41 results on '"Recurrent osteosarcoma"'
Search Results
2. Injectable hydrogels for Fenton-like Mn2+/Fe2+ delivery with enhanced chemodynamic therapy prevent osteosarcoma recurrence and promote wound healing after excision surgery
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Lutong Wang, Haoyu Guo, Weiyue Zhang, Xingyin Li, Ziliang Su, and Xin Huang
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Recurrent osteosarcoma ,Surgical wound healing ,Injectable hydrogel ,Chemodynamic therapy ,Fenton reaction ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Local recurrence of osteosarcoma and wound healing after excision surgery are major challenges in clinical research. The present anti-tumor treatments could inhibit normal tissues, resulting in difficulties in surgical wound healing. In this study, we constructed an injectable hydrogel as a platform to co-deliver MnO2 nanoparticles and ferrocene Fc, termed as (MnO2/Fc)@PLGA for osteosarcoma treatment and wound healing after excision. By simple local injection, the hydrogel could form a protective barrier on the surgical wound after osteosarcoma excision, which could promote wound healing and steady release of MnO2/Fc nanoparticles. The released MnO2/Fc might undergo the Fenton reaction through Mn2+/Fe2+ to inhibit osteosarcoma cells with chemodynamic therapy (CDT). Furthermore, MnO2 could catalyze endogenous H2O2 to produce O2, which eliminates the adverse effects of H2O2 and remodels the hypoxic state in the local lesions. The increased O2 facilitated surgical wound healing and anti-tumor effects by regulating the hypoxia inducible factor-1 functions. In conclusion, (MnO2/Fc)@PLGA hydrogel could effectively prevent local recurrence of osteosarcoma and promote wound healing after excision surgery, thereby providing a novel strategy for tumor treatment and tissue repair. more...
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- 2024
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Catalog
3. Phase 2 study of anti-disialoganglioside antibody, dinutuximab, in combination with GM-CSF in patients with recurrent osteosarcoma: A report from the Childrens Oncology Group.
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Hingorani, Pooja, Krailo, Mark, Buxton, Allen, Hutson, Paul, Sondel, Paul, Diccianni, Mitchell, Yu, Alice, Morris, Carol, Womer, Richard, Crompton, Brian, Teot, Lisa, DuBois, Steven, Janeway, Katherine, Gorlick, Richard, Isakoff, Michael, and Randall, R more...
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Dinutuximab ,GD2 ,Recurrent osteosarcoma ,Adolescent ,Antibodies ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,Bone Neoplasms ,Child ,Granulocyte-Macrophage Colony-Stimulating Factor ,Humans ,Neoplasm Recurrence ,Local ,Osteosarcoma ,Young Adult - Abstract
PURPOSE: Novel effective therapies are urgently needed in recurrent osteosarcoma. GD2 is expressed in human osteosarcoma tumours and cell lines. This study evaluated the disease control rate (DCR) in patients with recurrent osteosarcoma treated with the anti-GD2 antibody dinutuximab plus cytokine therapy as compared to historical outcomes. METHODS: AOST1421 was a single-arm Phase 2 study for patients with recurrent pulmonary osteosarcoma in complete surgical remission. Patients received up to five cycles of dinutuximab (70 mg/m2/cycle) with granulocyte-macrophage colony-stimulating factor (GM-CSF). Two different dinutuximab infusion schedules were studied: 35 mg/m2/day over 20 h (2 days) and 17.5 mg/m2/day over 10 h (4 days). Primary end point was DCR, defined as a proportion of patients event free at 12 months from enrolment. The historical benchmark was 12-month DCR of 20% (95% CI 10-34%). Dinutuximab would be considered effective if ≥ 16/39 patients remained event free. Secondary objectives included toxicity evaluation and pharmacokinetics. RESULTS: Thirty-nine eligible patients were included in the outcome analysis. Dinutuximab did not demonstrate evidence of efficacy as 11/39 patients remained event free for a DCR of 28.2% (95% CI 15-44.9%). One of 136 administered therapy cycles met criteria for unacceptable toxicity when a patient experienced sudden death of unknown cause. Other ≥ Grade 3 toxicities included pain, diarrhoea, hypoxia, and hypotension. Pharmacokinetic parameters were similar in the two schedules. CONCLUSIONS: The combination of dinutuximab with GM-CSF did not significantly improve DCR in recurrent osteosarcoma. Dinutuximab toxicity and pharmacokinetics in adolescent and young adult osteosarcoma patients were similar to younger patients. Other strategies for targeting GD2 in osteosarcoma are being developed. more...
- Published
- 2022
4. Recurrent Osteosarcoma Presenting as Hepatic Metastasis: A Case Report.
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Imran A, Naeem MQ, Fatima N, Muneer K, and Siddique K
- Abstract
Osteosarcoma is a malignant tumor, derived from primitive bone-forming mesenchymal cells, and its aggressive nature often leads to significant morbidity and mortality, with amputation being routinely performed in localized cases. Post-amputation morbidity has a significant impact on the quality of life of the affected individuals. The tumor frequently metastasizes to the lungs and bones, and widespread disease remains the leading cause of most patient deaths. Other metastatic sites are extremely rare. We report a rare case of a young boy who had developed osteosarcoma and was surgically treated, without any metastatic disease. Two years later, the patient developed an abdominal mass, which was diagnosed as metastatic osteosarcoma to the liver., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Imran et al.) more...
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- 2024
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5. Abdominal Wall Reconstruction with a Free Fibula Flap after Internal Extended Hemipelvectomy
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Pedro C. Cavadas and Daniela Téllez-Palacios
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medicine.medical_specialty ,Recurrent osteosarcoma ,Incisional hernia ,business.industry ,medicine.medical_treatment ,lcsh:Surgery ,Abdominal wall reconstruction ,Case Report ,lcsh:RD1-811 ,fibula flap ,medicine.disease ,Surgery ,Abdominal wall ,Hemipelvectomy ,surgical procedures, operative ,medicine.anatomical_structure ,Free fibula ,osteosarcoma ,hemipelvectomy ,medicine ,Osteosarcoma ,business ,Fixation (histology) - Abstract
Major pelvic resections for malignant tumors are infrequent and have significant morbidity and mortality, for instance, incisional hernias are postoperative complications uncommonly reported probably because most cases are overshadowed by more serious complications. Reconstruction depends on the extent of the resection and overall prognosis of the patient. A case of a late complex hypogastric and femoral incisional hernia after extended hemipelvectomy for recurrent osteosarcoma treated with distal abdominal wall fixation into a free fibula flap is reported. more...
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- 2020
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6. MSCT DIAGNOSIS OF RECURRENT OSTEOSARCOMA OF THE LOWER JAW AFTER SURGICAL TREATMENT
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A.A. Babkova, E.S. Pshenichnikova, and N.S. Serova
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medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business ,Surgical treatment - Published
- 2020
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7. Results of a Randomized, Double-Blinded, Placebo-Controlled, Phase 2.5 Study of Saracatinib (AZD0530), in Patients with Recurrent Osteosarcoma Localized to the Lung
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Kristin Baird, Scott H. Okuno, Noah Federman, Scott M. Schuetze, Eve T. Rodler, Leo Mascarenhas, John Glod, Joseph G. Pressey, Denise K. Reinke, Neyssa Marina, Joanne Lagmay, Seth M. Steinberg, Sheri L. Spunt, James E. Butrynski, Brian Turpin, John M. Goldberg, Arthur P. Staddon, Mohammed M. Milhem, Robin L. Jones, Sant P. Chawla, David M. Loeb, and Lee J. Helman more...
