Sarcoma

Soft tissue sarcoma (STS) is a relatively uncommon type of cancer and accounts for about 0.8% of all new cancer cases in the United States (US). According to an estimate, about 13040 new cases of STS and about 5150 deaths from the STS will be observed in 2018, in the US. Soft tissue sarcoma (STS) is more common among men and at an older age, with most cases reported in the individuals aged between 55 and 64 years. In the US, the overall incidence and mortality of STS have been increasing slightly with an improvement in the 5-year survival rates during the last decade. 

STS is a group of different neoplasms with variable characteristics and different types of cells affected. STS arises from soft tissues, such as muscle, fat, nerves, blood vessels, fibrous tissues, or deep skin tissues. STS may arise anywhere in the human body with limbs being the most common site. There are many different types of soft tissue tumors (abnormal growth of cells that remain confined to the site of origin) which are about 100 times more common than the STSs. Benign soft tissue tumors, such as fibroma, hemangioma, lipoma, leiomyoma, lymphangioma, myxoma, neurofibroma, neuroma, schwannoma, rhabdomyoma, and others are not discussed here. However, some soft tissue tumors with characteristics intermediate between cancer (abnormal growth of cells that can invade nearby tissue and can spread to distant body parts) and tumor are discussed below.

What are the Types of Sarcoma?

Based on the type of cells affected, STSs can be classified into the following main categories:

Liposarcoma

Liposarcoma is cancer that arises from the adipose (fatty) tissue anywhere in the body. It accounts for about 20% of all STSs in adults. Most common location of liposarcoma includes thigh, behind the knee, and retroperitoneal (backside of the abdomen). It mostly occurs in individuals aged 50 to 65 years. Liposarcoma can be further divided into 3 subgroups: 1) Well-differentiated and dedifferentiated, 2) myxoid-round cell, and 3) pleomorphic liposarcoma. Well-differentiated liposarcoma is generally present as a deep-seated, painless, enlarging mass that may become very large over time but does not spread to a distant location. Well-differentiated liposarcoma has a good prognosis for limbs but a poor prognosis for retroperitoneum or mediastinal location. Dedifferentiated liposarcoma is characterized by the presence of non-lipogenic area(s) within the main tumor. Myxoid-round cell liposarcoma is considered as a high-grade tumor that usually consists of small, evenly dispersed round cells with a variable number of fat cells. Greater the number of round cells more aggressive is the disease. Pleomorphic liposarcoma is a high-grade tumor that consists of different lipoblasts and tends to spread quickly to lungs. Pleomorphic liposarcoma has a worse prognosis. 

Fibrosarcoma

Sarcoma cancer doctor in gurgaon: Fibrosarcoma is cancer that arises from the fibrous tissue anywhere in the body, especially that of limbs, trunk, and head and neck region. It is relatively uncommon accounting for about 1% of all STSs in adults. It mostly affects middle-aged and older adults with a few cases reported in children. They show moderate aggressiveness with little tendency to spread to nearby tissues.

Leiomyosarcoma (LMS)

LMS mainly arises from the smooth muscles in the blood vessels, uterus, and other visceral organs/structures. They mostly affect middle-aged or older adults with the most common location being the smooth muscles of the large blood vessels in the retroperitoneum/abdomen or in the pelvis, especially uterus. The LMS may occur anywhere in the body and presentation depend upon the type of tissue involved. When a blood vessel is involved, obstruction in the blood flow is common with pain due to the involvement of the nearby nerves. Large size tumors and high-grade disease usually have a poor prognosis. 

Rhabdomyosarcoma (RMS)

RMS mainly arise from the skeletal muscles (voluntary muscles that control the body movement at will). RMS cells resemble cells those are formed during an early phase of development in a 6- to 8-week old embryo and eventually give rise to skeletal muscles. RMS generally affect children with a few cases reported in adults.

They can occur anywhere in the body. RMS can be categorized into the following 3 subtypes: 1) Embryonal RMS, 2) Alveolar RMS, and 3) Anaplastic or Pleomorphic RMS. Embryonal RMS is the most common subtype that mainly affects the children less than 5 years of age with a few cases reported in adults. The most common location includes orbit (eyeball), head and neck area, bladder, vagina, prostate, and testicles. Alveolar RMS generally affect skeletal muscles of the limbs and trunk in adolescents and young adults. These are rare in younger children and have poor prognosis in this population. Anaplastic or Pleomorphic RMS is an inherently aggressive disease that mostly affects adults. 

