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Desmoid Tumor

Updated : May 13, 2024





Background

  • Desmoid tumor are mesenchymal neoplasms which are invasive but do not metatstize. They are commonly referred to as musculoaponeurotic fibromatosis, deep fibromatosis, and aggressive fibromatosis.
  • Although desmoid tumors do not undergo metastasis, they are capable of causing severe morbidity and death.
  • A treatment plan which includes surgery, sometimes in conjunction with radiation therapy is generally suggested. Th
  • e local recurrence rate for desmoid tumors is high so the WHO has labeled them as, “intermediate locally aggressive tumors.”
  • The WHO describes a desmoid tumor as a “clonal fibroblastic proliferation that arises in the deep soft tissues and is characterized by infiltrative growth and a tendency toward local recurrence but an inability to metastasize,” Chemotherapy is a suggested option for DT cases which do not respond well to RT and surgery, or when both these options are not possible.

Epidemiology

  • Desmoid tumors are rare, with a meagre incidence of 2-4 individuals per million. They account only for 0.03% of all tumors.
  • Ages most affected by DT range between 30-40. Men between the ages of 15-60 are more affected than women.
  • Desmoid tumors develop on abdominal, intra-abdominal, and extra-abdominal sites.

Anatomy

Pathophysiology

  • Surgery, Radiation therapy, or a combination of both is suggested to patients with desmoid tumors.
  • In a study conducted in 1999, where 189 individuals were treated with surgery, resection and radiation therapy or only radiation, the overall relapse rates for patients were 30% and 33% for 5 and 10 years respectively.
  • Survival rates for 5, 10, and 15 years were 96%, 92%, and 87% respectively.
  • Tumors in the trunk have a better prognosis than tumors found in the extremities. The study concluded that for the majority of desmoid tumours, wide local excision with negative pathologic margins is the the best treatment.
  • Positive margins can be neutralised by adjuvant radiation therapy, therefore function-sparing resection is reasonable. Unresectable illness requires radiation therapy.

Etiology

  • Most cases of Desmoid tumors are idiopathic, and around 85% cases present a mutation in the CTNNB1 encoding beta-catenin pathway.
  • The three identified unique mutations are 41A, 45F, and 45. The mutation 45F is related with an elevated recurrence risk. The 5-year survival rate without recurrence was 23% for the 45F gene, 57% for the 41A gene, and 68% for no mutation.
  • In familial adenomatous polyposis (FAP), particularly abdominal FAP induced by a mutation in the APC gene, desmoid tumours are more prevalent. Patients
  • FAP-related DT shows a preference for the prior surgical location, and past surgery can increase risk of incidence. DT is a more significant source of morbidity and death in people treated with preventive colectomy than colon cancer.
  • DT occurs more frequently in women during or after pregnancy, and subjective data shows that abdominal wall damage and elevated oestrogen levels may be the cause. In general, outcomes are better for DT coupled with pregnancy.

Genetics

Prognostic Factors

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Lifestyle modifications in treating desmoid tumor

  • Dietary Modifications: Eating a diet high in fruits, vegetables, whole grains, and lean meats will strengthen the immune system and help you keep a healthy weight. Some individuals consider reducing or eliminating processed foods, sugar, and excessive saturated fats, although specific dietary restrictions should be discussed with a healthcare professional. 
  • Physical Activity: Regular exercise can contribute to improved overall health and well-being. Depending on the individual’s condition and treatment plan, low-impact workouts like yoga, swimming, or walking could be advised.  
  • Environmental Toxins: Minimizing exposure to environmental toxins may be beneficial for general health. This could include avoiding exposure to tobacco smoke, reducing exposure to harmful chemicals or pollutants, and using environmentally friendly household products. 
  • Stress Management: Chronic stress may impact overall health negatively. Strategies like mindfulness, meditation, relaxation techniques, or seeking support through counselling or support groups might assist in managing stress levels. 
  • Sleep and Rest: Adequate sleep and proper rest are essential for overall health and well-being. Establishing good sleep hygiene practices and ensuring a comfortable sleep environment can contribute to better rest. 
  • Support System: Having a strong support system and a circle of friends, family or support groups can be quite helpful in managing the difficulties brought on by the diagnosis and treatment of a desmoid tumour. 
  •  

Role of gamma secretase inhibitor in treating desmoid tumor: Specialty

  • nirogacestat (Ogsiveo) 
  • Nirogacestat is the first FDA-approved medication specifically for desmoid tumors. It works by inhibiting an enzyme called gamma-secretase, which plays a role in tumor growth. 
  • Nirogacestat is currently indicated for adult patients with progressive desmoid tumors who require systemic treatment.  

