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.     

Neoadjuvant chemotherapy for peripheral malignant neuroectodermal tumor of bone: recent experience at the istituto rizzoli.

PURPOSE: The results achieved in 44 patients with nonmetastatic peripheral neuroectodermal tumor (PNET) of bone treated with neoadjuvant chemotherapy are reported. PATIENTS AND METHODS: A six-drug regimen of chemotherapy (vincristine, doxorubicin, dactinomycin, cyclophosphamide, ifosfamide, and etoposide) was administered to all patients. Local treatment consisted of surgery in 20 patients, surgery followed by radiotherapy in 13, and radiotherapy only in 11. RESULTS: At a mean follow-up of 4.5 years (range, 2 to 7 years), 23 patients (52%) remain event-free, 20 have relapsed (45%), and one has died of chemotherapy-related toxicity. The 5-year event-free survival and overall survival were 54.2% and 62.7%, respectively. To assess the prognostic significance of neural differentiation in the family of Ewing's sarcoma, these results have been compared with the outcomes of 138 concomitant patients with typical Ewing's sarcoma (TES) who were treated according to the same protocol. Of these, 103 (75%) remained continuously event-free, 34 (24%) relapsed, and one died of chemotherapy-related toxicity. It follows that PNET patients treated with this chemotherapy regimen have a significantly worse prognosis than typical ES patients (5-year event-free survival, 54.2% v 70.6%, P <.012; 5-year overall survival, 62.7% v 78.3%, P <.002). CONCLUSION: The authors conclude that studies into new adjuvant therapy for Ewing's sarcoma modulated according to risk of relapse should also consider neural differentiation as a risk factor.     

Prognostic model of event-free survival for patients with androgen-independent prostate carcinoma

BACKGROUND: The current study was conducted to develop a prognostic model of event-free survival (EFS) in men with androgen-independent prostate carcinoma (AIPC). METHODS: Data from 160 patients diagnosed with AIPC between 1989-2002 were reviewed. No patient had received cytotoxic chemotherapy. A univariate Cox proportional hazards model identified significant predictors of EFS. Recursive partitioning analysis divided these significant variables into prognostic risk groups. The final prognostic model was tested with a Cox proportional hazards model. RESULTS: The final prognostic risk model included the presence of metastatic disease at the time of androgen-independent disease progression (P = 0.040), time to prostate-specific antigen (PSA) recurrence (P = 0.043), and PSA doubling time (P < 0.01). Three highly independent risk groups were identified. The observed median EFSs were 6.1 months (95% confidence interval [95= CI], 3.4-8.8 months), 33.6 months (95= CI, 25.3-41.9 months), and 96.1 months (95= CI, 57.9-134.3 months) for the low-risk, intermediate-risk, and high-risk groups, respectively. Each risk group was found to be independently predictive of EFS (P < 0.01). Patients who died of prostate carcinoma experienced significantly more clinical events than those who died of other causes (P < 0.01). CONCLUSIONS: The prognostic model in the current study stratified patients into three highly significant and independent risk groups for EFS. A detailed PSA history and knowledge of metastatic disease are sufficient to risk-stratify patients with AIPC. One very unique aspect of this model was that it was developed from a patient cohort that never received chemotherapy.     

Treatment outcome and recursive partitioning analysis-based prognostic factors in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy

