Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a retrospective analysis of children with metastatic soft tissue sarcoma (STS) registered in the major European STS studies: the SIOP MMT 75, the German CWS 1981 and 1986 studies, the Italian STS study, and the United Kingdom Children's Cancer Study Group centres in Britain. One hundred forty-six patients out of 164 were evaluable in this analysis. The median age was 7 years (1-18) and the male/female ratio was 1.3:1. The median follow-up was 80 months (7-171). The most common site of the primary tumor was the extremity (28%), which correlated well with the high preponderance (39%) of the alveolar type of RMS (aRMS). There was no dominant combination of metastatic sites and the most common single organ with metastasis was the lung (41%). Since the therapy depended on the country and period in which the patient was treated, we did not analyse the outcome and therapy together. Complete remission was achieved in 50% of the cases. Those with aRMS had a good chance of achieving CR (61%) but the majority of these patients relapsed (78%). The median time needed to relapse was 243 days (53 days to 47 months) for all patients. Analysis of the site of the primary tumor showed that the CR rate was best in the GU non-BP site (62%) and worst in PM cases (35%). The overall survival and DFS rate were 18% and 15%, respectively. The GU non-BP patients had a DFS rate of 50%, while the rate for all other sites varied between 12% and 18%. A total of 24 patients remained in CCR. The majority of them had embryonal type of RMS and metastases in only one anatomic site. Our analysis indicates that the best chance of prolonged survival was in metastatic GU non-BP cases, patients with embryonal type RMS, and those with metastases in only one organ. To try to improve the treatment of metastatic STS, a prospective European cooperative study was started in 1989.
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PMID:Metastatic rhabdomyosarcoma and histologically similar tumors in childhood: a retrospective European multi-center analysis. 157 30

Between 1968 and 1980, 107 consecutive patients with Ewing's sarcoma of bone were entered on three sequential combined modality treatment protocols (S2, S3, S4) at the National Cancer Institute (NCI). Protocol treatment involved 4 cycles of two drug [cyclophosphamide (CTX) and vincristine (VCR)] or three drug [CTX and VCR with either actinomycin-D (ACT-D) or doxorubicin (ADR)] regimens and local irradiation (50 Gy) to the involved bone. Eighty patients presented with localized disease and 27 patients had metastatic disease at presentation, including 11 patients with multiple metastatic sites. With a median potential follow-up of greater than 15 yrs (range 8-20 yrs), 28 pts (27%) remain alive. Disease-free (DFS) and overall survival (OS) decreased most rapidly during the initial 5 yrs of follow-up with 5-yr DFS of 29% and 5-yr OS of 39%. Only two patients with metastases at presentation are long term (greater than 5 yr) survivors. For localized disease patients, the 2, 5, 10, and 15 yr DFS and OS are 52%, 37%, 35%, and 33% DFS and 68%, 51%, 39%, and 34% OS, respectively. Eleven patients relapsed locally as the first site of failure. Using the Cox proportional hazards model, four significant variables for both DFS and OS were recognized, including metastatic disease at presentation, age greater than 25 yrs, high LDH in localized disease patients, and central primary tumor in localized disease patients in decreasing order of significance. We conclude that a majority of these patients with Ewing's sarcoma of bone relapsed within 5 yrs of presentation although late relapse (5-15 yrs) did occur. Local failure occurred in 20% of patients using these combined modality treatments but had no impact on overall survival.
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PMID:Long-term follow-up of Ewing's sarcoma of bone treated with combined modality therapy. 199 54

Forty-four evaluable, previously untreated patients with small cell lung cancer were treated with two courses of induction chemotherapy consisting of POCC. Subsequently, all limited-disease patients and extensive-disease patients in CR received 4,000 to 5,000 cGy irradiation over 4 to 5 weeks (or the equivalent) to the primary tumor, mediastinum and supraclavicular areas and 3,000 cGy prophylactic cranial irradiation during 2 weeks. All patients received maintenance chemotherapy for a full year after CR or until disease progression. Eleven continued POCC while 33 received vinblastine, cyclophosphamide, and either adriamycin or methotrexate on an alternating schedule (VCMA). For the 20 limited-disease patients, the CR rate was 70% and the PR rate was 20%. Median survival was 22 months, local control was 62%, 2-year DFS was 35% and 3-year DFS was 20%. Of the 24 extensive-disease patients only 21% achieved CR and 54% achieved PR. Median survival was only 8 months and there were no disease-free survivors at 2 years. Toxicity was moderate with nausea and vomiting in all patients, and there were two deaths from myelosuppression in the group that received POCC maintenance therapy; there were no drug-related deaths in the VCMA group. Since these results are similar to those obtained with simpler regimes, we cannot recommend our regimen for the treatment of small cell lung cancer. The optimal treatment for this disease has yet to be elucidated.
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PMID:Chemotherapy induction, consolidation radiotherapy and maintenance alternating chemotherapy in small cell carcinoma of the lung. 284 98