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Recurrent osteosarcoma ,Article Subject ,Double blinded ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Oncology and Carcinogenesis ,Placebo ,Complete resection ,03 medical and health sciences ,chemistry.chemical_compound ,Rare Diseases ,0302 clinical medicine ,Clinical Research ,Internal medicine ,Medicine ,Radiology, Nuclear Medicine and imaging ,In patient ,Oncology & Carcinogenesis ,Lung ,RC254-282 ,Cancer ,Pediatric ,Saracatinib ,business.industry ,Lung Cancer ,Evaluation of treatments and therapeutic interventions ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,6.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,Osteosarcoma ,business ,Research Article - Abstract
Purpose. Osteosarcoma is a rare cancer and a third of patients who have completed primary treatment will develop osteosarcoma recurrence. The Src pathway has been implicated in the metastatic behavior of osteosarcoma; about 95% of samples examined express Src or have evidence of downstream activation of this pathway. Saracatinib (AZD0530) is a potent and selective Src kinase inhibitor that was evaluated in adults in Phase 1 studies. The primary goal of this study was to determine if treatment with saracatinib could increase progression-free survival (PFS) for patients who have undergone complete resection of osteosarcoma lung metastases in a double-blinded, placebo-controlled trial. Patients and Methods. Subjects with recurrent osteosarcoma localized to lung and who had complete surgical removal of all lung nodules were randomized within six weeks after complete surgical resection. Saracatinib, or placebo, was administered at a dose of 175 mg orally, once daily, for up to thirteen 28-day cycles. Results. Thirty-seven subjects were included in the analyses; 18 subjects were randomized to receive saracatinib and 19 to receive placebo. Intent-to-treat analysis demonstrated a median PFS of 19.4 months in the saracatinib treatment group and 8.6 months in the placebo treatment group (p=0.47). Median OS was not reached in either arm. Conclusions. Although saracatinib was well tolerated in this patient population, there was no apparent impact of the drug in this double-blinded, placebo-controlled trial on OS, and Src inhibition alone may not be sufficient to suppress metastatic progression in osteosarcoma. There is a suggestion of potential clinical benefit as evidenced by longer PFS in patients randomized to saracatinib based on limited numbers of patients treated. more...
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- 2020
8. HER2-Targeted Therapy in Osteosarcoma
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Pooja Hingorani, Michael Roth, Jonathan Gill, and Richard Gorlick
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musculoskeletal diseases ,Oncology ,medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,medicine.medical_treatment ,Context (language use) ,medicine.disease ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Trastuzumab ,Internal medicine ,medicine ,Osteosarcoma ,030212 general & internal medicine ,Car t cells ,skin and connective tissue diseases ,business ,neoplasms ,medicine.drug - Abstract
In this chapter, we will review studies of HER2 in osteosarcoma and discuss the controversies that have existed in this field. Our present understanding of HER2 in the context of osteosarcoma is that it is expressed on a subset of patient samples, but that expression is not prognostic. We will review the two trials that have been conducted in osteosarcoma which have targeted HER2. Use of an antibody, trastuzumab, did not suggest activity, but a smaller study using HER2-targeted CAR T cells suggested activity may be present. A trial of an antibody-drug conjugate targeting HER2 for recurrent osteosarcoma is under consideration. Trials targeting other surface proteins for the treatment of osteosarcoma have occurred or are in development. Indeed, this leads us to discuss in a broader fashion therapeutic approaches to targeting surface proteins. It is hoped that some of these approaches will lead to new effective therapies for patients with osteosarcoma. more...
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- 2020
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9. The lncRNAs RP1-261G23.7, RP11-69E11.4 and SATB2-AS1 are a novel clinical signature for predicting recurrent osteosarcoma
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Qingshan Guo, Peng Li, Cen Yuan, Jin-Ling Dong, and Tang Ying
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Adult ,Genetic Markers ,Male ,Oncology ,medicine.medical_specialty ,Multivariate statistics ,Recurrent osteosarcoma ,Adolescent ,Bioinformatics ,Biophysics ,Bone Neoplasms ,Malignancy ,Risk Assessment ,Biochemistry ,Young Adult ,lncRNA ,Predictive Value of Tests ,Risk Factors ,osteosarcoma ,Internal medicine ,Databases, Genetic ,medicine ,Humans ,Gene Regulatory Networks ,RNA, Messenger ,Child ,Molecular Biology ,Diagnostics & Biomarkers ,Research Articles ,Cancer ,business.industry ,Proportional hazards model ,Gene Expression Profiling ,Wnt signaling pathway ,Univariate ,Cell Biology ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,Child, Preschool ,biomarker ,Osteosarcoma ,Biomarker (medicine) ,Female ,RNA, Long Noncoding ,Neoplasm Recurrence, Local ,Transcriptome ,recurrence rates ,business - Abstract
Background: Osteosarcoma is the most common primary bone malignancy in children and adolescents. In order to find factors related to its recurrence, and thus improve recovery prospects, a powerful clinical signature is needed. Long noncoding RNAs (lncRNAs) are essential in osteosarcoma processes and development, and here we report significant lncRNAs to aid in earlier diagnosis of osteosarcoma. Methods: A univariate Cox proportional hazards regression analysis and a multivariate Cox regression analysis were used to analyze osteosarcoma patients’ lncRNA expression data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET), a public database. Results: A lncRNA signature consisting of three lncRNAs (RP1-261G23.7, RP11-69E11.4 and SATB2-AS1) was selected. The signature was used to sort patients into high-risk and low-risk groups with meaningful recurrence rates (median recurrence time 16.80 vs. >128.22 months, log-rank test, P143.80 months, log-rank test, P=0.006). A multivariate Cox regression analysis showed that the significant lncRNA was an independent prognostic factor for osteosarcoma patients. Functional analysis suggests that these lncRNAs were related to the PI3K-Akt signaling pathway, the Wnt signaling pathway, and the G-protein coupled receptor signaling pathway, all of which have various, important roles in osteosarcoma development. The significant 3-lncRNA set could be a novel prediction biomarker that could aid in treatment and also predict the likelihood of recurrence of osteosarcoma in patients. more...
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- 2020
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10. Phase 2 study of anti-disialoganglioside antibody, dinutuximab, in combination with GM-CSF in patients with recurrent osteosarcoma: A report from the Children's Oncology Group.
- Author
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Hingorani P, Krailo M, Buxton A, Hutson P, Sondel PM, Diccianni M, Yu A, Morris CD, Womer RB, Crompton B, Randall RL, Teot LA, DuBois SG, Janeway KA, Gorlick RG, and Isakoff MS
- Subjects
- Adolescent, Antibodies, Monoclonal, Child, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Humans, Young Adult, Antineoplastic Combined Chemotherapy Protocols toxicity, Bone Neoplasms drug therapy, Neoplasm Recurrence, Local drug therapy, Osteosarcoma drug therapy
- Abstract
Purpose: Novel effective therapies are urgently needed in recurrent osteosarcoma. GD2 is expressed in human osteosarcoma tumours and cell lines. This study evaluated the disease control rate (DCR) in patients with recurrent osteosarcoma treated with the anti-GD2 antibody dinutuximab plus cytokine therapy as compared to historical outcomes., Methods: AOST1421 was a single-arm Phase 2 study for patients with recurrent pulmonary osteosarcoma in complete surgical remission. Patients received up to five cycles of dinutuximab (70 mg/m
2 /cycle) with granulocyte-macrophage colony-stimulating factor (GM-CSF). Two different dinutuximab infusion schedules were studied: 35 mg/m2 /day over 20 h (2 days) and 17.5 mg/m2 /day over 10 h (4 days). Primary end point was DCR, defined as a proportion of patients event free at 12 months from enrolment. The historical benchmark was 12-month DCR of 20% (95% CI 10-34%). Dinutuximab would be considered effective if ≥ 16/39 patients remained event free. Secondary objectives included toxicity evaluation and pharmacokinetics., Results: Thirty-nine eligible patients were included in the outcome analysis. Dinutuximab did not demonstrate evidence of efficacy as 11/39 patients remained event free for a DCR of 28.2% (95% CI 15-44.9%). One of 136 administered therapy cycles met criteria for unacceptable toxicity when a patient experienced sudden death of unknown cause. Other ≥ Grade 3 toxicities included pain, diarrhoea, hypoxia, and hypotension. Pharmacokinetic parameters were similar in the two schedules., Conclusions: The combination of dinutuximab with GM-CSF did not significantly improve DCR in recurrent osteosarcoma. Dinutuximab toxicity and pharmacokinetics in adolescent and young adult osteosarcoma patients were similar to younger patients. Other strategies for targeting GD2 in osteosarcoma are being developed., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SGD has received consulting fees from Amgen, Bayer, and Jazz as well as travel expenses from Loxo, Roche, and Salarius. MDK has received consulting fees from Merck, Sharpe and Dhome. KAJ has received consulting fees from Bayer and Ipsen and honoraria from Takeda and Foundation Medicine. The remaining authors have no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.) more...- Published
- 2022
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11. Recurrent Osteosarcoma Presenting as an Isolated Bone Marrow Relapse
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Lisa M. Kopp, Brandon T. Larsen, Phillip H. Kuo, Lee D. Cranmer, and Julia Liu
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0301 basic medicine ,Malignant bone tumor ,medicine.medical_specialty ,Recurrent osteosarcoma ,Adolescent ,Pancytopenia ,Diagnosis, Differential ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Distal femur ,Fatal Outcome ,0302 clinical medicine ,Neoplasm Recurrence ,stomatognathic system ,Bone Marrow ,Recurrence ,Humans ,Initial treatment ,Medicine ,Osteosarcoma ,business.industry ,Hematology ,medicine.disease ,Jaw Neoplasms ,Surgery ,stomatognathic diseases ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Female ,Bone marrow ,Neoplasm Recurrence, Local ,Bone Marrow Neoplasms ,business - Abstract
Osteosarcoma (OS) is a malignant bone tumor which is found primarily in adolescents, with the distal femur as the most common location. OS with a jaw primary is present in only about 10% of cases and the risk of recurrence is considered to be decreased in the jaw versus other primary locations. We present a unique case of a patient with localized OS of the jaw with an isolated recurrence in her bone marrow almost 5 years after completion of initial treatment. more...
