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Rationale for the use of tyrosine kinase inhibitors in the treatment of paediatric desmoid-type fibromatosis

British Journal of Cancer volume 124, pages 1637–1646 (2021)Cite this article

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Abstract

In children with desmoid-type fibromatosis (DTF) in whom disease progression occurs after an initial watch-and-wait strategy, prolonged low-dose chemotherapy using vinblastine and methotrexate (VBL-MTX) is currently the standard of care. These conventional drugs have been prospectively evaluated but their efficacy and safety profiles are limited, and alternative therapeutic options are therefore essential. Based on the results of clinical trials, the use of tyrosine kinase inhibitors (TKIs) in the treatment of DTF is currently considered only in adult patients. TKIs such as imatinib show superior therapeutic efficacy to VBL-MTX and tolerable short-term side effects for the treatment of adult DFT, supporting the concept of the use of TKIs for the treatment of paediatric DFT. Moreover, new-generation TKIs, such as pazopanib and sorafenib, have shown improved therapeutic efficacy compared to imatinib in adult non-comparative studies. A tolerable safety profile of TKI therapy in children with disease entities other than DTF, such as leukaemia, has been reported. However, the efficacy and, in particular, the long-term safety of TKIs, including childhood-specific aspects such as growth and fertility, for the treatment of children with DTF should be investigated prospectively, as DFT therapy requires long-term drug exposure.

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Fig. 1: Proposal for a prospective international strategy in paediatric DFT.

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References

  1. Schmidt, B. F., Koscielniak, E., Pilz, T. & Treuner, J. Radiation therapy in juvenile aggressive fibromatosis. Klin. Padiatr. 211, 296–299 (1999).

    Article  CAS  PubMed  Google Scholar 

  2. Reitamo, J. J., Scheinin, T. M. & Hayry, P. The desmoid syndrome. New aspects in the cause, pathogenesis and treatment of the desmoid tumor. Am. J. Surg. Feb. 151, 230–237 (1986).

    Article  CAS  Google Scholar 

  3. Anthony, T., Rodriguez-Bigas, M. A., Weber, T. K. & Petrelli, N. J. Desmoid tumors. J. Am. Coll. Surg. 182, 369–377 (1996).

    CAS  PubMed  Google Scholar 

  4. Orbach, D., Brennan, B., Bisogno, G., Van Noesel, M., Minard-Colin, V., Daragjati, J. et al. The EpSSG NRSTS 2005 treatment protocol for desmoid-type fibromatosis in children: an international prospective case series. Lancet Child Adolesc. Health 1, 284–292 (2017).

    Article  PubMed  Google Scholar 

  5. Fiore, M., Rimareix, F., Mariani, L., Domont, J., Collini, P., Le Pechoux, C. et al. Desmoid-type fibromatosis: a front-line conservative approach to select patients for surgical treatment. Ann. Surg. Oncol. 16, 2587–2593 (2009).

    Article  PubMed  Google Scholar 

  6. Fletcher, C. D. The evolving classification of soft tissue tumours—an update based on the new 2013 WHO classification. Histopathology. 64, 2–11 (2014).

    Article  PubMed  Google Scholar 

  7. Penel, N., Coindre, J. M., Bonvalot, S., Italiano, A., Neuville, A., Le Cesne, A. et al. Management of desmoid tumours: a nationwide survey of labelled reference centre networks in France. Eur. J. Cancer 58, 90–96 (2016).

    Article  PubMed  Google Scholar 

  8. Agresta, L., Kim, H., Turpin, B. K., Nagarajan, R., Plemmons, A., Szabo, S. et al. Pazopanib therapy for desmoid tumors in adolescent and young adult patients. Pediatr. Blood Cancer 65, e26968 (2018).

    Article  PubMed  CAS  Google Scholar 

  9. Trautmann, M., Rehkamper, J., Gevensleben, H., Becker, J., Wardelmann, E., Hartmann, W. et al. Novel pathogenic alterations in pediatric and adult desmoid-type fibromatosis—a systematic analysis of 204 cases. Sci. Rep. 25, 10:3368 (2020).

