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.

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]

scholarly journals Treatment Outcomes for Adult Patients with Localized Osteosarcoma Treated with Chemotherapy without Methotrexate

2020 ◽  
Author(s):  
MRM Silva ◽  
RC Bonadio ◽  
GDR Matos ◽  
D Toloi ◽  
M Nardo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Strategies ◽  
Additional Treatment ◽  
Adult Patients ◽  
Cancer Center ◽  
High Dose ◽  
High Grade ◽  
Grade 3 ◽  
High Grade Osteosarcoma ◽  
Cure Rates

AbstractBackgroundStandard treatment for pediatric patients with localized osteosarcoma include high-dose methotrexate (HDMTX) and cure rates greater than 60% are observed. In adult patients, however, the toxicity profile limits the use of HDMTX and it is usually excluded from chemotherapy protocols for this group. We aimed to evaluate the outcomes of adult patients with localized osteosarcoma treated with chemotherapy without methotrexate.MethodsIn this retrospective cohort, we evaluated adult patients with high-grade osteosarcoma who received treatment with chemotherapy without methotrexate in a reference cancer center from 2007 to 2018. Outcomes analyzed were recurrence-free survival (RFS), overall survival (OS), and prognostic factors associated with overall survival.ResultsA total of 48 patients had localized disease and received treatment with chemotherapy without methotrexate. The majority of them received chemotherapy with a combination of cisplatin and doxorubicin (N=42, 87.5%). Median age was 27 years. (range 16.8 – 66.7) With a median follow-up of 29.2 months, median RFS was 29.9 months. Median OS was not reached. 5-year RFS and OS rates were 35.1% (95% CI 20.3 – 50.2%) and 71.6% (95% CI 52.3 – 84.2%), respectively. Patients who received cumulative doses of doxorubicin ≥ 375 mg/m2 had better OS than those who received lower doses (HR 0.26, 95% CI 0.07 – 0.94, P = 0.041). Similarly, patients who received ≥ 6 cycles of neoadjuvant/ adjuvant cisplatin tended to have better OS than those who received < 6 cycles (HR 0.30, 95% CI 0.08 – 1.09, P = 0.069).Nineteen patients received less than 6 cycles of cisplatin and doxorubicin mainly because of grade 3 or 4 toxicities (11), disease progression (6),patient refusal(1), physician choice(1).ConclusionIn our study, adult patients with localized high-grade osteosarcoma who were treated with chemotherapy without methotrexate had unfavorable outcomes. The cumulative doxorubicin dose and the number of cisplatin/doxorubicin cycles were associated with improved OS. The investigation of additional treatment strategies is of utmost importance to improve adult patients outcomes.

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 Osteosarcoma Models: From Cell Lines to Zebrafish

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Alexander B. Mohseny ◽  
Pancras C. W. Hogendoorn ◽  
Anne-Marie Cleton-Jansen
Keyword(s):  
Age Of Onset ◽  
Treatment Strategies ◽  
Early Age ◽  
Zebrafish Embryos ◽  
High Grade ◽  
Aggressive Tumor ◽  
Histological Heterogeneity ◽  
High Grade Osteosarcoma

High-grade osteosarcoma is an aggressive tumor most commonly affecting adolescents. The early age of onset might suggest genetic predisposition; however, the vast majority of the tumors are sporadic. Early onset, most often lack of a predisposing condition or lesion, only infrequent (<2%) prevalence of inheritance, extensive genomic instability, and a wide histological heterogeneity are just few factors to mention that make osteosarcoma difficult to study. Therefore, it is sensible to design and use models representative of the human disease. Here we summarize multiple osteosarcoma models establishedin vitroandin vivo, comment on their utilities, and highlight newest achievements, such as the use of zebrafish embryos. We conclude that to gain a better understanding of osteosarcoma, simplification of this extremely complex tumor is needed. Therefore, we parse the osteosarcoma problem into parts and propose adequate models to study them each separately. A better understanding of osteosarcoma provides opportunities for discovering and assaying novel effective treatment strategies.

Long Term Neuropsychological Outcomes of Survivors of Young Childhood Brain Tumors Treated on the Head Start II Protocol

2021 ◽  
Author(s):  
Cara F Levitch ◽  
Benjamin Malkin ◽  
Lauren Latella ◽  
Whitney Guerry ◽  
Sharon L Gardner ◽  
...  
Keyword(s):  
Head Start ◽  
Brain Tumors ◽  
Hematopoietic Cell Transplantation ◽  
Treatment Strategies ◽  
Receptive Language ◽  
Age At Diagnosis ◽  
High Dose ◽  
Treatment Protocols ◽  
Significant Change