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- 2017
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12. Updated outcomes for patients with completely resected pulmonary recurrent osteosarcoma: A report from the Children’s Oncology Group
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Alexander J. Chou, Pooja Hingorani, Mark Krailo, Steven G. DuBois, Richard Gorlick, Katherine A. Janeway, Damon R. Reed, Allen Buxton, Ruxu Han, and Michael S. Isakoff
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Oncology ,Cancer Research ,medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,Internal medicine ,medicine ,business - Abstract
10023 Background: Amongst patients with recurrent osteosarcoma (OS), those with resectable pulmonary-only relapse appear to have the best outcomes. Prior analysis of patients with completely resected recurrent OS enrolled on a Children’s Oncology Group (COG) Phase 2 trial AOST0221, which studied the efficacy of inhaled GMCSF, showed a 12- month disease control rate (DCR12) of only 20% (95% CI, 10 – 34%). DCR12 based on this analysis was used as the historical benchmark for efficacy analysis in two recently completed trials, AOST1321 (completely resected cohort only) and AOST1421. We analyzed the stability of the DCR12 benchmark using data from these contemporary studies. Methods: Patients were eligible for AOST1321 if they had undergone resection of all sites of recurrent or refractory OS within 30 days of enrollment and for AOST1421 if they had lung only recurrent OS completely resected within 4 weeks of enrollment. AOST1321 evaluated denosumab while AOST1421 evaluated dinutuximab. Patients with refractory disease, extrapulmonary recurrence or without histological confirmation of relapse were excluded from this analysis. DCR12 was defined as having at least stable disease 12 months after the start of protocol therapy. We report the DCR12 observed on AOST1321, AOST1421 and AOST0221. Results: One hundred and twenty-eight evaluable patients with completely resected recurrent OS were enrolled on AOST0221 (N=49), AOST1321 (N=38) and AOST1421 (N=41). One hundred and one patients were included in this analysis (AOST0221: 37, AOST 1321: 25, AOST1421:39). DCR12 was 14 % (95% CI, 5% – 26%) for AOST0221, 24% (95%CI 10-42%) for AOST1321, and 31% (95% CI, 17% - 45%) for AOST1421. Risk for disease progression did not differ across the 3 included studies. DCR12 for all three studies combined was 23% (95% CI, 15% – 31%). Conclusions: Prognosis for recurrent OS remains dismal, even for those with resectable pulmonary-only disease. Although not statistically significant, dinutuximab may have activity in a select group of relapsed OS patients; combination studies using dinutuximab are planned. The previously described benchmark of disease control at 12 months remained relatively consistent in recent studies for those patients who have resectable pulmonary-only relapse. Therefore, DCR12 remains a useful outcome measure in fully resected OS with lung only metastases. Analyses are ongoing to better define the appropriate threshold to define investigational agent activity in this specific patient population. more...
- Published
- 2021
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13. Phase II trial of olaparib in combination with ceralasertib in patients with recurrent osteosarcoma
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Catherine Clinton, Simon Smith, Suzanne J. Forrest, Kieuhoa T. Vo, Wendy B. London, Katherine A. Janeway, E. Alejandro Sweet-Cordero, Kylene Desmith, Kerri Cavanaugh, Michael D. Kinnaman, Priscilla Merriam, Emma Dean, J. Andrew Livingston, Brunella Felicetti, and Pei-Chi Kao more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,medicine.disease ,Olaparib ,chemistry.chemical_compound ,Primary bone ,chemistry ,Internal medicine ,Medicine ,Osteosarcoma ,In patient ,Young adult ,business - Abstract
TPS11575 Background: Osteosarcoma is the most common primary bone tumor, occurring in children, adolescents, and young adults. In contrast to advances in treatment for most childhood cancers, there have been no significant improvements in osteosarcoma outcomes in the past 40 years. Forty percent of osteosarcoma patients will, at some point, have advanced disease which has a very poor outcome with a 5-year overall survival of approximately 20%. Genomic alterations and signatures associated with sensitivity to treatment with DNA damage response (DDR) inhibitors are observed frequently in osteosarcoma. Many osteosarcomas have a unique mutational signature (signature 3) similar to that seen in BRCA1 deficient cancer and response to PARP inhibitors has been seen in osteosarcoma cell lines. Additionally, ATRX, a protein involved in the alternative lengthening of telomeres (ALT), is often inactivated in osteosarcoma. Defects in the ALT pathway may sensitize tumor cells to ATR inhibitors and osteosarcoma cell lines have been shown to be sensitive to ATR inhibition. In vitro susceptibility of osteosarcoma cell lines to ATR and PARP inhibitors, the presence of mutations in genes involved in DDR and the presence of signature 3 in a subset of osteosarcomas serves as the basis for the development of this trial. Methods: This is an ongoing open label, multicenter, phase II clinical trial to evaluate the clinical activity of PARP inhibitor, olaparib, in combination with ATR inhibitor, ceralasertib, in 2 cohorts of patients aged 12-40 with recurrent osteosarcoma (NCT04417062). Patients with unresectable disease are enrolled into Cohort 1. Patients with resectable disease limited to the lung are enrolled into Cohort 2. Patients in both cohorts receive olaparib 300mg orally twice a day on days 1-28 and ceralasertib 160 mg orally once a day on days 1-7 of a 28-day cycle (adult maximum tolerated dose for the combination). For patients in Cohort 2, study treatment also includes surgical resection of lung metastases at protocol-specified timepoints. Patients can remain on treatment for up to 2 years if they have not progressed. For Cohort 1, the primary objective is to determine whether the combination treatment improves the 4-month event-free rate as compared to a historical benchmark from Children’s Oncology Group (COG) trials using a Simon’s two-stage design. In the first stage, ≥3 of 19 patients must be event-free at 4 months to proceed to stage 2. Enrollment into Cohort 2 continues as long as Cohort 1 enrollment is ongoing. For Cohort 2, the primary endpoint is the submission of paired pre- and post-treatment tumor samples for correlative studies. Secondary endpoints include objective response rate, event-free survival, and overall survival. Integrated correlative studies will assess tumor tissue for biomarkers of treatment response and measure circulating tumor DNA longitudinally. Enrollment began November 24, 2020 and is ongoing. Clinical trial information: NCT04417062. more...