Effectiveness of antineoplastic agents in the treatment of desmoid tumor

  • doxorubicin (Adriamycin,Rubex) 
  • Doxorubicin works by interfering with DNA replication, essentially preventing cancer cells from dividing and multiplying. This can slow or stop tumor growth. 
  • dacarbazine (DTIC-Dome) 
  • Dacarbazine prevents the synthesis of proteins, RNA, and DNA. All stages of the cell cycle are affected by its inhibition of cell replication. 
  • carboplatin (Paraplatin) 
  • Carboplatin is a chemotherapy medication that belongs to the platinum-based chemotherapy class of drugs.  
  • It functions by interfering with rapid dividing cells’ (especially cancer cells’) ability to replicate their DNA. Carboplatin binds chemically to DNA, preventing cell division and ultimately resulting in cell death. 

Role of targeted therapy in treating desmoid tumor

  • imatinib  
  • The recommended dose of imatinib to treat desmoid tumors is 800 mg orally a day. This treatment is successful in desmoid tumor patients. But no specific mechanism or mode of action is understood. 
  • Patients with no mutations in PDGFRB, PDGRA, or KIT areas also exhibited a response. 

Effectiveness of hormonal therapy in treating desmoid tumor

  • Tamoxifen, a selective estrogen receptor modulator, which is used as a treatment option for desmoid tumors. 
  • Hormonal medication, such as tamoxifen, has been investigated and found to be helpful, knowing that desmoid tumors can happen around pregnancy time. 
  • The regular recommended dose is 40 mg daily, and tamoxifen is also used in higher doses, like 120 mg to 200 mg daily. However, there are no controlled studies available. 

Role of surgical procedures in treating desmoid tumors

  • Surgical resection is a treatment option for desmoid tumors, particularly when the tumor is localized and can be completely removed without causing significant functional impairment or damage to be surrounding structures. However, due to the infiltrative nature of desmoid tumors, complete resection can be challenging, and there’s a risk of recurrence. 

Role of management in treating desmoid tumor

  • Diagnosis and Initial Assessment: 
  • Identification of the tumor through physical examination, imaging studies (MRI, CT scan, ultrasound), and sometimes biopsy to confirm the diagnosis. 
  • Assessment of the tumor’s location, size, growth rate, and potential impact on surrounding structures. 
  • Observation and Monitoring: 
  • Some small, stable desmoid tumors might be observed without immediate intervention, especially if they’re not causing significant symptoms or threatening nearby structures. 
  • Regular monitoring through imaging studies to track any changes in size or behavior of the tumor. 
  • Treatment Planning: 
  • Based on the tumor characteristics and the patient’s overall health, a treatment plan is developed. This may involve a multidisciplinary team comprising oncologists, surgeons, radiation oncologists, and other specialists. 
  • Treatment decisions often consider factors such as tumor size, location, symptoms, potential impact on function, and the patient’s preferences. 
  • Surgical Intervention: 
  • Surgery might be considered as the primary treatment for some desmoid tumors, especially if they’re small and in an accessible location. 
  • However, due to the nature of desmoid tumors invading surrounding tissues and their potential to recur after surgery, careful consideration and planning are essential. Complete surgical removal without causing significant damage to surrounding structures might be challenging. 
  • Medical Management: 
  • Non-surgical approaches may include systemic therapies like anti-inflammatory drugs, hormonal therapy (such as tamoxifen), targeted therapies, or chemotherapy in some cases. 
  • Newer treatment options like targeted therapies using medications that aim at specific molecular pathways might be considered, especially for tumors that are not amenable to surgery or have recurred after surgery. 
  • Radiation Therapy: 
  • Radiation therapy might be used as an adjunct to surgery or as a primary treatment for desmoid tumors in certain situations, particularly for tumors that are inoperable or recur after surgery. 
  • Follow-Up and Surveillance: 
  • Regular follow-up visits and imaging studies are crucial to monitor the tumor’s response to treatment, detect any recurrence, and manage any potential side effects from treatments. 
  • Supportive Care and Rehabilitation: 
  • Addressing symptoms, managing side effects of treatment, and supporting the patient’s overall well-being and functional status through rehabilitation if necessary. 

