What are the other Names for this Condition? (Also known as/Synonyms)

• SMARCA4-DTS (SMARCA4-Deficient Thoracic Sarcoma)
• SMARCA4 Gene Deficient Thoracic Sarcoma

What is SMARCA4-Deficient Thoracic Sarcoma? (Definition/Background Information)

• SMARCA4-Deficient Thoracic Sarcoma is a recently described and very uncommon malignancy that is predominantly observed in adult males. By definition, these cancer types show a loss of activity involving the SMARCA4 gene
• Sarcomas may be described as malignant tumors of the connective tissue (soft tissue) and primary sarcomas arising in the thorax (chest region between the collarbone and the diaphragm, surrounded by the ribcage) are typically rare
• SMARCA4-Deficient Thoracic Sarcoma is an aggressive tumor that may develop in the mediastinum, pleura, or lung. A vast majority of the cases are reported from tobacco smokers, mostly among those with several decades  of smoking history 
• These tumors of the chest are known to cause signs and symptoms such as chest pain, breathing difficulties, and fatigue. The SMARCA4-Deficient Thoracic Sarcoma can grow rapidly to large sizes causing compression of the surrounding structures and organs resulting in associated symptoms
• In order to diagnose SMARCA4-Deficient Thoracic Sarcoma, the healthcare provider may perform physical exams, blood tests, and radiological scans of the affected region. However, a definitive diagnosis can only be made on a surgically-biopsied tumor specimen that is examined under a microscope by a pathologist
• Following a diagnosis, surgery, chemotherapy, radiation therapy, and other measures may be used in treating SMARCA4-Deficient Thoracic Sarcoma based on the assessment of the physician. However, in general, the response of the malignancy to treatment is poor
• The prognosis of SMARCA4-Deficient Thoracic Sarcoma may depend on several factors including the stage of the tumor, progression of the condition, treatment effectiveness, and overall health of the individual. Nevertheless, the prognosis of this thoracic sarcoma is poor. And, reportedly over three-fourths of the tumor cases are present with metastasis during diagnosis

Who gets SMARCA4-Deficient Thoracic Sarcoma? (Age and Sex Distribution)

• SMARCA4-Deficient Thoracic Sarcomas are extremely rare tumor types
• The tumor is noted in adults in the age group 28 to 90 years; median age being 41 years
• The male to female ratio is 9:1, and hence, only 10% of the cases have been reported in women
• Current studies do not show any racial or ethnic predilection for this tumor type

What are the Risk Factors for SMARCA4-Deficient Thoracic Sarcoma? (Predisposing Factors)

The following risk factors may contribute towards the development of SMARCA4-Deficient Thoracic Sarcoma:

• Smoking:
  • Smoking cigarettes, cigars, or pipes, increase the risk due to damaging chemicals being inhaled into the lungs
  • Prolonged smoking damages the lung, resulting in reduced clearance of the chemical carcinogens that accumulate in the lungs. This can lead to an increased risk of developing lung cancer
  • Scientific literature reports that this tumor is observed in a vast majority of smokers. The median pack year of smoking is around 18.5 years; the total number of years smoked range from 5-60 years
• Exposure to secondhand smoke: Individuals, who do not smoke, but live with smokers, also have an increased risk

In general, researchers believe that certain factors may increase an individual’s risk for lung cancers and these include:

• Advancing age: The risk increases with age and most cases occur in individuals over the age of 65 years
• Air pollution: Exposure to polluted air may increase any individual’s risk. This is true, especially in the case of smokers, who are exposed to air pollution, than non-smokers
• Exposure to asbestos and other harmful chemicals: Prolonged exposure to asbestos and other harmful chemicals including arsenic, chromium, nickel, and tar
• Individuals who are immunocompromised; those with weak immune systems
• Radon causing indoor air pollution: Radon, a colorless, odorless, and tasteless radioactive gas is produced by the natural breakdown of uranium in soil and rocks. In certain geographical regions, hazardous levels of radon gas can develop inside building or households. Individuals exposed to excessive amounts of radon gas are vulnerable to lung cancer
• Family history: Individuals with one or more immediate family members or relatives with a history of lung cancer
• Certain longstanding lung diseases: Lung diseases, such as lung fibrosis, tuberculosis, bronchitis, or chronic obstructive pulmonary disease (COPD) over a prolonged period of time, may increase an individual’s risk
• Radiation therapy to the chest: Individuals who had radiation therapy to the chest for another cancer are increasingly prone to lung cancer
• Working in mines
• The presence of alpha 1 antitrypsin deficiency disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of SMARCA4-Deficient Thoracic Sarcoma? (Etiology)

The exact cause of SMARCA4-Deficient Thoracic Sarcoma is unknown. These thoracic sarcomas are malignancies that are characterized by inactivation of the SMARCA4 gene. The SMARCA4 gene is described as a tumor suppressor gene that lies on chromosome 19p.

