Expression of HER2/erbB-2 Correlates With Survival in Osteosarcoma

1999 ◽  
Vol 17 (9) ◽  
pp. 2781-2781 ◽  
Author(s):  
Richard Gorlick ◽  
Andrew G. Huvos ◽  
Glenn Heller ◽  
Alex Aledo ◽  
G. Peter Beardsley ◽  
...  
Keyword(s):  
San Francisco ◽  
Preoperative Chemotherapy ◽  
Clinical Stage ◽  
Cancer Center ◽  
Event Free Survival ◽  
Histologic Response ◽  
P53 Expression ◽  
Free Survival ◽  
P Glycoprotein ◽  
Initial Biopsy

PURPOSE: In osteosarcoma, prognostic factors at diagnosis other than clinical stage have not been clearly identified. The aim of this study was to determine whether human epidermal growth factor receptor 2 (HER2)/erbB-2, p-glycoprotein, or p53 expression correlated with histologic response to preoperative chemotherapy or event-free survival. PATIENTS AND METHODS: We performed a retrospective immunohistochemical study on material obtained from patients treated on the Memorial Sloan-Kettering Cancer Center T12 protocol between 1986 and 1993. Paraffin-embedded tissue was identified from 53 patients (73% of patients enrolled onto protocol) and stained for HER2/erbB-2, p53, and p-glycoprotein expression using standard monoclonal antibodies and methods. RESULTS: At the time of initial biopsy, 20 (42.6%) of 47 samples demonstrated high levels of HER2/erbB-2 expression. Higher frequencies of expression were observed in samples from patients with metastatic disease at presentation and at the time of relapse. Expression of HER2/erbB-2 correlated with a significantly worse histologic response (P = .03). In patients presenting with nonmetastatic disease, expression of HER2/erbB-2 at the time of initial biopsy was associated with a significantly decreased event-free survival (47% v 79% at 5 years, P = .05). p53 and p-glycoprotein expression did not correlate with histologic response or patient event-free survival. CONCLUSION: The correlation of HER2/erbB-2 expression with histologic response to preoperative chemotherapy and event-free survival in this study suggests that HER2/erbB-2 should be evaluated prospectively as a prognostic indicator. The correlation also suggests that clinical trials of antibodies that target this receptor, such as recombinant humanized anti-HER2 monoclonal antibody (Herceptin; Genentech, San Francisco, CA), should be considered for the treatment of osteosarcoma.

Intensification of preoperative chemotherapy for osteogenic sarcoma: results of the Memorial Sloan-Kettering (T12) protocol.

1998 ◽  
Vol 16 (7) ◽  
pp. 2452-2458 ◽  
Author(s):  
P A Meyers ◽  
R Gorlick ◽  
G Heller ◽  
E Casper ◽  
J Lane ◽  
...  
Keyword(s):  
Preoperative Chemotherapy ◽  
Osteogenic Sarcoma ◽  
Cancer Center ◽  
High Dose ◽  
Event Free Survival ◽  
Histologic Response ◽  
Free Survival ◽  
Subsequent Event ◽  
Localized Disease ◽  
Resected Primary Tumor

PURPOSE It has been observed previously in osteosarcoma (OS) that the degree of necrosis of the resected primary tumor following a period of preoperative chemotherapy is predictive of subsequent event-free survival (EFS). The aim of this study was to determine if more intensive preoperative chemotherapy would increase the proportion of patients with a good histologic response and improve EFS. PATIENTS AND METHODS Seventy-three patients with OS were treated at Memorial-Sloan Kettering Cancer Center (MSKCC) on the T12 protocol between 1986 and 1993. Patients were randomized between therapy based on the T10 protocol and therapy with more intensive preoperative chemotherapy. The more intensive preoperative regimen consisted of two courses of cisplatin (CDDP) and doxorubicin (DOX) in addition to the usual preoperative regimen of high-dose methotrexate (HD MTX) and bleomycin, cyclophosphamide, and dactinomycin (BCD). RESULTS The regimen with more intensive preoperative chemotherapy achieved a modest increase in the proportion of patients with a good histologic response (44% with a grade III or IV histologic response v 37% in the control arm, 33% with grade IV histologic response v 13% in the control arm). EFS continued to correlate with histologic response. The actuarial 5-year EFS in patients with localized disease was 78% for the regimen with more intensive preoperative chemotherapy and 73% for the control arm. CONCLUSION Despite modest increases in the proportion of patients with good histologic response with intensified preoperative chemotherapy, no improvement in EFS was observed.