PURPOSE: To analyze the clinical outcomes and devise a prognostic model for patients with operable esophageal carcinoma who underwent preoperative chemoradiotherapy (CRT). METHODS AND MATERIALS: A total of 269 patients were enrolled into three clinical trials assessing preoperative CRT at our institution. We assessed the significance of the pretreatment and treatment factors with regard to tumor recurrence and long-term survival and used recursive partitioning analysis to create a decision tree. RESULTS: At a median follow-up of 31 months for the surviving patients, the median overall survival of all 180 patients in this study was 31.8 months, and the 5-year overall survival rate was 33.9%. The median event-free survival was 24.1 months, and the 5-year event-free survival rate was 29.3%. Of the 180 patients, 129 (71.7%) also underwent esophagectomy, and the perioperative mortality rate was 7.8%. A pathologic complete response was achieved by 58 patients (45%). The 5-year overall survival rate was 57.1% for patients who attained a pathologic complete response and 22.4% for those with gross residual disease (p = 0.0008). Recursive partitioning analysis showed that female patients who achieved a clinical response and underwent esophagectomy had the most favorable prognosis (p <0.0001). Among the patients who underwent esophagectomy, the group with good performance status, clinical Stage II, and a major pathologic response to CRT had the most favorable prognosis (p = 0.0002). CONCLUSION: Although preoperative CRT was generally effective and well-tolerated, an individualized approach is necessary to improve outcomes. Strategies to increase the response and reduce treatment failure should be investigated.     

Prognostic significance of the immunophenotype versus the International Prognostic Index in aggressive non-Hodgkin's lymphoma

The International Prognostic Index (IPI) is currently the most widely accepted prognostic factor system for patients with aggressive non-Hodgkin's lymphoma (NHL). However, in constructing the model, the immunophenotype of the disease was not used as an independent variable. The purpose of the present study was to assess and compare the prognostic significance of the immunophenotype (B-cell vs. T-cell) of aggressive NHL with other well-established prognostic determinants, in particular the IPI. Between January 1995 and December 2000, a retrospective analysis was conducted of clinical and pathological data on 181 patients aged = 15 years who had been newly diagnosed with aggressive NHL. All pathology slides were reviewed and defined according to the Revised European-American Lymphoma classification. Forty-one patients (23%) had T-cell lymphoma and 140 patients (77%) had B-cell lymphoma. Diffuse large B-cell lymphoma and unspecified peripheral T-cell lymphoma were the 2 most common entities, comprising 63% and 14% of patients, respectively. Most of the pretreatment characteristics, including IPI risk groups, were not significantly different between B-cell and T-cell lymphomas. The rates of complete remission (71% vs. 54%, P = 0.038) and progressive disease (39% vs. 63%, P = 0.023) significantly favored patients with B-cell lymphoma. With a median follow-up time of 31 months (range, 10-81 months), the 5-year overall survival (49% vs. 27%; P < 0.001) and event-free survival (35% vs. 10%; P < 0.001) were significantly better in B-cell lymphoma. The 5-year disease-free survival was also in favor of the B-cell group (48% vs. 21%; P = 0.086). Patients with T-cell lymphoma yielded inferior survival in all IPI risk groups. Multivariate analysis revealed T-cell lymphoma as the most significant factor associated with short overall survival (relative risk [RR], 3.4; 95% CI, 1.9-5.9) and event-free survival (RR 2.7, 95% CI, 1.7-4.3). When a second multivariate analysis was done using IPI (age, stage, performance status, number of extranodal sites, and serum lactate dehydrogenase) as one independent variable, T-cell phenotype remained the strongest factor affecting the survival of patients (P < 0.001). T-cell lymphoma is an independent prognostic factor, the significance of which is at least comparable to the IPI for patients with aggressive NHL.     

Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of treatment

In 58 breast cancer patients with meningeal carcinomatosis (MC) pretreatment characteristics, clinical course, and response to treatment were evaluated. Forty-four patients were uniformly treated with intraventricular chemotherapy. Fourteen patients did not receive intraventricular treatment. In the intraventricularly treated group the median survival was 12 weeks. Multivariate analysis of the pretreatment characteristics of the intraventricularly treated patients demonstrated a prognostic significance with respect to survival for age older than 55 years, lung metastases, cranial nerve involvement, cerebrospinal fluid (CSF) glucose less than 2.5 mmol/l, and CSF protein 0.51 to 1.0 g/l. Based on the significance of these predicting factors a prognostic index (PI) identified four groups of patients with a median survival of 43 weeks, 22 weeks, 11 weeks, and 3 weeks, respectively. After 6 weeks of intraventricular treatment 22 patients showed a neurologic improvement or stabilization, and nine patients showed a worsening of the neurologic signs, whereas 13 patients (30%) had already died. The responders had a median additional survival of 5 months versus 1 month for nonresponders. No relation was found between survival and intensity of the intraventricular treatment after the first 6 weeks of treatment. Almost all long survivors had also received systemic treatment for systemic disease, whereas most patients who died within 6 months did not receive systemic therapy. Radiation therapy had no influence on the survival time. Early death due to the intensive treatment occurred in three patients. In 11 of the 17 patients who survived more than 4 months an often seriously debilitating late neurotoxicity developed. The survival curve of the nonintraventricularly treated patients appeared to be essentially the same as the curve of the intraventricularly treated patients. Using the same PI the predicted survival time was also the same as in the intraventricularly treated group. It is concluded that survival in MC from breast carcinoma may be more dependent on some pretreatment characteristics than on treatment intensity. On the basis of these pretreatment characteristics the survival time seems to be predictable. Finally, late neurotoxicity due to aggressive treatment leads to impairment of the quality of life in more than 50% of the long survivors. The exact value of intraventricular and systemic therapy in patients with MC still has to be determined.     

Clinical relevance of the expression of the CD31 ligand for CD38 in patients with B-cell chronic lymphocytic leukemia

BACKGROUND: CD31 (platelet endothelial cell adhesion molecule-1 [PECAM-1]) is the ligand for CD38, a transmembrane glycoprotein that is expressed on the surface of leukemic cells in many patients with B-cell chronic lymphocytic leukemia (B-CLL). In a previous study, the authors showed that CD38 expression was correlated with a poor prognosis in patients with B-CLL. In the current study, blood samples from patients with B-CLL were examined to identify CD31 surface marker expression, and CD31 expression was correlated with several other known prognostic variables, including CD38. METHODS: Using flow cytometry, peripheral blood samples from 120 patients with B-CLL were analyzed for CD31 and CD38 expression on CD19 positive leukemic B cells. RESULTS: Thirteen of 120 patients (11%) had CD31 expression on < 20% of their B cells, and the remaining patients had various levels of CD31 expression. The median expression of CD31 was 76% of leukemic, CD19 positive cells. Levels of CD31 expression were not correlated with survival outcomes or with any of the known prognostic parameters when all patients were considered. Patients who had high CD38 expression (>or= 20%), as expected, had significantly shorter survival (P = 0.001) compared with patients who had low CD38 expression (< 20%). However, in patients with low CD38 expression, a subgroup with low CD31 expression (< 76%) had significantly longer survival compared with the survival for the entire group (P = 0.0001). Moreover, the survival pattern of patients with low CD38 expression and high CD31 expression was not significantly different from the survival pattern seen in patients with high CD38 expression. CONCLUSIONS: CD31 expression further defined a subgroup of patients with B-CLL who had a different survival outcome. Defining the interaction between CD31 expression and CD38 expression in patients with CLL will require further exploration.     

Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89.