- Published
- 2021
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14. Comparison of18F-FDG-PET-CT and Bone Scintigraphy for Evaluation of Osseous Metastases in Newly Diagnosed and Recurrent Osteosarcoma
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Michael W. Bishop, Alberto S. Pappo, M. Beth McCarville, Fariba Navid, Jianrong Wu, Shenghua Mao, Najat C. Daw, Barry L. Shulkin, and Caitlin Hurley
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medicine.medical_specialty ,Recurrent osteosarcoma ,medicine.diagnostic_test ,business.industry ,Histology ,Hematology ,Newly diagnosed ,medicine.disease ,030218 nuclear medicine & medical imaging ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Bone scintigraphy ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Biopsy ,Medicine ,Osteosarcoma ,Fdg pet ct ,Radiology ,medicine.symptom ,business - Abstract
Background Bone scintigraphy (BS) is used to detect osseous metastases in osteosarcoma. 18F-fluorodeoxyglucose-positron emission tomography–computed tomography (18F-FDG-PET-CT) is being increasingly used for staging. We compared the sensitivity, specificity, and diagnostic accuracy of 18F-FDG–PET-CT and BS for detecting osseous metastases in osteosarcoma. Methods We retrospectively reviewed 39 patients with osteosarcoma who had paired PET–CT and BS at diagnosis and/or first recurrence from 2003 to 2012. Imaging studies were reviewed by two pediatric imaging specialists who were blinded to results of the opposing modality and reference standard. Reviewers categorized lesions as benign, malignant, or indeterminate. Reference standard for lesion histology was biopsy or clinical follow-up. Diagnostic performance of PET–CT, BS, and combined modalities were determined. Results There were 40 examinations from 39 patients and 65 distant lesions were evaluated. Median age was 12 years (range 5–19 years). Four patients had 15 osseous metastases at diagnosis (two biopsied and 13 clinically), and two had five osseous metastases at recurrence (one biopsied and five clinically). For distant sites, sensitivity, specificity, and diagnostic accuracy were 79%, 89% and 86% for PET–CT, 32%, 96%, and 77% for BS, and 95%, 85%, and 88% for PET–CT/BS combined. Sensitivity of PET–CT was superior to BS (P = 0.035); combined imaging modalities were superior to BS (P < 0.001) but not better than PET–CT alone (P = 0.25). Specificity for BS approached significance compared to combined imaging (P = 0.063). Examination-based analysis yielded similar results between individual and combined imaging modalities. Conclusions 18F-FDG–PET–CT demonstrated superior sensitivity over BS for detecting osseous metastases, supporting the use of 18F-FDG–PET–CT for staging of osteosarcoma. more...
- Published
- 2016
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15. Characterizing the landscape of genomic variants in high-risk pediatric osteosarcoma
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Liam F. Spurr, Abigail Ward, Andrew D. Cherniack, Katherine A. Janeway, Duong Doan, Laura Corson, Yvonne Y. Li, and Amanda Marinoff
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Oncology ,Cancer Research ,medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,Internal medicine ,medicine ,Treatment strategy ,business ,Pediatric Osteosarcoma - Abstract
11530 Background: Survival rates for patients with metastatic and/or recurrent osteosarcoma are poor, and treatment strategies have remained unchanged for more than three decades. Genomic characterization can identify new treatment strategies and improve risk stratification. To date, sequencing studies of osteosarcoma have focused on newly diagnosed patients. We present one of the first reports of osteosarcoma genomics in a high-risk cohort. Methods: 92 samples from 92 patients were sequenced in a CLIA/CAP laboratory with a targeted NGS panel test. Patients were enrolled in one of two studies. The PROFILE study enrolls all patients seen at Dana-Farber Cancer Institute, and the GAIN study enrolls patients with metastatic and/or recurrent cancer at 11 institutions. Sequencing was performed using primary tumor samples at biopsy and/or from sites of metastasis when available. Results: 33 patients were enrolled on the PROFILE study, and 59 were enrolled on GAIN. Diagnostic stage was available for 65 (67%) of patients. 37% had metastatic disease at diagnosis. The 3-year overall survival (OS) was 71% for the entire study population, 56% for patients with metastatic disease at diagnosis, and 81% for patients with initially localized disease. The presence of metastases at diagnosis was significantly associated with poor outcome (p < 0.0087) and was the only independent clinical prognostic factor identified. Genomic analysis revealed frequent alterations in TP53 (37%), RB1 (15%), CDKN2A (13%), MYC (12%), CDKN1A (12%), ATRX (10%), and CCND3 (8%). Patients whose tumors had MYC amplification (defined as ≥ 6 copies) had a 3-year OS of 39% compared with a 3-year OS of 76% in the absence of MYC amplification, a difference with borderline statistical significance (p = 0.051). Conclusions: In the first study to examine genomic alterations detected by targeted gene panel sequencing in a CAP-certified laboratory in a large population of pediatric patients with higher risk osteosarcoma, the most frequently occurring events were similar to those found in prior reports. MYC amplification, reported as a possible poor prognostic factor in other studies, was present in 12% of patients and was associated with a worse OS, though this finding did not reach statistical significance. more...
- Published
- 2020
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16. Phase II study of antidisialoganglioside antibody, dinutuximab, in combination with GM-CSF in patients with recurrent osteosarcoma (AOST1421): A report from the Children’s Oncology Group
- Author
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Pooja Hingorani, Richard Gorlick, Katherine A. Janeway, Allen Buxton, Michael S. Isakoff, Justin Davis, Mark Krailo, and Paul R. Hutson
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Recurrent osteosarcoma ,biology ,business.industry ,Dinutuximab ,Phases of clinical research ,Disease control ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,biology.protein ,In patient ,Antibody ,business ,030215 immunology - Abstract
10508 Background: Treatment of patients with recurrent osteosarcoma (OS) is challenging and novel effective therapies are urgently needed. This study evaluated disease control rate (DCR) in patients with recurrent pulmonary OS, when treated with dinutuximab plus cytokine therapy as compared to a historical benchmark. The rationale for dinutuximab was the ubiquitous ( > 95%) GD2 positivity in OS tumors and cell lines. Methods: AOST1421 was a single-arm phase 2 study. Patients with recurrent pulmonary OS in complete surgical remission were eligible. Patients received five cycles of dinutuximab 70mg/m2/cycle with GM-CSF. Two different dinutuximab infusion schedules were used - 35mg/m2/day over 20 hours (2-day) and 17.5mg/m2/day over 10 hours (4-day) schedule. Primary end point was DCR, defined as proportion of patients event-free at 12 months from enrollment. Events were progressive disease or death within 12 months attributed to treatment or progression. The historical benchmark was AOST0221 with a 12-month DCR of 20% (95% CI 10-34%). Success was defined as ≥16/ 39 patients ( > 40%) event-free at 12 months from enrollment. Secondary objectives included toxicity evaluation and dinutuximab pharmacokinetics (PK). Results: Forty-one patients were enrolled from Nov 2015 - Jan 2018. Thirty nine were eligible and evaluable (age 7-26 yr; median 15 yr). Data current to December 31, 2019 was used for analysis. Accrual rate was higher than expected (22.1 vs. 19.2 patients/ yr.) despite a concurrently open competing study. One of 136 administered therapy cycles met criteria for unacceptable toxicity when one patient receiving the 2-day schedule died after cycle 2 due to an unknown cause, attributed as probably related to protocol therapy. The protocol was revised to allow only the 4-day schedule. Other ≥ Grade 3 toxicities occurring in > 10 % participants were expected dinutuximab toxicities such as pain, diarrhea, hypoxia and hypotension. Dinutuximab did not demonstrate sufficient evidence of efficacy as 27/ 39 patients experienced an event for a DCR of 30.7% (95% CI 17- 47%). PK studies are pending and will be reported. Conclusions: Dinutuximab toxicity in adolescent and young adult OS patients was similar to younger patients. While GD2 remains a relevant target in OS, combination of dinutuximab with GM-CSF did not meet the targeted successful DCR in patients with completely resected tumor. Other strategies for targeting GD2 or dinituximab combination therapy may still be warranted. Clinical trial information: NCT02484443. more...
