had less than 90% of the scheduled dose-intensity (76.5% v.s. 57.3%; p<0.02). These results seem to suggest that in neoadjuvant treatment of osteosarcoma the dose-intensity of chemotherapy is crucial for outcome, therefore every effort should be made to avoid reductions of doses and/or delays in performing the cycles of chemotherapy.     

Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy

Background: Most of the studies of the treatment of non-metastaticosteosarcoma of the extremity have reported results in terms of probabilityof survival up to five years with a minimum follow-up of less than two tothree years. Definition of reliable indicators of prognosis and predictivefactors for survival require mature data derived from a long-term survivalanalysis.Patients and methods: A review of 127 patients with non-metastaticosteosarcoma of the extremity, treated between March 1983 and June 1986, wasperformed. The treatment protocol consisted of primary chemotherapy with MTX(randomization to high vs. moderate dosages) and CDP followed by surgery.Postoperatively, patients with <60% tumor necrosis received ADMand BCD; those with tumor necrosis 60% < 90% (FairResponders FR) were given MTX, CDP and ADM. Up to January 1984, patientswith tumor necrosis >90% received MTX and CDP only, and after thenthey were given the same treatment as for FR. A multivariate analysis totest predictive factors for survival was performed.Results: With a median follow-up of 134 months (range 114–153), the12-year DFS was 46%. A good histologic response, an LDH baselinevalue within the normal range, and the use of high-dose MTX were positivepredictive factors for DFS. With a median time of observation for survivorsof 130 months, the 12-year overall survival was 53%. None of thepatients who relapsed with local or distant recurrences other than lungmetastasis are now alive. Patients with a relapse-free interval longer than24 months had a significantly better post-relapse survival than those with ashorter relapse-free interval (40% vs. 7%; P = 0.0159). All ofthe patients who were not surgically treated had disease progression anddied within 40 months after the first recurrence. The surgically-treatedpatients had a 30% post-relapse survival probability.Conclusions: In non-metastatic osteosarcoma of the extremity,chemotherapy-induced tumor necrosis, the baseline LDH serum value and the useof HDMTX are significant predictive factors for DFS. The relapse-free intervaland the possibility of metastasectomy are significant factors conditioning thepost-relapse survival.     

长期生存儿童骨肉瘤患者心理行为与生存质量的研究

目的分析新辅助化疗及保肢治疗对长期生存儿童骨肉瘤患者心理行为及生存质量的影响。方法回顾分析1999年12月～2005年11月应用新辅助化疗及保肢治疗的25例儿童骨肉瘤患者。男11例,女14例,平均年龄12岁（5～16岁）。股骨远端17例,胫骨近端7例,肱骨近端1例。Enneking外科分期均为IIB期。对所有患者进行随访,计算5年无瘤生存率,对长期生存的13例患者参照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25例患者术后中位随访时间21个月（12～120个月）,5年无瘤生存率为44．0％。13例长期生存的患者MSTS93评分平均21．6分（14～29分）,优良率为69．2％;SCL－90量表各因子分均值在1．46～2．31之间,其中人际关系、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、生理功能得分较低,其生存质量各维度得分由大到小依次为情感职能、社会功能、精神健康、生理职能、躯体疼痛、生理功能、总体健康、活力。结论骨肉瘤新辅助化疗及保肢治疗可使患儿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了一定程度的影响,提示需要加强骨肉瘤患儿的心理支持,提高患儿生存质量。     

Influence of local recurrence on survival in patients with extremity osteosarcoma treated with neoadjuvant chemotherapy: the experience of a single institution with 44 patients

BACKGROUND: Risk factors for local recurrence (LR) after osteosarcoma, such as surgical margins and histologic response to preoperative treatment, have been well documented, whereas the outcome for patients who locally recur has not been well established yet. METHODS: Retrospective analysis of the management and outcome of 44 patients who developed LR after treatment of osteosarcoma of the extremities with neoadjuvant chemotherapy was performed in a single institution between 1983 and 1999. RESULTS: In 24 patients (54.5%), LR was the first sign of recurrence; in 8 patients (18.2%) LR followed systemic recurrence and in 12 patients (27.3%), the 2 events, local and systemic recurrence, were concurrent. Of the 44 patients, 26 with local recurrences were free of disease, but only 5 were long-term event-free survivors, and 39 patients developed further recurrences: 37 died of the tumor and 2 were alive with uncontrolled disease at the time of last follow-up. The 5-year disease-free survival rate after the last recurrence was 15.9%; it was 25.9% for patients who achieved remission and 0% for the others. The only prognostic factor identified for post-LR disease-free survival was the presence of systemic recurrence at the time of diagnosis of LR or before (5-year postrecurrence event-free survival rate of 29.1% for patients without metastases at the time of local recurrence vs. 0% for those with metastases; P = .02). CONCLUSIONS: These results confirm that patients with osteosarcoma of the extremities who develop LR are at a very significantly high risk of developing metastatic disease and dying of the tumor.     

