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Clinical outcomes of medical treatments for progressive desmoid tumors following active surveillance: a systematic review

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Abstract

Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered in cases of disease progression. This systematic review aimed to evaluate the effectiveness and toxicity of each medical treatment by reviewing only the studies that included progressive disease as the inclusion criterion. We searched the EMBASE, PubMed, and CENTRAL databases to identify published studies for progressive DTs. The disease control rates of the medical treatments, such as low-dose chemotherapy with methotrexate plus vinblastine or vinorelbine, imatinib, sorafenib, pazopanib, nilotinib, anlotinib, doxorubicin-based agents, liposomal doxorubicin, hydroxyurea, and oral vinorelbine for progressive DTs were 71–100%, 78–92%, 67–96%, 84%, 88%, 86%, 89–100%, 90–100%, 75%, and 64%, respectively. Low-dose chemotherapy, sorafenib, pazopanib, nilotinib, anlotinib, and liposomal doxorubicin had similar toxicities. Sorafenib and pazopanib were less toxic than imatinib. Doxorubicin-based chemotherapy was associated with the highest toxicity. Hydroxyurea and oral vinorelbine exhibited the lowest toxicity. Stepwise therapy escalation from an initial, less toxic treatment to more toxic agents is recommended for progressive DTs. Sorafenib and pazopanib had limited on-treatment side effects but had the possibility to induce long-term treatment-related side effects. In contrast, low-dose chemotherapy has some on-treatment side effects and is known to have very low long-term toxicity. Thus, for progressive DTs following active surveillance, low-dose chemotherapy is recommended in young patients as long-term side effects are minor, whereas therapies such as sorafenib and pazopanib is recommended for older patients as early side effects are minor.

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References

  1. Fritchie KJ, Crago AM, van de Rijn M (2020) Desmoid fibromatosis. In: The WHO classification of tumours editorial board (Ed.) WHO classification of tumours. 5th edn. Soft tissue and bone tumours. IARC, Lyon, pp 93–95

  2. Kasper B, Baumgarten C, Bonvalot S et al (2015) Management of sporadic desmoid-type fibromatosis: a European consensus approach based on patients’ and professionals’ expertise - a sarcoma patients EuroNet and European organisation for research and treatment of cancer/soft tissue and bone sarcoma group initiative. Eur J Cancer 51:127–136. https://doi.org/10.1016/j.ejca.2014.11.005

    Article  CAS  PubMed  Google Scholar 

  3. Fiore M, Rimareix F, Mariani L et al (2009) Desmoid-type fibromatosis: a front-line conservative approach to select patients for surgical treatment. Ann Surg Oncol 16:2587–2593. https://doi.org/10.1245/s10434-009-0586-2

    Article  PubMed  Google Scholar 

  4. Penel N, Le Cesne A, Bonvalot S et al (2017) Surgical versus non-surgical approach in primary desmoid-type fibromatosis patients: a nationwide prospective cohort from the French Sarcoma Group. Eur J Cancer 83:125–131. https://doi.org/10.1016/j.ejca.2017.06.017

    Article  PubMed  Google Scholar 

  5. Orbach D, Brennan B, Bisogno G et al (2017) The EpSSG NRSTS 2005 treatment protocol for desmoid-type fibromatosis in children: an international prospective case series. Lancet Child Adolesc Health 1:284–292. https://doi.org/10.1016/S2352-4642(17)30045-7

    Article  PubMed  Google Scholar 

  6. Kasper B, Baumgarten C, Garcia J et al (2017) An update on the management of sporadic desmoid-type fibromatosis: a European consensus initiative between Sarcoma PAtients EuroNet (SPAEN) and European organization for research and treatment of cancer (EORTC)/soft tissue and bone sarcoma group (STBSG). Ann Oncol 28:2399–2408. https://doi.org/10.1093/annonc/mdx323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Desmoid Tumor Working Group (2020) The management of desmoid tumours: a joint global consensus-based guideline approach for adult and paediatric patients. Eur J Cancer 127:96–107. https://doi.org/10.1016/j.ejca.2019.11.013

    Article  Google Scholar 

  8. Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  9. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  10. Common Terminology Criteria for Adverse Events (CTCAE) | Protocol Development | CTEP. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. Accessed 30 Nov 2020

  11. Kim SY, Park JE, Lee YJ et al (2013) Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity. J Clin Epidemiol 66:408–414. https://doi.org/10.1016/j.jclinepi.2012.09.016

