scholarly journals May P-glycoprotein status be used to stratify high-grade osteosarcoma patients? Results from the Italian/Scandinavian Sarcoma Group 1 treatment protocol

2006 ◽  
Author(s):  
Massimo Serra ◽  
Michela Pasello ◽  
Maria Manara ◽  
Katia Scotlandi ◽  
Stefano Ferrari ◽  
...  
Keyword(s):  
Treatment Protocol ◽  
High Grade ◽  
P Glycoprotein ◽  
High Grade Osteosarcoma ◽  
Group 1

ABCB1/P-glycoprotein (Pgp) expression as stratification factor for treatment of patients with non-metastaticextremity high-grade osteosarcoma: A merged analysis of an Italian (ISG) and a Spanish (GEIS) sarcoma groups' multicentric prospective trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11527-11527
Author(s):  
Emanuela Palmerini ◽  
Catalina Marquez ◽  
Cristina Meazza ◽  
Angela Tamburini ◽  
Gianni Bisogno ◽  
...  
Keyword(s):  
Poor Response ◽  
High Dose ◽  
High Grade ◽  
Histologic Response ◽  
P Glycoprotein ◽  
Metastatic Osteosarcoma ◽  
Diagnostic Biopsy ◽  
Prospective Trials ◽  
High Grade Osteosarcoma

11527 Background: Overexpression of ABCB1/P-glycoprotein (Pgp) predicts poor outcome in retrospective osteosarcoma series.Two prospective trials with Pgp expression and post-induction histologic response as stratification factors were activated in Italy (ISG/OS-2) and Spain (GEIS-33). Methods: Patients ≤ 40 years with extremity non-metastatic high-grade osteosarcoma were eligible. Analysisi of Pgp expression from diagnostic biopsy was centralized. Preoperatively, all patients received methotrexate, adriamycin, cisplatinum (MAP). Surgery was performed at week 8. All patients received a dose of adriamycin following surgery. In case of Pgp overexpression (Pgp+), mifamurtide (2 mg/m2 twice/week for 3 months then weekly for 6 months) was added after surgery, with 4 consecutive cycles of ifosfamide 3 gr/m2/day, day 1-5 (HDIFO) in case of poor histologic response (necrosis < 90%) to MAP. Patients without overexpression of Pgp (Pgp-) received MAP postoperatively, regardless the pathological response. From March 2013, an amendment increased high dose methotrexate cumulative dose from 60 g/m2 (5 cycles) to 120 mg/m2 (10 cycles). The post-amendment regimen was adopted in the observational prospective study by GEIS. Here we present the merged analysis of ISG/OS-2 patients treated post-amendment and GEIS-33. Results: From March 2013 to April 2018, 274 patients were included. Median age was 14 years (range 4-38), male/female: 163/111; 90 were Pgp-, 164 were Pgp+, 20 not evaluable. With a median follow-up of 48 months (1.3-78.5 months), the 3-year EFS and OS were 71.9% (95%CI 66-76.9) and 88% (95%CI: 83.2-91.5) respectively, with no inferior survival for Pgp positive patients and improved survival for good responders (Table). Conclusions: In this prospective uncontrolled study with a risk-adapted strategy for non-metastatic osteosarcoma, survival is superior to that of all ISG/GEIS previous series. The 3-year EFS of 71.9% compares favorably with other reports. Pgp+ patients performed well in this study, in which mifamurtide and HDIFO were added after a poor response to MAP. Clinical trial information: NCT01459484; NCT04383288. [Table: see text]

Value of P-Glycoprotein and Clinicopathologic Factors as the Basis for New Treatment Strategies in High-Grade Osteosarcoma of the Extremities

2003 ◽  
Vol 21 (3) ◽  
pp. 536-542 ◽  
Author(s):  
Massimo Serra ◽  
Katia Scotlandi ◽  
Gemma Reverter-Branchat ◽  
Stefano Ferrari ◽  
Maria C. Manara ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Tumor Volume ◽  
Proportional Hazards ◽  
Treatment Strategies ◽  
High Dose ◽  
Postoperative Phase ◽  
High Grade ◽  
Treatment Protocols ◽  
P Glycoprotein ◽  
High Grade Osteosarcoma

Purpose: To evaluate the prognostic value of P-glycoprotein and clinicopathologic parameters in a large series of high-grade osteosarcoma (OS) patients treated at the Rizzoli Institute. Patients and Methods: With the use of immunohistochemistry, P-glycoprotein was assessed in 149 patients with primary, nonmetastatic, high-grade OS who were homogeneously treated with chemotherapy protocols based on doxorubicin, high-dose methotrexate, and cisplatin and the addition of ifosfamide in the postoperative phase. Results: P-glycoprotein positivity was found in 47 of 149 cases (32%) and was significantly associated with a higher incidence of relapse and a worse outcome, as was age younger than 12 years and tumor volume greater then 150 mL at diagnosis. Multivariate analysis further confirmed the prognostic value of these parameters, which all were independent adverse prognostic factors. Event-free survival and proportional hazards regression analyses confirmed that overexpression of P-glycoprotein at clinical onset is the most important adverse prognostic factor for high-grade OS patients treated with these chemotherapy protocols. Conclusion: Increased P-glycoprotein levels, together with tumor volume and age, should be taken into consideration to identify, at time of diagnosis, subgroups of OS patients with a higher risk of recurrence. This subgroup identification will constitute the basis for drawing individualized treatment protocols on the basis of risk evaluation, with the aim of using more aggressive chemotherapy, or combination chemotherapy with other adjuvants, only in those patients for which more aggressive regimens are strictly necessary and warranted.