  10. Meazza, C., Belfiore, A., Busico, A., Settanni, G., Paielli, N., Cesana, L. et al. AKT1 and BRAF mutations in pediatric aggressive fibromatosis. Cancer Med. 5, 1204–1213 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Meazza, C., Bisogno, G., Gronchi, A., Fiore, M., Cecchetto, G., Alaggio, R. et al. Aggressive fibromatosis in children and adolescents: the Italian experience. Cancer 116, 233–240 (2010).

    CAS  PubMed  Google Scholar 

  12. Oudot, C., Orbach, D., Minard-Colin, V., Michon, J., Mary, P., Glorion, C. et al. Desmoid fibromatosis in pediatric patients: management based on a retrospective analysis of 59 patients and a review of the literature. Sarcoma 2012, 475202 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Woltsche, N., Gilg, M. M., Fraissler, L., Liegl-Atzwanger, B., Beham, A., Lackner, H. et al. Is wide resection obsolete for desmoid tumors in children and adolescents? Evaluation of histological margins, immunohistochemical markers, and review of literature. Pediatr. Hematol. Oncol. 32, 60–69 (2015).

    Article  CAS  PubMed  Google Scholar 

  14. Rutenberg, M. S., Indelicato, D. J., Knapik, J. A., Lagmay, J. P., Morris, C., Zlotecki, R. A. et al. External-beam radiotherapy for pediatric and young adult desmoid tumors. Pediatr. Blood Cancer 57, 435–442 (2011).

    Article  PubMed  Google Scholar 

  15. Buitendijk, S., van de Ven, C. P., Dumans, T. G., den Hollander, J. C., Nowak, P. J., Tissing, W. J. et al. Pediatric aggressive fibromatosis: a retrospective analysis of 13 patients and review of literature. Cancer 104, 1090–1099 (2005).

    Article  PubMed  Google Scholar 

  16. Kasper, B., Baumgarten, C., Garcia, J., Bonvalot, S., Haas, R., Haller, F. et al. 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 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Penel, N., Le Cesne, A., Bonvalot, S., Giraud, A., Bompas, E., Rios, M. et al. 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 (2017).

    Article  PubMed  Google Scholar 

  18. Gounder, M. M., Mahoney, M. R., Van Tine, B. A., Ravi, V., Attia, S., Deshpande, H. A. et al. Sorafenib for advanced and refractory desmoid tumors. N. Engl. J. Med. 379, 2417–2428 (2018). 20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Salas, S., Brulard, C., Terrier, P., Ranchere-Vince, D., Neuville, A., Guillou, L. et al. Gene expression profiling of desmoid tumors by cDNA microarrays and correlation with progression-free survival. Clin. Cancer Res. 21, 4194–4200 (2015).

    Article  CAS  PubMed  Google Scholar 

  20. Colombo, C., Miceli, R., Lazar, A. J., Perrone, F., Pollock, R. E., Le Cesne, A. et al. CTNNB1 45F mutation is a molecular prognosticator of increased postoperative primary desmoid tumor recurrence: an independent, multicenter validation study. Cancer 119, 3696–3702 (2013).

    Article  CAS  PubMed  Google Scholar 

  21. Meazza, C., Alaggio, R. & Ferrari, A. Aggressive fibromatosis in children: a changing approach. Minerva Pediatr. 63, 305–318 (2011).

    CAS  PubMed  Google Scholar 

  22. Skapek, S. X., Ferguson, W. S., Granowetter, L., Devidas, M., Perez-Atayde, A. R., Dehner, L. P. et al. Vinblastine and methotrexate for desmoid fibromatosis in children: results of a Pediatric Oncology Group Phase II Trial. J. Clin. Oncol. 25, 501–506 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. Azzarelli, A., Gronchi, A., Bertulli, R., Tesoro, J. D., Baratti, D., Pennacchioli, E. et al. Low-dose chemotherapy with methotrexate and vinblastine for patients with advanced aggressive fibromatosis. Cancer 92, 1259–1264 (2001).

