Inflammatory myofibroblastic tumour (IMT) is a rare condition that sits somewhere between benign growth and cancer, requiring careful treatment decisions based on tumour location, size, and molecular characteristics. While surgery remains the primary approach, new targeted therapies are changing how doctors manage cases that cannot be surgically removed.

Understanding Treatment Goals for Inflammatory Myofibroblastic Tumour

The main goal when treating inflammatory myofibroblastic tumour is to completely remove or control the tumour while preserving as much normal function as possible. Treatment planning depends heavily on where the tumour is located in the body, how large it has grown, and whether it can be safely removed through surgery. Doctors also consider the patient’s age and overall health when making treatment decisions.^[1]

Another important goal is preventing the tumour from coming back. IMTs have a tendency to recur locally, meaning they can grow back in the same area after treatment, which happens in approximately 25% of cases. The recurrence rate is particularly higher when tumours develop in the abdominal space or when they measure more than 8 centimeters in size.^[8]

Treatment approaches for IMT have evolved significantly in recent years. There are standard treatments that have been used for decades, including surgical removal and traditional chemotherapy. At the same time, ongoing research into the molecular biology of these tumours has opened doors to innovative targeted therapies that are being tested in clinical trials. These newer treatments specifically target the genetic abnormalities found in many IMT cases.^[5]

The overall outlook for patients with IMT is generally favorable, especially when complete surgical removal is possible. However, treatment becomes more complex when the tumour is located near vital organs, has grown too large to remove safely, or has already spread to other parts of the body. In these situations, medical therapies become essential tools in managing the disease.^[3]

Standard Treatment Approaches

Surgical Removal

Surgery is considered the first-line treatment and the gold standard for inflammatory myofibroblastic tumour. When doctors can completely remove the tumour with clear margins (meaning no tumour cells are left at the edges of the removed tissue), patients have an excellent prognosis. The surgical approach depends on where the tumour is located. For lung tumours, this might mean removing part of a lung lobe or, in some cases, an entire lobe. For tumours in the abdomen, surgery might involve removing the affected portion of tissue while carefully preserving nearby organs and blood vessels.^[10]

The challenge with surgical treatment is that IMTs can grow in difficult locations where complete removal is risky or impossible. Some tumours may wrap around important blood vessels or grow into vital organs like the stomach, liver, or intestines. In these cases, attempting complete removal could cause more harm than the tumour itself. Even when surgery is successful, patients need careful follow-up because the tumour can return in the same location.^[2]

Recovery from surgery varies depending on the extent of the operation. Patients who undergo lung surgery may need several weeks to recover and may experience temporary breathing difficulties. Those who have abdominal surgery typically spend several days in the hospital and may need a few weeks before returning to normal activities. Regular imaging scans are necessary after surgery to watch for any signs of recurrence.^[15]

Traditional Chemotherapy

For cases where surgery is not possible or when the tumour has returned after surgery, doctors have historically used chemotherapy. Traditional chemotherapy regimens for IMT have included combinations of drugs like methotrexate and cisplatin. These medications work by interfering with the ability of cells to divide and grow. In one reported case, a 14-year-old patient with a retroperitoneal IMT responded well to a combination of methotrexate and cisplatin following biopsy, with the tumour becoming undetectable on CT scans after treatment.^[7]

However, the effectiveness of conventional chemotherapy for IMT has been inconsistent. Some studies report an overall response rate of approximately 50% based on retrospective data, meaning about half of patients see their tumours shrink or stop growing with chemotherapy. The variability in response is partly because IMTs are biologically diverse, with different molecular characteristics that affect how they respond to treatment.^[5]

Chemotherapy comes with well-known side effects that can affect quality of life during treatment. Common side effects include nausea, vomiting, hair loss, fatigue, and increased risk of infections due to lowered immune system function. The severity of side effects varies from person to person and depends on the specific drugs used, the doses given, and how long treatment lasts.^[6]

Anti-inflammatory Medications

Because IMTs contain a significant inflammatory component, with abundant plasma cells, lymphocytes, and other immune cells, some doctors have explored using anti-inflammatory medications. Non-steroidal anti-inflammatory drugs, or NSAIDs (medications like diclofenac or ibuprofen that reduce inflammation and pain), have been used in selected cases with some success. In the same case mentioned earlier, the patient also received oral diclofenac sodium alongside chemotherapy.^[7]

More recently, corticosteroids (a type of steroid medication that strongly suppresses inflammation) have shown promise in some cases. One particularly interesting case involved a 49-year-old man with an IMT invading the first rib who received oral steroids due to his history of asthma before planned surgery. Surprisingly, follow-up CT scans showed significant tumour shrinkage after just a short period of steroid administration, and the patient remained disease-free for over a year without surgery.^[9]

Treatment in Clinical Trials

Understanding the Molecular Biology of IMT

A major breakthrough in understanding IMT came from discovering that many of these tumours have specific genetic abnormalities. Researchers found that in approximately 50% to 80% of IMT cases, the tumour cells contain rearrangements in a gene called ALK (anaplastic lymphoma kinase). When this gene is rearranged, it joins with another gene to create an abnormal fusion protein that sends constant signals telling cells to grow and divide.^[1]

The ALK gene is located on chromosome 2, and when it breaks and rejoins incorrectly with various different partner genes, it creates these fusion proteins. Other potentially targetable genetic changes have been identified in IMTs that don’t have ALK rearrangements, including fusions involving genes called ROS1, NTRK3, RET, and PDGFRB. These discoveries have been crucial because they identified specific molecular targets that new drugs could attack.^[10]

Testing for these genetic abnormalities has become an important part of diagnosing IMT. When a biopsy sample is examined under the microscope, pathologists can perform special tests to look for ALK protein expression or directly test for gene rearrangements. This molecular information helps doctors predict how the tumour might behave and, more importantly, whether it might respond to targeted therapies.^[3]

