@article{db4cfb4996a84b2c94fe3118aab20e2a,
title = "The Activity of Chemotherapy in Inflammatory Myofibroblastic Tumors: A Multicenter, European Retrospective Case Series Analysis",
abstract = "Background: This study aimed to review the activity of cytotoxic chemotherapy in patients with inflammatory myofibroblastic tumors (IMTs) treated at nine European sarcoma reference centers. Materials and Methods: Patients of any age, with histologically proven IMT, treated with anthracycline-based methotrexate plus/minus vinorelbine/vinblastine (MTX-V) or other chemotherapeutic regimens between 1996 and 2018 were retrospectively reviewed. Diagnosis was confirmed at the local level by an expert pathologist. Response was retrospectively assessed by local investigators by RECIST v1.1. Progression-free survival (PFS), relapse-free survival (RFS), and overall survival (OS) were computed by Kaplan-Meier method. Results: Thirty-eight patients were included. Twenty-five patients (8 localized, 17 advanced disease) received an anthracycline-based regimen; 21 were evaluable for response. Overall response rate (ORR) was 10/21 (47.6%). At a 70.8-month median follow-up (FU), median RFS and median OS were not reached (NR) in patients with localized disease; median PFS and median OS were 6.3 (interquartile range [IQR]: 1.9–13.4) and 21.2 (IQR: 7.7–40.7) months in patients with advanced disease. Thirteen patients received MTX-V (4 localized, 9 advanced disease), all evaluable for response. ORR was 7/13 (53.8%). At a 56.6-month median FU, median RFS and median OS were 42.5 (IQR: 12.9–61.2) months and NR (no death events) in patients with localized disease, and NR (IQR: 24.9 to NR) and 83.4 months (IQR: 83.4 to NR) in patients with advanced disease. In the “other-regimens group,” responses were seen in 3/4 patients treated with oral cyclophosphamide and 1/2 with docetaxel/gemcitabine. Conclusion: Anthracycline-based and MTX-V regimens are very effective in IMT, with a similar ORR in both groups. MTX-V achieved a prolonged disease control. Responses were also seen with oral cyclophosphamide and docetaxel/gemcitabine, but few patients were treated with these schedules. Implications for Practice: Inflammatory myofibroblastic tumor (IMT) is an ultrarare sarcoma with known sensitivity to anaplastic lymphoma kinase (ALK) inhibitors in ALK-fused cases, although ALK inhibitors are not licensed in the disease. The current knowledge on the activity of cytotoxic chemotherapy is limited. This multi-institutional retrospective study on pediatric and adult patients with IMT shows that cytotoxic chemotherapy, and in particular anthracycline-based and methotrexate plus/minus vinorelbine/vinblastine regimens, represents a treatment option and can be considered in IMT patients irrespectively from ALK status. This study provides a benchmark for future studies on new medical therapies. {\textcopyright} AlphaMed Press 2020",
keywords = "Chemotherapy, Doxorubicin, Inflammatory myofibroblastic tumor, Methotrexate, Sarcoma, Vinblastine, Vinorelbine",
author = "G.G. Baldi and M. Brahmi and {Lo Vullo}, S. and E. Cojocaru and O. Mir and M. Casanova and B. Vincenzi and {De Pas}, T.M. and G. Grignani and M.A. Pantaleo and J.Y. Blay and R.L. Jones and {Le Cesne}, A. and A.M. Frezza and A. Gronchi and P. Collini and {Dei Tos}, A.P. and C. Morosi and L. Mariani and P.G. Casali and S. Stacchiotti",