• However, in general, it is known that cancers form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor
• The transformation of normally healthy cells into cancerous cells may be the result of genetic mutations. Mutations allow the cancer cells to grow and multiply uncontrollably to form new cancer cells
• These tumors can invade nearby tissues and adjoining body organs, and even metastasize and spread to other regions of the body

What are the Signs and Symptoms of SMARCA4-Deficient Thoracic Sarcoma?

The signs and symptoms of SMARCA4-Deficient Thoracic Sarcoma may include the following:

• Shortness of breath that gets worse with time; difficulty in breathing
• Cough that may be persistent; blood in cough/sputum (hemoptysis)
• Chest pain, heaviness in the chest
• Changes to voice, hoarseness, or loss of voice

During the later stages, the following signs and symptoms may be noted:

• Fever and excessive night sweats 
• Sudden weight loss; unintentional weight loss; changes in appetite
• The individual is easily tired, resulting in fatigue even with minimal activity
• Headache
• Low blood pressure

Some features of the tumor include:

• A majority of the tumors occur in the mediastinum, pleura, or lung, within the thorax; a majority of the recorded cases involve the mediastinum
• The tumors are highly aggressive and exhibit rapid growth; they are known to grow to large sizes
• In the mediastinum, tumors are found to grow to larger sizes, from 9 to 16 cm or more; while within the lung they may be smaller at 1 to 2 cm
• Large tumors can cause compression of the adjoining organ structures in the chest, leading to associated symptoms
• These carcinomas are known to disseminate/spread in the body through the blood and lymphatic system

How is SMARCA4-Deficient Thoracic Sarcoma Diagnosed?

The following tests and procedures may be used in the diagnosis of SMARCA4-Deficient Thoracic Sarcoma. However, a diagnosis of the tumor can be challenging, since there are rare malignancies.

• Physical examination: During a physical exam, a physician will check the individual’s overall health status, listen to their breathing, and check for possible fluid buildup in the lungs (auscultation)
• Pulmonary function tests (PFTs) can help determine the extent of lung damage; it can also help the healthcare provider assess the ability of lungs to deliver oxygen to the body
• Chest X-ray: Two-dimensional pictures using tiny amounts of radiation are taken, in order to detect any tumors or other medical issues associated with the lungs or chest region, such as pneumonia. Tumors inside the lung or thoracic cavity may be detected using a chest X-ray; although, sometimes, these tumors are too small to visualize (tumors less than 1 cm in size may be missed on an X-ray)
• Computerized tomography (CT) scan: Also known as CAT scan, this radiological procedure creates detailed three-dimensional images of structures inside the body. CT scans may be helpful in detecting recurrences, or if the cancer has metastasized to the surrounding lymph nodes of the lungs
• Magnetic resonance imaging (MRI) scan: An MRI scan uses magnetic fields that create high quality pictures of certain body parts, such as tissues, muscles, nerves, and bones. These high-quality images may indicate to a physician, if any tumor is present
• Positron emission tomography (PET): A PET scan is a nuclear medicine imaging technique that uses three-dimensional images to show how tissue and organs are functioning. A small amount of radioactive material may be injected into a vein, inhaled or swallowed. A PET scan is also helpful in detecting recurrences, or if any metastasis (to the surrounding lymph nodes of the lungs) has occurred
• Sputum cytology: Sputum cytology is test that involves the collection of mucus (sputum), coughed-up by a patient. After the mucus is collected, a pathologist examines it in an anatomic pathology laboratory, to see if any cell abnormalities are present
• Bone scan: A bone scan is a nuclear imaging test that involves injecting a radioactive tracer into an individual’s vein. Bone scans are primarily used to detect if the cancerous cells have metastasized to the bones and formed secondary tumors
• Bone marrow biopsy: Bone marrow is a soft tissue found within bones. Occasionally, a bone marrow biopsy may used to detect blood abnormalities, or if a physician believes that metastasis to the bone marrow may have occurred

A biopsy refers to a medical procedure that involves the removal of cells or tissues, which are then examined by a pathologist. Some of the different biopsy procedures include:

