{"entity":{"id":"inflammatory-myofibroblastic-tumour","kind":"cancer","name":"Inflammatory myofibroblastic tumour (IMT)","aka":["IMT","Pulmonary inflammatory myofibroblastic tumour","Inflammatory pseudotumour","Epithelioid inflammatory myofibroblastic sarcoma"],"tldr":"IMT is a rare tumour, grouped with the sarcomas, of spindle cells mixed with inflammatory cells, most often in the lung or abdomen of children and young adults. Surgery cures most, and about half carry an ALK gene fusion, so the ALK-blocking pill crizotinib is approved for those that cannot be removed, one of the first targeted approvals for a childhood solid tumour.","summary":"IMT is an intermediate-grade mesenchymal neoplasm of myofibroblastic spindle cells with a plasma cell and lymphocyte infiltrate. Around half harbour ALK rearrangements with diverse partners (TPM3, TPM4, CLTC, RANBP2 and others); most ALK-negative cases carry ROS1, NTRK3, PDGFRB or RET fusions, so nearly every IMT has a druggable kinase fusion. The epithelioid inflammatory myofibroblastic sarcoma variant, driven by RANBP2-ALK or RRBP1-ALK, is aggressive and intra-abdominal. Presentation ranges from an incidental lung mass to fever, weight loss and anaemia from cytokine release.\n\nComplete surgical resection is curative for most patients and remains first line. For unresectable, recurrent or metastatic ALK-positive IMT, crizotinib produced objective responses in the EORTC 90101 CREATE phase 2 (Lancet Respir Med 2018) and in the Children's Oncology Group ADVL0912 study, leading to FDA approval in July 2022 for adults and children aged one year and older, the first approval of an ALK inhibitor for a non-lung indication in children. Second-generation ALK inhibitors (alectinib, ceritinib, lorlatinib) are used at resistance, and ROS1 or NTRK fusion cases respond to crizotinib, entrectinib, larotrectinib or repotrectinib respectively.\n\nOpen questions are treatment duration in children who reach complete response, whether neoadjuvant kinase inhibition can make surgery less mutilating, and how to manage the ALK-negative, fusion-negative minority.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Inflammatory_myofibroblastic_tumour","links":[{"label":"NCI PDQ: childhood soft tissue sarcoma (includes IMT)","url":"https://www.cancer.gov/types/soft-tissue-sarcoma/hp/child-soft-tissue-treatment-pdq"},{"label":"FDA approval of crizotinib for ALK-positive IMT (archived copy)","url":"https://web.archive.org/web/20260213082319/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-crizotinib-alk-positive-inflammatory-myofibroblastic-tumor"},{"label":"EORTC 90101 CREATE (Lancet Respir Med 2018)","url":"https://doi.org/10.1016/S2213-2600(18)30116-4"}],"tags":["nci-coverage","rare","sarcoma","paediatric"],"related":["gist","dermatofibrosarcoma-protuberans","desmoid-tumour","tenosynovial-giant-cell-tumour","pecoma"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","limb-salvage-surgery","rna-seq"],"targets":["alk","ros1","ntrk","pdgfra","ret"],"drugs":["crizotinib","alectinib","ceritinib","lorlatinib","entrectinib","larotrectinib","repotrectinib","imatinib"],"companies":["pfizer","childrens-oncology-group","curie-nki-eortc"],"institutions":[],"pathways":["rtk-activation","ras-mapk"],"terms":["gene-fusion","race-for-children-act","rare-cancers"],"trials":[],"people":[],"bottlenecks":["b-rare-cancers"],"keyPapers":["paper-schoffski-lancet-respir-med"],"journals":[],"dependsOn":[],"notes":[],"group":"sarcoma","burden":"Rare at any age but the most common primary lung tumour of children; also arises in the mesentery, bladder and soft tissue.","subtypes":["Classic IMT (ALK-rearranged, about half)","ALK-negative IMT (ROS1, NTRK3, PDGFRB, RET fusions)","Epithelioid inflammatory myofibroblastic sarcoma (RANBP2-ALK or RRBP1-ALK)"],"biomarkers":["ALK immunohistochemistry and FISH or RNA fusion panel","ROS1, NTRK, PDGFRB, RET fusions in ALK-negative tumours","Inflammatory markers (anaemia, raised CRP) as systemic markers","Site and resectability"],"standardOfCare":[{"setting":"Resectable","approach":"Complete surgical excision; no adjuvant therapy in most cases, surveillance imaging for recurrence.","refs":["limb-salvage-surgery"],"guideline":{"version":"NCI PDQ: childhood soft tissue sarcoma","url":"https://www.cancer.gov/types/soft-tissue-sarcoma/hp/child-soft-tissue-treatment-pdq"}},{"setting":"Unresectable, recurrent or metastatic, ALK-positive","approach":"Crizotinib (FDA approval July 2022, children 1 year and older and adults); alectinib, ceritinib or lorlatinib at progression.","refs":["crizotinib","alectinib","lorlatinib","ceritinib"],"guideline":{"nccn":"Category 