To bring to the fore the most important prognostic factors in Ewing's sarcoma (ES) with current protocols, we studied the classical prognostic factors, dose intensity (DI) of actual received drugs, age and histological response to induction therapy and their correlation in 39 patients with localized ES treated from 11/85 to 06/95 to identify eventual predictors of event-free survival (EFS). Inclusion criteria were age 35 yr or less, definitive local treatment by our team and chemotherapy including at least 4 drugs: vincristine (VCR), dactinomycin (DACT), doxorubicin (DOXO) cyclophosphamide (CPX). The endpoint was the absence of relapse. Parameters related to the status of patients were tested using the Chi square test or Fisher's exact test. The non parametric Kruskal-Wallis test was used for quantitative data. When necessary stratified analysis was done using the Mantel Cox test. With a median follow-up of 7 yr, overall survival (OS) and EFS were both 67% at 7 yr. According to univariate analysis, the significant predictors of survival were the DI of VCR and DACT, the histological response to preoperative chemotherapy (CT), the patient's age (< 18 yr DFS: 84%; > 18 yr DFS: 38%). The risk of metastases was almost tenfold higher in patients with low received DI of VCR (DFS 40% versus 95%) and of DACT (DFS 48% versus 94%). The prognostic value of primary tumor characteristics (tumoral volume or location) was erased by the comprehensive treatment. Following multivariate analysis, the actual received DI of VCR (p < 0.02) and DACT (p < 0.03) and the histological response to preoperative CT (p < 0.05) were retained as the only significant independent predictors of EFS. Taking into account the actual received DI of VCR and DACT, the prognostic value of age disappears. In conclusion, this study points out the main role of the drug DI in ES (particularly VCR and DACT) and of histological response to preoperative CT.
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PMID:Prognostic factors in patients with localized Ewing's sarcoma: the effect on survival of actual received drug dose intensity and of histologic response to induction therapy. 937 91

The purpose of this study was to assess the prognostic significance of the detection of circulating melanoma cells by reverse transcriptase-PCR in long-term clinically disease-free melanoma patients. Patients with melanoma who were free of clinical relapse for at least 6 months after primary tumor diagnosis were included and prospectively followed. Tyrosinase mRNA in peripheral blood from these patients was assayed by reverse transcriptase-PCR at the time of their inclusion in the study. One hundred six blood samples from 57 melanoma patients were analyzed. The median time between melanoma diagnosis and inclusion in the study was 24 months (range, 7-51 months). The median follow-up time calculated from the time of inclusion in the study was 27 months (range, 11-36 months). Tyrosinase mRNA in blood was detected in 10 (17.5%) of 57 patients: 2 (18%) of 11 stage I patients, 6 (19%) of 33 stage II patients, and 2 (15%) of 13 stage III patients. Actuarial 2-year DFS was 89% for the tyrosinase-negative patients versus 30% for the positive patients (P = 0.003). Actuarial 2-year OS was 97% for the tyrosinase-negative patients versus 72% for the positive patients (P = 0.001). Tyrosinase mRNA could be detected in the blood of a proportion of long-term disease-free melanoma patients, regardless of their initial clinical stage. The presence of late circulating melanoma cells in this selected group of clinically disease-free patients was significantly associated with a subsequent high risk of relapse and death.
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PMID:Prognostic significance of the detection of circulating malignant cells by reverse transcriptase-polymerase chain reaction in long-term clinically disease-free melanoma patients. 1043 90