• Tissue biopsy from the affected region:
  • A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, flow cytometric analysis and very rarely, electron microscopic studies, to assist in the diagnosis
• The biopsy may be performed through any of the following procedures:
  • Bronchoscopy: A special medical instrument, called a bronchoscope, is inserted through the nose and into the lungs to collect small tissue samples
  • Thoracentesis: During thoracentesis, physicians use a special medical device called a cannula, to remove fluid between the lungs and the chest wall for examination
  • Thoracoscopy: A medical instrument called a thoracoscope is inserted into the chest through tiny incisions, in order to examine and remove tissue from the chest wall, which is then analyzed further
  • Thoracotomy: Thoracotomy is a surgical invasive procedure with special medical instruments to open-up the chest and remove tissue from the chest wall or the surrounding lymph nodes of the lungs
  • Mediastinoscopy: A medical instrument called a mediastinoscope is inserted into the chest wall to examine and remove samples
  • Fine needle aspiration biopsy (FNAB) or transthoracic needle biopsy: A device called a cannula is used to extract tissue or fluid from the lungs, or surrounding lymph nodes
  • Open lung biopsy

A differential diagnosis with respect to other tumor types may be necessary prior to establishing a definite diagnosis, by excluding the following:

• Differentiated carcinoma
• Melanoma
• NUT carcinoma
• Rhabdomyosarcoma

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of SMARCA4-Deficient Thoracic Sarcoma?

The complications of SMARCA4-Deficient Thoracic Sarcoma can include:

• Dyspnea (shortness of breath): If the cancerous tumor expands to block important, large, or small airways of the chest or lung
• Hemoptysis (coughing-up blood): Individuals may cough-up blood, due to excessive amounts of blood in the airways
• Pain: In advanced stages, the tumor that has metastasized to the pleural cavity (lining surrounding the lungs), invaded the chest wall, or other areas of the body, may cause excessive pain
• Pleural effusion: Excessive fluid accumulation in the chest, resulting from cancerous cells spreading inside or outside the lungs
• Irreversible lung damage such as due to lung fibrosis
• Development of pneumothorax (collapsed lung)
• Recurrence following surgical removal of the tumor

Involvement of local and distant organs:

• Most tumor cases are diagnosed during advanced stages
• The common sites of metastasis include the lymph nodes, bones, gastrointestinal tract, liver, adrenal glands, kidneys, and brain
• The malignancy is known to result in severe skeletal-related events (SREs or metastatic bone disease)
• Loss of function of the organ/area to which the cancer has spread due to systemic involvement

There may be complications related to the methods used in treating the condition which may include:

• Side effects of radiation therapy that may include sunburn-like rashes, where radiation was targeted, red or dry skin, heaviness of the breasts, and general fatigue
• Side effects of chemotherapy, which may include nausea, vomiting, hair loss, decreased appetite, mouth sores, fatigue, low blood cell counts, and a higher chance of developing infections
• The treatment can also cause infertility in men and women. Hence, measures to protect the individual’s fertility must be considered, before starting chemotherapy

How is SMARCA4-Deficient Thoracic Sarcoma Treated?

Treatment options available for individuals with SMARCA4-Deficient Thoracic Sarcoma are dependent upon the following:

• Specific location of the tumor
• The staging of the malignancy
• Overall health status of the individual
• Personal preferences
• Type of gene mutation involved: This factor can determine the treatment possibilities or relative treatment resistance

In general, sarcomas can be treated using the following methods that include surgery (commonly), chemotherapy, and radiation therapy. Depending on each specific case, the healthcare provider may choose to employ a combination therapy that may increase the effectiveness of the different treatment types. But, it has to be noted that the side effects are usually cumulative.

However, currently, no effective therapies have been established towards treating SMARCA4-Deficient Thoracic Sarcomas.

The surgical options may include:

• Wedge resection: Wedge resection is a partial removal of the wedge-shape portion of the lung that contains cancerous cells (along with any surrounding healthy tissue)
• Segmentectomy: It is the partial removal of the cancerous lung and any surrounding healthy tissue
• Pulmonary lobectomy: It is a type of surgical procedure performed to partially remove a portion of a lung
• Sleeve lobectomy: It is another surgical procedure to partially remove a portion of the lung and a part of the airway (bronchus)
• Pneumonectomy: It is the surgical removal of the entire lung

Chemotherapy:

• Chemotherapy drugs are typically taken as pills, or injected directly into a vein. These drugs travel through the body to kill any cancer cells
• But, they can also kill healthy cells, located within the gastrointestinal tract and in hair follicles. The side effects include vomiting, nausea, and hair loss

Radiation therapy:

• Radiation therapy involves using X-rays to kill cancerous cells. High-powered radiation beams are directed to particular body regions to target cancer. In the process, healthy cells can also be damaged
• Radiation therapy can be administered in the following ways:
  • Either by a machine, placed outside the body (called external beam radiation)
  • Or it may be administered internally, by a device positioned directly at, or close to the malignant tumor, inside the lungs (called brachytherapy)

Targeted drug therapy: The healthcare professional will determine if there are newly-developed and effective targeted drug therapies for SMARCA4-Deficient Thoracic Sarcoma.