Angiosarcoma

Angiosarcoma may arise either from the blood vessels (hemangiosarcomas) or from lymph vessels (lymphangiosarcomas). Most angiosarcomas start in the superficial soft tissues including skin with less than one-fourth starting in the deeper soft tissues. The incidence of these tumors has been linked with the history of radiation treatment, especially in the breast where these tumors generally occur after initial radiation therapy along with lymphedema. These tumors generally have a poor prognosis.

Kaposi sarcoma (KS)

KS is cancer that arises from the cells lining the blood vessels and lymph vessels. It may develop anywhere in the body including the lymph nodes and visceral organs like lungs and those of digestive system. It is mostly presented as a dark-colored, irregular tumor on the skin or in the mucosa of the mouth. It can be life-threatening when it involves visceral organs. KS can be further divided into four classes: 1) Epidemic/AIDS-related KS, 2) Classic/Mediterranean KS, 3) Endemic/African KS, and 4) Iatrogenic/transplant-related KS. The epidemic/AIDS-related KS is the most common type of KS in the US. It occurs in individuals with AIDS, that is when the immune system has been severely compromised due to the HIV infection. Classic KS is mostly reported in Mediterranean, Eastern European, and Middle Eastern countries. It does not require prior significant immunosuppression and is mostly observed in old-aged individuals with relatively higher incidences reported in males. However, a herpes-virus infection may develop in the patient with classic KS. It is usually presented as single or multiple tumors in the lower limbs. Endemic KS is common among individuals living in the Equatorial African countries. It mostly affects young adults and children. In children before attaining puberty, KS may occur as an aggressive form affecting lymph nodes. KS-related herpes virus infection is more common in Africa. Iatrogenic KS is observed in individuals with a suppressed immune system due to a prior organ/hematopoietic stem cell transplant and who usually receive medicines to keep the immune system from attacking the transplanted organ/cells.

Gastrointestinal Stromal Tumor (GIST)

GISTs arise from the interstitial cells of Cajal (ICC) in the gastrointestinal (GI) tract. The ICCs are a part of the autonomous nervous system that regulates the smooth muscles in the GI tract. Thus, ICCs are sometimes referred to as pacemaker of the GI tract. GISTs may occur anywhere in the GI tract with the stomach being the most common site followed by the small intestine. They may even start outside of the GI tract, such as the tissue in the vicinity of the digestive system, e.g. the omentum or peritoneum. GISTs are rare and mostly affect old-aged individuals. They show variable behavior in different individuals. They may spread to nearby and distant body parts. 

Alveolar Soft Part Sarcoma (ASPS)

ASPS generally arise from the soft tissue in the lower limbs of young adults. These are a rare type of sarcoma accounting for less than 1% of all STSs. These are presented as a painless slow-growing mass without any other symptom but can spread readily to distant body parts. Thus, ASPSs have a poor prognosis. 

Epithelioid sarcoma

Epithelioid sarcoma arises from the tissue under the skin of upper and lower limbs in adolescent and young adults. The lesions are multinodular with a central region of tissue necrosis. These cancers can spread to lymph nodes and generally have a poor prognosis. 

Myxofibrosarcoma

Myxofibrosarcoma arises from the fibrous tissue with a variable myxoid component. They are mostly presented as a painless mass in the limbs and the trunk. They generally occur as a low-grade disease that can progress to a high-grade variant upon recurrence. The high-grade disease tends to spread to lungs, lymph nodes, and bones.  

Malignant Peripheral Nerve Sheath Tumor (MPNST)

These tumors arise from the nerve sheath rather than from the nerve itself. They mostly affect the major nerves of the body, especially those in the lower limbs and the trunk of middle-aged adults. Most of these tumors are high-grade with an elevated tendency to spread to distant body parts. 

Extraskeletal Osteosarcoma

As the name indicate the extraskeletal osteosarcoma arise from osteoid cells not attached to the skeleton. The most common location for extraskeletal osteosarcoma are limbs with few cases reported in breast, urinary bladder, retroperitoneum, and other visceral organs. They mostly affect individuals older than 50 years.

Synovial Sarcoma

Synovial sarcoma arises from deep soft tissue (not necessarily the synovial tissue) around the joints – hip, knee, ankle, and shoulder. It generally affects males aged between 15 to 35 years. It is presented as a slow-growing painful (or sometimes painless) mass and can spread to nearby tissues.