    Article  PubMed  Google Scholar 

  12. Higgins JPT, Altman DG, Gøtzsche PC et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928. https://doi.org/10.1136/bmj.d5928

    Article  PubMed  PubMed Central  Google Scholar 

  13. Gounder MM, Mahoney MR, Van Tine BA et al (2018) Sorafenib for advanced and refractory desmoid tumors. N Engl J Med 379:2417–2428. https://doi.org/10.1056/NEJMoa1805052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Toulmonde M, Pulido M, Ray-Coquard I et al (2019) Pazopanib or methotrexate-vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study. Lancet Oncol 20:1263–1272. https://doi.org/10.1016/S1470-2045(19)30276-1

    Article  CAS  PubMed  Google Scholar 

  15. Skapek SX, Hawk BJ, Hoffer FA et al (1998) Combination chemotherapy using vinblastine and methotrexate for the treatment of progressive desmoid tumor in children. J Clin Oncol 16:3021–3027. https://doi.org/10.1200/JCO.1998.16.9.3021

    Article  CAS  PubMed  Google Scholar 

  16. Azzarelli A, Gronchi A, Bertulli R et al (2001) Low-dose chemotherapy with methotrexate and vinblastine for patients with advanced aggressive fibromatosis. Cancer 92:1259–1264. https://doi.org/10.1002/1097-0142(20010901)92:5%3c1259::aid-cncr1446%3e3.0.co;2-y

    Article  CAS  PubMed  Google Scholar 

  17. Constantinidou A, Jones RL, Scurr M et al (2011) Advanced aggressive fibromatosis: effective palliation with chemotherapy. Acta Oncol 50:455–461. https://doi.org/10.3109/0284186X.2010.509105

    Article  CAS  PubMed  Google Scholar 

  18. Li S, Fan Z, Fang Z et al (2017) Efficacy of vinorelbine combined with low-dose methotrexate for treatment of inoperable desmoid tumor and prognostic factor analysis. Chin J Cancer Res 29:455–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ingley KM, Burtenshaw SM, Theobalds NC et al (2019) Clinical benefit of methotrexate plus vinorelbine chemotherapy for desmoid fibromatosis (DF) and correlation of treatment response with MRI. Cancer Med 8:5047–5057. https://doi.org/10.1002/cam4.2374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nishida Y, Hamada S, Urakawa H et al (2020) Desmoid with biweekly methotrexate and vinblastine shows similar effects to weekly administration: a phase II clinical trial. Cancer Sci. https://doi.org/10.1111/cas.14626

    Article  PubMed  PubMed Central  Google Scholar 

  21. Napolitano A, Provenzano S, Colombo C et al (2020) Familial adenomatosis polyposis-related desmoid tumours treated with low-dose chemotherapy: results from an international, multi-institutional, retrospective analysis. ESMO Open. https://doi.org/10.1136/esmoopen-2019-000604

    Article  PubMed  PubMed Central  Google Scholar 

  22. de Camargo VP, Keohan ML, D’Adamo DR et al (2010) Clinical outcomes of systemic therapy for patients with deep fibromatosis (desmoid tumor). Cancer 116:2258–2265. https://doi.org/10.1002/cncr.25089

    Article  PubMed  Google Scholar 

  23. Kasper B, Dimitrakopoulou-Strauss A, Strauss LG, Hohenberger P (2010) Positron emission tomography in patients with aggressive fibromatosis/desmoid tumours undergoing therapy with imatinib. Eur J Nucl Med Mol Imag 37:1876–1882. https://doi.org/10.1007/s00259-010-1498-x

    Article  Google Scholar 

  24. Penel N, Le Cesne A, Bui BN et al (2011) Imatinib for progressive and recurrent aggressive fibromatosis (desmoid tumors): an FNCLCC/French Sarcoma Group phase II trial with a long-term follow-up. Ann Oncol 22:452–457. https://doi.org/10.1093/annonc/mdq341

    Article  CAS  PubMed  Google Scholar 

  25. Kasper B, Dimitrakopoulou-Strauss A, Pilz LR et al (2013) Positron emission tomography as a surrogate marker for evaluation of treatment response in patients with desmoid tumors under therapy with imatinib. Biomed Res Int 2013:389672. https://doi.org/10.1155/2013/389672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kasper B, Gruenwald V, Reichardt P et al (2017) Imatinib induces sustained progression arrest in RECIST progressive desmoid tumours: final results of a phase II study of the German Interdisciplinary Sarcoma Group (GISG). Eur J Cancer 76:60–67. https://doi.org/10.1016/j.ejca.2017.02.001