肢体软组织肉瘤保肢综合治疗疗效观察

目的:探讨术前新辅助化疗对软组织肉瘤的疗效及在保肢治疗中的意义.方法:28例肢体软组织肉瘤中恶性纤维组织细胞瘤18例,滑膜肉瘤3例,脂肪肉瘤6例,原始神经外胚层肿瘤(PNET)1例 .术前均给予选择性肿瘤供血动脉灌注化疗2-3周期,化疗药物为阿霉素/顺铂和异环磷酰胺.化疗后均行保肢手术治疗.结果:28例术前化疗后均有疼痛缓解、皮温降低、肿胀减轻、瘤体不同程度缩小、边缘变清楚及关节活动度增加.化疗后均行肿瘤广泛切除术,术中获得良好的外科切除界限.随访16-56个月,2例死亡,1例局部复发行截肢术.术后12个月后采用MSTS 93评分系统评分为24.0-29.0分,平均为27.0分.28例3年生存率为92.9%,初次保肢率100%,最终保肢率89.3%.结论:术前新辅助化疗后广泛切除手术是肢体软组织肉瘤的有效保肢治疗方法.     

Metachronous skeletal osteosarcoma in patients treated with adjuvant and neoadjuvant chemotherapy for nonmetastatic osteosarcoma.

PURPOSE: The prognosis for patients who develop metachronous skeletal osteosarcoma (OS) has been considered grave compared with that for patients with relapse limited to the lungs. We investigated the incidence and outcome of metachronous skeletal OS after initial treatment of the primary tumor. PATIENTS AND METHODS: Twenty-three (median age 18.7 years) of 426 patients with nonmetastatic, high-grade primary OS treated at Memorial Sloan-Kettering Cancer Center (New York, NY) between February 1973 and May 2000 developed metachronous skeletal OS. Initial therapy included combination chemotherapy and surgery. Treatment of subsequent relapses consisted of chemotherapy or radiation alone or surgery with or without additional individualized chemotherapy. RESULTS: The median time from the diagnosis of primary OS to the development of metachronous OS was 1.4 years (range, 0.2 to 11.3 years). Median survival was 1.5 years (95% confidence interval [CI], 0.8 to 6.9 years). Two- and 5-year postmetachronous overall survival was 43.5% (95% CI, 23.2% to 63.7%) and 33% (95% CI, 13% to 53%), respectively. At last follow-up (range, 0.1 to 12.8 years), five (30.4%) patients were alive with no evidence of disease (range, 1.7 to 12.8 years; median, 4.4 years). For 11 patients who developed metachronous OS 24 months or more from initial diagnosis, 5-year postmetachronous survival rate for patients receiving combined modality versus monotherapy was 83% (95% CI, 54% to 100%) and 40% (95% CI, 0% to 83%), respectively. CONCLUSION: In a small subset of patients who developed late metachronous OS, combined-modality therapy with surgery and aggressive chemotherapy may result in long-term postmetachronous survival. This implies that principles used in treatment of primary OS may be applied to patients with late metachronous skeletal OS.     

Twenty-year follow-up of osteosarcoma of the extremity treated with adjuvant chemotherapy

We have updated the results of an adjuvant chemotherapy study of 106 patients with osteosarcoma of the extremities published 17 years ago, treated by surgery followed by adjuvant chemotherapy with vincristine (VCR), methotrexate (MTX) and doxorubicin (ADM), between 1980-1983, and followed-up for at least 20 years (20-23 years). In comparison with the results reported 17 years ago with a median follow-up of 38 months (range: 27-66), this updated study showed 24 more deaths, 9 more relapses and 3 second malignancies. Consequently, event-free survival (EFS) and overall survival (OS) are significantly lower compared to the previous study with a 3-year follow up (EFS 38% vs 53%; OS 43.8% vs 67%). We conclude that osteosarcoma patients treated with chemotherapy are at risk of late adverse events. Protracted medical follow-up and long-term updated results are useful to identify, at an early stage, late relapses and late treatment-related complications.