Clear Cell Sarcoma

Clear cell sarcoma mostly affect tendons in the lower and upper limbs of young adults. The tumors are presented with a painful or painless soft tissue mass composed of epithelioid-type cells that behave like melanoma (cancer of melanin-producing skin cells). The tumor cells contain melanin and tend to spread to nearby lymph nodes. Clear cell sarcoma cells typically contain translocation t(12;22) resulting in fusion of the EWSRI and ATF1 genes.

Undifferentiated Pleomorphic Sarcoma (UPS)

UPS was previously known as malignant fibrous histiocytoma (MFH). UPS is a type of sarcoma that does not contain any line of differentiation and usually presents as a painless, deep-sited tumor that can grow locally and can spread to nearby tissues. It mostly affects individuals in their 60s. The most common location is limbs and retroperitoneum.  

Desmoplastic Small Round Cell Tumor

These tumors contain monotonous cells that are stained by hematoxylin or eosin stains. Translocation t(11;22) resulting in fusion of the EWSRI and WT1 genes is the characteristic feature of these tumors. These tumors are mostly seen in children and young adults with abdomen being the most common location. These tumors usually have a poor prognosis and are difficult to treat.

Aggressive Fibromatoses/Desmoid Tumor

These tumors arise from the fibrous tissue and have characteristics intermediate between fibrosarcoma and fibroma. These tumors can spread to a nearby tissue with rare chances of spread to a distant body part. Abdominal wall (specifically after pregnancy), the mesentery of the small intestine, and limbs are the most common location for these tumors. These tumors are usually presented as a painful slowly growing mass that may cause compression of nearby structures or obstruction problems depending upon the location. 

Dermatofibrosarcoma Protuberans (DFSP)

It is the sarcoma of the fibrous tissue beneath the skin including both dermis and subcutis. These are rare sarcomas that mostly affect individuals aged between 30 to 50 years. These cancers generally show an infiltrative pattern and spread locally with multifocal nodules. The skin of the limbs and the trunk is the most common location. They grow slowly but have high recurrence due to their infiltrative nature.

Solitary fibrous tumor (SFT)/Hemangiopericytoma

These tumors arise from the fibrous and/or fatty tissue and are characterized by the presence of branching vascular pattern within the tumor mass. They are usually presented as a slow-growing painless mass in the thoracic cavity, retroperitoneum, pelvis, orbit, underarms and lower limbs. They mostly affect middle-aged adults. They are mostly benign but can be malignant. Previously called hemangiopericytomas are now considered solitary fibrous tumors.

Hemangioendothelioma

It is a tumor that arises in the blood vessel supplying to soft tissues or to internal organs, such as the liver or lungs. It is generally a slow-growing low-grade cancer that can spread to nearby tissues and sometimes to distant body parts.

How do I know if I am at risk for Sarcoma? What are the causes of Sarcoma?

Different epidemiological studies have revealed various risk factors that can predispose STSs. Different STSs may have different risk factors along with some common factors that can predispose their development. Following is the list of such risk factors:

Radiation Exposure

History of exposure to radiation for the treatment of another tumor/cancer has been implicated for the development of STSs, especially fibrosarcoma, undifferentiated pleomorphic sarcoma (UPS), angiosarcoma, malignant peripheral nerve sheath tumor (MPNST), and osteosarcoma. It generally takes around 10 years from the initial radiation treatment for the development of secondary cancer.

Genetic Cancer Predisposition Syndrome

Some inherited cancer predisposition syndromes (caused by a mutation in certain genes which are generally transferred from one generation to other) have been reported to be associated with the increased incidence rate of STSs. Following are certain examples of such genetic syndromes:

• Neurofibromatosis Type 1 Or Recklinghausen Disease (caused by a mutation in the NF1 gene) may elevate the risk of developing malignant peripheral nerve sheath tumors (MPNST) and gastrointestinal stromal tumors (GISTs)
• Gardner Syndrome(caused by a mutation in the APC gene) may lead to the increased incidence of the desmoid tumors
• Li-Fraumeni Syndrome (caused by a mutation in the TP53 gene) may increase the chances of developing STSs, especially after a prior radiation treatment
• Gorlin Syndrome Or Nevoid Basal Cell Carcinoma Syndrome (caused by a mutation in the PTCH1 gene) may increase the chances of developing fibrosarcoma and rhabdomyosarcoma
• Tuberous Sclerosis Or Bourneville Disease (caused by a mutation in the TSC1 or TSC2 gene) may elevate the risk of developing rhabdomyosarcoma
• Werner Syndrome Or Adult Progeria (caused by a mutation in the RECQL2 gene) increase the possibility of developing STSs in children
• Primary Familial GIST Syndrome (caused by a mutation in the KIT or PDGFRA gene) may increase the risk of developing GISTs

Other syndromes, such as Beckwith-Wiedemann syndrome, Costello syndrome, Noonan syndrome, and Carney-Stratakis syndrome have also been implicated in enhancing the risk of developing STSs.