Abstract Background The Head Start treatment protocols have focused on curing young children with brain tumors while avoiding or delaying radiotherapy through using a combination of high-dose, marrow-ablative chemotherapy and autologous hematopoietic cell transplantation (AuHCT). Late effects data from treatment on the Head Start II (HS II) protocol have previously been published for short-term follow-up (STF) at a mean of 39.7 months post-diagnosis. The current study examines longer-term follow up (LTF) outcomes from the same cohort. Methods Eighteen HS II patients diagnosed with malignant brain tumors &lt;10 years of age at diagnosis completed a neurocognitive battery and parents completed psychological questionnaires at a mean of 104.7 months post-diagnosis. Results There was no significant change in Full Scale IQ at LTF compared to baseline or STF. Similarly, most domains had no significant change from STF, including verbal IQ, performance IQ, academics, receptive language, learning/memory, visual-motor integration, and externalizing behaviors. Internalizing behaviors increased slightly at LTF. Clinically, most domains were within the average range, except for low average mathematics and receptive language. Additionally, performance did not significantly differ by age at diagnosis or time since diagnosis. Of note, children treated with high-dose methotrexate for disseminated disease or atypical teratoid/rhabdoid tumor displayed worse neurocognitive outcomes. Conclusions These results extend prior findings of relative stability in intellectual functioning for a LTF period. Ultimately, this study supports that treatment strategies for avoiding or delaying radiotherapy using high-dose, marrow-ablative chemotherapy and AuHCT may decrease the risk of neurocognitive and social-emotional declines in young pediatric brain tumor survivors.

Prognostic Value of Various Nutritional Assessment Indicators on Long Term and Short Term Outcomes for Patients with High Grade Osteosarcoma Receiving Surgical Resection

2020 ◽  
Author(s):  
Yuhan Yang ◽  
Ma Xuelei ◽  
Xinyan Ding
Keyword(s):  
Prognostic Value ◽  
Nutritional Assessment ◽  
Prognostic Score ◽  
Surgical Excision ◽  
Secondary Outcome ◽  
Brier Score ◽  
High Grade ◽  
High Grade Osteosarcoma ◽  
Length Of Hospitalization ◽  
Conut Score

Abstract Background: Many researchers have focused on exploring the association between patients’ nutritional status and clinical outcomes with some easy-to-reach indicators, especially in some carcinoma with high incidence. However, there was little attention on sarcomas and the objective of this study was to evaluate the prognostic value of some innovative nutrition associated indexes on patients with high grade osteosarcoma receiving surgical excision. Method: We retrospectively included patients’ clinical characteristics diagnosed as high grade osteosarcomas histologically receiving surgical excision from January 2008 to June 2018. Body mass index (BMI), Glasgow prognostic score (GPS), systematic inflammatory index (SII), and controlling nutritional (CONUT) score were calculated as nutritional associated factors to evaluate their prognostic value. The primary outcome was overall survival (OS) while the secondary outcome was the postoperative length of hospitalization. The relationship between clinical features and outcomes were performed by Cox and logistic regression analysis, respectively. The independent prognostic factors were chosen to construct predicted model whose internal and external accuracy were validated by concordance index (C-index), Brier score, and calibration plots.Results: High score of GPS predicted worse OS [HR (95% CI): 3.122 (1.982-4.918) versus 2.208 (1.014-4.804)] and higher rank of CONUT predicted poorer prognosis [HR (95% CI): 2.573 (1.616-4.097)] independently. The CONUT score was selected as the only prognostic factor on the length of hospitalization [HR (95% CI): 2.137 (1.270-3.596)]. The nomogram plots were used to visualize the results of predicted models whose performance was evaluated from the aspects of calibration and discrimination. Conclusion: Our study suggested prognostic value of nutritional assessment indexes including GPS and CONUT score that appropriate preoperative intervention which could optimize patients’ nutrition associated indicators may improve prognosis on patients with high grade osteosarcoma receiving surgical excision.Level of evidence: Level Ⅲ, prognostic study