    Article  CAS  PubMed  Google Scholar 

  27. Agresta L, Kim H, Turpin BK et al (2018) Pazopanib therapy for desmoid tumors in adolescent and young adult patients. Pediatr Blood Cancer 65:e26968. https://doi.org/10.1002/pbc.26968

    Article  CAS  PubMed  Google Scholar 

  28. Gounder MM, Lefkowitz RA, Keohan ML et al (2011) Activity of Sorafenib against desmoid tumor/deep fibromatosis. Clin Cancer Res 17:4082–4090. https://doi.org/10.1158/1078-0432.CCR-10-3322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zheng C, Zhou Y, Wang Y et al (2020) The activity and safety of anlotinib for patients with extremity desmoid fibromatosis: a retrospective study in a single institution. Drug Des Devel Ther 14:3941–3950. https://doi.org/10.2147/DDDT.S271008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schnitzler M, Cohen Z, Blackstein M et al (1997) Chemotherapy for desmoid tumors in association with familial adenomatous polyposis. Dis Colon Rectum 40:798–801. https://doi.org/10.1007/BF02055435

    Article  CAS  PubMed  Google Scholar 

  31. Poritz LS, Blackstein M, Berk T et al (2001) Extended follow-up of patients treated with cytotoxic chemotherapy for intra-abdominal desmoid tumors. Dis Colon Rectum 44:1268–1273. https://doi.org/10.1007/BF02234783

    Article  CAS  PubMed  Google Scholar 

  32. Gega M, Yanagi H, Yoshikawa R et al (2006) Successful chemotherapeutic modality of doxorubicin plus dacarbazine for the treatment of desmoid tumors in association with familial adenomatous polyposis. J Clin Oncol 24:102–105. https://doi.org/10.1200/JCO.2005.02.1923

    Article  CAS  PubMed  Google Scholar 

  33. Bertagnolli MM, Morgan JA, Fletcher CDM et al (2008) Multimodality treatment of mesenteric desmoid tumours. Eur J Cancer 44:2404–2410. https://doi.org/10.1016/j.ejca.2008.06.038

    Article  PubMed  Google Scholar 

  34. Ananth P, Werger A, Voss S et al (2017) Liposomal doxorubicin: Effective treatment for pediatric desmoid fibromatosis. Pediatr Blood Cancer. https://doi.org/10.1002/pbc.26375

    Article  PubMed  Google Scholar 

  35. Ferrari A, Orbach D, Affinita MC et al (2019) Evidence of hydroxyurea activity in children with pretreated desmoid-type fibromatosis: a new option in the armamentarium of systemic therapies. Pediatr Blood Cancer 66:e27472. https://doi.org/10.1002/pbc.27472

    Article  CAS  PubMed  Google Scholar 

  36. Gennatas S, Chamberlain F, Smrke A et al (2020) A timely oral option: single-agent vinorelbine in desmoid tumors. Oncologist. https://doi.org/10.1002/ONCO.13516

    Article  PubMed  PubMed Central  Google Scholar 

  37. Timbergen MJM, Schut A-RW, Grünhagen DJ et al (2020) Active surveillance in desmoid-type fibromatosis: a systematic literature review. Eur J Cancer 137:18–29. https://doi.org/10.1016/j.ejca.2020.06.022

    Article  PubMed  Google Scholar 

  38. Shimizu K, Hamada S, Sakai T et al (2019) Efficacy of low-dose chemotherapy with methotrexate and vinblastine for patients with extra-abdominal desmoid-type fibromatosis: a systematic review. Jpn J Clin Oncol. https://doi.org/10.1093/jjco/hyz204

    Article  PubMed  PubMed Central  Google Scholar 

  39. Shimizu K, Kawashima H, Kawai A et al (2020) Effectiveness of doxorubicin-based and liposomal doxorubicin chemotherapies for patients with extra-abdominal desmoid-type fibromatosis: a systematic review. Jpn J Clin Oncol 50:1274–1281. https://doi.org/10.1093/jjco/hyaa125

    Article  PubMed  Google Scholar 

  40. Smith K, Desai J, Lazarakis S, Gyorki D (2018) Systematic review of clinical outcomes following various treatment options for patients with extraabdominal desmoid tumors. Ann Surg Oncol 25:1544–1554. https://doi.org/10.1245/s10434-018-6408-7

    Article  PubMed  Google Scholar 

  41. Janinis J, Patriki M, Vini L et al (2003) The pharmacological treatment of aggressive fibromatosis: a systematic review. Ann Oncol 14:181–190. https://doi.org/10.1093/annonc/mdg064