Occupation Exposure

Higher risk of STSs has also been reported in individuals with chronic exposure to certain chemicals like vinyl chloride, arsenic, Agent Orange, chlorophenols, insecticides, herbicides that contain phenoxyacetic acid generally experienced by the workers of plastic, textile, dyestuffs, paint, leather, dry-cleaning, metal, wood, and agriculture industries.

Weakened Immune System

Individuals with a weak immune system that may be due to HIV infection, auto-immune disease, or medicines used to suppress the immune system in patients who have undergone an organ/hematopoietic stem cell transplant are considered at higher risk of developing certain types of STSs, for example, Kaposi sarcoma (KS).

Kaposi Sarcoma-associated Herpesvirus (KSHV) Infection

KSHV or Human herpesvirus 8 (HHV8) is responsible for the development of Kaposi sarcoma (KS). KSHV infection is common in some geographical location, like some areas in Africa. However, all individuals with KSHV infection do not develop KS. KSHV infection is more common in individuals infected with HIV. It may lead to suppression of the immune system and KS later in life.

Other Factors

Risk of developing certain STSs increases in an individual with a history of the same or a different type of STS. Also, certain studies have reported an increased incidence of STSs in individuals with a history of trauma, especially in limbs.

Chronic lymphedema and prior chronic use of alkylating chemotherapeutic agents are the risk factors for the development of angiosarcoma and osteosarcoma, respectively.

Older age individuals especially males are generally at increased risk of developing STSs. However, there are certain exceptions, such as rhabdomyosarcoma (RMS) is more common in children.

What are the Symptoms and Signs of Sarcoma? How do I know if I have Sarcoma or not?

Early diagnosis of STSs is generally associated with the improved prognosis and better chances of cure by surgical resection of the tumors (limited to a specific region). The most common site for the development of STSs includes limbs (43%), visceral organs (19%), retroperitoneum (15%), the trunk (10%), and head and neck region (9%). Due to some easily visible early symptoms, some types of STSs are found at an early stage. Following are some common signs and symptoms of STSs, which may help in early diagnosis of the disease:

• The most common symptom of STS is a painless slow-growing mass under the skin. In about one-third cases the mass may be painful.
• A pain in the abdomen or in the affected organ/tissue that usually gets worse over time
• Blood in vomitus, urine, or stool depending upon the site of the tumor
• Obstruction of the gastrointestinal tract by a tumor may lead to change in bowel habit, indigestion, feeling of fullness, loss of appetite, nausea, vomiting, and other related symptoms
• Obstruction of blood vessels by a growing tumor may cause fluid retention, edema, or swelling in the related area supplied/drained by the affected blood vessel
• Tumors affecting the eyes may cause blurred vision or other vision-related problems
• Unexplained weight loss, anemia, fatigue, and weakness may develop in some cases due to chronic blood loss

What are the Tests or Investigations to be done to confirm the diagnosis of Sarcoma?

If a person is suspected to have STS due to the presence of some signs and symptoms sarcoma or based on the physical examination, some investigations are required to confirm the diagnosis of the disease.

Further, these investigations can help in determining the extent of invasion and spread of disease to other body parts, which in turn help in selecting an appropriate treatment option. Following are some commonly used diagnostic tools for STSs:

Endoscopy

Endoscopy is a diagnostic technique which uses an endoscope – a long, flexible, slender tube usually equipped with a camera, a light source, and some special instruments for biopsy or surgery. A variant of the endoscopy, like the colonoscopy, double balloon endoscopy, or bronchoscope may be utilized depending upon the specific site involved. These techniques enable the doctors to examine the lining of the specific structures and to determine the presence of any cancerous changes. The biopsy samples can also be collected with the help of special instruments if an abnormal area is observed during the procedure. The endoscopy and related procedures are considered safe and do not have any side-effects; however, if biopsy samples are collected during the procedure local bleeding and pain may occur.