Nomograms to Predict Pathologic Complete Response and Metastasis-Free Survival After Preoperative Chemotherapy for Breast Cancer

2005 ◽  
Vol 23 (33) ◽  
pp. 8331-8339 ◽  
Author(s):  
Roman Rouzier ◽  
Lajos Pusztai ◽  
Suzette Delaloge ◽  
Ana M. Gonzalez-Angulo ◽  
Fabrice Andre ◽  
...  
Keyword(s):  
Preoperative Chemotherapy ◽  
Proportional Hazards ◽  
Estrogen Receptor Status ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Cox Proportional Hazards ◽  
Cancer Center ◽  
Free Survival ◽  
Validation Set

Purpose To combine clinical variables associated with pathologic complete response (pCR) and distant metastasis–free survival (DMFS) after preoperative chemotherapy (PC) into a prediction nomogram. Patients and Methods Data from 496 patients treated with anthracycline PC at the Institut Gustave Roussy were used to develop and calibrate a nomogram for pCR based on multivariate logistic regression. This nomogram was tested on two independent cohorts of patients treated at the M.D. Anderson Cancer Center. The first cohort (n = 337) received anthracycline; the second cohort (n = 237) received a combination of paclitaxel and anthracycline PC. A separate nomogram to predict DMFS was developed using Cox proportional hazards regression model. Results The pCR nomogram based on clinical stage, estrogen receptor status, histologic grade, and number of preoperative chemotherapy cycles had good discrimination and calibration in the training and the anthracycline-treated validation sets (concordance indices, 0.77, 0.79). In the paclitaxel plus anthracycline group, when the predicted pCR rate was less than 14%, the observed rate was 7.5%; for a predicted rate of ≥ 38%, the actual rate was 85%. For a predicted rate between 14% to 38%, the observed rates were 50% with weekly and 27% with 3-weekly paclitaxel. This indicates that patients with intermediate chemotherapy sensitivity benefit the most from the optimized schedule of paclitaxel. Patients unlikely to achieve pCR to anthracylines remain at low probability for pCR, even after inclusion of paclitaxel. The nomogram for DMFS had a concordance index of 0.72 in the validation set and outperformed other prediction tools (P = .02). Conclusion Our nomograms predict pCR accurately and can serve as a basis to integrate future molecular markers into a clinical prediction model.

scholarly journals Mutant p53 and Twist1 Co-Expression Predicts Poor Prognosis and Is an Independent Prognostic Factor in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yong-Qu Zhang ◽  
Fan Zhang ◽  
Yun-Zhu Zeng ◽  
Min Chen ◽  
Wen-He Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Stage ◽  
Lymph Node Involvement ◽  
Mutant P53 ◽  
Breast Cancer Patients ◽  
P53 Expression ◽  
Free Survival ◽  
Node Involvement ◽  
Patient Prognosis

