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

Author(s):  
MRM Silva ◽  
RC Bonadio ◽  
GDR Matos ◽  
D Toloi ◽  
M Nardo ◽  
...  

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.

2003 ◽  
Vol 21 (3) ◽  
pp. 536-542 ◽  
Author(s):  
Massimo Serra ◽  
Katia Scotlandi ◽  
Gemma Reverter-Branchat ◽  
Stefano Ferrari ◽  
Maria C. Manara ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qunying Yang ◽  
Chengcheng Guo ◽  
Xiaoping Lin ◽  
Lili Luo ◽  
Zhenqiang He ◽  
...  

Background: Anlotinib is a multi-target anti-angiogenic agent. This retrospective study aimed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide for the treatment of recurrent high-grade glioma.Materials and Methods: The clinical data of patients with recurrent high-grade glioma treated with anlotinib alone or in combination with temozolomide in our cancer center were collected and analyzed. Treatment response was evaluated according to the response assessment for neuro-oncology criteria. Progression-free survival, progression-free survival at 6 months, overall survival, and overall survival at 12 months were evaluated by Kaplan–Meier method and compared by log-rank test.Results: Between August 2019 and December 2020, 31 patients with recurrent high-grade glioma (21 of grade 4 and 10 of grade 3) were enrolled in this study. Seventeen patients received anlotinib alone and 14 received anlotinib plus temozolomide. All patients were heavily treated, the median lines of previous treatments were 2, and the median Karnofsky score was 60. At the data cutoff date, the median progression-free survival was 4.5 months and the progression-free survival at 6 months was 43.5%. The median overall survival was 7.7 months, and the overall survival at 12 months was 26.7%. The progression-free survival at 6 months and the overall survival at 12 months for 21 patients with grade 4 glioma was 40.2 and 27.9%, respectively. The tumor objective response rate was 41.9% in all patients and 33.3% in patients with grade 4 glioma. No grade 3 or worse treatment-related adverse events were recorded during the treatment.Conclusion: Anlotinib alone or in combination with temozolomide showed encouraging efficacy and favorable tolerability in patients with recurrent high-grade glioma who had been heavily treated.


2020 ◽  
Vol 102-B (6) ◽  
pp. 795-803 ◽  
Author(s):  
Yusuke Tsuda ◽  
Kim Tsoi ◽  
Michael C. Parry ◽  
Jonathan D. Stevenson ◽  
Tomohiro Fujiwara ◽  
...  

Aims To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. Methods Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson’s correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. Results OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. Conclusion Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795–803.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11527-11527
Author(s):  
Emanuela Palmerini ◽  
Catalina Marquez ◽  
Cristina Meazza ◽  
Angela Tamburini ◽  
Gianni Bisogno ◽  
...  

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]


Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Alexander B. Mohseny ◽  
Pancras C. W. Hogendoorn ◽  
Anne-Marie Cleton-Jansen

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.


Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1047
Author(s):  
Justin Z. Amarin ◽  
Razan Mansour ◽  
Sura Al-Ghnimat ◽  
Maysa Al-Hussaini

Women with endometrial carcinomas that express PD-L1 may respond better to immunotherapy. Our aim was to investigate the differential characteristics of PDL1–positive endometrial carcinomas and the prognostic significance of PDL1. We performed a retrospective chart review of 231 women with endometrial carcinomas who were managed at King Hussein Cancer Center (2007–2016) and performed immunohistochemistry for MLH1, PMS2, MSH2, MSH6, p53, and PD-L1. Overall, 89 cases (38.5%) were MMR-deficient. PD-L1 was expressed in 49 cases (21.2%) and its expression was significantly associated with MLH1/PMS2 deficiency (p = 0.044) but not MSH2/MSH6 deficiency (p = 0.59). p53 was mutant in 106 cases (46.5%), and its mutation was significantly associated with MMR proficiency (p < 0.001) but not PDL1 expression (p = 0.78). In women with endometrioid adenocarcinomas, PD-L1 expression was significantly associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade (p = 0.008). Overall, PDL1 expression did not significantly predict overall survival in unadjusted or adjusted analyses (p = 0.92 and 0.54, respectively). In conclusion, tumors with MLH1/PMS2 loss and high-grade endometrioid adenocarcinomas were more likely to express PDL1 in tumor cells. Further research is required to investigate whether the presence of either characteristic signals a higher likelihood of a favorable response if immunotherapy is administered.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhihong Yao ◽  
Zunxian Tan ◽  
Jifei Yang ◽  
Yihao Yang ◽  
Cao Wang ◽  
...  