Medication

 

sorafenib 

(Orphan)
sorafenib is designated as orphan for the treatment of the above condition



nirogacestat 

Recommended for adult individuals experiencing the progression of desmoid tumors necessitating systemic treatment
The standard recommendation is to take 150 mg orally twice a day



Dose Adjustments

Limited data is available

 
 

Media Gallary

References

Desmoid Tumor

Updated : May 13, 2024




  • Desmoid tumor are mesenchymal neoplasms which are invasive but do not metatstize. They are commonly referred to as musculoaponeurotic fibromatosis, deep fibromatosis, and aggressive fibromatosis.
  • Although desmoid tumors do not undergo metastasis, they are capable of causing severe morbidity and death.
  • A treatment plan which includes surgery, sometimes in conjunction with radiation therapy is generally suggested. Th
  • e local recurrence rate for desmoid tumors is high so the WHO has labeled them as, “intermediate locally aggressive tumors.”
  • The WHO describes a desmoid tumor as a “clonal fibroblastic proliferation that arises in the deep soft tissues and is characterized by infiltrative growth and a tendency toward local recurrence but an inability to metastasize,” Chemotherapy is a suggested option for DT cases which do not respond well to RT and surgery, or when both these options are not possible.
  • Desmoid tumors are rare, with a meagre incidence of 2-4 individuals per million. They account only for 0.03% of all tumors.
  • Ages most affected by DT range between 30-40. Men between the ages of 15-60 are more affected than women.
  • Desmoid tumors develop on abdominal, intra-abdominal, and extra-abdominal sites.
  • Surgery, Radiation therapy, or a combination of both is suggested to patients with desmoid tumors.
  • In a study conducted in 1999, where 189 individuals were treated with surgery, resection and radiation therapy or only radiation, the overall relapse rates for patients were 30% and 33% for 5 and 10 years respectively.
  • Survival rates for 5, 10, and 15 years were 96%, 92%, and 87% respectively.
  • Tumors in the trunk have a better prognosis than tumors found in the extremities. The study concluded that for the majority of desmoid tumours, wide local excision with negative pathologic margins is the the best treatment.
  • Positive margins can be neutralised by adjuvant radiation therapy, therefore function-sparing resection is reasonable. Unresectable illness requires radiation therapy.
  • Most cases of Desmoid tumors are idiopathic, and around 85% cases present a mutation in the CTNNB1 encoding beta-catenin pathway.
  • The three identified unique mutations are 41A, 45F, and 45. The mutation 45F is related with an elevated recurrence risk. The 5-year survival rate without recurrence was 23% for the 45F gene, 57% for the 41A gene, and 68% for no mutation.
  • In familial adenomatous polyposis (FAP), particularly abdominal FAP induced by a mutation in the APC gene, desmoid tumours are more prevalent. Patients
  • FAP-related DT shows a preference for the prior surgical location, and past surgery can increase risk of incidence. DT is a more significant source of morbidity and death in people treated with preventive colectomy than colon cancer.
  • DT occurs more frequently in women during or after pregnancy, and subjective data shows that abdominal wall damage and elevated oestrogen levels may be the cause. In general, outcomes are better for DT coupled with pregnancy.

  • Dietary Modifications: Eating a diet high in fruits, vegetables, whole grains, and lean meats will strengthen the immune system and help you keep a healthy weight. Some individuals consider reducing or eliminating processed foods, sugar, and excessive saturated fats, although specific dietary restrictions should be discussed with a healthcare professional. 
  • Physical Activity: Regular exercise can contribute to improved overall health and well-being. Depending on the individual’s condition and treatment plan, low-impact workouts like yoga, swimming, or walking could be advised.  
  • Environmental Toxins: Minimizing exposure to environmental toxins may be beneficial for general health. This could include avoiding exposure to tobacco smoke, reducing exposure to harmful chemicals or pollutants, and using environmentally friendly household products. 
  • Stress Management: Chronic stress may impact overall health negatively. Strategies like mindfulness, meditation, relaxation techniques, or seeking support through counselling or support groups might assist in managing stress levels. 
  • Sleep and Rest: Adequate sleep and proper rest are essential for overall health and well-being. Establishing good sleep hygiene practices and ensuring a comfortable sleep environment can contribute to better rest. 
  • Support System: Having a strong support system and a circle of friends, family or support groups can be quite helpful in managing the difficulties brought on by the diagnosis and treatment of a desmoid tumour. 
  •  

  • nirogacestat (Ogsiveo) 
  • Nirogacestat is the first FDA-approved medication specifically for desmoid tumors. It works by inhibiting an enzyme called gamma-secretase, which plays a role in tumor growth. 
  • Nirogacestat is currently indicated for adult patients with progressive desmoid tumors who require systemic treatment.  