PURPOSE: To evaluate a multimodal approach including surgery and cisplatinum chemotherapy for treatment of children with malignant sacrococcygeal germ cell tumors (GCT) and to compare adjuvant and neoadjuvant strategies in advanced tumors. PATIENTS AND METHODS: Between 1983 and 1995, 71 patients with malignant sacrococcygeal GCT were prospectively enrolled onto the German protocols for nontesticular GCT Maligne Keimzelltumoren 83/86 and 89. Five patients who received no chemotherapy (n = 2) or nonplatinum chemotherapy (n = 2) or who did not undergo tumor resection (n = 1) were excluded from this analysis. Among the 66 patients analyzed were 14 boys and 52 girls. The median age was 17.4 months (range, 7 months to 119 months). Median follow-up was 79 months (range, 4 months to 145 months). RESULTS: Fifty-two patients presented with locally advanced stage T2 tumors, and 30 patients had distant metastases at diagnosis. Patients received a median of eight cycles (range, four to nine cycles) of cisplatinum-based chemotherapy. Thirty-five patients underwent tumor resection at diagnosis and received adjuvant cisplatinum-based chemotherapy (group A). Thirty-one patients received up-front chemotherapy followed by delayed tumor resection (group B). Group B included more metastatic tumors than group A (group B, 19 of 31 patients; group A, 11 of 35 patients, P =.01). Preoperative chemotherapy facilitated complete tumor resections (group B, 20 of 31 patients; group A, five of 35 patients, P <.001) and avoided second-look surgery. Metastases at diagnosis and completeness of the first attempt of tumor resection were significant prognostic predictors; however, metastases were not predictive for patients treated with up-front chemotherapy. At 5 years follow-up, event-free survival was 0.76 +/- 0.05 (50 of 66 patients), and overall survival was 0.81 +/- 0.05 (54 of 66 patients). Four patients died as a result of therapy-related complications, and eight patients died of their tumors. Patients with locally advanced and metastatic tumors (T2b M1) fared better with neoadjuvant treatment [overall survival: 0.83 +/- 0.09 (16 of 19 patients) versus 0.45 +/- 0.15 (five of 11 patients), P =.01]. CONCLUSION: Even locally advanced and metastatic sacrococcygeal GCT can be successfully treated with up-front cisplatinum-based chemotherapy followed by delayed but complete tumor resection.     

Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study.

PURPOSE: Because interferon gave promising results in the management of metastatic renal cell carcinoma in the 1980s, a multicentric randomized controlled trial was planned to compare adjuvant recombinant interferon alfa-2b (rIFNalpha2b) with observation after radical nephrectomy in patients with Robson stages II and III renal cell carcinoma. Overall and event-free survival were to be evaluated together with prognostic factors. PATIENTS AND METHODS: Overall and event-free survival curves for 247 patients (124 controls and 123 treated) were estimated by the Kaplan-Meier method and compared using the log-rank test. Cox's multiple regression models were adopted to perform a joint analysis of treatment and prognostic factors. RESULTS: The 5-year overall and event-free survival probabilities were 0.665 and 0.671, respectively, for controls and 0.660 and 0.567, respectively, for the treated group; the differences were not statistically significant (2P = .861 for overall and 2P = .107 for event-free survival with the log-rank test). Regarding prognostic factors, only grade, pT, and pN demonstrated a significant prognostic role. First-order interactions of treatment with pT and pN category were investigated; a significant interaction was found between pN and treatment. A harmful effect of rIFNalpha2b in the 97 treated pN0 patients and a protective effect in the 13 treated pN2/pN3 patients were statistically significant. CONCLUSION: Adjuvant rIFNalpha2b is not indicated after radical nephrectomy for renal cell carcinoma. The protective effect in the small group of pN2/pN3 patients requires further investigation.     

Is invasive lobular carcinoma different from invasive ductal carcinoma?

AIMS: The purpose of this study is to determine whether the histopathologic features and outcome in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are different, and whether the histologic type is a prognostic factor for outcome. METHODS: A retrospective cohort study was conducted in consecutive 510 stage I/II breast carcinoma patients who underwent modified radical mastectomy. The features of 65 patients with ILC were compared with those of 445 patients with IDC. In patients with median follow-up period of 44 months, univariate and multivariate prognostic factor analyses for cancer-specific death and relapse were carried out. RESULTS: The median ages in patients with ILC and those with IDC were 52 and 41 (P=0.04). Tumor size, estrogen receptor positive expression and nodal positivity were not significantly different between the histologic types. Patients with ILC had more frequently (81.5%) low grade tumors and less lymphatic vascular invasion (9.3%) in primary tumor than those with IDC (P<0.05). Whereas the rates of 5-year overall survival were 94% in ILC and 90% in IDC, the rates of 5-year event-free survival were 71 and 67%, respectively (P=NS). Multivariate analyses in all patients demonstrated that tumor size, pathologic lymph node status and age at diagnosis were the most important prognostic factors for overall and event-free survival. Histologic type was not statistically significant for both outcomes. CONCLUSIONS: Although patients with ILC had older age, low grade tumor and less lymphatic vascular invasion, they had no survival advantage comparing with their counterparts. Histologic type was not an independent prognostic factor for outcome.     