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- 2020
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17. Late post-operative recurrent osteosarcoma: Three case reports with a review of the literature
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Ming Xu, Sujia Wu, Xuquan Wang, Songfeng Xu, Ye Yuan, and Xiuchun Yu
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Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Recurrent osteosarcoma ,Every Six Months ,treatment ,business.industry ,medicine.medical_treatment ,Cancer ,Articles ,medicine.disease ,Acetabulum ,Surgery ,Radiation therapy ,Oncology ,osteosarcoma ,late recurrence ,medicine ,Osteosarcoma ,prognosis ,Post operative ,business - Abstract
The aim of the present study was to investigate the clinical characteristics and treatment of late recurrent osteosarcoma following surgery. The cases of three patients with late recurrent osteosarcoma, who were treated at the General Hospital of Jinan Military Command, General Hospital of Nanjing Military Command and Xinan Hospital of The Third Military Medical University, were analyzed retrospectively. Furthermore, 10 cases of late recurrent osteosarcoma were retrieved from the literature. In total, eight male and five female cases were selected for the present study. The mean age at recurrence was 25.56 years (range, 13–42 years). The locations of the osteosarcomas were as follows: five cases in the distal femur, two cases in the distal tibia and acetabulum, respectively, and one case in the proximal tibia (the remaining cases were not described). The tumors were histologically classified into three cases of fibroblastic, two cases of traditional-type; two cases of mixed-type and one case each of osteoblastic-, chondroblastic- and telangiectasia-type osteosarcoma (the remaining cases were not described). The mean recurrence time following surgery was 10.02 years (range, 5.2–19.3 years). With regard to the treatment modalities, five patients accepted surgery and chemotherapy, one patient accepted surgery and radiotherapy, two patients accepted surgery alone and one patient did not complete the treatment (the remaining cases were not described). From the 12 cases that were followed-up for between 0.5 and 4.7 years (mean, 2.28 years), one case was lost to follow-up, six patients survived (up to 4.5 years) and six patients succumbed to their condition (0.6–4.7 years). The present study highlights the fact that more focus should be placed upon the long-term follow-up of patients with osteosarcoma. A follow-up is required once every six months, from five years after the diagnosis. The abnormal changes in the surgical site should also receive further attention, in addition to the pulmonary and systemic metastases. Following a diagnosis of late post-operative recurrence, surgery and post-operative chemotherapy are commonly used in clinical treatment, however, the clinical outcome of osteosarcoma requires further observation. more...
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- 2013
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18. Retrospective analysis of prognostic factors for sixty osteosarcoma patients with local recurrence
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Yuanjue Sun, Jingjing Sha, Yang Yao, Zan Shen, Haiyan Hu, and Wei-Xiang Qi
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musculoskeletal diseases ,Oncology ,medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,medicine.disease ,Surgery ,Surgical oncology ,Internal medicine ,medicine ,Retrospective analysis ,Osteosarcoma ,business ,neoplasms - Abstract
Objective The aim of this study was to identify prognostic factors and imply the appropriate management for local recurrent osteosarcoma.
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- 2013
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19. Hyperthermia in the Treatment of Post-Actinic Osteosarcomas: Our Anecdotal Experience
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Roberto Scaramuzzi, Gerardo Scaramuzzi, Antonio Tancredi, Luigi Ciuffreda, Rosanna Sabatino, and Antonello Cuttitta
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Hyperthermia ,Chemotherapy ,medicine.medical_specialty ,lcsh:R5-920 ,Recurrent osteosarcoma ,Radiation ,business.industry ,medicine.medical_treatment ,Early detection ,Case Report ,Sarcoma ,General Medicine ,medicine.disease ,Radiation therapy ,medicine ,Effective treatment ,Radiology ,business ,lcsh:Medicine (General) ,Adjuvant - Abstract
Irradiation-induced sarcomas are a late sequelae of irradiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gys and above, with a dose ranging from 16 Gys to 112 Gys. These tumours are very aggressive and an early detection is needed for a timely intervention. Surgery is only effective treatment for local control instead chemotherapy is a valuable tool for systemic control of disease. Irradiation therapy use is controversial because of its side effects on a site previously irradiated. Irradiation therapy combined with hyperthermia is a new treatment that overcomes these problems without limiting the effect of radiation therapy. It may become a tool for local control of the unresectable tumours or an adjuvant treatment of the surgery. In this report we present a rare case of irradiation-induced recurrent osteosarcoma involving the chest wall that was treated with surgical resection followed by radiation therapy combined with hyperthermia as an adjuvant treatment of the surgery. more...
- Published
- 2011
20. Limb Salvage Strategy by Intra-Arterial Chemotherapy for Local Recurrent Osteosarcoma in Extremities
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Fan Xiong, Qiu Cui, Cheng Liu, Jun Guo, Dingfeng Li, and Yanjun Zeng
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Chemotherapy ,medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,medicine.medical_treatment ,Limb salvage ,Lung metastasis ,Normal tissue ,Intra arterial chemotherapy ,General Medicine ,medicine.disease ,Prosthesis ,Surgery ,Medicine ,Osteosarcoma ,business - Abstract
Objective: The feasibility of intra-arterial chemotherapy for local recurrent extremity osteosarcoma with prosthesis replacement. Methods: 9 local recurrent limb osteosarcoma patients with prosthesis replacement who received treatment during the period from April 2010 to June 2013 at our hospital were recruited, including 3 patients with lung metastasis. All patients were treated with intra-arterial chemotherapy via implanted pump at affected limb. Results: The local recurrent neoplasms calcified and formed clear boundary with normal tissues after 3 to 5 cycles intra-arterial intervention chemotherapy, which indicates the osteosarcoma was controlled effectively to facilitate the osteosarcoma excision. No local recurrence happened during the follow-up visit varied from 12 to 38 months. The late result was better in 6 patients without lung metastasis than 3 patients with lung metastasis, 2 of who died and 1 currently survive without tumor. Conclusion: Intra-arterial intervention chemotherapy could effectively curb the progress of local recurrent osteosarcoma to facilitate the subsequent limb salvage treatment, and prolong the lifetime of patients with lung metastasis. more...
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- 2015
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21. Recurrent Bone Tumors
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Joanne Lagmay and Nicholas D. Yeager
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Oncology ,medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,Multimodal therapy ,Disease ,medicine.disease ,Therapeutic approach ,Zoledronic acid ,Internal medicine ,Medicine ,Osteosarcoma ,Sarcoma ,business ,Survival rate ,medicine.drug - Abstract
Multimodal approach to treatment has led to the dramatically improved outcome of patients with osteosarcoma and Ewing sarcoma. However, despite intensive therapies and incorporation of novel agents in trials, the therapeutic plateau in recurrent osteosarcoma and Ewing sarcoma has not yet been overcome. Cure for these patients remain a daunting challenge with dismal survival rate after relapse despite best efforts. Certain clinical factors help prognosticate quality of relapse of these tumors. Because patient characteristics are different upon disease recurrence, therapeutic approach to these patients vary widely. more...
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- 2015
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22. A Phase II Study of Docetaxel for the Treatment of Recurrent Osteosarcoma
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Anne McTiernan and Jeremy Whelan
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Oncology ,musculoskeletal diseases ,medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,Cell ,Phases of clinical research ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,medicine.anatomical_structure ,Docetaxel ,Internal medicine ,Toxicity ,medicine ,Radiology, Nuclear Medicine and imaging ,business ,therapeutics ,neoplasms ,medicine.drug - Abstract
Purpose: To determine the response and toxicity of docetaxel in recurrent osteosarcoma and related spindle cell tumours of bone.Patients and methods: Fourteen patients, 10 males and four females, were enrolled, median age 30.5 years (range, 17–46). Diagnosis was: conventional osteosarcoma, 12 patients; periosteal osteosarcoma, one patient; and malignant fibrous histiocytoma of bone, one patient. Initial chemotherapy had been with doxorubicin and cisplatin in 10 patients, and multiagent regimens in four. Nine had been treated with second line chemotherapy before receiving docetaxel. Thirteen patients had lung metastases and one intra-abdominal disease. Docetaxel 100 mg/m2was given as a 1-h infusion every 3 weeks. Response was assessed every two cycles to a maximum of six.Results: A total of 43 cycles were given, median of two per patient (range 1–6). Thirteen patients were evaluable for response. A single partial remission was seen, for a response rate of 8%. Two patients had stable disease, and one patient a mixed response. Forty cycles were evaluable for toxicity. The principle toxicity was haematological, with a median neutrophil count of 0.9 (range 0–9.6). There were four episodes of neutropenic sepsis (10%). The only non-haematological toxicity ≥grade 3 was stomatitis, occurring in just one patient. There were no toxic deaths.Conclusion: Docetaxel at this dose and schedule is well tolerated, but is not associated with significant activity in patients with relapsed osteosarcoma. more...