  • doxorubicin (Adriamycin,Rubex) 
  • Doxorubicin works by interfering with DNA replication, essentially preventing cancer cells from dividing and multiplying. This can slow or stop tumor growth. 
  • dacarbazine (DTIC-Dome) 
  • Dacarbazine prevents the synthesis of proteins, RNA, and DNA. All stages of the cell cycle are affected by its inhibition of cell replication. 
  • carboplatin (Paraplatin) 
  • Carboplatin is a chemotherapy medication that belongs to the platinum-based chemotherapy class of drugs.  
  • It functions by interfering with rapid dividing cells’ (especially cancer cells’) ability to replicate their DNA. Carboplatin binds chemically to DNA, preventing cell division and ultimately resulting in cell death. 

  • imatinib  
  • The recommended dose of imatinib to treat desmoid tumors is 800 mg orally a day. This treatment is successful in desmoid tumor patients. But no specific mechanism or mode of action is understood. 
  • Patients with no mutations in PDGFRB, PDGRA, or KIT areas also exhibited a response. 

  • Tamoxifen, a selective estrogen receptor modulator, which is used as a treatment option for desmoid tumors. 
  • Hormonal medication, such as tamoxifen, has been investigated and found to be helpful, knowing that desmoid tumors can happen around pregnancy time. 
  • The regular recommended dose is 40 mg daily, and tamoxifen is also used in higher doses, like 120 mg to 200 mg daily. However, there are no controlled studies available. 

  • Surgical resection is a treatment option for desmoid tumors, particularly when the tumor is localized and can be completely removed without causing significant functional impairment or damage to be surrounding structures. However, due to the infiltrative nature of desmoid tumors, complete resection can be challenging, and there’s a risk of recurrence. 

  • Diagnosis and Initial Assessment: 
  • Identification of the tumor through physical examination, imaging studies (MRI, CT scan, ultrasound), and sometimes biopsy to confirm the diagnosis. 
  • Assessment of the tumor’s location, size, growth rate, and potential impact on surrounding structures. 
  • Observation and Monitoring: 
  • Some small, stable desmoid tumors might be observed without immediate intervention, especially if they’re not causing significant symptoms or threatening nearby structures. 
  • Regular monitoring through imaging studies to track any changes in size or behavior of the tumor. 
  • Treatment Planning: 
  • Based on the tumor characteristics and the patient’s overall health, a treatment plan is developed. This may involve a multidisciplinary team comprising oncologists, surgeons, radiation oncologists, and other specialists. 
  • Treatment decisions often consider factors such as tumor size, location, symptoms, potential impact on function, and the patient’s preferences. 
  • Surgical Intervention: 
  • Surgery might be considered as the primary treatment for some desmoid tumors, especially if they’re small and in an accessible location. 
  • However, due to the nature of desmoid tumors invading surrounding tissues and their potential to recur after surgery, careful consideration and planning are essential. Complete surgical removal without causing significant damage to surrounding structures might be challenging. 
  • Medical Management: 
  • Non-surgical approaches may include systemic therapies like anti-inflammatory drugs, hormonal therapy (such as tamoxifen), targeted therapies, or chemotherapy in some cases. 
  • Newer treatment options like targeted therapies using medications that aim at specific molecular pathways might be considered, especially for tumors that are not amenable to surgery or have recurred after surgery. 
  • Radiation Therapy: 
  • Radiation therapy might be used as an adjunct to surgery or as a primary treatment for desmoid tumors in certain situations, particularly for tumors that are inoperable or recur after surgery. 
  • Follow-Up and Surveillance: 
  • Regular follow-up visits and imaging studies are crucial to monitor the tumor’s response to treatment, detect any recurrence, and manage any potential side effects from treatments. 
  • Supportive Care and Rehabilitation: 
  • Addressing symptoms, managing side effects of treatment, and supporting the patient’s overall well-being and functional status through rehabilitation if necessary. 

sorafenib 

(Orphan)
sorafenib is designated as orphan for the treatment of the above condition



nirogacestat 

Recommended for adult individuals experiencing the progression of desmoid tumors necessitating systemic treatment
The standard recommendation is to take 150 mg orally twice a day



Dose Adjustments

Limited data is available