How can SMARCA4-Deficient Thoracic Sarcoma be Prevented?

Currently, there is no known prevention method for SMARCA4-Deficient Thoracic Sarcoma. Although there are no preventable measures for lung cancer, in general, various steps can be taken to help decrease the risk of its formation. These measures include:

• Complete smoking cessation and avoiding exposure to secondhand smoke: The risk for the malignancy decreases drastically following quitting or giving up smoking
• Physical activity: Individuals, who participate in a moderate amount of physical activity, may decrease their risk for cancer
• Adequate consumption of fruits and vegetables: A healthy diet, low in saturated fats and rich in fruits and vegetables, may help decrease one’s risk
• Avoid exposure to certain materials and chemicals (including asbestos, arsenic, chromium, nickel, and tar): Individuals who work with such substances should follow proper usage principles and occupational safety instructions, since a prolonged exposure to harmful chemicals may increase the risk for lung cancers. This risk is multiplied in smokers who are exposed to these harmful chemicals
• Avoid exposure to radioactive gas: Radon, a radioactive gas, produced by the natural breakdown of uranium in soil and rocks, may develop to hazardous levels inside building spaces. Individuals exposed to excessive amounts of radon gas are vulnerable to cancers involving the lung
• Limit alcohol consumption: Alcoholic beverages have been linked to increasing an individual’s risk for certain types of cancers, such as those affecting the lungs, mouth, throat, esophagus, breast, colon, and liver
• CT screening in high-risk groups can decrease the incidence of lung-associated cancer, or at least help detect such cancers early. A low-dose CT scan is good to identify the tumors early. It is generally known that CT scans are about 3-4 times more effective than X-ray studies

What is the Prognosis of SMARCA4-Deficient Thoracic Sarcoma? (Outcomes/Resolutions)

SMARCA4-Deficient Thoracic Sarcoma is a very rare and highly-aggressive malignancy.

• The prognosis of individuals with the tumor is generally poor. The death rates are high even when the tumor is diagnosed during the early stages
• The median survival period is around 6 months and according to some literature, the 2-year survival rate is about 12.5%. Also, nearly 77% of the tumors are known to have metastasized to the vital organs, such as the bone, liver, and brain, at the time of diagnosis
• Surgical intervention, chemotherapy, and radiation therapy is not known to be very effective in treating this malignancy
• The prognosis of lung cancer, in general, depends upon a set of several factors that include: 
  • The grade of the lung tumor such as grade1, grade2, and grade 3. Grade1 indicates a well-differentiated tumor, grade 2 a moderately-differentiated tumor, whereas grade 3 indicates a poorly-differentiated tumor. Grade 3 tumors are higher prone to metastasis to the lymph nodes and recurrences
  • Stage of lung cancer: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • The size of the lung tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • Individuals with bulky disease of the lung cancer have a poorer prognosis
  • Involvement of the lymph node, which can adversely affect the prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of the tumor (meaning, if the tumor can be removed completely)
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur 
  • Response to treatment of lung cancer: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment. The response of SMARCA4-Deficient Thoracic Sarcoma to therapy is usually poor
  • Progression of the condition makes the outcome worse
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
• The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity) that primarily affects the elderly adults or those with other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

It is important to have follow-up appointments with a physician, to evaluate the effects of the current treatment method, and to monitor for any returning tumors.

Additional and Relevant Useful Information for SMARCA4-Deficient Thoracic Sarcoma:

• An absence of the SMARCA4 gene is characteristic of several tumors including:
  • Small cell carcinoma of the ovary, hypercalcemic type
  • SMARCA4-deficient undifferentiated uterine sarcoma
  • And, SMARCA4 Deficient Thoracic Sarcoma
• Smoking is highly-associated with squamous cell carcinomas and small cell carcinomas; nevertheless, for all lung cancer forms, smoking is the single most important risk factor