Long-term results of the co-operative German–Austrian–Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs

Fuchs, Nicola; Bielack, Stefan; Epler, D; Bieling, P; Delling, G.; Körholz, Dieter; Graf, Norbert; Heise, U.; Jürgens, Heribert; Kotz, R.; Salzer-Kuntschik, M.; Weinel, P.; Werner, Mathias; Winkler, Kurt

doi:10.1023/a:1008391103132

Cited by 303 publications

(129 citation statements)

References 28 publications

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“…Of these patients 43% were “good responders.” Surprisingly, the 5-year EFS in the good responders was only 61%. The 5-year OS was 70% and this is comparable with that reported in larger studies8–10 as described above. The patients who were deemed “good responders” to neoadjuvant chemotherapy relapsed at a higher rate than expected but were salvageable.…”

Section: Discussionsupporting

confidence: 90%

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Characterization of Localized Osteosarcoma of the Extremity in Children, Adolescents, and Young Adults From a Single Institution in South Texas

Sugalski

Jiwani

Ketchum

et al. 2014

Journal of Pediatric Hematology/Oncology

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Background:Osteosarcoma is the most common bone malignancy in children, adolescents, and young adults. Most study cohorts have 10% to 15% Hispanic patients that encompass many different Hispanic backgrounds. This study characterizes the effect of mainly Mexican American ethnicity on the outcome of children, adolescents, and young adults with osteosarcoma.Methods:A retrospective analysis of demographics, tumor characteristics, response to treatment, and survival outcome of all localized osteosarcoma of the extremity patients below 30 years of age was performed. A Kaplan-Meier estimates with log-rank tests and Cox proportional hazard regression models were used.Results:Fifty patients (median age, 15; range, 2 to 28 y) with localized high-grade osteosarcoma of the extremity were diagnosed between January 2000 and December 2010. The cohort was 70% Mexican Americans. With a median follow-up of 39 months (range, 5 to 142 mo), patients had a 5-year overall survival and event-free survival of 65% and 48%, respectively. We observed a significantly decreased 5-year event-free survival in patients diagnosed before age 12 relative to patients diagnosed between ages 12 and 29 (11% vs. 57%, P<0.001). We also found that tumor necrosis was not predictive of outcome in our patients.Conclusions:The preadolescent patients of predominately Mexican American ethnicity had an increased rate of relapse when compared with previous studies. Tumor necrosis is not directly predictive of outcome in this population.

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Section: Discussionsupporting

confidence: 90%

“…In previous studies, good responders (>90% necrosis) had a 5-year EFS of 67% to 78%, whereas the poor responders had a 5-year EFS of 49% to 51% 8–10. In our cohort, tumor necrosis assessment was available for 40 patients.…”

Section: Discussionmentioning

confidence: 90%

Characterization of Localized Osteosarcoma of the Extremity in Children, Adolescents, and Young Adults From a Single Institution in South Texas

Sugalski

Jiwani

Ketchum

et al. 2014

Journal of Pediatric Hematology/Oncology

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“…The median age was 18 years (range: [15][16][17][18][19][20][21][22][23][24][25]. A total of 344 cycles, including the pre-operative and post-operative treatments, were evaluable for toxicity and for HDMTX pharmacokinetics (Table 4).…”

Section: Resultsmentioning

confidence: 99%

“…HDMTX was given as a single agent (8)(9)(10)(11)(12) g/m²) on day 1, then on days 8 and 15. In addition, patients received ifosfamide (5 g/m², 4 courses), cisplatin (100 mg/m², 1 course) and doxorubicin (60 mg/m², 2 courses) given sequentially, as previously described [16][17][18]. Anti-emetic prophylaxis included anti-5HT3…”

Section: Treatment Protocolmentioning

confidence: 99%

Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma

Mir

Ropert

Babinet

et al. 2010

Cancer Chemother Pharmacol

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(204 words)Purpose: To evaluate the reliability and renal safety of an original schedule of high-dose methotrexate (HDMTX) administration with hyper-alkalinization, and without hyperhydration.Methods: Osteosarcoma patients received HDMTX (8-12 g/m²) as a 4-hour infusion.Hypertonic 8.4% sodium bicarbonate was infused prior to HDMTX, then once daily for 3 days. Methotrexate serum concentrations was measured at hour 4 (Cmax), hour 24, hour 48 and hour 72. Urinary pH was measured on each miction. Serum creatinine was assessed on days 1, 3 and 8.Results: Twenty-six patients (median age: 18 years, range: 15-25) received a total of 344 cycles of HDMTX, including 16 patients treated in an outpatient basis. Urinary pH remained constantly higher than 7.5 in all patients. Grade 1 creatininemia toxicity was observed in 31 cycles (9%), and grade 2 creatinine toxicity was observed in one patient. No episode of acute severe nephrotoxicity was observed. No significant worsening was observed in serum creatinine and calculated creatinine clearance from baseline to the end of therapy (p = 0.74).The main extra-renal toxicity was alkalinization-related hypokalemia from H48. No rehospitalisation was required. Conclusion:Hyper-alkalinization appears an efficient and reliable method to prevent the acute renal toxicity of HDMTX, and allows its safe administration in the outpatient setting.

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“…Despite advances in treatment, the outcome of the disease remains unpredictable (Fuchs et al, 1998;Provisor et al, 1997). Elucidation of the genetic changes critical to osteosarcoma formation may facilitate prognostic and therapeutic evaluation, but is hampered by the complex patterns of structural and numerical chromosomal abnormalities (Biegel et al, 1989;Bridge et al, 1997;Fletcher et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Two novel tumor suppressor gene loci on chromosome 6q and 15q in human osteosarcoma identified through comparative study of allelic imbalances in mouse and man

et al. 2002

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We have performed a comparative study of allelic imbalances in human and murine osteosarcomas to identify genetic changes critical for osteosarcomagenesis. Two adjacent but discrete loci on mouse chromosome 9 were found to show high levels of allelic imbalance in radiationinduced osteosarcomas arising in (BALB/c6CBA/CA) F1 hybrid mice. The syntenic human chromosomal regions were investigated in 42 sporadic human osteosarcomas. For the distal locus (OSS1) on mouse chromosome 9 the syntenic human locus was identified on chromosome 6q14 and showed allelic imbalance in 77% of the cases. Comparison between the human and mouse syntenic regions narrowed the locus down to a 4 Mbp fragment flanked by the marker genes ME1 and SCL35A1. For the proximal locus (OSS2) on mouse chromosome 9, a candidate human locus was mapped to chromosome 15q21 in a region showing allelic imbalance in 58% of human osteosarcomas. We have used a combination of synteny and microsatellite mapping to identify two potential osteosarcoma suppressor gene loci. This strategy represents a powerful tool for the identification of new genes important for the formation of human tumors.

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Long-term results of the co-operative German–Austrian–Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs

Abstract: In a multicenter setting, intensive treatment of osteosarcoma according to protocol COSS-86 led to long-term disease-free survival for two thirds of patients. We saw no benefit of using the intraarterial route to administer cisplatin.

Cited by 303 publications

References 28 publications

Characterization of Localized Osteosarcoma of the Extremity in Children, Adolescents, and Young Adults From a Single Institution in South Texas

Characterization of Localized Osteosarcoma of the Extremity in Children, Adolescents, and Young Adults From a Single Institution in South Texas

Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma

Two novel tumor suppressor gene loci on chromosome 6q and 15q in human osteosarcoma identified through comparative study of allelic imbalances in mouse and man

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