    Article  CAS  PubMed  Google Scholar 

  24. Toulmonde, M., Pulido, M., Ray-Coquard, I., Andre, T., Isambert, N., Chevreau, C. et al. 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 (2019).

    Article  CAS  PubMed  Google Scholar 

  25. Duhil de Benaze, G., Vigan, M., Corradini, N., Minard-Colin, V., Marie-Cardine, A., Verite, C. et al. Functional analysis of young patients with desmoid-type fibromatosis: initial surveillance does not jeopardize long term quality of life. Eur. J. Surg. Oncol. 46, 1294–1300 (2020).

    Article  CAS  PubMed  Google Scholar 

  26. Skapek, S. X., Ferguson, W. S., Granowetter, L., Devidas, M., Perez-Atayde, A. R., Dehner, L. P. et al. Vinblastine and methotrexate for desmoid fibromatosis in children: results of a Pediatric Oncology Group Phase II Trial. J. Clin. Oncol. 25, 501–506 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. Group, D. T. W. The management of desmoid tumours: a joint global consensus-based guideline approach for adult and paediatric patients. Eur. J. Cancer 127, 96–107 (2020).

    Article  Google Scholar 

  28. Sparber-Sauer, M., Seitz, G., von Kalle, T., Vokuhl, C., Leuschner, I., Scheer, M. et al. Systemic therapy of aggressive fibromatosis in children and adolescents: report of the Cooperative Weichteilsarkom Studiengruppe (CWS). Pediatr. Blood Cancer 65, e26943 (2018).

    Article  PubMed  Google Scholar 

  29. Skapek, S. X., Anderson, J. R., Hill, D. A., Henry, D., Spunt, S. L., Meyer, W. et al. Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: results of a Children’s Oncology Group (COG) phase II study. Pediatr. Blood Cancer 60, 1108–1112 (2013).

    Article  CAS  PubMed  Google Scholar 

  30. Ferrari, A., Orbach, D., Affinita, M. C., Chiaravalli, S., Corradini, N., Meazza, C. et al. 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 (2019).

    Article  PubMed  CAS  Google Scholar 

  31. Constantinidou, A., Jones, R. L., Scurr, M., Al-Muderis, O. & Judson, I. Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis. Eur. J. Cancer 45, 2930–2934 (2009).

    Article  CAS  PubMed  Google Scholar 

  32. Crago, A. M., Chmielecki, J., Rosenberg, M., O’Connor, R., Byrne, C., Wilder, F. G. et al. Near universal detection of alterations in CTNNB1 and Wnt pathway regulators in desmoid-type fibromatosis by whole-exome sequencing and genomic analysis. Genes Chromosomes Cancer 54, 606–615 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zambo, I. & Vesely, K. WHO classification of tumours of soft tissue and bone 2013: the main changes compared to the 3rd edition. Cesk Patol. 50, 64–70 (2014).

    PubMed  Google Scholar 

  34. Coindre, J. M. New WHO classification of tumours of soft tissue and bone. Ann. Pathol. 32, S115–S116 (2012).

    Article  PubMed  Google Scholar 

  35. Li, C., Bapat, B. & Alman, B. A. Adenomatous polyposis coli gene mutation alters proliferation through its beta-catenin-regulatory function in aggressive fibromatosis (desmoid tumor). Am. J. Pathol. 153, 709–714 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Enzo, M. V., Rastrelli, M., Rossi, C. R., Hladnik, U. & Segat, D. The Wnt/beta-catenin pathway in human fibrotic-like diseases and its eligibility as a therapeutic target. Mol. Cell Ther. 3, 1 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Matono, H., Tamiya, S., Yokoyama, R., Saito, T., Iwamoto, Y., Tsuneyoshi, M. et al. Abnormalities of the Wnt/beta-catenin signalling pathway induce tumour progression in sporadic desmoid tumours: correlation between beta-catenin widespread nuclear expression and VEGF overexpression. Histopathology. 59, 368–375 (2011).