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- 2004
23. Gemcitabine With or Without Docetaxel and Resection for Recurrent Osteosarcoma
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Jill Woodman, Yasmin Gosiengfiao, David O. Walterhouse, Jennifer Reichek, and Tamar Ben-Ami
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Male ,Oncology ,medicine.medical_specialty ,Recurrent osteosarcoma ,Adolescent ,Antineoplastic Agents ,Bone Neoplasms ,Docetaxel ,Deoxycytidine ,Neurosurgical Procedures ,Resection ,Refractory ,Internal medicine ,medicine ,Humans ,Combined Modality Therapy ,Child ,neoplasms ,Retrospective Studies ,Osteosarcoma ,business.industry ,Retrospective cohort study ,Hematology ,medicine.disease ,Gemcitabine ,Surgery ,Treatment Outcome ,Pediatrics, Perinatology and Child Health ,Female ,Taxoids ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
It remains unclear how to optimally incorporate gemcitabine and docetaxel into the management of patients with recurrent osteosarcoma. We describe 4 pediatric patients with recurrent osteosarcoma who were treated with gemcitabine ± docetaxel and resection. One patient had a partial response and 2 had stable disease. Two patients subsequently underwent surgical resections. Median duration of response was 8 months and was longer for patients who underwent resection. One patient remains disease-free 57 months from recurrence. Our limited series provides additional support for the use of gemcitabine ± docetaxel for recurrent osteosarcoma and suggests benefit of concurrent local control measures if possible. more...
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- 2012
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24. Survival after recurrent osteosarcoma: Data from 3 European Osteosarcoma Intergroup (EOI) randomized controlled trials
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P.S. Rose
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Oncology ,medicine.medical_specialty ,Recurrent osteosarcoma ,Randomized controlled trial ,business.industry ,law ,Internal medicine ,Medicine ,Osteosarcoma ,business ,medicine.disease ,law.invention - Published
- 2012
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25. Recurrent osteosarcoma with calcified liver metastases: Uncommon development of a common disease
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Shikha Goyal and Pramod Kumar Julka
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Adult ,musculoskeletal diseases ,Limb salvage surgery ,Pathology ,medicine.medical_specialty ,Recurrent osteosarcoma ,Common disease ,medicine.medical_treatment ,lcsh:RC254-282 ,Calcification ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Humerus ,Osteosarcoma ,Chemotherapy ,business.industry ,Liver Neoplasms ,Calcinosis ,Neoplasms, Second Primary ,General Medicine ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,medicine.anatomical_structure ,Lymphatic system ,Oncology ,030220 oncology & carcinogenesis ,Female ,Neoplasm Recurrence, Local ,business ,liver metastases - Abstract
Osteosarcoma is the commonest primary malignant bone tumor. Since bones lack a lymphatic system, metastatic spread in these tumors is exclusively hematogenous, the commonest sites being lungs and bone. We report a case of osteosarcoma humerus which recurred locally after primary therapy consisting of neoadjuvant chemotherapy and limb salvage surgery, who developed calcified liver metastases in addition to local and pulmonary relapse. Liver, though a common site of hematogenous spread in most solid tumors, has rarely been reported to be involved in metastatic osteosarcomas. more...
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- 2017
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26. Oncogenic Osteomalacia as a Harbinger of Recurrent Osteosarcoma
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Elizabeth B. Lamont, Bruce Brockstein, and Melissa K. Cavaghan
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musculoskeletal diseases ,Osteomalacia ,Pathology ,medicine.medical_specialty ,Chemotherapy ,Recurrent osteosarcoma ,business.industry ,medicine.medical_treatment ,nutritional and metabolic diseases ,medicine.disease ,urologic and male genital diseases ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Pathophysiology ,Oncogenic osteomalacia ,Oncology ,medicine ,Etiology ,Radiology, Nuclear Medicine and imaging ,business ,Research Article - Abstract
Discussion. Oncogenic osteomalacia is a rare paraneoplastic syndrome of skeletal demineralization from renal phosphate loss. Patients with this disorder have the characteristic clinical, laboratory, and radiographic findings of hyperphosphaturic osteomalacia. Although the pathophysiology has not yet been clearly delineated, a humoral factor produced by the tumor is suspected to be the cause. Purpose. We report the first case of oncogenic osteomalacia that improved with chemotherapy, discuss this paraneoplastic syndrome, and review the medical literature regarding its etiology. more...
- Published
- 1999
27. Factors influencing survival after recurrence in osteosarcoma: A report from the Children's Oncology Group.
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Spraker-Perlman HL, Barkauskas DA, Krailo MD, Meyers PA, Schwartz CL, Doski J, Gorlick R, Janeway KA, and Isakoff MS
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- Adolescent, Bone Neoplasms pathology, Bone Neoplasms therapy, Child, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Male, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local therapy, Osteosarcoma secondary, Osteosarcoma therapy, Prognosis, Prospective Studies, Retrospective Studies, Risk Factors, Survival Rate, Bone Neoplasms mortality, Neoplasm Recurrence, Local mortality, Osteosarcoma mortality
- Abstract
Background: Despite drastic improvement in overall survival for pediatric patients with cancer, those with osteosarcoma have stable rates of survival since the 1980s. This project evaluates the effect of several variables on survival after first recurrence in patients with osteosarcoma., Methods: Data from three prospective North American cooperative group trials for newly diagnosed osteosarcoma are included: INT-0133, POG-9754, and AOST0121. The analytic population for this study is all enrolled patients with first event-free survival (EFS) event of relapse. The primary outcome measure for this retrospective analysis was survival after recurrence (SAR)., Results: The analytic population consisted of N = 431 patients. SAR was statistically significantly associated with age at enrollment (<10 years, P = 0.027), presence of metastatic disease at diagnosis (localized, P < 0.0001), site of relapse (combination lung + bone, unfavorable, P = 0.005), and time to first relapse (2+ years, favorable, P < 0.0001) in multivariate analysis. Ethnicity, primary site of tumor, race, and sex were not significantly related to SAR., Conclusions: Prolonged SAR in patients with relapsed osteosarcoma is associated with age, extent of disease at diagnosis, site of and time to relapse. Adolescent and young adult patients with osteosarcoma have shorter SAR than younger patients, consistent with studies showing decreased overall survival in this group. Although patients with primary metastatic disease have shorter SAR, there is a subset of patients who relapse greater than 2 years from initial diagnosis that will become survivors. Histological response was significantly associated with time to relapse, but was not predictive of SAR., (© 2018 Wiley Periodicals, Inc.) more...
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- 2019
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28. (99m)Tc-MDP- and (18F)-FDG-avid florid reactive periostitis ossificans mimicking recurrent osteosarcoma
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Ji Young Yoo, Sang Moo Lim, Jae-Soo Koh, Byung Hyun Byun, and Chang-Bae Kong
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musculoskeletal diseases ,Male ,Pathology ,medicine.medical_specialty ,Recurrent osteosarcoma ,Technetium Tc 99m Medronate ,Diagnosis, Differential ,Periostitis ,Fluorodeoxyglucose F18 ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Femur ,Radionuclide imaging ,Child ,Radionuclide Imaging ,Osteosarcoma ,business.industry ,Florid reactive periostitis ,General Medicine ,Benign lesion ,medicine.disease ,body regions ,Tracer uptake ,Neoplasm Recurrence, Local ,business - Abstract
Florid reactive periostitis ossificans is a rare benign lesion usually affecting the tubular bones of the hands and feet, and its histological features may be confused with those of infection and osteosarcoma. We report a case with florid reactive periostitis ossificans of the femur showing increased tracer uptake on both Tc-MDP bone scan and F-FDG PET/CT mimicking a local recurrence in a 15-year-old patient with high-grade osteosarcoma. more...