PurposeThe basic helix-loop-helix transcription factor (bHLH) transcription factor Twist1 plays a key role in embryonic development and tumorigenesis. p53 is a frequently mutated tumor suppressor in cancer. Both proteins play a key and significant role in breast cancer tumorigenesis. However, the regulatory mechanism and clinical significance of their co-expression in this disease remain unclear. The purpose of this study was to analyze the expression patterns of p53 and Twist1 and determine their association with patient prognosis in breast cancer. We also investigated whether their co-expression could be a potential marker for predicting patient prognosis in this disease.MethodsTwist1 and mutant p53 expression in 408 breast cancer patient samples were evaluated by immunohistochemistry. Kaplan-Meier Plotter was used to analyze the correlation between co-expression of Twist1 and wild-type or mutant p53 and prognosis for recurrence-free survival (RFS) and overall survival (OS). Univariate analysis, multivariate analysis, and nomograms were used to explore the independent prognostic factors in disease-free survival (DFS) and OS in this cohort.ResultsOf the 408 patients enrolled, 237 (58%) had high mutant p53 expression. Two-hundred twenty patients (53.9%) stained positive for Twist1, and 188 cases were Twist1-negative. Furthermore, patients that co-expressed Twist1 and mutant p53 (T+P+) had significantly advanced-stage breast cancer [stage III, 61/89 T+P+ (68.5%) vs. 28/89 T-P- (31.5%); stage II, 63/104 T+P+ (60.6%)vs. 41/104 T-P- (39.4%)]. Co-expression was negatively related to early clinical stage (i.e., stages 0 and I; P = 0.039). T+P+ breast cancer patients also had worse DFS (95% CI = 1.217–7.499, P = 0.017) and OS (95% CI = 1.009–9.272, P = 0.048). Elevated Twist1 and mutant p53 expression predicted shorter RFS in basal-like patients. Univariate and multivariate analysis identified three variables (i.e., lymph node involvement, larger tumor, and T+P+) as independent prognostic factors for DFS. Lymph node involvement and T+P+ were also independent factors for OS in this cohort. The total risk scores and nomograms were reliable for predicting DFS and OS in breast cancer patients.ConclusionsOur results revealed that co-expression of mutant p53 and Twist1 was associated with advanced clinical stage, triple negative breast cancer (TNBC) subtype, distant metastasis, and shorter DFS and OS in breast cancer patients. Furthermore, lymph nodes status and co-expression of Twist1 and mutant p53 were classified as independent factors for DFS and OS in this cohort. Co-evaluation of mutant p53 and Twist1 might be an appropriate tool for predicting breast cancer patient outcome.

Localized Ewing Tumor of Bone: Final Results of the Cooperative Ewing’s Sarcoma Study CESS 86

2001 ◽  
Vol 19 (6) ◽  
pp. 1818-1829 ◽  
Author(s):  
M. Paulussen ◽  
S. Ahrens ◽  
J. Dunst ◽  
W. Winkelmann ◽  
G.U. Exner ◽  
...  
Keyword(s):  
High Risk ◽  
Tumor Volume ◽  
Ewing's Sarcoma ◽  
Central Axis ◽  
Event Free Survival ◽  
Histologic Response ◽  
Free Survival ◽  
Risk Patients ◽  
Standard Risk ◽  
Ewing Tumor

PURPOSE: Cooperative Ewing’s Sarcoma Study (CESS) 86 aimed at improving event-free survival (EFS) in patients with high-risk localized Ewing tumor of bone. PATIENTS AND METHODS: We analyzed 301 patients recruited from January 1986 to July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at central-axis sites qualified patients for “high risk” (HR, n = 241), and small extremity lesions for “standard risk” (SR, n = 52). Standard-risk patients received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating with actinomycin D (VACA); HR patients received ifosfamide instead of cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%), femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in 33% of cases and ≥100 mL in 67%. Local therapy was surgery (23%), surgery plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test, and risk factors were analyzed by Cox models. RESULTS: On May 1, 1999 (median time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did not differ between SR-VACA (0.52) and HR-VAIA (0.51, P = .92). Tumor volume of >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P = .0001) and poor histologic response (EFS, 0.38 v 0.64 for good responders; P = .0007) had negative impacts on EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients (2%) died under treatment, and four patients (1.3%) developed second malignancies. CONCLUSION: Fifty-two percent of CESS 86 patients survived after risk-adapted therapy. High-risk patients seem to have benefited from intensified treatment that incorporated ifosfamide.

scholarly journals Multiple gene promoter methylation and clinical stage in adjacent normal tissues: Effect on prognosis of colorectal cancer in Taiwan

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chih-Hsiung Hsu ◽  
Cheng-Wen Hsiao ◽  
Chien-An Sun ◽  
Wen-Chih Wu ◽  
Tsan Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Tumor Tissue ◽  
Clinical Stage ◽  
Methylation Status ◽  
Aberrant Methylation ◽  
Event Free Survival ◽  
Free Survival ◽  
Normal Tissues ◽  
Colorectal Cancer Patients