Prognostic Value of P-Glycoprotein in High-Grade Osteosarcoma

2007 ◽  
Vol 25 (30) ◽  
pp. 4858-4860 ◽  
Author(s):  
Massimo Serra ◽  
Piero Picci ◽  
Stefano Ferrari ◽  
Gaetano Bacci
Keyword(s):  
Prognostic Value ◽  
High Grade ◽  
P Glycoprotein ◽  
High Grade Osteosarcoma

scholarly journals Evaluation of P-glycoprotein, HER-2/ErbB-2, p53, and Bcl-2 in primary tumor and metachronous lung metastases in patients with high-grade osteosarcoma

Cancer ◽  
2004 ◽  
Vol 100 (9) ◽  
pp. 1936-1942 ◽  
Author(s):  
Stefano Ferrari ◽  
Franco Bertoni ◽  
Licciana Zanella ◽  
Elisabetta Setola ◽  
Patrizia Bacchini ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Lung Metastases ◽  
High Grade ◽  
P Glycoprotein ◽  
Her 2 ◽  
High Grade Osteosarcoma

Relationship between P-glycoprotein expression and p53 status in high-grade osteosarcoma.

1999 ◽  
Author(s):  
M Serra ◽  
D Maurici ◽  
K Scotlandi ◽  
G Barbanti-Brodano ◽  
M C Manara ◽  
...  
Keyword(s):  
High Grade ◽  
P Glycoprotein ◽  
P53 Status ◽  
High Grade Osteosarcoma

scholarly journals A Pharmacological Analysis of the Activity and Failure of the Medical Treatment of High-Grade Osteosarcoma

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 141
Author(s):  
Alessandro Comandone ◽  
Antonella Boglione ◽  
Tiziana Comandone ◽  
Fausto Petrelli
Keyword(s):  
Bone Cells ◽  
Age Groups ◽  
The Elderly ◽  
New Drugs ◽  
High Grade ◽  
Secondary Resistance ◽  
Orthopedic Surgeons ◽  
Close Cooperation ◽  
High Grade Osteosarcoma ◽  
Effective Drugs

Osteosarcomas (OSs) are a group of neoplasms originating from bone cells, usually presenting in three specific age groups: children, young adults, and the elderly. High-grade OS is an extremely malignant tumor mainly due to evolution into metastatic disease, usually in the lungs. Survival of these patients has improved since the 1980s thanks to close cooperation between oncologists, oncological surgeons and orthopedic surgeons. Unfortunately, no progress has been made in the last 30 years and new, more effective drugs are needed. This article reviews the biological and pharmacological basis of the treatment of OS. Models of clinical pharmacology of the active drugs, toxic effects and reasons for primary and secondary resistance to old and new drugs are discussed.

scholarly journals Survival Analysis of 3 Different Age Groups and Prognostic Factors among 402 Patients with Skeletal High-Grade Osteosarcoma. Real World Data from a Single Tertiary Sarcoma Center

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 486
Author(s):  
Richard E. Evenhuis ◽  
Ibtissam Acem ◽  
Anja J. Rueten-Budde ◽  
Diederik S. A. Karis ◽  
Marta Fiocco ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Medical Center ◽  
Age Groups ◽  
High Grade ◽  
Real World Data ◽  
Poor Overall Survival ◽  
Histopathological Response ◽  
Curative Intent ◽  
Entire Cohort ◽  
High Grade Osteosarcoma

Age is a known prognostic factor for many sarcoma subtypes, however in the literature there are limited data on the different risk profiles of different age groups for osteosarcoma survival. This study aims to provide an overview of survival in patients with high-grade osteosarcoma in different age groups and prognostic variables for survival and local control among the entire cohort. In this single center retrospective cohort study, 402 patients with skeletal high-grade osteosarcoma were diagnosed and treated with curative intent between 1978 and 2017 at the Leiden University Medical Center (LUMC). Prognostic factors for survival were analyzed using a Cox proportional hazard model. In this study poor overall survival (OS) and event-free survival (EFS) were associated with increasing age. Age groups, tumor size, poor histopathological response, distant metastasis (DM) at presentation and local recurrence (LR) were important independent prognostic factors influencing OS and EFS. Differences in outcome among different age groups can be partially explained by patient and treatment characteristics.

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