    Article  PubMed  Google Scholar 

  38. Chugh, R., Wathen, J. K., Patel, S. R., Maki, R. G., Meyers, P. A., Schuetze, S. M. et al. Efficacy of imatinib in aggressive fibromatosis: results of a phase II multicenter sarcoma alliance for research through Collaboration (SARC) trial. Clin. Cancer Res. 16, 4884–4891 (2010).

    Article  CAS  PubMed  Google Scholar 

  39. Heinrich, M. C., Joensuu, H., Demetri, G. D., Corless, C. L., Apperley, J., Fletcher, J. A. et al. Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases. Clin. Cancer Res. 14, 2717–2725 (2008).

    Article  CAS  PubMed  Google Scholar 

  40. Heinrich, M. C., McArthur, G. A., Demetri, G. D., Joensuu, H., Bono, P., Herrmann, R. et al. Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor). J. Clin. Oncol. 24, 1195–1203 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Corless, C. L., Fletcher, J. A. & Heinrich, M. C. Biology of gastrointestinal stromal tumors. J. Clin. Oncol. 22, 3813–3825 (2004).

    Article  CAS  PubMed  Google Scholar 

  42. Maki, R. G., Awan, R. A., Dixon, R. H., Jhanwar, S. & Antonescu, C. R. Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans. Int. J. Cancer 100, 623–626 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. Fields, R. C., Hameed, M., Qin, L. X., Moraco, N., Jia, X., Maki, R. G. et al. Dermatofibrosarcoma protuberans (DFSP): predictors of recurrence and the use of systemic therapy. Ann. Surg. Oncol. 18, 328–336 (2011).

    Article  PubMed  Google Scholar 

  44. Blay, J. Y., El Sayadi, H., Thiesse, P., Garret, J. & Ray-Coquard, I. Complete response to imatinib in relapsing pigmented villonodular synovitis/tenosynovial giant cell tumor (PVNS/TGCT). Ann. Oncol. 19, 821–822 (2008).

    Article  PubMed  Google Scholar 

  45. Penel, N., Le Cesne, A., Bui, B. N., Perol, D., Brain, E. G., Ray-Coquard, I. et al. 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 (2011).

    Article  CAS  PubMed  Google Scholar 

  46. Kasper, B., Gruenwald, V., Reichardt, P., Bauer, S., Rauch, G., Limprecht, R. et al. 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 (2017).

    Article  CAS  PubMed  Google Scholar 

  47. Desmoid Tumor Working Group. The management of desmoid tumours: a joint global consensus-based guideline approach for adult and paediatric patients. Eur. J. Cancer 127, 96–107 (2020).

    Article  Google Scholar 

  48. Kroschwald, L. M., Tauer, J. T., Kroschwald, S. I., Suttorp, M., Wiedenfeld, A., Beissert, S. et al. Imatinib mesylate and nilotinib decrease synthesis of bone matrix in vitro. Oncol. Lett. 18, 2102–2108 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Suttorp, M., Metzler, M., Millot, F., Shimada, H., Bansal, D., Gunes, A. M. et al. Generic formulations of imatinib for treatment of Philadelphia chromosome-positive leukemia in pediatric patients. Pediatr. Blood Cancer 65, e27431 (2018).

    Article  PubMed  Google Scholar 

  50. Suttorp, M., Schulze, P., Glauche, I., Gohring, G., von Neuhoff, N., Metzler, M. et al. Front-line imatinib treatment in children and adolescents with chronic myeloid leukemia: results from a phase III trial. Leukemia. 32, 1657–1669 (2018).

    Article  CAS  PubMed  Google Scholar 

  51. Suttorp, M., Bornhauser, M., Metzler, M., Millot, F. & Schleyer, E. Pharmacology and pharmacokinetics of imatinib in pediatric patients. Expert Rev. Clin. Pharmacol. 11, 219–231 (2018).