AbstractThis study provide an insight that the panel genes methylation status in different clinical stage tended to reflect a different prognosis even in matched normal tissues, to clinical recommendation. We enrolled 153 colorectal cancer patients from a medical center in Taiwan and used the candidate gene approach to select five genes involved in carcinogenesis pathways. We analyzed the relationship between DNA methylation with different cancer stages and the prognostic outcome. There were significant trends of increasing risk of 5-year time to progression and event-free survival of subjects with raising number of hypermethylation genes both in normal tissue and tumor tissue. The group with two or more genes with aberrant methylation in the advanced cancer stages (Me/advanced) had lower 5-year event-free survival among patients with colorectal cancer in either normal or tumor tissue. The adjusted hazard ratios in the group with two or more genes with aberrant methylation with advanced cancer stages (Me/advanced) were 8.04 (95% CI, 2.80–23.1; P for trend <0.01) and 8.01 (95% CI, 1.92–33.4; P for trend <0.01) in normal and tumor tissue, respectively. DNA methylation status was significantly associated with poor prognosis outcome. This finding in the matched normal tissues of colorectal cancer patients could be an alternative source of prognostic markers to assist clinical decision making.

scholarly journals Neoadjuvant Chemotherapy With Methotrexate, Cisplatin, and Doxorubicin With or Without Ifosfamide in Nonmetastatic Osteosarcoma of the Extremity: An Italian Sarcoma Group Trial ISG/OS-1

2012 ◽  
Vol 30 (17) ◽  
pp. 2112-2118 ◽  
Author(s):  
Stefano Ferrari ◽  
Pietro Ruggieri ◽  
Graziella Cefalo ◽  
Angela Tamburini ◽  
Rodolfo Capanna ◽  
...  
Keyword(s):  
Primary Phase ◽  
Pathologic Response ◽  
Limb Salvage Surgery ◽  
Hematologic Toxicity ◽  
Event Free Survival ◽  
Good Responder ◽  
Histologic Response ◽  
Free Survival ◽  
Group Trial

Purpose We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity. Patients and Methods Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m2, MTX 120 g/m2, CDP 600 mg/m2, and IFO 30 g/m2) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS). Results From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B. Conclusion IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM.

scholarly journals High expression of 5-hydroxymethylcytosine is associated with a more favorable hepatoblastoma prognosis in Chinese patients

2021 ◽  
Author(s):  
Junting Huang ◽  
Yang Hu ◽  
Huadong Chen ◽  
Binbin Chen ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Cox Regression ◽  
Prognostic Indicator ◽  
Chinese Patients ◽  
Cancer Center ◽  
Event Free Survival ◽  
Recurrence Rates ◽  
Tissue Samples ◽  
Free Survival ◽  
Kaplan Meier

Abstract Background To analyze associations between the strength of expression of 5-hydroxymethylcytosine (5hmC) and survival outcomes of Chinese hepatoblastoma patients. Methods We collected and analyzed clinical data of hepatoblastoma patients aged <15 years treated at the Sun Yat-Sen University Cancer Center or the First Affiliated Hospital of Sun Yat-sen University from Feb 2010 to Sept 2018. Patients were treated according to the Children's Oncology Group protocol. Specimens for pathology were collected by biopsy or surgical resection before initiation of chemotherapy. The level of expression of 5hmC was analyzed in tissue samples from 100 patients by immunohistochemistry. The prognostic value of 5hmC was evaluated by Cox regression and Kaplan-Meier analyses. Results We enrolled 100 patients with hepatoblastoma (median follow-up, 43.0 months; range, 18.4–131.6). The total recurrence rate was 30.0%. Three-year overall survival (OS) rates of high and low 5hmC expressors was 92.6%±3.6% and 80.3%±5.9%, respectively. Three-year event-free survival (EFS) of high and low expressors was 84.4%±5.1% and 49.8%±7.7%, respectively. Thus, high levels of 5hmC expression are associated with more favorable OS and EFS. Multivariate analysis indicated that 5hmC expression level was an independent prognostic indicator for OS and EFS. Conclusions Our findings showed that strong hepatoblastoma 5hmC expression was associated with lower recurrence rates and longer EFS and OS. Thus, 5hmC expression may have prognostic relevance in hepatoblastoma.

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