Advanced soft-tissue sarcoma: a disease that is potentially curable for a subset of patients treated with chemotherapy

Adult patients with metastatic or locally advanced irresectable soft-tissue sarcoma (ASTS) are generally considered as incurable. Whether some of these patients achieve long-term survival after first-line treatment with chemotherapy is not known. Patients with ASTS still alive 5 years after initial treatment with a doxorubicin-containing regimen, i.e. long-term survivors, were analysed among the 2187 patients included in first-line chemotherapy protocols between 1976 and 1990 in seven trials of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC STBSG) group. 1888 patients were followed for at least 5 years. The initial clinical characteristics and the outcome of the long-term survivors were investigated. 66 of the 1888 patients were alive at 5 years and the projected 5-year survival was 8% in this series. Age or histological subtypes were similar in the long-term survivors compared with the other patients. The percentages of females (69%), of grade 1 tumours (35%), of patients with an initial performance status (PS) of 0 (63%) were significantly higher in the long-term survivors while liver metastasis (6% versus 21%) were significantly less frequent. Long-term survivors were observed in all subgroups of patients. 31, 31, 31 and 6% of the long-term survivors were in complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, after the first-line regimen. A CR to a doxorubicin-containing regimen was the major parameter correlated to 5-year survival. In multivariate analysis using a logistic model, independent parameters correlated to 5-year survival were PS, female gender, grade I tumours, and the achievement of a CR after first-line treatment, which was retained as the most powerful predictor for 5-year survival. 10 of the 66 patients died after 5 years in this series, including 8 patients in PD or SD after first-line treatment versus 2 patients in PR or CR (P=0.01). 8% of patients with ASTS are alive 5 years after first-line chemotherapy with a doxorubicin-containing regimen. Long-term survivors are observed in all prognostic subgroups of patients, in particular those achieving a CR to first-line chemotherapy.     

CXCL12 Expression is Predictive of a Shorter Time to Tumor Progression in Low-Grade Glioma: A Single-Institution Study in 50 Patients

Summary The clinical course of 50 patients with low-grade glioma (31 male, 19 female) undergoing surgery at a single Institution from 1992 to 1996 was analyzed in relationship with known prognostic factors as far as time to tumor progression (TTP) and survival time (ST) are concerned. Moreover, microvessel density (MVD) and expression of the angiogenesis-related chemokine CXCL12 were investigated in surgical specimens. Age at diagnosis ranged from 1 to 68 years (median 30). Histology revealed 11 fibrillary, 6 protoplasmatic, 5 gemistocytic astrocytoma, 18 oligoastrocytoma and 10 oligodendroglioma. Mean follow-up was 86 months. Four patients were lost to follow-up. Of the remaining 46, twenty-four have shown disease progression and 14 have died. Median overall survival was not achieved; an estimated 75% percentage of survivors was found at 78 months. Complete gross tumor removal was associated to a longer TTP (P = 0.04 logrank). Of the investigated immunohistochemical parameters, while MVD was not predictive of subsequent TTP, expression of CXCL12 was associated with a significantly shorter TTP (P = 0.01 logrank): this predictive value remained significant (P = 0.02) at multivariate analysis. The data suggest the possible prognostic value for CXCL-12 (an angiogenesis- and tumor-growth-related chemokine) on TTP in low-grade gliomas.     

Relationship between time interval from primary surgery to the start of taxane- plus platinum-based chemotherapy and clinical outcome of patients with advanced epithelial ovarian cancer: results of a multicenter retrospective Italian study.