AbstractThis study aimed to construct a widely accepted prognostic nomogram in Chinese high-grade osteosarcoma (HOS) patients aged ≤ 30 years to provide insight into predicting 5-year overall survival (OS). Data from 503 consecutive HOS patients at our centre between 12/2012 and 05/2019 were retrospectively collected. Eighty-four clinical features and routine laboratory haematological and biochemical testing indicators of each patient at the time of diagnosis were collected. A prognostic nomogram model for predicting OS was constructed based on the Cox proportional hazards model. The performance was assessed by the concordance index (C-index), receiver operating characteristic curve and calibration curve. The utility was evaluated by decision curve analysis. The 5-year OS was 52.1% and 2.6% for the nonmetastatic and metastatic patients, respectively. The nomogram included nine important variables based on a multivariate analysis: tumour stage, surgical type, metastasis, preoperative neoadjuvant chemotherapy cycle, postoperative metastasis time, mean corpuscular volume, tumour-specific growth factor, gamma-glutamyl transferase and creatinine. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.795 (range, 0.703–0.887). Moreover, the decision curve analysis curve also demonstrated the clinical benefit of this model. The nomogram provides an individualized risk estimate of the 5-year OS in patients with HOS aged ≤ 30 years in a Chinese population-based cohort.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2811-2811 ◽  
Author(s):  
Anjali Advani ◽  
Marc Earl ◽  
Dan Douer ◽  
Michael Rytting ◽  
Archie Bleyer

Abstract Background: With the multiple reports of asparaginase-containing regimens used in pediatric ALL therapy achieving a greater survival rate that non-asparaginase treatment regimens used in adult patients, asparaginase therapy is now being increasingly applied in chemotherapy regimens for adults with ALL. One reason for this resurgence is the availability of a long-acting form of the enzyme, pegylated asparaginase, and more recently, flexibility in administration of pegasparaginase via either intramuscular or intravenous routes (Oncaspar®). Given an initial impression in the 1970s that adults were more vulnerable to the toxicities of asparaginase than were children, we assessed the initial experience of intravenous asparaginase in adults with ALL. Methods: The intial experience with pegylated asparaginase at the University of Southern California (USC), Cleveland Clinic, and University of Texas M.D. Anderson Cancer Center were compiled and compared between institutions and with published results in pediatric patients. Results (Table): In 76 adult patients administered 192 doses of pegasparaginase in combination with other chemotherapy agents for ALL, hepatotoxicity was most common, with grade 3–4 elevation of serum liver enzymes and grade 3–4 hyperbilirubinemia in 36% and 14% of the patients, respectively. Hyperglycemia and chemical pancreatitis were next most common, having occurred at grade 3–4 levels in 25% and 5% of patients, respectively. Grade 3–4 toxicities in the 5–10% range were thrombosis, hypofibrinogenemia, nausea/vomiting, and fatigue. Grade 3–4 allergy/hypersensitivity, neuropathy, and CNS ischemia were reported in 1–5% of patients. Conclusions: Intravenous pegasparaginase is hepatotoxic in ∼1/3 of adult patients and has a variety of other, non-hepatic toxicities in <10% of patients, of which the most common are pancreatitis, thrombosis, nausea/vomiting and fatigue. Intravenous pegasparaginase has a toxicity profile, in combination with other chemotherapy agents used in ALL therapy, in adult patients that similar to that in pediatric patients, and warrants increased use in adult patients with ALL. Grade 3–4 Toxicities of IV Pegasparaginase in Adults USC Cleveland Clinic MD Anderson Total Median Age (Years) 28 37 20 33 Age Range (Years) 17–57 20–68 14–28 17–68 No. Doses / Patients 81 / 45 41 / 18 70 / 13 192 / 76 % Patients with Grade 3–4 Toxicity Elevated liver enzymes 31% 28% 62% 36% Hyperbilirubinemia 13% 22% 15% 14% Hyperglycemia 27% 17% 31% 25% Elevated serum amylase 0% 0%R 0% 5% Fatigue 7% 0% 0% 7% Thrombosis 4% 6% 6% 0% Hypofibrinogenemia 0% 28% 28% 0% Elevated PT/INR 0% 0% 0% 7% Bleeding 0% 0% 0% 8% Nausea/vomiting 2% 17% 17% 1% Allergy/hypersensitivity 0% 0% 0% 1% Neuropathy 2% 0% 0% 4% CNS ischemia 0% 0% 15% 3%


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1289-1289 ◽  
Author(s):  
Michael J. Overman ◽  
Lei Feng ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Mark Hess ◽  
...  

