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3 results on '"Sebastian D. Asaftei"'

1. Precision Medicine in Osteosarcoma: MATCH Trial and Beyond

Author

Elisa Tirtei, Anna Campello, Sebastian D. Asaftei, Katia Mareschi, Matteo Cereda, and Franca Fagioli

Subjects
osteosarcoma, precision medicine, next generation sequencing, target-therapy, clinical trials, Cytology, QH573-671
Abstract

Osteosarcoma (OS) is a rare bone malignant tumour with a poor prognosis in the case of recurrence. So far, there is no agreement on the best systemic therapy for relapsed OS. The availability of next generation sequencing techniques has recently revolutionized clinical research. The sequencing of the tumour and its matched normal counterpart has the potential to reveal a wide landscape of genetic alterations with significant implications for clinical practice. The knowledge that the genomic profile of a patient’s tumour can be precisely mapped and matched to a targeted therapy in real time has improved the development of precision medicine trials (PMTs). PMTs aiming at determining the effectiveness of targeted therapies could be advantageous for patients with a tumour refractory to standard therapies. Development of PMTs for relapsed OS is largely encouraging and is in its initial phase. Assessing OS features, such as its rarity, its age distribution, the technical issues related to the bone tissue origin, and its complex genomic landscape, represents a real challenge for PMTs development. In this light, a multidisciplinary approach is required to fully exploit the potential of precision medicine for OS patients.

Published
2021
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2. Unresectable Clival Giant Cell Tumor, Tumor Control With Denosumab After Relapse: A Case Report and Systematic Review of the Literature

Author

Maria Grazia, Pionelli, Sebastian D, Asaftei, Elisa, Tirtei, Anna, Campello, Gianpaolo, Di Rosa, and Franca, Fagioli

Subjects
Giant Cell Tumor of Bone, clival bone, Adolescent, skull base, Bone Neoplasms, pediatric oncology, Hematology, GCT, Skull Base Neoplasms, Cranial Fossa, Posterior, Oncology, Pediatrics, Perinatology and Child Health, Humans, Female, Denosumab, Neoplasm Recurrence, Local
Abstract

Giant cell tumors (GCTs) of the skull base are rare entities. Although considered histologically benign, GCTs are locally aggressive with a high rate of local recurrence. The present case describes a 14-year-old girl with a clival GCT who underwent long-term therapy with denosumab after local relapse. To our knowledge, it is the second case described with a follow-up term2 years from the start of denosumab and who did not receive any other adjuvant treatment besides denosumab. The patient achieved a local control of the disease. According to the few available data, radical excision with adjuvant therapy helps in long-term control in uncommon sites, such as the skull. However, the definitive treatment is still controversial because of their rarity and few follow-up data. The present case highlights the benefit of denosumab and its safety as long-term therapy and contributes to the existing literature with analysis and evaluation of the management strategies and prognosis.

Published
2022

3. Phase 2 study for nonmetastatic extremity high-grade osteosarcoma in pediatric and adolescent and young adult patients with a risk-adapted strategy based on ABCB1/P-glycoprotein expression: An Italian Sarcoma Group trial (ISG/OS-2)

Author

Emanuela Palmerini, Cristina Meazza, Angela Tamburini, Gianni Bisogno, Virginia Ferraresi, Sebastian D. Asaftei, Giuseppe M. Milano, Luca Coccoli, Carla Manzitti, Roberto Luksch, Massimo Serra, Marco Gambarotti, Davide M. Donati, Katia Scotlandi, Rossella Bertulli, Claudio Favre, Alessandra Longhi, Massimo E. Abate, Silverio Perrotta, Maurizio Mascarin, Paolo D’Angelo, Marilena Cesari, Eric L. Staals, Emanuela Marchesi, Elisa Carretta, Toni Ibrahim, Paolo G. Casali, Piero Picci, Franca Fagioli, Stefano Ferrari, Palmerini, E., Meazza, C., Tamburini, A., Bisogno, G., Ferraresi, V., Asaftei, S. D., Milano, G. M., Coccoli, L., Manzitti, C., Luksch, R., Serra, M., Gambarotti, M., Donati, D. M., Scotlandi, K., Bertulli, R., Favre, C., Longhi, A., Abate, M. E., Perrotta, S., Mascarin, M., D'Angelo, P., Cesari, M., Staals, E. L., Marchesi, E., Carretta, E., Ibrahim, T., Casali, P. G., Picci, P., Fagioli, F., and Ferrari, S.

Subjects
Adult, Cancer Research, ATP Binding Cassette Transporter, Subfamily B, ATP binding cassette subfamily B member 1 (ABCB1), P-glycoprotein, adolescents and young adults (AYAs), chemotherapy, high-grade bone sarcoma, mifamurtide, osteosarcoma, pediatric bone tumors, Adolescent, Antineoplastic Combined Chemotherapy Protocols, Child, Disease-Free Survival, Extremities, Humans, Ifosfamide, Italy, Methotrexate, Prospective Studies, Retrospective Studies, Treatment Outcome, Young Adult, Bone Neoplasms, Osteosarcoma, Settore MED/06 - Oncologia Medica, ATP Binding Cassette Transporter, Oncology, Subfamily B
Abstract

Background: According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed. Methods: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m2/d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp– patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed. Results: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp–, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp– patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%). Conclusions: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.

Published
2022

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