PURPOSE: To assess whether the interval from primary surgery to the start of taxane- plus platinum-based chemotherapy has any impact on the clinical outcome of advanced ovarian cancer patients. PATIENTS AND METHODS: The study was conducted on 313 patients who underwent surgery followed by taxane- plus platinum-based chemotherapy. The median follow-up of survivors was 30.7 months (range, 6 to 109 months). RESULTS: The 25%, 50%, and 75% quantiles of intervals from surgery to the start of chemotherapy were 11, 21, and 31 days, respectively. After the sixth cycle, 102 patients achieved a pathologic complete response at second-look surgery and 98 obtained a clinical complete response but were not submitted to second-look surgery. Taking into consideration the best assessed response, a complete (either clinical or pathologic) response was found in 200 patients. Residual disease (< or = 1 v > 1 cm; P < .0001) and ascites (absent v present; P = .003) were independent predictive factors for achieving a complete response, whereas residual disease (P = .001) and stage (IIc to III v IV; P = .04) were independent prognostic variables for survival. Conversely, statistical analyses failed to detect significant differences in complete response rates and survival among patients with an interval from surgery to chemotherapy shorter than 11 days, 12 to 21 days, 22 to 31 days, and longer than 31 days. CONCLUSION: The interval from surgery to the start of taxane- plus platinum-based chemotherapy seems to have neither a predictive value for response to treatment nor a prognostic relevance for survival of advanced ovarian cancer patients.     

术前血小板、血浆纤维蛋白原及D-二聚体水平与小细胞肺癌预后的相关性分析

目的:回顾性分析术前血小板（platelet,PLT）、血浆纤维蛋白原（fibrinogen,Fib）及D-二聚体（D-dimer,D-D）水平对小细胞肺癌（SCLC）患者预后的影响。方法:选取2005年1月至2017年12月在中日友好医院初次就诊的57例SCLC患者术前血小板、血浆纤维蛋白原及D-二聚体等指标,所有患者均经组织病理学确诊。采用SPSS 25.0统计软件对相关临床病理因素及生存期进行分析。结果:术前血小板、血浆纤维蛋白原及D-二聚体水平升高的发生率分别为7.0%、31.6%、19.3%,术前血小板和/或血浆纤维蛋白原和/或D-二聚体水平升高的SCLC患者术后生存期有下降趋势。单因素分析提示,卡氏评分（P=0.038）、TNM分期（P=0.001）、淋巴结转移（P=0.049）及术前D-二聚体水平（P=0.003）均与 SCLC预后相关;多因素分析提示,TNM分期（P=0.005）、术前D-二聚体水平（P=0.021）为 SCLC的独立预后因素,TNM分期为Ⅲ期、术前D-二聚体水平升高的SCLC患者预后较差。结论:术前伴有高血凝状态的SCLC患者预后较差,术前D-二聚体水平测定可作为SCLC预后预测的潜在指标,具有一定的临床意义。     

Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling.

EXPERIMENTAL DESIGN: To determine whether the clinical benefit of complete remission (CR) may depend on prognostic subgroups of patients with multiple myeloma. PATIENTS AND METHODS: Newly diagnosed patients with myeloma received a tandem autotransplant regimen. Using multivariate regression analyses, we examined the prognostic implications of time-dependent onset of CR on overall survival and event-free survival in the context of standard prognostic factors (SPF) and gene expression profiling-derived data available for 326 patients. RESULTS: CR benefited patients regardless of risk status when only SPFs were examined. With knowledge of gene array data, a survival (and event-free survival) benefit of CR only pertained to the small high-risk subgroup of 13% of patients (hazard ratio, 0.23; P = 0.001), whereas the majority of patients with low-risk disease had similar survival expectations whether or not CR was achieved (hazard ratio, 0.68; P = 0.128). CONCLUSIONS: Access to gene expression information permitted the recognition of a small very high-risk subgroup of 13% of patients, in whom prolonged survival critically depended on achieving CR. Absence of such benefit in the remainder should lead to a reassessment of clinical trial designs that rely on this end point as a surrogate for long-term prognosis.     