Imaging Tests

These tests help in scanning a larger body area to assess the exact size and location of the disease and the spread of disease to distant body parts. The extent of invasion within the primary tissue affected and in the nearby tissue can also be assessed with the help of these techniques. These tests are primarily employed after the establishment of the pathological diagnosis to estimate the extent of disease. Also, these tests are employed after treatment to evaluate the treatment efficacy and to detect any signs of disease progression/recurrence. 

Ultrasound

Sarcoma cancer surgeon in gurgaon: In ultrasound, a transducer is used which directs very high-frequency sound waves towards the tissue to be examined. The sound waves are reflected off the internal structures depending on their ability to reflect these waves. The reflected sound waves are collected by a special detector (fixed near the transducer) to produce a real-time image of the internal tissues on a computer screen. This helps the doctor to examine the deeper tissues for any abnormality. This test can distinguish between fluid-filled cysts (usually benign) and solid tumor masses. The ultrasound test does not use any ionizing radiation and is considered as safe.

Chest X-ray
This is a relatively simple imaging technique and is generally employed for detecting the spread of cancer to the lungs or trachea after the STS diagnosis has been established. 

Computed tomography (CT) scan

In this technique, detailed cross-sectional images of body organs are generated using x-rays with or without intravenous/oral contrast (like barium). This technique can accurately detect the tumor’s size, location, invasion to nearby structures (for example, the bones), and spread to distant body parts (for example, the lungs and the liver). This technique is generally employed when detailed imaging is required, for example in case of a disease limited to a particular site. This technique can also be utilized for assessing the spread of disease by scanning the complete body, especially the head and neck, chest, abdomen (belly), and pelvis. This is very helpful for planning the treatment in case radiation therapy is indicated for the treatment. This technique can sometimes be used to guide a biopsy needle to collect biopsy samples from the affected area.

Magnetic resonance imaging (MRI) scan

This technique provides detailed images of soft tissues in the body using radio waves, strong magnetic field, and gadolinium – the contrast material, which is used via intravenous injection to improve the clarity of the MRI images. Similar to CT, this technique can accurately diagnose the size, location, extent of invasion, and spread of disease to distant body parts, especially soft tissues like the muscles, eyeballs, blood vessels, brain, and spinal cord. Sometimes this technique can distinguish between a benign and a cancerous change and can even reveal the type of tissue involved (and thus the type of STS). This technique is better than CT for the examination of soft tissues in the limbs, but inferior to CT for examining the bones. Additionally, similar to CT, this technique can be used in planning radiation treatment for STSs.

Positron emission tomography (PET) scan

This technique uses a radioactive substance (known as fluorodeoxyglucose or FDG) that is given via intravenous injection prior to the procedure. Cancer cells absorb larger amounts of the radioactive substance than normal cells. The areas of higher radioactivity indicate cancerous tissue on the PET scan. Thus, this technique can diagnose occult disease and is generally employed when an advanced disease is suspected but is not evident from other imaging tests. This technique can also be combined with CT scan (PET/CT) to accurately diagnose the extent of disease in distant body parts.

Bone Scan

This test is performed for patients with symptoms suggesting the spread of disease to bones, for example, pain in bones. In this test, a radioactive material is first injected into the vein of the patient. The radioactive substance gets accumulated in the areas of bones affected by the disease and such areas are then detected with the help of radioactivity detectors.

Biopsy

Biopsy samples contain a small number of cells or a tiny piece of tissue collected from the affected area with the help of a biopsy instrument. Biopsy sample(s) are generally collected simultaneously with the imaging study in case an abnormal area(s) is observed during the procedure or during the physical examination indicating STS. It is very important to obtain a biopsy sample because the biopsy sample can establish the diagnosis of STS. It can also provide other useful information about the cancerous cells, such as the type of STS, the severity of cancerous changes involved (grade of cancer), and the presence of specific defective genes. The detected defect(s) can be targeted with the help of an appropriate treatment approach. Following are common techniques used for collecting the biopsy samples from the affected area/lymph nodes:

Core Needle Biopsy

In this technique, a hollow needle attached to a syringe is used to collect the biopsy sample from the affected area/lymph node. A small sample of tissue or cells is usually obtained with this technique that can be tested to establish the diagnosis of the STS. This technique can help in ruling out any infectious cause of lymph node swelling and can be utilized for estimating the extent of disease when STS has already been diagnosed. This technique is most commonly used and very easy to perform with minimum side effects. A fine needle biopsy can be utilized to diagnose disease progression or recurrence in patients who have received treatment.