2A","version":"NCCN Soft Tissue Sarcoma"}},{"setting":"Unresectable, ALK-negative with other fusion","approach":"Match to fusion: entrectinib or crizotinib for ROS1, larotrectinib or entrectinib for NTRK, imatinib for PDGFRB; steroids or NSAIDs for symptom control in indolent disease.","refs":["entrectinib","larotrectinib","imatinib","repotrectinib"]}],"stateOfArt":["IMT is close to a fully genotype-directed disease: nearly every tumour carries a kinase fusion with an approved inhibitor.","The 2022 crizotinib approval used adult (CREATE) and paediatric (COG ADVL0912) data together, a model for age-agnostic approvals under the RACE for Children Act.","Epithelioid inflammatory myofibroblastic sarcoma, which no treatment used to touch, responds to ALK inhibition and is managed with sequential ALK inhibitors.","Surgery remains curative for the majority; drugs are for the minority with unresectable disease."],"history":[{"year":1939,"title":"First description as inflammatory pseudotumour of the lung","refs":[]},{"year":1999,"title":"ALK rearrangements found in IMT","note":"Griffin and colleagues identify 2p23 rearrangements, the first ALK fusions outside lymphoma.","refs":[]},{"year":2010,"title":"Crizotinib response in ALK-positive IMT","note":"Butrynski and colleagues, NEJM case report.","refs":[]},{"year":2018,"title":"EORTC 90101 CREATE phase 2","note":"Schöffski and colleagues, Lancet Respir Med: high response rate in ALK-positive IMT.","refs":["crizotinib"]},{"year":2022,"title":"Crizotinib approved for ALK-positive IMT","note":"FDA, 14 July 2022, adults and children aged 1 year and older.","refs":["crizotinib","race-for-children-act"]}],"pipeline":["crizotinib","lorlatinib","repotrectinib"],"openProblems":["How long to continue ALK inhibition in children with complete response, and whether surgery after response can allow stopping.","The fusion-negative minority: RNA sequencing to find drivers.","Rare aggressive epithelioid variants that develop resistance mutations to sequential ALK inhibitors."],"parent":"sarcoma"},"route":"/cancers/inflammatory-myofibroblastic-tumour/","neighbours":{"cancer":[{"id":"pleuropulmonary-blastoma","kind":"cancer","name":"Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours)","route":"/cancers/pleuropulmonary-blastoma/"},{"id":"dermatofibrosarcoma-protuberans","kind":"cancer","name":"Dermatofibrosarcoma protuberans","route":"/cancers/dermatofibrosarcoma-protuberans/"},{"id":"desmoid-tumour","kind":"cancer","name":"Desmoid tumour","route":"/cancers/desmoid-tumour/"},{"id":"gist","kind":"cancer","name":"Gastrointestinal stromal tumour (GIST)","route":"/cancers/gist/"},{"id":"pecoma","kind":"cancer","name":"Perivascular epithelioid cell tumour (PEComa)","route":"/cancers/pecoma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"tenosynovial-giant-cell-tumour","kind":"cancer","name":"Tenosynovial giant cell tumour (TGCT)","route":"/cancers/tenosynovial-giant-cell-tumour/"}],"technology":[{"id":"limb-salvage-surgery","kind":"technology","name":"Limb-salvage surgery and endoprosthetic reconstruction","route":"/technologies/limb-salvage-surgery/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/"},{"id":"pdgfra","kind":"target","name":"PDGFRA","route":"/targets/pdgfra/"},{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/"},{"id":"ros1","kind":"target","name":"ROS1","route":"/targets/ros1/"}],"drug":[{"id":"alectinib","kind":"drug","name":"Alectinib","route":"/drugs/alectinib/"},{"id":"ceritinib","kind":"drug","name":"Ceritinib","route":"/drugs/ceritinib/"},{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"},{"id":"entrectinib","kind":"drug","name":"Entrectinib","route":"/drugs/entrectinib/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"larotrectinib","kind":"drug","name":"Larotrectinib","route":"/drugs/larotrectinib/"},{"id":"lorlatinib","kind":"drug","name":"Lorlatinib","route":"/drugs/lorlatinib/"},{"id":"repotrectinib","kind":"drug","name":"Repotrectinib","route":"/drugs/repotrectinib/"}],"company":[{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"},{"id":"curie-nki-eortc","kind":"company","name":"EORTC","route":"/companies/curie-nki-eortc/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"race-for-children-act","kind":"term","name":"RACE for Children Act","route":"/terms/race-for-children-act/"},{"id":"rare-cancers","kind":"term","name":"Rare cancers","route":"/terms/rare-cancers/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"}],"paper":[{"id":"paper-schoffski-lancet-respir-med","kind":"paper","name":"Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial","route":"/key-papers/paper-schoffski-lancet-respir-med/"}]}}