骨和软组织肿瘤的3.0T磁共振磷谱变化研究

目的 探讨骨和软组织肿瘤磁共振磷谱(31P-MRS)的变化特点.方法 对41例经病理证实的骨和软组织肿瘤患者的18个良性肿瘤病灶、28个恶性肿瘤病灶及其相邻部位正常肌肉组织,应用3.0T MR机进行31P-MRS分析,测量波谱中磷酸单酯(PME)、无机磷(Pi)、磷酸二酯(PDE)、磷酸肌酸(Pcr)、三磷酸腺苷γ-峰(γ-ATP)、α-峰(α-ATP)和β-峰(β-ATP)的峰下面积.分别以β-ATP、三磷酸核苷(NTP)和Pcr为参照,计算各代谢产物的相对比值.根据Pi相对于Pcr化学位移的变化计算细胞内pH值.结果 良、恶性肿瘤组中Pcr/PME、PME/NTP与正常对照组比较,差异均有统计学意义(P<0.05).良、恶性肿瘤组中PME/β-ATP与PME/NTP比较,差异有统计学意义(P<0.05).结论 Pcr/PME和PME/NTP是诊断骨和软组织肿瘤的潜在指标,PME/β-ATP和PME/NTP是鉴别骨和软组织肿瘤良、恶性的潜在指标.     

Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome--the French pediatric experience

BACKGROUND: The objective of this report was to estimate long-term outcome and prognostic factors in children and adolescents who presented with metastatic osteosarcoma at diagnosis. Patients were treated in six French pediatric oncology centers with surgery and multiagent chemotherapy, mainly with high-dose methotrexate. Their medical records were reviewed retrospectively. METHODS: The medical records of patients who were treated for metastatic osteosarcoma from 1987 to 2000 were reviewed. Patients were treated with the chemotherapy regimens recommended for nonmetastatic disease in children (the French Society of Pediatric Oncology OS 87 and OS 94 protocols) or, in a few patients, with other chemotherapy regimens. Surgical excision of the primary tumor and, when possible, of all metastatic sites was performed based on a personalized assessment of each patient's situation. RESULTS: Seventy-eight patients age < 20 years were treated. Forty-six patients (59%) had only 1 metastatic site (35 to the lungs and 11 to bone). Twenty-eight patients (36%) achieved a complete remission after combination chemotherapy and surgery. The event-free survival and overall survival rates at 5 years were 14% and 19%, respectively. To date, 14 patients (18%) have remained alive with a median follow-up of 112 months. Pretreatment features associated with a shorter event-free survival in the multivariate analysis were metastasis to at least two organs and high alkaline phosphatase level. Patients with at least 1 of these poor prognostic factors had a 2.6% event-free survival rate at 5 years despite treatment. CONCLUSIONS: The survival of patients with metastatic osteosarcoma were treated with conventional chemotherapy and surgery remained very poor. Patients should be classified into different prognostic groups and treated accordingly. New therapeutic approaches are warranted to improve the prognosis for patients with the most severe disease.     

The predictive value of initial cytostatic response in primary unresectable rhabdomyosarcoma in children

The relation between the initial tumour regression produced by chemotherapy and the later event-free survival was studied in a prospective multicentre study on soft-tissue sarcomas in children. The event-free survival rate in patients with complete remission after seven weeks of chemotherapy was 95%; in patients with incomplete tumour reduction of greater than 2/3, 61%; and in patients with tumour reduction of less than 2/3 but greater than 1/3, 31%. Patients with partial remission at week 7, who achieved complete remission by week 16 after additional chemotherapy had an event-free survival rate of 64%. A multivariate analysis suggested that the response per unit of time was an important prognostic factor.