    Article  CAS  PubMed  Google Scholar 

  52. Proschmann, R., Baldow, C., Rothe, T., Suttorp, M., Thiede, C., Tauer, J. T. et al. Response dynamics of pediatric patients with chronic myeloid leukemia on imatinib therapy. Haematologica. 102, e39–e42 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Kroschwald, L., Suttorp, M., Tauer, J. T., Zimmermann, N., Gunther, C. & Bauer, A. Offtarget effect of imatinib and nilotinib on human vitamin D3 metabolism. Mol. Med. Rep. 17, 1382–1388 (2018).

    CAS  PubMed  Google Scholar 

  54. Yin, X. F., Wang, J. H., Li, X., Yu, M. X., Ma, Z. X. & Jin, J. Incidence of second malignancies of chronic myeloid leukemia during treatment with tyrosine kinase inhibitors. Clin. Lymphoma Myeloma Leuk. 16, 577–581 (2016).

    Article  PubMed  Google Scholar 

  55. Choeyprasert, W., Yansomdet, T., Natesirinilkul, R., Wejaphikul, K. & Charoenkwan, P. Adverse effects of imatinib in children with chronic myelogenous leukemia. Pediatr. Int. 59, 286–292 (2017).

    Article  CAS  PubMed  Google Scholar 

  56. Samis, J., Lee, P., Zimmerman, D., Arceci, R. J., Suttorp, M. & Hijiya, N. Recognizing endocrinopathies associated with tyrosine kinase inhibitor therapy in children with chronic myelogenous leukemia. Pediatr. Blood Cancer 63, 1332–1338 (2016).

    Article  PubMed  Google Scholar 

  57. Tauer, J. T., Hofbauer, L. C., Jung, R., Gerdes, S., Glauche, I., Erben, R. G. et al. Impact of long-term exposure to the tyrosine kinase inhibitor imatinib on the skeleton of growing rats. PLoS ONE 10, e0131192 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Ulmer, A., Tabea Tauer, J., Glauche, I., Jung, R. & Suttorp, M. TK inhibitor treatment disrupts growth hormone axis: clinical observations in children with CML and experimental data from a juvenile animal model. Klin. Padiatr. 225, 120–126 (2013).

    Article  CAS  PubMed  Google Scholar 

  59. Jaeger, B. A., Tauer, J. T., Ulmer, A., Kuhlisch, E., Roth, H. J. & Suttorp, M. Changes in bone metabolic parameters in children with chronic myeloid leukemia on imatinib treatment. Med. Sci. Monit. 18, CR721–CR728 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hosokawa, T., Hara, T., Arakawa, Y., Oguma, E. & Yamada, Y. Periosteal reaction possibly induced by pazopanib: a case report and literature review. J. Pediatr. Hematol. Oncol. 42, e822–e825 (2020).

    Article  PubMed  Google Scholar 

  61. Wang, E., DuBois, S. G., Wetmore, C. & Khosravan, R. Population pharmacokinetics-pharmacodynamics of sunitinib in pediatric patients with solid tumors. Cancer Chemother. Pharmacol. 86, 181–192 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Jo, J. C., Hong, Y. S., Kim, K. P., Lee, J. L., Lee, J., Park, Y. S. et al. A prospective multicenter phase II study of sunitinib in patients with advanced aggressive fibromatosis. Investig. New Drugs 32, 369–376 (2014).

    Article  CAS  Google Scholar 

  63. Wang, E., DuBois, S. G., Wetmore, C. & Khosravan, R. Population pharmacokinetics-pharmacodynamics of sunitinib in pediatric patients with solid tumors. Cancer Chemother. Pharmacol. 86, 181–192 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. van der Graaf, W. T., Blay, J. Y., Chawla, S. P., Kim, D. W., Bui-Nguyen, B., Casali, P. G. et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 379, 1879–1886 (2012).