ALK Inhibitors: Crizotinib

Crizotinib represents the most significant advance in IMT treatment in recent years. This drug is a tyrosine kinase inhibitor, meaning it blocks the abnormal enzyme activity created by ALK fusion proteins. Crizotinib was first developed and approved for treating ALK-positive non-small-cell lung cancer, where it showed remarkable effectiveness. Researchers and clinicians then recognized that it might also work for ALK-positive IMTs.^[8]

In 2020, the U.S. Food and Drug Administration officially approved crizotinib for treating unresectable (cannot be surgically removed) ALK-positive IMT. This approval was based on compelling evidence from clinical studies. One study included 14 patients with ALK-positive IMT who had either unresectable or recurrent disease. The overall response rate was impressive at 79%, with some patients achieving complete responses. Many patients maintained their responses for extended periods, demonstrating the durability of treatment effect.^[10]

Patients taking crizotinib typically take it as an oral medication twice daily. The drug works by continuously blocking the abnormal signaling from the ALK fusion protein, essentially shutting down the growth signals that drive the tumour. One remarkable case involved a patient with an inoperable tumour at diagnosis who was started on crizotinib and achieved complete remission, meaning no evidence of tumour could be detected on scans.^[11]

The side effects of crizotinib are generally manageable but can include vision disturbances (particularly light sensitivity and visual trails), nausea, diarrhea, vomiting, swelling, and liver enzyme elevations. Some patients also experience fatigue or dizziness. Most side effects can be managed with dose adjustments or supportive medications, and serious side effects are relatively uncommon. Patients need regular monitoring of liver function and other blood tests while taking crizotinib.^[5]

Next-Generation ALK Inhibitors

Following the success of crizotinib, several next-generation ALK inhibitors have been developed and tested in IMT patients. These newer drugs include ceritinib, alectinib, brigatinib, and lorlatinib. Each has slightly different properties and may work in patients whose tumours stop responding to crizotinib or who cannot tolerate crizotinib’s side effects.^[8]

Ceritinib has shown promising activity in several case reports. One particularly interesting case involved a patient whose tumour had a YWHAE-ROS1 fusion rather than an ALK fusion. This patient received ceritinib and achieved more than 90% reduction in tumour volume, demonstrating that some of these inhibitors can work against other genetic abnormalities besides ALK.^[11]

Entrectinib is another targeted therapy that has produced objective responses in patients with unresectable or recurrent IMTs. This drug is particularly interesting because it can target multiple different fusion proteins, including those involving NTRK genes. This broader activity means it may be useful for the subset of IMT patients whose tumours don’t have ALK rearrangements but have other targetable genetic changes.^[10]

The sequential use of different ALK inhibitors—starting with crizotinib and then switching to next-generation inhibitors if the tumour stops responding—is an emerging treatment strategy. This approach, borrowed from experience with ALK-positive lung cancer, may provide long-term disease control even when tumours develop resistance to the first drug used. Clinical trials are ongoing to better understand the optimal sequence of these medications.^[8]

Phase and Location of Clinical Trials

Clinical trials for IMT are being conducted at major medical centers around the world, including in the United States, Europe, and Asia. Because IMT is so rare—with only an estimated 150 to 200 new cases diagnosed annually in the United States—many trials are conducted as multi-center studies that involve multiple hospitals working together to enroll enough patients.^[2]

The trials testing ALK inhibitors in IMT have included various phases of clinical investigation. Phase I trials primarily assess safety and determine the appropriate dose of a new drug. Phase II trials evaluate whether the drug works against the disease and continue to monitor safety. Phase III trials compare the new treatment against the current standard treatment. For very rare diseases like IMT, most trials have been Phase II studies that focus on demonstrating effectiveness, since there are not enough patients to conduct large Phase III comparison trials.^[6]

Patient eligibility for these trials typically requires confirmation that the tumour is indeed IMT, usually through biopsy and pathological examination. For trials of ALK inhibitors, patients must have testing showing that their tumour is ALK-positive. Other common eligibility criteria include having disease that cannot be surgically removed or has returned after surgery, adequate organ function (particularly liver and kidney function), and reasonable overall health status to tolerate the experimental treatment.^[5]

Most Common Treatment Methods

• Surgical Resection
  • Complete removal of the tumour with clear surgical margins is the treatment of choice for localized IMT
  • Approach varies by tumour location (lung lobectomy for pulmonary IMTs, abdominal resection for intra-abdominal tumours)
  • Patients with completely resected tumours have excellent prognosis
  • Regular follow-up imaging is necessary to monitor for local recurrence
• ALK-Targeted Therapy
  • Crizotinib is FDA-approved for unresectable ALK-positive IMT
  • Taken orally, typically twice daily
  • Overall response rate of approximately 79% in clinical studies
  • Next-generation ALK inhibitors (ceritinib, alectinib, brigatinib, lorlatinib) available for patients who don’t respond to or cannot tolerate crizotinib
  • Entrectinib works against multiple fusion proteins including NTRK
• Chemotherapy
  • Used for unresectable or metastatic tumours when targeted therapy is not an option
  • Regimens include combinations like methotrexate and cisplatin
  • Overall response rate approximately 50% based on retrospective data
  • Associated with typical chemotherapy side effects including nausea, fatigue, and increased infection risk
• Anti-inflammatory Medications
  • Non-steroidal anti-inflammatory drugs (NSAIDs) like diclofenac used in selected cases
  • Corticosteroids have shown tumor shrinkage in isolated case reports
  • Not considered standard treatment but may be useful in specific situations
  • Typically used alongside other treatments rather than as sole therapy