    Article  CAS  PubMed  Google Scholar 

  42. Kasper B, Raut CP, Gronchi A (2020) Desmoid tumors: to treat or not to treat, that is the question. Cancer. https://doi.org/10.1002/cncr.33233

    Article  PubMed  Google Scholar 

  43. Skubitz KM (2017) Biology and treatment of aggressive fibromatosis or desmoid tumor. Mayo Clin Proc 92:947–964. https://doi.org/10.1016/j.mayocp.2017.02.012

    Article  PubMed  Google Scholar 

  44. Buchdunger E, Cioffi CL, Law N et al (2000) Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 295:139–145

    CAS  PubMed  Google Scholar 

  45. Carroll M, Ohno-Jones S, Tamura S et al (1997) CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood 90:4947–4952

    Article  CAS  PubMed  Google Scholar 

  46. Wilhelm SM, Carter C, Tang L et al (2004) BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109. https://doi.org/10.1158/0008-5472.CAN-04-1443

    Article  CAS  PubMed  Google Scholar 

  47. Wang Z, Wu J, Tian X, Hao C (2019) Targeted therapy of desmoid-type fibromatosis: mechanism, current situation, and future prospects. Front Med 13:427–437. https://doi.org/10.1007/s11684-018-0672-6

    Article  PubMed  Google Scholar 

  48. Weisberg E, Manley P, Mestan J et al (2006) AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. Br J Cancer 94:1765–1769. https://doi.org/10.1038/sj.bjc.6603170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Manley PW, Stiefl N, Cowan-Jacob SW et al (2010) Structural resemblances and comparisons of the relative pharmacological properties of imatinib and nilotinib. Bioorg Med Chem 18:6977–6986. https://doi.org/10.1016/j.bmc.2010.08.026

    Article  CAS  PubMed  Google Scholar 

  50. Manley PW, Drueckes P, Fendrich G et al (2010) Extended kinase profile and properties of the protein kinase inhibitor nilotinib. Biochim Biophys Acta 1804:445–453. https://doi.org/10.1016/j.bbapap.2009.11.008

    Article  CAS  PubMed  Google Scholar 

  51. Sun Y, Niu W, Du F et al (2016) Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors. J Hematol Oncol 9:105. https://doi.org/10.1186/s13045-016-0332-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wehl G, Rossler J, Otten JE et al (2004) Response of progressive fibromatosis to therapy with liposomal doxorubicin. Onkologie 27:552–556. https://doi.org/10.1159/000081337

    Article  CAS  PubMed  Google Scholar 

  53. Constantinidou A, Jones RL, Scurr M et al (2009) Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis. Eur J Cancer 45:2930–2934. https://doi.org/10.1016/j.ejca.2009.08.016

    Article  CAS  PubMed  Google Scholar 

  54. Platt OS (2008) Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med 358:1362–1369. https://doi.org/10.1056/NEJMct0708272

    Article  CAS  PubMed  Google Scholar 

  55. Messersmith WA, Shapiro GI, Cleary JM et al (2015) A Phase I, dose-finding study in patients with advanced solid malignancies of the oral γ-secretase inhibitor PF-03084014. Clin Cancer Res 21:60–67. https://doi.org/10.1158/1078-0432.CCR-14-0607

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Mr. Takaaki Suzuki, of the Library at Nara Medical University, Japan, for his help with the literature search.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Nara Medical University, 840, Shijo-cho, Kashihara, Nara, 634-8521, Japan

    S. Tsukamoto & Y. Tanaka

  2. Department of Medical Oncology, Kindai University Nara Hospital, Nara, 630-0293, Japan

    T. Takahama

  3. First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, 41 Ventouri Street, Holargos, 15562, Athens, Greece

    A. F. Mavrogenis

  4. Department of Anesthesiology, Nara Medical University, 840, Shijo-cho, Kashihara, Nara, 634-8521, Japan

    Y. Tanaka

  5. Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136, Bologna, Italy

    C. Errani

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ST designed the study, collected the data, and wrote the manuscript. TT collected the data and wrote the manuscript. YT integrated the study. YT, AFM, and CE designed the study and revised the manuscript. All authors have read and approved the final manuscript.

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Tsukamoto, S., Takahama, T., Mavrogenis, A.F. et al. Clinical outcomes of medical treatments for progressive desmoid tumors following active surveillance: a systematic review. Musculoskelet Surg 107, 7–18 (2023). https://doi.org/10.1007/s12306-022-00738-x

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