Treatment Intensification of Traditional BFM Therapy with 3 Chemotherapy Blocks and Double Delayed Intensification (Protocol II) Improves Outcome in Infants with High Risk (HR) Acute Lymphoblastic Leukemia (ALL): Results of Two Consecutive AIEOP Studies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 871-871 ◽  
Author(s):  
Carmelo Rizzari ◽  
Maria Grazia Valsecchi ◽  
Paola De Lorenzo ◽  
Maurizio Aricò ◽  
Giuseppe Basso ◽  
...  
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Treatment Strategies ◽  
High Dose Chemotherapy ◽  
P Value ◽  
High Dose ◽  
Treatment Intensification ◽  
Treatment Protocols ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Introduction: Cure rates of ALL in children aged less than one year (i.e. infants) at diagnosis are in the range of 35–40%. Encouraging results have been recently reported in infants by using intensified treatment, including high dose chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). Aim: To evaluate the impact of the two treatment strategies adopted in the AIEOP ALL 91 and 95 studies on the outcome of ALL in infants. Patients and Methods: Fifty-two infants with ALL were enrolled between 1991 and 1999 in two consecutive studies, named AIEOP ALL 91 and ALL 95. Infants with an identified t(4;11) translocation had to be included in the high risk (HR) groups whilst those without this genetic abnormality could be treated in the intermediate (IR) or HR groups according to presenting features and treatment response. Patients belonging to the IR groups received a traditional BFM back-bone based treatment (protocols I, M and II), while those classified in the HR groups underwent an tensified treatment including induction (BFM protocol IA only, in study AIEOP ALL 91, and IA+IB in study ALL 95), consolidation with either 9 blocks of non-cross-resistant drugs (ALL 91) or 3 blocks followed by the 8-drug reinduction regimen - BFM protocol II - repeated twice (ALL 95). All patients were given a continuation phase (reinforced in HR patients of study ALL 95 by vincristine/prednisone pulses). Overall treatment duration was 2 years in both studies. Results: Infants in studies ALL 91 (n=21) and ALL 95 (n=31) had similar biological and clinical characteristics. The overall event-free survival (EFS) at 5 years was 45.0% (SE 7.0%). The EFS, after censoring for HSCT in 1st CR, was 38.1% (SE 11.4%) in ALL 91 and 51.6% (SE 9.9%) in ALL 95 (p-value=0.29). Patients treated in the IR arm of the two studies had a similar outcome. Better results were obtained in patients treated in the HR arm of ALL 95 study, where 9/17 chemotherapy-only patients and 3/4 HSCT patients are alive in CCR as compared to 1/7 and 0/2, respectively, in patients treated in the ALL 91 study. Discussion: These data show that full traditional BFM therapy intensified by 3 post-induction chemotherapy blocks and double protocol II (adopted in study ALL 95), is associated with a better outcome in infants with HR ALL.

scholarly journals Prognostic Value of Metabolic Tumor Volume on 11C-Methionine PET in Predicting Progression-Free Survival in High-Grade Glioma

2015 ◽  
Vol 49 (4) ◽  
pp. 291-297 ◽  
Author(s):  
Min Young Yoo ◽  
Jin Chul Paeng ◽  
Gi Jeong Cheon ◽  
Dong Soo Lee ◽  
June-Key Chung ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Metabolic Tumor Volume ◽  
High Grade ◽  
Free Survival

Results with the intensive chemotherapy Mexican regimen in the treatment of pediatric high-grade osteosarcoma: Experience at the Instituto Nacional de Pediatria.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10058-10058
Author(s):  
Araceli Castellanos-Toledo ◽  
Marta Zapata-Tarres ◽  
Humberto Peña-del-Castillo ◽  
Jose de Jesus Figueroa Carbajal
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Volume ◽  
Chemotherapy Regimen ◽  
Distal Tibia ◽  
Local Relapse ◽  
High Grade ◽  
Intensive Chemotherapy ◽  
High Incidence ◽  
High Grade Osteosarcoma

10058 Background: In Mexico, pediatric high-grade osteosarcoma (HGO) occupies the fifth place of all pediatrics cancers, representing the 4.4%. It presents with a high incidence of metastatic pulmonary disease and large primary tumor volume at diagnosis, resulting in poor survival. The results of the named 2005 Chemotherapy Regimen are very promising. Methods: A retrospective, longitudinal, clinical study was performed from January 2005 to January 2012, including 55 patients (<18 years old) with extremity HGO and no prior chemotherapy treatment. All patients received a 10-week neoadjuvant-chemotherapy regimen (6 curses), with cisplatino 120mg/m2 plus doxorrubicina 75mg/m2 and a 15-week adjuvant-treatment (5 curses) with ciclofosfamide 1800 mg/m2 plus etoposide 900 mg/m2. Results: Median age was 12 years, 51% boys and 49% girls. There were 51% distal femur, 11% proximal humerus, 18.2% proximal tibia, 7.3% distal tibia, 5.4% fibula and 5.5% proximal femur. Thirty-two patients (58.2%) had pulmonary metastases at diagnosis. There were 76.4% osteoblastic tumors, 16% chondroblastic and 7.3% telangiectatic. Twenty patients (36.4%) had an amputation procedure and 15 (27%) a limb desarticulation, 18 by a great tumor volume at diagnosis and two by eventual local relapse. Twelve patients (22%) had limb-sparing surgery. There were 10 (18.2%) good-responder patients and 38 (69%) bad-responders to neoadjuvant-chemotherapy. The overall survival (OS) for non-metastatic patients was 70% and 35% for metastatic patients (p 0.016). The event-free survival for non-metastatic patients was 65% and 30% for metastatic patients (p 0.032). OS for good-responders was 80% and 50% for bad-responders (p 0.009). No important toxicity and no second malignancies were reported. Conclusions: In spite of the presence of significant unfavorable prognostic factors in our patients, this intensive chemotherapy regimen showed improved results in overall survival as compared to other standard regimens, being short, inexpensive and with relatively few adverse events. This regimen can be useful in other developing countries.

Sign in / Sign up

Export Citation Format

Share Document