Evidence map›Paper›PMID 35201621›Full record

Trial reportCancer2022

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).

Emanuela Palmerini, Cristina Meazza, Angela Tamburini, Gianni Bisogno, Virginia Ferraresi, Sebastian D Asaftei, Giuseppe M Milano, Luca Coccoli, Carla Manzitti, Roberto Luksch and 20 more

Open access · bronzeAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
5.0field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Guideline
  3. Trial
  4. Review
  5. Article
  6. Review
  7. Article
  8. A comprehensive clinico-pathological review of a series of pediatric, adolescents and young adults with high-grade osteosarcoma: from clinics to biomarker discovery.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. The Interplay Between theInternational journal of molecular sciences · 2024
    Review
  16. Article
  17. Strategies to Overcome Resistance to Immune-Based Therapies in Osteosarcoma.International journal of molecular sciences · 2023
    Review
  18. Exosomes and osteosarcoma drug resistance.Frontiers in oncology · 2023
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors at 11 institutions in 1 country.

Emanuela PalmeriniOsteoncology, Bone and Soft Tissue Sarcomas, and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Cristina MeazzaPediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Angela TamburiniAzienda Ospedaliera Universitaria A. Meyer, Florence, Italy.
Gianni BisognoHematology Oncology Division, Department of Women's and Children's Health, University of Padova, Padua, Italy.
Virginia FerraresiIRCCS Regina Elena National Cancer Institute, Rome, Italy.
Sebastian D AsafteiAzienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Giuseppe M MilanoPediatric Oncology Department, Regina Margherita Children's Hospital, Azienda Ospedaliera Universitaria, Città della Salute e della Scienza di Torino, Turin, Italy.
Luca CoccoliIRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Carla ManzittiIRCCS Istituto G. Gaslini-Ospedale Pediatrico, Genoa, Italy.
Roberto LukschPediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Massimo SerraOsteoncology, Bone and Soft Tissue Sarcomas, and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Marco GambarottiDepartment of Pathology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Davide M DonatiThird Orthopedic and Traumatologic Clinic Prevalently Oncologic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Katia ScotlandiLaboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Rossella BertulliPediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Claudio FavreAzienda Ospedaliera Universitaria A. Meyer, Florence, Italy.
Alessandra LonghiOsteoncology, Bone and Soft Tissue Sarcomas, and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Massimo E AbatePediatric Oncology, National Medical Specialization Center Santobono-Pausilipon, Napoli, Italy.
Silverio PerrottaEmatologia ed Oncologia Pediatrica, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy.
Maurizio MascarinAYA Oncology and Pediatric Radiotherapy Unit, IRCCS Centro di Riferimento Oncologico, Aviano, Italy.
Paolo D'AngeloOncoematologia Pediatrica Palermo, Palermo, Italy.
Marilena CesariOsteoncology, Bone and Soft Tissue Sarcomas, and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Eric L StaalsThird Orthopedic and Traumatologic Clinic Prevalently Oncologic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Emanuela MarchesiItalian Sarcoma Group, Bologna, Italy.
Elisa CarrettaOsteoncology, Bone and Soft Tissue Sarcomas, and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Toni IbrahimOsteoncology, Bone and Soft Tissue Sarcomas, and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Paolo G CasaliPediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Piero PicciItalian Sarcoma Group, Bologna, Italy.
Franca FagioliAzienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Stefano FerrariOsteoncology, Bone and Soft Tissue Sarcomas, and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Istituto Ortopedico Rizzoli · ITFondazione IRCCS Istituto Nazionale dei Tumori · ITIstituti di Ricovero e Cura a Carattere Scientifico · ITAzienda Ospedaliera Universitaria Pisana · ITItalian Sarcoma Group · ITMeyer Children's Hospital · ITAzienda Ospedaliera Citta' della Salute e della Scienza di Torino · ITAzienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli · ITBambino Gesù Children's Hospital · ITSantobono Children's Hospital · ITUniversity of Padua · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAccording 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.

methodsThis 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/m

resultsIn 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%).

conclusionsThis 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.

Indexed as

Bone NeoplasmsOsteosarcomaAdolescentAdultAntineoplastic Combined Chemotherapy ProtocolsATP Binding Cassette Transporter, Subfamily BChildDisease-Free SurvivalExtremitiesHumansIfosfamideItalyMethotrexateProspective StudiesRetrospective StudiesTreatment OutcomeABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BIfosfamideMethotrexateadolescents and young adults (AYAs)ATP binding cassette subfamily B member 1 (ABCB1)chemotherapyhigh-grade bone sarcomamifamurtideosteosarcomapediatric bone tumorsP-glycoprotein

Identifiers

PMID35201621
PMCPMC9305236
OpenAlexW4213431093

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.