Long-term results of the Spanish Protocol SO-95 for the treatment of non-metastatic high-grade osteosarcoma of the extremities in children

Muñoz, Alvaro; Alfaro, J; Pardo, Núria; García‐Miguel, Purificación; Quintero, Víctor; Gros, Luis; Melero, Carmen; Antuña, M.; Ocete, Guillermo; Heras, Jorge de las; Portal, Manuel Ruiz del; Huguet, R.; Maldonado, M S

doi:10.1007/s12094-009-0373-3

Cited by 17 publications

(11 citation statements)

References 26 publications

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“…[1,2] Multiagent regimens may include doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide. [1][2][3][4][5][6][7][8] Tumor necrosis evaluated in surgical specimens after induction chemotherapy is a welldocumented predictor of long-term outcome in osteosarcoma; [9] patients with >90% tumor necrosis after induction chemotherapy have 65-80% 5-year EFS versus 40-50% EFS for those with <90% tumor necrosis. [1][2][3][4][5][6][7][8] These data suggest the need to improve treatment efficacy, especially in the latter cohort.…”

Section: Introductionmentioning

confidence: 99%

Intensified Chemotherapy With Dexrazoxane Cardioprotection in Newly Diagnosed Nonmetastatic Osteosarcoma: A Report From the Children's Oncology Group

Schwartz

Wexler

Krailo

et al. 2015

Pediatric Blood & Cancer

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Background Although chemotherapy has improved outcome of osteosarcoma, 30–40% of patients succumb to this disease. Survivors experience substantial morbidity and mortality from anthracycline-induced cardiotoxicity. We hypothesized that the cardioprotectant dexrazoxane would 1) support escalation of the cumulative doxorubicin dose (600 mg/m2) and 2) not interfere with the cytotoxicity of chemotherapy measured by necrosis grading in comparison to historical control data.9 Procedure Children and adolescents with non-metastatic osteosarcoma were treated with MAP (methotrexate, doxorubicin, cisplatin) or MAPI (MAP/ifosfamide). Dexrazoxane was administered with all doxorubicin doses. Cardioprotection was assessed by measuring left ventricular fractional shortening. Interference with chemotherapy-induced cytotoxicity was determined by measuring tumor necrosis after induction chemotherapy. Feasibility of intensifying therapy with either high cumulative-dose doxorubicin or high-dose ifosfamide/etoposide was evaluated for ‘standard responders’ (SR, <98% tumor necrosis at definitive surgery). Results Dexrazoxane did not compromise response to induction chemotherapy. With doxorubicin (450–600 mg/m2) and dexrazoxane, grade 1 or 2 left ventricular dysfunction occurred in 5 patients; 4/5 had transient effects. Left ventricular fractional shortening z-scores (FSZ) showed minimal reductions (0.0170 ±0.009/week) over 78 weeks. Two patients (<1%) had secondary leukemia, one as a first event, a similar rate to what has been observed in prior trials. Intensification with high-dose ifosfamide/etoposide was also feasible. Conclusions Dexrazoxane cardioprotection was safely administered. It did not impair tumor response or increase the risk of secondary malignancy. Dexrazoxane allowed for therapeutic intensification, increasing the cumulative doxorubicin dose in SR to induction chemotherapy. These findings support the use of dexrazoxane in children and adolescents with osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

Intensified Chemotherapy With Dexrazoxane Cardioprotection in Newly Diagnosed Nonmetastatic Osteosarcoma: A Report From the Children's Oncology Group

Schwartz

Wexler

Krailo

et al. 2015

Pediatric Blood & Cancer

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“…Despite an ambitious multidisciplinary treatment approach combining radical surgery with neoadjuvant and adjuvant chemotherapy, the 5-year overall survival rates for OS patients with localized disease do not exceed 70% [3,21]. Approximately 30% of these patients will not survive, probably because of resistance against current treatment protocols.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, the published series differ notably regarding the HER-2 antibodies used, the scoring schemes of the immunoreactions, the analyzed samples (pretherapeutic biopsies versus posttherapeutic samples versus metastases), and the clinicopathological data given, making it difficult to compare the different results and to draw unequivocal conclusions [4,24]. However, all kinds of interpretations have been published, including those who found HER-2 expression to be correlated with a poor prognosis [12,13,23,25], with a favorable outcome [17], or those who could not find any correlation at all [16,21,26]. In our series, we investigated only well-characterized and un-decalcified pretherapeutic biopsy samples and used the most widely used antibodies for the assessment of HER-2 expression.…”

Section: Discussionmentioning

confidence: 99%

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Aberrant expression of the human epidermal growth factor receptor 2 oncogene is not a common feature in osteosarcoma

Baumhoer

Smida²,

Specht³

et al. 2011

Human Pathology

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“…The choice of agents may take into account the prior disease-free interval and often includes ifosfamide ± etoposide, or possibly docetaxel/gemcitabine. The use of second-line chemotherapy has been shown to correlate with limited prolongation of survival in patients with inoperable metastatic recurrences, and a positive correlation in operable disease was observed in one series [82–84]. Radiotherapy to inoperable sites may be indicated for palliation.…”

Section: Specific Treatmentmentioning

confidence: 99%

UK Guidelines for the Management of Bone Sarcomas

Grimer

Athanasou

Gerrand

et al. 2010

Sarcoma

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These guidelines have been developed in order to provide an overview and a set of broad-based key recommendations for the management of patients with bone sarcomas in the UK. They have taken into consideration the most up-to-date scientific literature along with the recent recommendations by the European Society of Medical Oncology. The principles of the NICE guidance on both “improving outcomes for patients with sarcomas” and “improving outcomes with children and young people with cancer” have been incorporated. As care evolves, it is acknowledged that these guidelines will need updating. The key recommendations are that bone pain or a palpable mass should always lead to further investigation and patients with clinicoradiological findings suggestive of a primary bone tumour should be sent to a reference centre. Patients should then have their care managed at such a specialist centre by a fully accredited multidisciplinary team.

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Long-term results of the Spanish Protocol SO-95 for the treatment of non-metastatic high-grade osteosarcoma of the extremities in children

Abstract: This therapeutic protocol achieved good oncologic and orthopaedic results. We observed a significant treatment-related toxicity.

Cited by 17 publications

References 26 publications

Intensified Chemotherapy With Dexrazoxane Cardioprotection in Newly Diagnosed Nonmetastatic Osteosarcoma: A Report From the Children's Oncology Group

Intensified Chemotherapy With Dexrazoxane Cardioprotection in Newly Diagnosed Nonmetastatic Osteosarcoma: A Report From the Children's Oncology Group

Aberrant expression of the human epidermal growth factor receptor 2 oncogene is not a common feature in osteosarcoma

UK Guidelines for the Management of Bone Sarcomas

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