    Article  PubMed  CAS  Google Scholar 

  65. Szucs, Z., Messiou, C., Wong, H. H., Hatcher, H., Miah, A., Zaidi, S. et al. Pazopanib, a promising option for the treatment of aggressive fibromatosis. Anticancer Drugs 28, 421–426 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Bulut, G., Ozluk, A., Erdogan, A. P., Uslu, R., Elmas, N. & Karaca, B. Pazopanib: a novel treatment option for aggressive fibromatosis. Clin. Sarcoma Res. 6, 22 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Martin-Liberal, J., Benson, C., McCarty, H., Thway, K., Messiou, C. & Judson, I. Pazopanib is an active treatment in desmoid tumour/aggressive fibromatosis. Clin. Sarcoma Res. 3, 13 (2013). 26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Nishida, Y., Sakai, T., Koike, H. & Ito, K. Pazopanib for progressive desmoid tumours: children, persistant effects, and cost. Lancet Oncol. 20, e555 (2019).

    Article  PubMed  Google Scholar 

  69. Glade Bender, J. L., Lee, A., Reid, J. M., Baruchel, S., Roberts, T., Voss, S. D. et al. Phase I pharmacokinetic and pharmacodynamic study of pazopanib in children with soft tissue sarcoma and other refractory solid tumors: a children’s oncology group phase I consortium report. J. Clin. Oncol. 31, 3034–3043 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Weiss, A. R., Chen, Y. L., Scharschmidt, T. J., Chi, Y. Y., Tian, J., Black, J. O. et al. Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 21, 1110–1122 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gounder, M. M., Lefkowitz, R. A., Keohan, M. L., D’Adamo, D. R., Hameed, M., Antonescu, C. R. et al. Activity of sorafenib against desmoid tumor/deep fibromatosis. Clin. Cancer Res. 17, 4082–4090 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Walko, C. M., Aubert, R. E., La-Beck, N. M., Clore, G., Herrera, V., Kourlas, H. et al. Pharmacoepidemiology of clinically relevant hypothyroidism and hypertension from sunitinib and sorafenib. Oncologist 22, 208–212 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Widemann, B. C., Kim, A., Fox, E., Baruchel, S., Adamson, P. C., Ingle, A. M. et al. A phase I trial and pharmacokinetic study of sorafenib in children with refractory solid tumors or leukemias: a Children’s Oncology Group Phase I Consortium report. Clin. Cancer Res. 18, 6011–6022 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kim, A., Widemann, B. C., Krailo, M., Jayaprakash, N., Fox, E., Weigel, B. et al. Phase 2 trial of sorafenib in children and young adults with refractory solid tumors: a report from the Children’s Oncology Group. Pediatr. Blood Cancer 62, 1562–1566 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kim, A., Dombi, E., Tepas, K., Fox, E., Martin, S., Wolters, P. et al. Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas. Pediatr. Blood Cancer 60, 396–401 (2013).

    Article  CAS  PubMed  Google Scholar 

  76. Navid, F., Baker, S. D., McCarville, M. B., Stewart, C. F., Billups, C. A., Wu, J. et al. Phase I and clinical pharmacology study of bevacizumab, sorafenib, and low-dose cyclophosphamide in children and young adults with refractory/recurrent solid tumors. Clin Cancer Res. 19, 236–246 (2013).

    Article  CAS  PubMed  Google Scholar 

  77. Karajannis, M. A., Legault, G., Fisher, M. J., Milla, S. S., Cohen, K. J., Wisoff, J. H. et al. Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas. Neuro Oncol. 16, 1408–1416 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Inaba, H., Panetta, J. C., Pounds, S. B., Wang, L., Li, L., Navid, F. et al. Sorafenib population pharmacokinetics and skin toxicities in children and adolescents with refractory/relapsed leukemia or solid tumor malignancies. Clin. Cancer Res. 25, 7320–7330 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Skapek, S. X., Ferguson, W. S., Granowetter, L., Devidas, M., Perez-Atayde, A. R., Dehner, L. P. et al. Vinblastine and methotrexate for desmoid fibromatosis in children: results of a Pediatric Oncology Group Phase II Trial. J. Clin. Oncol. 25, 501–506 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Federico, S. M., Caldwell, K. J., McCarville, M. B., Daryani, V. M., Stewart, C. F., Mao, S. et al. Phase I expansion cohort to evaluate the combination of bevacizumab, sorafenib and low-dose cyclophosphamide in children and young adults with refractory or recurrent solid tumours. Eur. J. Cancer 132, 35–42 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Okada, K., Nakano, Y., Yamasaki, K., Nitani, C., Fujisaki, H. & Hara, J. Sorafenib treatment in children with relapsed and refractory neuroblastoma: an experience of four cases. Cancer Med. 5, 1947–1949 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Paul, A., Blouin, M. J., Minard-Colin, V., Galmiche, L., Coulomb, A., Corradini, N. et al. Desmoid-type fibromatosis of the head and neck in children: a changing situation. Int. J. Pediatr. Otorhinolaryngol. 123, 33–37 (2019).