Surgical biopsy

In this technique, a tissue sample from the affected site is removed surgically. When only a part of the affected tissue is removed, the procedure is known as the incisional biopsy. While in the case of excisional biopsy, the whole tumor is removed surgically. The magnitude of the procedure depends upon the location and the size of the tumor. The incisional biopsy is generally recommended to be performed for deeper sited tumors while the excisional biopsy is usually performed when the tumor is located at an accessible site and do not involve any critical structure. The excisional biopsy usually combines both diagnosis and treatment for the STS.

Certain blood tests may also be employed in the STS patients for the estimation of overall health, nutritional status, liver and kidney functions, and blood cells counts. These tests help in assessing whether the standard treatment like surgery, chemotherapy, or radiotherapy can be safely employed for the patient.

How do I know my Stage of Sarcoma? What is Grading and Risk Stratification of Sarcoma?

Staging systems are used to describe the severity of cancer, based on the size, extent of invasion, and the spread of disease to different body parts. Staging helps doctors to determine disease prognosis and treatment strategy. Staging also acts as a tool for sharing information about a person’s disease among healthcare professionals as standardized language.

STSs of the Trunk, Extremities, and Retroperitoneum

TNM is the most commonly used system for staging STSs of the trunk, extremities (limbs), and retroperitoneum by the medical community. “T” stands for “Tumor Size”, “N” for “Lymph Nodes”, and “M” for “Metastasis”. Numbers and/or letters after T (1, 2, 3, and 4), N (0 and 1), and M (0 and 1) provide more details about each of these factors. Higher the number means higher the severity of the disease. 

Additionally, STSs of the trunk, extremities (limbs), and retroperitoneum are graded to assess the aggressiveness of the disease. A three-tiered French Federation of Cancer Centers Sarcoma Group (FNCLCC) grade system is the most commonly used system to grade the STSs. In this system, the grade of a tumor is determined with the help of 3 parameters: differentiation (appearance of cell morphology under the microscope), mitotic activity (rate of cancerous cell division), and extent of necrosis (extent of dead tissue present in the tumor mass). Each parameter is scored as follows: differentiation (1–3), mitotic activity (1–3), and necrosis (0–2), where a higher score indicates abnormal cells morphology, high rate of cell division, and presence of high amount of dead tissue, respectively. The scores are added to assign the grade to a tumor, where G1 = a score of 2 or 3; G2 = a score of 4 or 5; and G3 = a score of 6 to 8. A higher grade indicates more aggressive disease and more chances of disease recurrence after treatment.

Once T, N, and M categories and the overall grade of a tumor are determined through different diagnostic techniques, this information is combined to assign an overall stage (from 0 to IV) to the disease. Higher the stage more advanced is the disease, and consequently, more difficult is the treatment. Following table describe the characteristics of different stages assigned to the STSs of the trunk, extremities (limbs), and retroperitoneum:

Stage	TNM & Grade Score	Stage Description
		Trunk & Extremities	Retroperitoneum
IA	T1 N0 M0 G1/X	The primary tumor is </=5 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is G1 or grade could not be assigned or is unknown.	The primary tumor is </=5 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is G1 or grade could not be assigned or is unknown.
IB	T2-4 N0 M0 G1/X	The primary tumor size may range from >5 cm to >15 cm. No spread to nearby lymph nodes or distant body parts. The assigned grade is G1 or grade could not be assigned or is unknown.	The primary tumor size may range from >5 cm to >15 cm. No spread to nearby lymph nodes or distant body parts. The assigned grade is G1 or grade could not be assigned or is unknown.
II	T1 N0 M0 G2-3	The primary tumor is </=5 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is G2 or G3.	The primary tumor is </=5 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is G2 or G3.
IIIA	T2 N0 M0 G2-3	The primary tumor is >5 cm but </=10 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is G2 or G3.	The primary tumor is >5 cm but </=10 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is G2 or G3.
IIIB	T3-4 N0 M0 G2-3	The primary tumor size may range from >10 cm to >15 cm. No spread to nearby lymph nodes or distant body parts. The assigned grade is G2 or G3.	The primary tumor size may range from >10 cm to >15 cm. No spread to nearby lymph nodes or distant body parts. The assigned grade is G2 or G3.
	Any T N1 M0 Any G	N/A	The primary tumor of any size. The disease has spread to nearby lymph nodes. No spread to distant body parts. The assigned grade may have any value.
IV	Any T N1 M0 Any G	The primary tumor of any size. The disease has spread to nearby lymph nodes. No spread to distant body parts. The assigned grade may have any value.	N/A
	Any T Any N M1 Any G	The primary tumor of any size that might or might not have spread to nearby lymph nodes. The disease has spread to distant body parts, such as the lungs. The assigned grade may have any value.	The primary tumor of any size that might or might not have spread to nearby lymph nodes. The disease has spread to distant body parts, such as the liver or lungs. The assigned grade may have any value.