- Published
- 2013
29. Emerging concepts for PI3K/mTOR inhibition as a potential treatment for osteosarcoma
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Michael W. Bishop and Katherine A. Janeway
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musculoskeletal diseases ,0301 basic medicine ,Recurrent osteosarcoma ,Cell cycle checkpoint ,Cell Growth & Division ,Review ,inhibition treatment ,PI3K ,General Biochemistry, Genetics and Molecular Biology ,Cancer Therapeutics ,03 medical and health sciences ,0302 clinical medicine ,Cell Signaling ,osteosarcoma ,Clinical investigation ,medicine ,General Pharmacology, Toxicology and Pharmaceutics ,neoplasms ,PI3K/AKT/mTOR pathway ,General Immunology and Microbiology ,business.industry ,Cell growth ,Sarcomas ,Articles ,General Medicine ,medicine.disease ,Preclinical data ,030104 developmental biology ,Pediatric Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Immunology ,mTOR ,Cancer research ,Osteosarcoma ,business ,Medical Genetics - Abstract
Patients with metastatic and recurrent osteosarcoma fare poorly, and new therapeutic strategies are needed to improve survival. Several recent complementary genomic and pathway analyses of both murine and human osteosarcoma have revealed common aberrations of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway in osteosarcoma. Preclinical data demonstrate that inhibition of PI3K and mTOR with either a combination of single agents or dual inhibiting compounds can decrease cell proliferation and induce cell cycle arrest and apoptosis. With a lack of available clinical agents active in osteosarcoma, PI3K/mTOR inhibition represents a potential vulnerability in osteosarcoma that warrants clinical investigation. more...
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- 2016
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30. Recurrent osteosarcoma of maxilla presenting as fungating mass: A case report
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Saira E. Denny, T T Sivakumar, Anna P. Joseph, Subramonian Sivaraj, Varun B. Raghavanpillai, and Pratheep Jeevadhas
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musculoskeletal diseases ,medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,Osteoid ,Fungating Mass ,Mesenchymal stem cell ,Electronic journal ,030206 dentistry ,medicine.disease ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Maxilla ,medicine ,Osteosarcoma ,Hematopoietic Neoplasms ,business - Abstract
Introduction: Osteosarcoma is the most common primary malignant bone tumor excluding hematopoietic neoplasms. It is thought to arise from a primitive mesenchymal bone-forming cell and is characterized by production of osteoid. Despite osteosarcomas of the jaws being less aggressive than those occurring in the long bones, local recurrence after surgical therapy is a major complication. more...
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- 2016
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31. Outcome of recurrent osteosarcoma patients enrolled in seven phase II trials through CCG, POG, and COG: Learning from the past to move forward
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Katherine A. Janeway, Susan M. Blaney, Richard Gorlick, Joanne Lagmay, Orren Beaty, Ha Dang, Mark Krailo, Douglas S. Hawkins, Holcombe E. Grier, AeRang Kim, Brenda J. Weigel, Theodore Zwerdling, Lisa Bomgaars, Anne-Marie R Langevin, and Brigitte C. Widemann more...
- Subjects
Oncology ,Cancer Research ,Treatment response ,medicine.medical_specialty ,Recurrent osteosarcoma ,business.industry ,medicine.disease ,Surgery ,Cog ,Internal medicine ,Clinical endpoint ,medicine ,Osteosarcoma ,business - Abstract
10042 Background: The use of radiographic response as the primary endpoint in phase II osteosarcoma (OS) trials may limit optimal detection of treatment response due to the calcified tumor matrix. ... more...
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- 2015
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32. Comparison of 18F-FDG-PET-CT and bone scintigraphy for evaluation of osseous metastases in newly diagnosed and recurrent osteosarcoma
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Caitlin Hurley, Barry L. Shulkin, Fariba Navid, Shenghua Mao, M. Beth McCarville, Najat C. Daw, Jianrong Wu, Alberto S. Pappo, and Michael W. Bishop
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musculoskeletal diseases ,Cancer Research ,medicine.medical_specialty ,Recurrent osteosarcoma ,medicine.diagnostic_test ,business.industry ,Newly diagnosed ,medicine.disease ,Oncology ,Bone scintigraphy ,medicine ,Osteosarcoma ,Fdg pet ct ,Radiology ,Positron emission ,Tomography ,business ,neoplasms - Abstract
10047 Background: Bone scintigraphy (BS) is routinely used to detect osseous metastases in osteosarcoma. The use of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-... more...
- Published
- 2015
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33. Treatment and outcome of recurrent osteosarcoma: experience at Rizzoli in 235 patients initially treated with neoadjuvant chemotherapy
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Gaetano Bacci, Stefano Ferrari, Franca Faggioli, Mario Mercuri, Alessandra Longhi, Piero Picci, Michela Versari, and Antonio Briccoli
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Male ,medicine.medical_specialty ,Recurrent osteosarcoma ,Adolescent ,medicine.medical_treatment ,Salvage therapy ,Bone Neoplasms ,Disease ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Neoadjuvant therapy ,Salvage Therapy ,Chemotherapy ,Osteosarcoma ,business.industry ,Hematology ,General Medicine ,medicine.disease ,Prognosis ,Neoadjuvant Therapy ,Surgery ,Radiation therapy ,Treatment Outcome ,Oncology ,Chemotherapy, Adjuvant ,Female ,Neoplasm Recurrence, Local ,business ,Adjuvant - Abstract
The pattern of relapse, treatment and final outcome of 235 patients with osteosarcoma of the extremity who relapsed after neoadjuvant treatments performed between 1986 and 1998 at a single institution is reported. The 235 relapses were treated by surgery, surgery plus second line chemotherapy, and only second line chemotherapy or radiotherapy. The 5-year post-relapse-event-free-survival (PREFS) was 27.6% and the post-relapse-overall-survival (PROS) 28.7%. All 69 patients who are presently alive and free of disease were treated by surgery, alone or combined with chemotherapy. None of patients treated only by chemotherapy or radiotherapy survived. We conclude that it is possible to obtain prolonged survival and cure in about 1/4 of relapsing osteosarcoma patients with aggressive treatments. The complete removal of the recurrence is essential for outcome, while the role of the association of second-line chemotherapy remains to be defined. more...
- Published
- 2005
34. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS)
- Author
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Gernot Jundt, Kurt Winkler, Rainer Maas, Heribert Jürgens, Wolfgang E. Berdel, Detlev Branscheid, Beate Kempf-Bielack, Jörn Treuner, G. Ulrich Exner, Knut Helmke, Rainer Kotz, Andreas Zoubek, Thomas Klingebiel, Michael Semik, Hartmut Kabisch, Mathias Kevric, Rudolf Schwarz, Ulrich Göbel, and Stefan S. Bielack more...
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Recurrent osteosarcoma ,Time Factors ,Adolescent ,Bone Neoplasms ,Cohort Studies ,Risk Factors ,Biopsy ,Antineoplastic Combined Chemotherapy Protocols ,Overall survival ,medicine ,Combined Modality Therapy ,Humans ,Child ,Survival analysis ,Aged ,Osteosarcoma ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,Surgery ,Oncology ,Child, Preschool ,Female ,Sarcoma ,Neoplasm Recurrence, Local ,business ,Cohort study - Abstract
Purpose To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. Patients and Methods Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). Results After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. Conclusion Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome. more...
- Published
- 2005
35. Case 16: Successful Delivery After a Hemipelvectomy in a 28-Year-Old Woman with Recurrent Osteosarcoma of the Proximal Femur
- Author
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Akira Ogose
- Subjects
Pregnancy ,medicine.medical_specialty ,Recurrent osteosarcoma ,Proximal femur ,business.industry ,medicine.medical_treatment ,medicine.disease ,Surgery ,Hemipelvectomy ,medicine ,Pelvic tumor ,Radiology ,business ,reproductive and urinary physiology - Abstract
A patient with a pelvic tumor, who was treated by a hemipelvectomy, became pregnant and delivered a healthy child by Cesarean section without complications.
- Published
- 2003
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36. A randomized, double-blinded, placebo-controlled, multi-institutional, cross-over, phase II.5 study of saracatinib (AZD0530), a selective Src kinase inhibitor, in patients with recurrent osteosarcoma localized to the lung
- Author
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Neyssa Marina, Scott H. Okuno, Scott M. Schuetze, Joseph G. Pressey, Kristin Baird, Sant P. Chawla, Katherine A. Janeway, Eve T. Rodler, James E. Butrynski, Sheri L. Spunt, Brian Turpin, John M. Goldberg, Lee J. Helman, Joanne Pigues Lagmay, David M. Loeb, Mohammed M. Milhem, Denise K. Reinke, Noah Federman, Leo Mascarenhas, and Arthur P. Staddon more...