Abstract Background: FL3 is a subcategory of follicular lymphomas that is challenging in that it behaves aggressively like large cell lymphomas. If treated with CHOP, however it has a clinical course of relapse and treatment failure similar to grade 1–2 follicular lymphoma. We looked at the outcome of FL3 patients treated with RCHOP, combining rituximab with CHOP. There are no large study reports of this regimen’s results in FL3 to our knowledge. Patients and Methods: We retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center (UTMDACC). Response rate (RR), failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to 111 CHOP only treated patients was made. Results: The International Prognostic Index (IPI) distribution was: 47% Low, 36% Low-Intermediate, 13% High-intermediate, and 4% High-risk. The complete response rate was 96%. Forty-four out of 45 patients are still alive. Median follow-up is 3.5 years. The 3-year FFS rate according to IPI was 80% (95% CI: 64% to 100%) in low risk, 81% in low-intermediate (95% CI 64% to 100%), and was 50% (95% CI: 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI: 58% to 87%) compared to 44% of CHOP alone (95% CI: 36% to 55%) with p-value of 0.019 and 5-year OS, 98% (95% CI: 93% to 100%) compared to 75% (95% CI: 67% to 84) with p-valule of 0.0034. The addition of rituximab to CHOP improve the FFS compared to CHOP alone when subgroups of IPI were analyzed and compared (p=.002) Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor risk patients continue to demonstrate a high rate of failure despite the use of rituximab.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3955-3955
Author(s):  
Ravin Jain Garg ◽  
Hagop M Kantarjian ◽  
D. A Thomas ◽  
Stefan Faderl ◽  
Farhad Ravandi ◽  
...  

Abstract Among the well-described cytogenetic abnormalities in adults with acute lymphoblastic leukemia (ALL), a translocation involving chromosomes 1 and 19 [t(1;19) (q23;p13)] occurs in a small subset but has varyingly been associated with a good or bad prognosis in different studies. Adults with ALL and t(1;19) treated at M.D. Anderson Cancer Center were reviewed. Their clinical features and outcome were compared to those with other cytogenetic abnormalities. Endpoints included complete remission rate (CR), complete response duration (CRD) and overall survival (OS). Of 411 adults with pre-BALL, 12 patients had t(1;19). Ten of the 12 patients with t(1;19) received Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, Dexamethasone alternating with Methotrexate and high-dose Cytarabine); the other 2 were treated with VAD (Vincristine, Adriamycin, Dexamethasone). All 12 patients achieved CR; the 3-year survival rate was 73%. Patients with t(1;19) had significantly better CRD and OS when compared to all other patients combined as well as individually to patients with Ph+, t(4;11), and lymphoma-like abnormalities [6q(−), 14q+, t(11;14), t(14;18)]. Adults with ALL and t(1;19) have an excellent prognosis when treated with the Hyper-CVAD regimen. Outcome of patients by cytogenetic group: t(1;19) vs. individual cytogenetic groups OVERALL SURVIVAL N Fail 3-Year % Median (weeks) P-value T(1,19) 12 3 73 Not recorded Diploid 138 72 52 179 0.09 Lymphoma-like 20 17 35 54 0.008 Ph+ 117 88 23 68 0.0002 Miscellaneous 112 56 56 236 0.17 T(4,11) 12 10 0 58 0.002 COMPLETE RESPONSE DURATION (CRD) N Fail 3-Year % Median (weeks) P-value T(1,19) 12 2 80 Not recorded Diploid 133 59 54 177 0.06 Lymphoma-like 16 13 34 89 0.009 Ph+ 102 52 42 63 0.006 Miscellaneous 100 41 59 401 0.16 T(4,11) 11 7 NR 45 0.018


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