Inflammatory myofibroblastic tumour (IMT)
IMT is a rare tumour 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.
Overview
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.
Complete 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.
Open 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.
State of the art today
- 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, once uniformly lethal, 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.
Where it starts and where it drains
Central tumours arise in the large airways, peripheral ones in the alveoli; both drain to hilar then mediastinal nodes, and the pleural lining is a separate cancer site.
- Central airways (squamous, small-cell)Epithelioid inflammatory myofibroblastic sarcoma (RANBP2-ALK or RRBP1-ALK)
- Periphery (adenocarcinoma)Classic IMT (ALK-rearranged, about half) · ALK-negative IMT (ROS1, NTRK3, PDGFRB, RET fusions) · Epithelioid inflammatory myofibroblastic sarcoma (RANBP2-ALK or RRBP1-ALK)
- Apex (Pancoast)
- Pleura (mesothelioma)Epithelioid inflammatory myofibroblastic sarcoma (RANBP2-ALK or RRBP1-ALK)
- Thymus (anterior mediastinum)
- hilar (N1)
- mediastinal (N2)
- supraclavicular (N3)
Same organ: Non-small-cell lung cancer, Small-cell lung cancer, Mesothelioma, Thymoma and thymic carcinoma, Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours)
Rare at any age but the most common primary lung tumour of children; also arises in the mesentery, bladder and soft tissue.
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- High-risk pancreatic surveillance (CAPS / PRECEDE)Established
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Complete surgical excision; no adjuvant therapy in most cases, surveillance imaging for recurrence.
Crizotinib (FDA approval July 2022, children 1 year and older and adults); alectinib, ceritinib or lorlatinib at progression.
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.
Subtypes & biomarkers
top- Classic IMT (ALK-rearranged, about half)
- ALK-negative IMT (ROS1, NTRK3, PDGFRB, RET fusions)
- Epithelioid inflammatory myofibroblastic sarcoma (RANBP2-ALK or RRBP1-ALK)
- 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
Target prevalence in this cancer
- 1939First description as inflammatory pseudotumour of the lung
- 1999ALK rearrangements found in IMT
Griffin and colleagues identify 2p23 rearrangements, the first ALK fusions outside lymphoma.
- 2010Crizotinib response in ALK-positive IMT
Butrynski and colleagues, NEJM case report.
- 2018EORTC 90101 CREATE phase 2
Schöffski and colleagues, Lancet Respir Med: high response rate in ALK-positive IMT.
- 2022Crizotinib approved for ALK-positive IMT
FDA, 14 July 2022, adults and children aged 1 year and older.
Open problems, and what is being done about each
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.
and how the field plans to fix it →What is being done about thisRare cancers and small trialsAvailable now- LarotrectinibApproved
- Limb-salvage surgery and endoprosthetic reconstructionStandard of care
- AI trial matching & clinical decision supportEstablished
- Comprehensive genomic profilingStandard of care
- Dinutuximab (ch14.18) / dinutuximab betaApproved
- Eflornithine (DFMO)Approved
In trials- ACTIONRecruiting
- COG AALL1731Positive
- COG ANBL0032Positive
- DeFiPositive
- Euro Ewing 2012Positive
- Functional (ex vivo) drug testingEmerging
Ideas and roadmaps- A digital second-opinion network answering community oncologists within 72 hours
- A DRUP-style protocol for off-label generic targeted drugs in rare tumours
- A funded expert second opinion for every new high-stakes or rare cancer diagnosis
- A global first-in-human network for academic cancer trials with single ethics review
- A global open trials operating system any hospital can plug into
- A live 'seats available' feed for trial slots, like airline inventory
Background: Basket, umbrella, and platform trials, Centralisation and high-volume centres, FNCLCC grade (soft-tissue sarcoma), Histotype-tailored therapy, INRG staging and risk groups. Also on OnCo: Find a trial · Expert centres.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- via Crizotinib, Lorlatinib, Entrectinib, Larotrectinib
- Children's Hospital of PhiladelphiaPhiladelphia, PA, USvia Crizotinib, Lorlatinib
- Children's Oncology Group (COG)Monrovia, CA, USvia this cancer, RACE for Children Act
- ACCELERATEBrussels, BEvia RACE for Children Act
- Central Drugs Standard Control OrganizationNew Delhi, INvia Imatinib
- EORTCBrussels, BEvia this cancer
- European Medicines AgencyAmsterdam, NLvia RACE for Children Act
- FDA Oncology Center of ExcellenceSilver Spring, MD, USvia RACE for Children Act
- GIMEMARome, ITvia Imatinib
- Innovative Therapies for Children with Cancer (ITCC)Villejuif, FRvia RACE for Children Act
- via Imatinib
- Seoul St. Mary's HospitalSeoul, KRvia Imatinib
- Shanghai Chest HospitalShanghai, CNvia Lorlatinib
Questions to ask
topQuestions to ask your oncologist about Inflammatory myofibroblastic tumour
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example ALK immunohistochemistry and FISH or RNA fusion panel, ROS1, NTRK, PDGFRB, RET fusions in ALK-negative tumours, Inflammatory markersas systemic markers, Site and resectability), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Classic IMT, ALK-negative IMT, Epithelioid inflammatory myofibroblastic sarcoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Resectable
- For my situation (resectable), which of the standard options do you recommend and why?Why: Guideline options include: Complete surgical excision; no adjuvant therapy in most cases, surveillance imaging for recurrence.
Unresectable, recurrent or metastatic, ALK-positive
- For my situation (unresectable, recurrent or metastatic, alk-positive), which of the standard options do you recommend and why?Why: Guideline options include: Crizotinib (FDA approval July 2022, children 1 year and older and adults); alectinib, ceritinib or lorlatinib at progression.
- Am I a candidate for Crizotinib, Alectinib, Lorlatinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Unresectable, ALK-negative with other fusion
- For my situation (unresectable, alk-negative with other fusion), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Entrectinib, Larotrectinib, Imatinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Crizotinib, Lorlatinib, Repotrectinib?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “How long to continue ALK inhibition in children with complete response, and whether surgery after response can allow stopping”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “The fusion-negative minority: RNA sequencing to find drivers”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
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1Latest papers
topQuery for this cancer: (TITLE:"Inflammatory myofibroblastic tumour" OR ABSTRACT:"Inflammatory myofibroblastic tumour" OR TITLE:"IMT" OR ABSTRACT:"IMT" OR TITLE:"Pulmonary inflammatory myofibroblastic tumour" OR ABSTRACT:"Pulmonary inflammatory myofibroblastic tumour" OR TITLE:"Inflammatory pseudotumour" OR ABSTRACT:"Inflammatory pseudotumour" OR TITLE:"Epithelioid inflammatory myofibroblastic sarcoma" OR ABSTRACT:"Epithelioid inflammatory myofibroblastic sarcoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Inflammatory myofibroblastic tumour (IMT), not a curated reading list.
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