EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma

2018 ◽  
Vol 104 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Stefano Ferrari ◽  
Stefan S. Bielack ◽  
Sigbjørn Smeland ◽  
Alessandra Longhi ◽  
Gerlinde Egerer ◽  
...  
Keyword(s):  
Present Report ◽  
International Study ◽  
Bone Sarcoma ◽  
Hematological Toxicity ◽  
High Grade ◽  
Aggressive Approach ◽  
Younger Patients ◽  
Probability Of Survival ◽  
Localized Disease ◽  
High Grade Osteosarcoma

Introduction: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. Methods: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators’ choice were also eligible for the study. Results: The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity. Conclusions: In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.

Chemotherapy in the Management of Osteosarcoma and Ewing's Sarcoma

2007 ◽  
Vol 5 (4) ◽  
pp. 449-455 ◽  
Author(s):  
Scott M. Schuetze
Keyword(s):  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Disease Patient ◽  
Bone Sarcoma ◽  
The United States ◽  
High Grade ◽  
Medical Oncologists ◽  
Bone Sarcomas ◽  
Localized Disease ◽  
Relapsed Disease

Sarcomas of bone are rare malignancies diagnosed in fewer than 3000 individuals yearly in the United States. Ewing's sarcoma and most osteosarcoma are high-grade neoplasms and account for approximately one half of bone sarcoma cases. Fewer than 20% of patients presenting with localized Ewing's sarcoma or osteosarcoma are cured with surgery alone. Current management typically involves collaboration among orthopedic oncologists, medical oncologists, musculoskeletal radiologists, sarcoma pathologists, and radiation oncologists. Modern multidisciplinary management of Ewing's sarcoma and osteosarcoma has improved the cure rate of patients with localized disease to more than 50%. Primary chemotherapy for high-grade bone sarcomas often involves intensive, multiagent regimens, and few secondary chemotherapy options are available to treat refractory or relapsed disease. Patient participation in clinical trials of novel therapies for Ewing's sarcoma and osteosarcoma should be strongly encouraged.

Osteosarcoma in patients over 65 years old

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10037-10037
Author(s):  
A. Longhi ◽  
C. Errani ◽  
C. Ferrari ◽  
F. Bertoni ◽  
P. Bacchini ◽  
...  
Keyword(s):  
Major Complication ◽  
Palliative Surgery ◽  
High Grade ◽  
Cure Rate ◽  
Younger Age ◽  
Sex Type ◽  
Localized Disease ◽  
High Grade Osteosarcoma ◽  
Few Data ◽  
Free Status

10037 Background: Few data are available in literature about osteosarcoma in patients older than 65.We reviewed the incidence and outcome of osteosarcoma in elderly over 65 in our casistic. Materials and Methods: Patients with high grade osteosarcoma treated in our Institute from 1961 to 2006 aged >65. End point was overall survival (OS). Results: 43 patients aged more than 65 treated for high grade osteosarcoma at our Institute were found: 22 male and 21 females, median age was 69 (range 65–80), 29 had localized disease and 13 were metastatic, 33 had extremity localization and 10 axial, 29 patients had a primitive osteosarcoma and 13 (30%) had a sarcoma in Paget's disease, 1 pt ha post-RT osteosarcoma. Median interval from symptoms to diagnosis was 4 months (0–73) 32 out of 43 received surgery for primitive tumour: 18 had a resection with endoprosthesis, 13 had amputation, 1 pt had palliative surgery, the others received palliative RT, 14 patients received chemotherapy (anthracycline, cisplatin, ifosfamide).2 major complication related to chemotherapy were observed: one toxic death and one septic shock. Twenty-one patients reached a disease free status after surgery. Median OS for all 43 pts was 19 months (SE 3),mean 35 mos (range 3–229), 3 years OS for the all group was 25%. Three years OS (Kaplan-Meyer) for pts with localized disease was 41,5% vs 0% for metastatic pts, 3 yrs OS for pts who had surgery was 30% compared to 0% for those without surgical treatment.Significant prognostic factors (Breslow statistic) were: localized vs metastatic (P<0,004) and surgery vs no surgery (P<0.00005,) The other variables (sex, type of surgery, chemotherapy) were not statistically significant.In another study on patients aged 40–60 with localized osteosarcoma of the extremity we found an OS at 8 years of 62%. Conclusions: Osteosarcoma in this subgroup of elderly is frequently associated to Paget disease and their OS is worse compared to adult of younger age. We need to improve our strategy of treatment to increase the cure rate of these elderly patients. No significant financial relationships to disclose.