Gastrointestinal Stromal Tumors (GISTs):

TNM is the most commonly used system for staging GISTs by the medical community. “T” stands for “Tumor Size”, “N” for “Lymph Nodes”, and “M” for “Metastasis”. Numbers and/or letters after T (1, 2, 3, and 4), N (0 and 1), and M (0 and 1) provide more details about each of these factors. Higher the number means higher the severity of the disease. 

Additionally, GISTs are graded to assess the aggressiveness of the disease. The grading of GISTs is based on the mitotic activity (the rate of cancerous cell division). The grade is assigned as Low or High, where Low grade = low rate of cell division. A higher grade indicates more aggressive disease and more chances of disease recurrence after treatment.

Once T, N, and M categories and the overall grade of a tumor are determined through different diagnostic techniques, this information is combined to assign an overall stage (from 0 to IV) to the disease. Higher the stage more advanced is the disease, and consequently, more difficult is the treatment. Following table describe the characteristics of different stages assigned to GISTs of the stomach/omentum (a layer of fatty tissue covering the abdominal organs), small intestine, esophagus, colon, rectum, or peritoneum:

Stage	TNM & Grade	Stage Description
		Stomach/Omentum	Small Intestine, Esophagus, Colon, Rectum, Or Peritoneum
IA	T1-2 N0 M0 Low	The primary tumor is </=5 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is Low.	N/A
IB	T3 N0 M0 Low	The primary tumor size is >5 cm but </=10 cm. No spread to nearby lymph nodes or distant body parts. The assigned grade is Low.	N/A
I	T1-2 N0 M0 Low	N/A	The primary tumor is </=5 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is Low.
II	T3 N0 M0 Low	N/A	The primary tumor size is >5 cm but </=10 cm. No spread to nearby lymph nodes or distant body parts. The assigned grade is Low.
	T1-2 N0 M0 High	The primary tumor is </=5 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is High.	N/A
	T4 N0 M0 Low	The primary tumor size is >10 cm. No spread to nearby lymph nodes or distant body parts. The assigned grade is Low.	N/A
IIIA	T1 N0 M0 High	N/A	The primary tumor is </=2 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is High.
	T4 N0 M0 Low	N/A	The primary tumor size is >10 cm. No spread to nearby lymph nodes or distant body parts. The assigned grade is Low.
	T3 N0 M0 High	The primary tumor is >5 cm but </=10 cm in size. No spread to nearby lymph nodes or distant body parts. The assigned grade is High.	N/A
IIIB	T4 N0 M0 High	The primary tumor size is >10 cm. No spread to nearby lymph nodes or distant body parts. The assigned grade is High.	N/A
	T2-4 N0 M0 High	N/A	The primary tumor size may range from >2 cm to >10 cm. No spread to nearby lymph nodes or distant body parts. The assigned grade is High.
IV	Any T N1 M0 Any G	The primary tumor of any size. The disease has spread to nearby lymph nodes. No spread to distant body parts. The assigned grade may have any value.	The primary tumor of any size. The disease has spread to nearby lymph nodes. No spread to distant body parts. The assigned grade may have any value.
	Any T Any N M1 Any G	The primary tumor of any size that might or might not have spread to nearby lymph nodes. The disease has spread to distant body parts, such as the liver. The assigned grade may have any value.	The primary tumor of any size that might or might not have spread to nearby lymph nodes. The disease has spread to distant body parts, such as the liver. The assigned grade may have any value.

Rhabdomyosarcoma (RMS)

Sarcoma Committee of the Children’s Oncology Group prescribed system is mostly used for assigning a stage, clinical group, and risk group to RMSs by the medical community. 

Staging: TNM system is used for assigning a stage to RMSs. “T” stands for “Tumor Size” and invasiveness, “N” for “Lymph Nodes”, and “M” for “Metastasis”. Numbers and/or letters after T (1, 1a, 1b, 2, 2a, and 2b), N (0 and 1), and M (0 and 1) provide more details about each of these factors. Higher the number means higher the severity of the disease. Additionally, the sites of RMS are grouped into favorable (F) and unfavorable (UF) sites based on the prognosis of disease in different sites. Favorable sites include Orbit (eyeball); head and neck area except the para-meningeal area (nasal passages and nearby sinuses, middle ear, and the uppermost part of the pharynx); genitourinary tract except the kidney, bladder, and prostate; and the biliary duct. All other sites are considered as unfavorable.