We report on the clinical course and outcome of 28 patients, treated at The Istituti Ortopedici Rizzoli between 1995 and 1997 for osteosarcoma of the extremities metastatic to the lung at presentation. The treatment for these patients was the following: primary chemotherapy with cisplatin, adriamycin and high dose of methotrexate and ifosfamide followed by simultaneous resection of primary and metastatic lesions (when feasible), and further chemotherapy. After primary chemotherapy, lung metastases disappeared in 6 patients, whereas metastases in 3 remained surgically unresectable. These 9 patients received surgical treatment of the primary tumor only. In the remaining 19 patients, after chemotherapy, a simultaneous resection of the primary and metastatic tumor was performed. The resection of metastatic lesions was complete in 18 cases and incomplete in one. Three of the 4 patients who did not achieve a tumor-free status died in a few months and one is still alive with uncontrolled disease. With a median follow-up of 32 months (19-43) of the 24 patients who achieved remission, 12 (55%) remained continuously free of disease, 11 relapsed with new metastases and 1 died of chemotherapy-related toxicity. The 2-year DFS and OS were 36% and 53% respectively. These results are much worse than those achieved in 114 contemporary patients with localised disease (2-year DFS: 81%) treated in the same period and they are superimposible to the results achieved in 23 patients previously treated with the same protocol, but with standard dose of ifosfamide (2-year DFS: 32%). However, it must be underlined that, as regards prognosis, patients with metastatic disease at presentation are a hetero-geneous group. The DFS was significantly higher for patients with only one or two metastatic lesions than for patients with 3 or more lesions (2 year DFS: 78% vs. 28%). In 12 of the 19 patients who had a complete simultaneous resection of the primary and metastatic tumor, a strong correlation between the degree of necrosis of the primary and metastatic lesions was found. We conclude that in patients with osteosarcoma of the extremity with lung metastases at presentation: a) the combination of aggressive chemotherapy with simultaneous resection of primary and metastatic tumors works very well only for those patients who present with one or two metastatic nodules whereas for patients with 3 or more pulmonary metastases the prognosis is very poor; b) within the 4-drug regimen used in this study, the increment of ifosfamide dose from 10 g/m2 to 15 g/m2 for cycle does not improve prognosis; c) the strong correlation found between the histologic response of the primary tumor and metastases supports the strategy, largely used nowadays in the neoadjuvant treatment of osteosarcoma, of tailoring postoperative chemo-therapy on the basis of the primary tumor histologic response to preoperative chemotherapy.
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PMID:Neoadjuvant chemotherapy for osteosarcoma of the extremities with synchronous lung metastases: treatment with cisplatin, adriamycin and high dose of methotrexate and ifosfamide. 1067 83

Our purpose was to determine the predictive value of tumor biologic parameters in patients with HRPBC who received HDCT with ASCT as first-line treatment. From September 1992 to May 2000, 149 stage II or III HRPBC patients were enrolled in a single-arm trial using a tandem HDCT regimen followed by ASCT. Her2/neu, p53, Ki67 and bcl-2 protein expression was studied using immunohistochemic staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA index) and tumor cell proliferation (SPF) were measured by DNA flow cytometry. The relationship between these tumor biologic parameters, on the one hand, and DFS, DDFS and OS, on the other, was analyzed. With a median follow-up of 43 months (range 7-106), p53 protein accumulation (p = 0.000004), negative combined hormone receptor status (p = 0.003) and Her2/neu overexpression (p = 0.02) were significant negative predictors of OS in univariate analysis. A poorer DFS was associated with p53 positivity (p = 0.04) and nodal ratio > or = 0.8 (p = 0.008). Poorer DDFS was associated with p53 positivity (p = 0.03). In multivariate analysis, Her2/neu overexpression (RR = 3.86, 95% CI 1.48-10.1, p = 0.006) and p53 overexpression (RR = 6.06, 95% CI 2.22-16.52, p < 0.001) proved to be independent predictors of adverse OS. p53 overexpression was the only independent predictor of DFS (RR = 2.21, 95% CI 1.07-4.57, p = 0.03). p53 overexpression and Her2/neu overexpression are independent negative predictors of survival in HRPBC treated with HDCT. The adverse impact of these biologic features was probably not altered by HDCT. For HRPBC patients with tumors not overexpressing Her2/neu or p53, HDCT may be an appropriate approach to achieve long-term survival and tumor control.
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PMID:P53 is the strongest predictor of survival in high-risk primary breast cancer patients undergoing high-dose chemotherapy with autologous blood stem cell support. 1211 43