A European treatment protocol for bone sarcoma in patients older than 40 years

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10516-10516 ◽  
Author(s):  
S. Ferrari ◽  
S. Smeland ◽  
S. Bielack ◽  
A. Comandone ◽  
P. Dileo ◽  
...  
Keyword(s):  
Complete Remission ◽  
Treatment Protocol ◽  
International Study ◽  
Bone Sarcoma ◽  
Poor Responders ◽  
High Grade ◽  
Dedifferentiated Chondrosarcoma ◽  
Peripheral Neurotoxicity ◽  
Central Location ◽  
Synchronous Metastases

10516 Background: EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) is the first prospective multicenter international study for patients 41 - 65 years old with high-grade bone sarcoma. Methods: Patients with HG Osteosarcoma (OS), HG sarcoma NOS (S), Fibrosarcoma, MFH, Leiomyosarcoma, Dedifferentiated Chondrosarcoma (DCh) were included. Chemotherapy: Combinations of cisplatin/doxorubicin (CDP 100mg/m2/ADM 60mg/m2), ifosfamide/CDP(IFO 6g/m2/CDP 100mg/m2) and IFO/ADM (IFO 6g/m2/ADM 60mg/m2) were repeated three times (9 cycles). Surgery was planned after 3 cycles. Methotrexate (8g/m2) was postoperatively added in poor responders. Immediate surgery was allowed and 9 cycles with CDP, ADM, IFO were postoperatively given. Results: In December 2007, 140 patients were registered (median age 51 years). OS (51%), S (16%), and DCh (11%) were the more frequent histotypes. Synchronous metastases in 30 (21%) patients, central location of tumor in 45 (32%). Surgical complete remission (SCR) was achieved in 84% of patients, (localized 91%, metastatic 37%) without difference among the histology groups. One surgical-related and one chemotherapy-related death were reported. Grade 4 WBC and PLT incidence was 55% and 17%.Renal toxicity and peripheral neurotoxicity were reported in 16% and 20% of patients. With a median follow-up of 25 months (4–68) 3 year OS was 58% (95%CI 48–68%) [7% (95%CI 0–19%) without SCR]. In patients with SCR, 3 year OS and EFS were 46% (95%CI 9–83%) and 0% in case of synchronous metastases and 69% (95%CI58–80%) and 45% (95%CI33–57%) for localized patients; 50% (95%CI 29–71%) and 40% (95%CI 20–59%) for patients with central tumor, 73% (95%CI61–85%) and 44% (95%CI31–57%) for those with extremity tumor; 68% (95%CI 52–83%) and 46% (95%CI 32–54%) for OS, 64% (95%CI 42–85%) and 48% (95%CI 25–71%) for S, 48% (95%CI 13–82%) and 27% (95%CI 1–54%) for DCh. Conclusions: The protocol is feasible, but the chemotherapy-related toxicity is remarkable. Surgical complete remission is the main factor influencing survival. Central location and synchronous metastases are negative prognostic factors, but 50% 3-year OS can be achieved with aggressive local and systemic treatment. Osteosarcoma and high-grade sarcoma NOS benefit from chemotherapy more than patients with dedifferentiated chondrosarcoma. No significant financial relationships to disclose.

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.

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]

KAI-1 Expression in Pediatric High-Grade Osteosarcoma

2006 ◽  
Vol 9 (3) ◽  
pp. 219-224 ◽  
Author(s):  
Patrick J. Leavey ◽  
Charles Timmons ◽  
William Frawley ◽  
Donald Lombardi ◽  
Raheela Ashfaq
Keyword(s):  
Prognostic Markers ◽  
Clinical Phenotype ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Surface Proteins ◽  
High Grade ◽  
Free Survival ◽  
Treatment Groups ◽  
High Grade Osteosarcoma

Recent evidence implicates cell surface proteins of the tetraspanin superfamily in the process of metastasis whereas the downregulation of KAI-1, a member of the tetraspanin family, is associated with an aggressive clinical phenotype in several types of human cancers. To determine if expression of KAI-1-1 is associated with any known prognostic marker or clinical outcome in high-grade osteosarcoma, we examined 91 nondecalcified archival samples from 47 patients for the expression of KAI-1. Archival, paraffin-embedded, and decalcified pathologic samples were examined by immunohistochemistry and results were correlated to clinical outcomes and known prognostic markers. There were 46 samples from diagnostic biopsies (1 diagnostic sample was not available), 32 tumor resection samples, and 13 metastasis samples. Thirty-three percent (n = 30) of the samples expressed KAI-1 (16 biopsies, 9 resections, and 5 metastasis). KAI-1 expression was not significantly related to known prognostic markers or to either tumor necrosis after neoadjuvant therapy or the incidence of metastasis at diagnosis. KAI-1 expression was not significantly different between paired diagnostic tumor samples and either resection or metastasis tumor samples. Twenty-five patients remain alive at a median follow-up of 95 months. The overall and progression-free survival percentages at 5 years were 62% and 47% for KAI-1-positive patients and 49% and 38% for KAI-1-negative patients, respectively. This difference was not statistically significant. We conclude that KAI-1 is expressed in a proportion of high-grade osteosarcoma but is not of clinical significance and cannot be used to stratify treatment groups for these patients.

Differentially amplified chromosome 12 sequences in low- and high-grade osteosarcoma

2001 ◽  
Vol 33 (2) ◽  
pp. 133-140 ◽  
Author(s):  
David Gisselsson ◽  
Eva Pålsson ◽  
Mattias Höglund ◽  
Henryk Domanski ◽  
Fredrik Mertens ◽  
...  
Keyword(s):  
Chromosome 12 ◽  
High Grade ◽  
High Grade Osteosarcoma
Sign in / Sign up

Export Citation Format

Share Document