    Article  PubMed  Google Scholar 

  83. Crombe, A., Kind, M., Ray-Coquard, I., Isambert, N., Chevreau, C., Andre, T. et al. Progressive desmoid tumor: radiomics compared with conventional response criteria for predicting progression during systemic therapy—a multicenter study by the French Sarcoma Group. Am. J. Roentgenol. 215, 1539–1548 (2020).

    Article  Google Scholar 

  84. Sheth, P. J., Del Moral, S., Wilky, B. A., Trent, J. C., Cohen, J., Rosenberg, A. E. et al. Desmoid fibromatosis: MRI features of response to systemic therapy. Skeletal Radiol. 45, 1365–1373 (2016).

    Article  PubMed  Google Scholar 

  85. Macagno, N., Fina, F., Penel, N., Bouvier, C., Nanni, I., Duffaud, F. et al. Proof of concept: prognostic value of the plasmatic concentration of circulating cell free DNA in desmoid tumors using ddPCR. Oncotarget 9, 18296–18308 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Authors want to thank the ‘SOS Desmoid association' for the review of the manuscript.

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Author notes

  1. These authors contributed equally: Monika Sparber-Sauer, Daniel Orbach

Authors and Affiliations

  1. Klinikum Stuttgart - Olgahospital, Stuttgart Cancer Center, Zentrum für Kinder-, Jugend- und Frauenmedizin, Pediatrics 5 (Oncology, Hematology, Immunology), Stuttgart, Germany

    Monika Sparber-Sauer

  2. SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), PSL University, Institut Curie, Paris, France

    Daniel Orbach

  3. Department of Pediatrics, Children’s Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA

    Fariba Navid

  4. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Simone Hettmer

  5. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Stephen Skapek

  6. Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Stephen Skapek

  7. Institut d’Hematologie et d’Oncologie Pediatrique, Centre Leon Berard, Lyon, France

    Nadège Corradini

  8. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy

    Michela Casanova & Andrea Ferrari

  9. Department of Pediatrics, Maine Medical Center, Portland, ME, USA

    Aaron Weiss

  10. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

    Matthias Schwab

  11. Departments of Clinical Pharmacology, Pharmacy, and Biochemistry, University of Tübingen, Tübingen, Germany

    Matthias Schwab

Authors
  1. Monika Sparber-Sauer
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  2. Daniel Orbach
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  3. Fariba Navid
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  4. Simone Hettmer
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  5. Stephen Skapek
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  6. Nadège Corradini
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  7. Michela Casanova
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  8. Aaron Weiss
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  9. Matthias Schwab
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  10. Andrea Ferrari
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Contributions

M.S.S., D.O. and A.F.: conceptualisation, formal analysis, methodology, writing and editing; F.N., S.H., S.S., N.C., M.C., A.W. and M.S.: formal analysis, methodology, writing and editing.

Corresponding author

Correspondence to Daniel Orbach.

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The authors declare no conflict of interest in relation with this manuscript. M.S. is supported by the Robert Bosch Stiftung, Stuttgart, Germany.

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Sparber-Sauer, M., Orbach, D., Navid, F. et al. Rationale for the use of tyrosine kinase inhibitors in the treatment of paediatric desmoid-type fibromatosis. Br J Cancer 124, 1637–1646 (2021). https://doi.org/10.1038/s41416-021-01320-1

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  • DOI: https://doi.org/10.1038/s41416-021-01320-1

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