Synucleins are emerging as central players in the fundamental neural processes and in the formation of pathologically insoluble deposits characteristic of neurodegenerative diseases. However, synuclein gamma (SNCG), previously identified as a breast cancer specific gene (BCSG1), is also highly expressed in breast carcinomas, but not expressed in normal or benign breast tissues. We analyzed SNCG gene expression in 93 clinical breast specimens and associated it with clinical outcome. Overall SNCG mRNA expression was detectable in 36% breast cancers. However, 81% of stage III/IV breast cancers were positive for SNCG expression, while only 15% of stage I/II breast cancers were positive for SNCG expression. In contrast, SNCG was undetectable in benign breast lesions. Expression of SNCG in the primary tumor also significantly associated with lymph node involvement and metastasis. There was no significant correlation between SNCG gene expression and age, menstruation, and status of ER, PR, PCNA, and HER-2. Patients whose tumors expressed SNCG had a significantly shorter DFS and a high probability of death when compared with those whose tumors did not express SNCG. The hazard ratio of metastasis or recurrence according to the SNCG status was 4.515 (95% CI, 1,188-17.154; P = 0.027). Cox multivariate analysis showed that SNCG had independent prognostic significance above and beyond conventional variables. This study suggests that the expression of SNCG is an independent predictive marker for recurrence and metastasis in breast cancer progression. SNCG is expected to be a useful marker for breast cancer progression and a potential target for breast cancer treatment.
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PMID:Expression of neuronal protein synuclein gamma gene as a novel marker for breast cancer prognosis. 1682 Oct 81

Melanoma patients with clinically evident regional lymph node metastases are treated with therapeutic lymph node dissections (TLNDs). The aim of this study was to evaluate morbidity and mortality following TLND in our institution. Moreover, disease-free (DFS) and overall (OS) survival were evaluated and factors that influence prognosis after TLND were assessed. Between 1982 and 2005, 236 patients underwent a TLND. Patients, who received a palliative LND or a sentinel node procedure, were not included. The median Breslow thickness was 2.4mm. Ulceration was present in 23% of patients and unknown in 66%. 37 patients had unknown primary tumors. There were 129 ilio-inguinal, 50 axillary and 61 cervical dissections performed. 37% of the patients experienced at least one operation related complication. The most frequently seen complications were wound infections/necrosis and chronic lymph edema. Ilio-inguinal dissection patients experienced significantly more complications and a longer duration of hospitalization compared to axillary or cervical patients. The duration of hospitalization has been reduced in recent years from 12 to 5days. The mean follow-up was 29months. Kaplan-Meier estimated 5-year regional control was 79%, 5-year DFS was 19% and 5-year OS was 26%. The number of positive lymph nodes, the site of the primary tumor and extra capsular extension (ECE) were independent prognostic factors for DFS and only site and ECE for OS. In conclusion, TLND for stage III melanoma is accompanied with considerable short-term complications, and can achieve regional control and potential curation in approximately one in every four patients.
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PMID:Morbidity and prognosis after therapeutic lymph node dissections for malignant melanoma. 1716 77

Bone marrow (BM) involvement in diffuse large B-cell lymphoma (DLBCL) can be morphologically discordant from the primary tumor. Concordant BM infiltration has been shown associated with a poorer outcome in patients treated with CHOP. In order to evaluate tumor-related factors leading to BM involvement in DLBCL, we performed an integrated analysis of i) genomic profiles obtained with a high-density genome wide SNP-based arrays ii) immunomorphological and iii) clinical data from 133 patients uniformly treated with R-CHOP. BM infiltration was found in 27 of 133 (20%) cases; and it was concordant in 18/27 (67%) cases. Concordant infiltration, but not discordant, influenced negatively OS, PFS and DFS and was associated with higher serum LDH, lower CR and higher PD rates. No association with cell of origin was found between BM+ and BM- DLBCL. As compared with BM- cases, BM+ DLBCL showed absence of 7q gain.
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PMID:Diffuse large B-cell lymphoma with concordant bone marrow involvement has peculiar genomic profile and poor clinical outcome. 2063 29


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