note = "Cited By :2 Export Date: 1 March 2021 CODEN: OCOLF Correspondence Address: Stacchiotti, S.; Department of Medical Oncology, Italy; email: silvia.stacchiotti@istitutotumori.mi.it References: Meis, J.M., Enzinger, F.M., Inflammatory fibrosarcoma of the mesentery and retroperitoneum. A tumor closely simulating inflammatory pseudotumor (1991) Am J Surg Pathol, 15, pp. 1146-1156; Coffin, C.M., Watterson, J., Priest, J.R., Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases (1995) Am J Surg Pathol, 19, pp. 859-872; Myint, M.A., Medeiros, L.J., Sulaiman, R.A., Inflammatory pseudotumor of the ileum. A report of a multifocal, transmural lesion with regional lymph node involvement (1994) Arch Pathol Lab Med, 118, pp. 1138-1142; Wenig, B.M., Devaney, K., Bisceglia, M., Inflammatory myofibroblastic tumor of the larynx. A clinicopathologic study of eight cases simulating a malignant spindle cell neoplasm (1995) Cancer, 76, pp. 2217-2229; Sciot, R., Dal Cin, P., Fletcher, C.D., Inflammatory myofibroblastic tumor of bone: Report of two cases with evidence of clonal chromosomal changes (1997) Am J Surg Pathol, 21, pp. 1166-1172; Ramachandra, S., Hollowood, K., Bisceglia, M., Inflammatory pseudotumour of soft tissues: A clinicopathological and immunohistochemical analysis of 18 cases (1995) Histopathology, 27, pp. 313-323; Hausler, M., Schaade, L., Ramaekers, V.T., Inflammatory pseudotumors of the central nervous system: Report of 3 cases and a literature review (2003) Hum Pathol, 34, pp. 253-262; Rabban, J.T., Zaloudek, C.J., Shekitka, K.M., Inflammatory myofibroblastic tumor of the uterus: A clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors (2005) Am J Surg Pathol, 29, pp. 1348-1355; Coffin, C.M., Fletcher, J.A., Inflammatory myofibroblastic tumour (2013) WHO Classification of Tumours of Soft Tissue and Bone, pp. 83-84. , Fletcher CDM, Bridge JA, Hongendoorn PCW, eds., 4th ed, Lyon, France, International Agency for Research on Cancer; Janik, J.S., Janik, J.P., Lovell, M.A., Recurrent inflammatory pseudotumors in children (2003) J Pediatr Surg, 38, pp. 1491-1495; Cerfolio, R.J., Allen, M.S., Nascimento, A.G., Inflammatory pseudotumors of the lung (1999) Ann Thorac Surg, 67, pp. 933-936; Cook, J.R., Dehner, L.P., Collins, M.H., Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumour: A comparative immunohistochemical study (2001) Am J Surg Pathol, 25, pp. 1364-1371; Coffin, C.M., Hornick, J.L., Fletcher, C.D., Inflammatory myofibroblastic tumour: Comparison of clinico-pathologic, hostologic and immunohistochemical features including ALK expression in atypical and aggressive cases (2007) Am J Surg Pathol, 31, pp. 509-520; Gleason, B.C., Hornick, J.L., Inflammatory myofibroblastic tumours: Where are we now? (2008) J Clin Pathol, 61, pp. 428-437; Moss{\'e}, Y.P., Voss, S.D., Lim, M.S., Targeting ALK with crizotinib in pediatric anaplastic large cell lymphoma and inflammatory myofibroblastic tumor: A Children's Oncology Group Study (2017) J Clin Oncol, 35, pp. 3215-3221; Lovly, C.M., Gupta, A., Lipson, D., Inflammatory myofibroblastic tumour harbor multiple potentially actionable kinase fusions (2014) Cancer Discov, 4, pp. 889-895; Antonescu, C.R., Suurmeijer, A.J., Zhang, L., Molecular characterization of inflammatory myofibroblastic tumours with frequent ALK and ROS1 gene fusions and rare novel RET rearrangements (2015) Am J Surg Pathol, 39, pp. 957-967; Yamamoto, H., Yoshida, A., Taguchi, K., ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours (2016) Histopathology, 69, pp. 72-83; Lopez-Nunez, O., John, I., Panasiti, R., Infantile inflammatory myofibroblastic tumors: Clinicopathological and molecular characterization of 12 cases (2020) Mod Pathol, 33, pp. 576-590; Chang, J.C., Zhang, L., Drilon, A.E., Expanding the molecular characterization of thoracic inflammatory myofibroblastic