- Subjects
Cross over ,Oncology ,Cancer Research ,medicine.medical_specialty ,Recurrent osteosarcoma ,Lung ,Saracatinib ,business.industry ,Placebo ,medicine.disease ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Internal medicine ,medicine ,Osteosarcoma ,In patient ,business ,Proto-oncogene tyrosine-protein kinase Src - Abstract
TPS10591 Background: Osteosarcoma is a rare cancer and 33% of patients who have completed primary treatment will recur. The Src pathway has been implicated in the metastatic behavior of several tumors including osteosarcoma where 95% of samples express Src or have evidence of downstream activation of this pathway. Saracatinib (AZD0530) is a potent and selective Src kinase inhibitor. The recommended phase II dose in adults was found to be 175mg daily. The primary goal of this study is to determine if treatment with Saracatinib can increase progression free survival (PFS) for patients who have undergone complete resection of metastatic osteosarcoma nodules in the lung. Secondary goals are evaluation of overall survival, time to treatment failure, and evaluation of several biological correlatives. Methods: This is a multi-institutional, phase II.5, placebo-controlled study with an accrual goals of 88 randomized patients. Patients between 15 and 75 years, with histological confirmation of recurrent osteosarcoma, localized to the lung, who have potential for complete surgical resection, are eligible for enrollment. After complete resection, patients are randomized to treatment with saracatinib or placebo, of a daily oral dose of 175 mg, continuously for up to 1 year or until progression. Patients who recur in the lung while on-study and who are amenable to complete surgical resection will be un-blinded. Those patients who received placebo may have the option to undergo surgical resection. If fully resected, they will be offered therapy with saracatinib under the same treatment guidelines as above. As of January 2013, 38 patients have enrolled and 32 patients met the criteria to be randomized and began oral therapy with either saracatinib or placebo. An interim analysis is planned after 40 patients have been randomized. Clinical trial information: NCT00752206. more...
- Published
- 2013
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37. Bone-specific alkaline phosphatase in plasma as tumour marker for osteosarcoma
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K.M. Lee, K.S. Leung, Shekhar M. Kumta, P.P.L. Liu, and K.P. Fung
- Subjects
musculoskeletal diseases ,Adult ,Cancer Research ,medicine.medical_specialty ,Phosphoric monoester hydrolases ,Recurrent osteosarcoma ,Adolescent ,Bone Specific Alkaline Phosphatase ,Bone Neoplasms ,Biology ,Gastroenterology ,Bone and Bones ,Tumour tissue ,Recurrence ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Neoplasm Metastasis ,Child ,Osteosarcoma ,Wheat germ ,General Medicine ,medicine.disease ,Alkaline Phosphatase ,Isoenzymes ,medicine.anatomical_structure ,Endocrinology ,Oncology ,Alkaline phosphatase ,Hong Kong ,Cortical bone - Abstract
The levels of bone-specific alkaline phosphatase (BALP) in plasma and tumour tissue samples of 20 Chinese patients with osteosarcoma in Hong Kong were measured by the wheat germ lectin precipitation technique. The plasma BALP levels in these patients were significantly higher than those of the normal subjects (p < 0.001), and also significantly higher than those of patients with benign bone tumor and those of patients with malignant tumor metastasized to the bone (p < 0.0001). Considering the prognostic value of BALP for osteosarcoma, the plasma BALP levels at the time of diagnosis were found to be significantly related to the rate of disease recurrence (p < 0.05). Furthermore, at the time of relapse, the plasma BALP levels in the group of recurrent osteosarcoma patients were significantly higher than those of osteosarcoma patients showing no recurrence (p < 0.05). When ALP was assayed in the tumor tissue, the BALP levels were also significantly higher than those of the control cortical bone extracts in the same group of patients (p < 0.05). We conclude that plasma BALP is a sensitive and specific biochemical parameter in the diagnosis and the subsequent monitoring of osteosarcoma. more...
- Published
- 1996
38. Michael S. Aldrich, MD (1949–2000)
- Author
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Sid Gilman
- Subjects
medicine.medical_specialty ,Recurrent osteosarcoma ,Family medicine ,education ,Neurology Residency ,medicine ,University medical ,Neurology (clinical) ,Sister ,Psychology ,Left behind ,Assistant professor - Abstract
Michael S. Aldrich, MD, Professor of Neurology and Director of the Sleep Disorders Program at the University of Michigan, died on July 18, 2000 at the age of 51 from the effects of a recurrent osteosarcoma. He left behind a wonderful family: Leslie Brown Aldrich, MD, Clinical Assistant Professor of Medicine at the University of Michigan and a gastroenterologist; three children, Brian, Matthew, and Jennifer; a sister, Carol Barkin; two brothers, Bob and Tom; and parents, Knight and Julie. I first met Mike when he came to Ann Arbor as an applicant to our neurology residency program. He was then a medical student at the University of Virginia School of Medicine in Charlottesville. He made a strong impression upon me. He was clearly a highly intelligent student with many interesting life experiences, but he presented himself in a quiet, humble, and somewhat shy manner. He had a sterling academic record and an intense interest in academic neurology. Later, I was very pleased when he matched to this program, and indeed, he proved to be an exceptionally fine resident. As he progressed here, he developed into an outstanding clinical neurologist—kind and considerate to his patients, and adept in diagnosis, management, and treatment. He was also academically productive, writing a succession of papers on stroke, epilepsy, and cortical blindness from observations he made during his residency. Upon completing his residency, he entered a fellowship in electroencephalography and clinical neurophysiology in this department, but he requested permission to receive special training in clinical sleep disorders at Stanford University Medical School. This was granted, and he spent several months … more...
- Published
- 2001
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- View/download PDF
39. Totally implantable venous access system (TIVAS) Complicated by Tracheo-Venous Fistula
- Author
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Samer Khaled, Arunbai Patel, and Vladimir Gotlieb
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medicine.medical_specialty ,Chemotherapy ,Recurrent osteosarcoma ,business.industry ,Fistula ,medicine.medical_treatment ,TIVAS, totally implantable venous access system ,food and beverages ,medicine.disease ,Article ,CT, computed tomography ,Surgery ,Venous access ,Catheter ,Port (medical) ,medicine ,Radiology, Nuclear Medicine and imaging ,Innominate vein ,business ,Complication - Abstract
Totally implantable venous access system (TIVAS) are widely used for various indications including chemotherapy infusion. The use of TIVAS is associated with number of complications that can occur as early as the time of insertion or can take place months later. We report a case of a 64 year old female with recurrent osteosarcoma of the mandible. She had a port-a-catheter placed for chemotherapy infusion. The patient developed fistula between the Innominate Vein and the trachea, which found to be secondary to a spontaneous migration of the tip of the catheter. To our knowledge this is the first case of this kind to be reported. This complication, although very rare, can be life threatening, and should be considered when there is a malfunction of the TIVAS. more...
- Published
- 2009
- Full Text
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40. Survival after recurrent osteosarcoma: Data from three European Osteosarcoma Intergroup (EOI) randomized controlled
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Matthew R. Sydes, Antonie H. M. Taminiau, M. Nooij, Hans Gelderblom, Jeremy Whelan, Ian Lewis, Rachel C Morgan, and Pancras C.W. Hogendoorn
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Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,Recurrent osteosarcoma ,Postoperative chemotherapy ,business.industry ,fungi ,medicine.disease ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Medicine ,Osteosarcoma ,business - Abstract
10505 Background: Between 1983 and 2002, the EOI accrued to three randomized controlled trials of pre- and postoperative chemotherapy for patients (pts) with resectable nonmetastatic high-grade ost... more...
- Published
- 2008
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41. Muscle necrosis simulating recurrent osteosarcoma. A case report
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Alvin H. Crawford, Richard B. Towbin, and Edgar T. Ballard
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Pathology ,medicine.medical_specialty ,Recurrent osteosarcoma ,Text mining ,business.industry ,Medicine ,MUSCLE NECROSIS ,Orthopedics and Sports Medicine ,Surgery ,General Medicine ,business - Published
- 1980
- Full Text
- View/download PDF
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