tumours beyond ALK gene rearrangements (2019) J Thorac Oncol, 14, pp. 825-834; Chun, Y.S., Wang, L., Nascimento, A.G., Pediatric inflammatory myofibroblastic tumor: Anaplastic lymphoma kinase (ALK) expression and prognosis (2005) Pediatr Blood Cancer, 45, pp. 796-801; Marino-Enriquez, A., Wang, W.L., Roy, A., Epithelioid inflammatory myofibroblastic sarcoma: An aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK (2011) Am J Surg Pathol, 35, pp. 135-144; Webb, T.R., Slavish, J., George, R.E., Anaplastic lymphoma kinase: Role in cancer pathogenesis and small-molecule inhibitor development for therapy (2009) Expert Rev Anticancer Ther, 9, pp. 331-356; Blackhall, F., Cappuzzo, F., Crizotinib: From discovery to accelerated development to front-line treatment (2016) Ann Oncol, 27 (3), pp. iii35-iii41. , (suppl; Dalton, B.G., Thomas, P.G., Sharp, N., Inflammatory myofibroblastic tumors in children (2016) J Pediatr Surg, 51, pp. 541-544; Alaggio, R., Cecchetto, G., Bisogno, G., Inflammatory myofibroblastic tumours in childhood: A report from the Italian Cooperative Group studies (2010) Cancer, 116, pp. 216-226; Favini, F., Resti, A.G., Collini, P., Inflammatory myofibroblastic tumour of the conjunctiva: Response to chemotherapy with low-dose methotrexate and vinorelbine (2010) Pediatr Blood Cancer, 54, pp. 483-485; Kube, S., Vokuhl, C., Dantonello, T., Inflammatory myofibroblastic tumours – A retrospective analysis of the Cooperative Weichteilsarkom Studien-Gruppe (2018) Pediatr Blood Cancer, 65; Casanova, M., Brennan, B., Alaggio, R., Inflammatory myofibroblastic tumour: Experience of European pediatric Soft Tissue Sarcoma Study Group (EpSSG) (2020) Eur J Cancer, 127, pp. 123-129; Eisenhauer, E.A., Therasse, P., Bogaerts, J., New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) (2009) Eur J Cancer, 45, pp. 228-247; Palassini, E., Frezza, A.M., Mariani, L., Long term efficacy of methotrexate and vinblastine/vinorelbine in a large series of patients affected by desmoid-type fibromatosis (2017) Cancer J, 23, pp. 86-91; Su, W., Ko, A., O'Connell, T., Treatment of pseudotumours with nonsteroidal antinflammatory drugs (2000) J Pediatr Surg, 35, pp. 1635-1637; Berger, A., Kim, C., Hagstrom, N., Successful preoperative treatment of pediatric bladder inflammatory myofibroblastic tumour with antinflammatory therapy (2007) Urology, 70, pp. 372.e13-e15; Chavez, C., Hoffman, M.A., Complete remission of ALK-negative plasma cell granuloma (inflammatory myofibroblastic tumour) of the lung induced by celecoxib: A case report and review of literature (2013) Oncol Lett, 5, pp. 1672-1676; Applebaum, H., Kieran, M.W., Cripe, T.P., The rationale for nonsteroidal anti-inflammatory drug therapy for inflammatory myofibroblastic tumours: A Children's Oncology Group study (2005) J Pediatr Surg, 40, pp. 999-1003; Shoffski, P., Sufliarsky, J., Gelderblom, H., Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumors with and without anaplastic lymphoma kinase gene alterations (European Organization for Research and Treatment of Cancer 90101 CREATE): A multicentre, single-drug, prospective, non-randomized phase 2 trial (2018) Lancet Respir Med, 6, pp. 431-441; Moss{\'e}, Y.P., Voss, S.D., Lim, M.S., Targeting ALK with crizotinib in pediatric anaplastic large cell lymphoma and inflammatory myofibroblastic tumor: A Children's Oncology Group Study (2017) J Clin Oncol, 35, pp. 3215-3221",
year = "2020",
doi = "10.1634/theoncologist.2020-0352",
language = "English",
volume = "25",
pages = "e1777--e1784",
journal = "Oncologist",
issn = "1083-7159",
publisher = "Wiley-Blackwell",
number = "11",
}