Once T, N, and M categories and the site of a tumor are determined through different diagnostic techniques, this information is combined to assign an overall stage (from 0 to IV) to the disease. Higher the stage more advanced is the disease, and consequently, more difficult is the treatment. Following table describe the characteristics of different stages assigned to RMSs:

Stage	Site & TNM	Stage Description
I	F; Any T, Any N, M0	The primary tumor is present at a favorable site, which may be of any size. It might or might not have invaded into a nearby tissue and/or spread to nearby lymph nodes, but has not spread to distant body parts.
II	UF; T1a-2a N0 M0	The primary tumor is present at an unfavorable site, which is </=5 cm in size. It might or might not have invaded into a nearby tissue, but has not spread to nearby lymph nodes. No spread to distant body parts.
III	UF; T1a-2a N1 M0	The primary tumor is present at an unfavorable site, which is </=5 cm in size. It might or might not have invaded into a nearby tissue, but has spread to nearby lymph nodes. No spread to distant body parts.
	UF; T1b-2b N0 M0	The primary tumor is present at an unfavorable site, which is >5 cm in size. It might or might not have invaded into a nearby tissue and/or spread to nearby lymph nodes. No spread to distant body parts.
IV	Any site; Any T Any N M1	The primary tumor is present at a favorable or an unfavorable site. It may be of any size. It might or might not have invaded into a nearby tissue and/or spread to nearby lymph nodes. It has spread to distant body parts, like the lungs, liver, bones, or bone marrow.

Clinical Grouping:Based on the extent of the disease and the extent of primary surgical/biopsy excision, RMSs are assigned a clinical group as described in the following table:

Clinical Group	Description
I	A localized tumor that has been completely removed by surgery/biopsy with negative/clear margins and no sign of lymph node involvement (no cancer left behind).
II	A localized tumor that has been completely removed by surgery/biopsy with a microscopic positive margin and/or sign of lymph node involvement (minor cancer left behind).
III	A localized tumor that was not completely removed by surgery/biopsy with a positive margin. Sign of lymph node involvement may be present but no sign of disease spread to distant body parts.
IV	The diagnosis has revealed the spread of disease to distant body parts or presence of cancer cells in the cerebral spinal fluid, pleural, or peritoneal fluids.

Risk Stratification: Based on the overall stage, clinical group, and type of RMS (embryonal or alveolar), a risk group is assigned to the disease. Risk group help in selecting appropriate treatment for the disease. Following table describe the characteristics of the diseases according to different risk groups:

Risk Group	Description
Low risk	Embryonal RMS; TNM stage 1; and Clinical groups I, II, or III OR Embryonal RMS; TNM stage 2 or 3; and Clinical groups I or II
Intermediate risk	Embryonal RMS; TNM stage 2 or 3; and Clinical group III OR Alveolar RMS; TNM stage 1, 2, or 3; and Clinical groups I, II, or III
High-risk	Embryonal/Alveolar RMS; TNM stage 4; and Clinical group IV

Kaposi sarcoma (KS)

No universally accepted staging system for KS is available today. The AIDS Clinical Trials Group (ACTG) described risk group stratification system for Epidemic/AIDS-related KS is the most widely used grading system. This system divides Epidemic/AIDS-related KS into 2 risk groups (i.e. Good and Poor) based on the extent of disease, status of the immune system, and presence of systemic illness. Following table describes the characteristics of the 2 risk groups:

Good (Low) Risk	Poor (High) Risk
Localized disease CD4 cell count >/=150 cells/mm^3 No systemic illness present (No opportunistic infections, No B symptoms, Karnofsky performance status score >/=70)	Widespread disease CD4 cell count <150 cells/mm^3 Systemic illness present (History of opportunistic infection, B symptoms, Karnofsky performance status score <70, or HIV-related illness, such as neurological disease or lymphoma)

What is the Treatment for Sarcoma? Where can I get the best treatment for Sarcoma in Gurgaon?

Oncoexperts is a cancer clinic in Gurgaon for treatment for sarcoma from our team of cancer experts that include surgical oncologists, medical oncologists, and radiation oncologists who are experts in treating all types of sarcoma.

The treatment for STSs usually depends on many factors, including but not limited to the stage of disease, the location of the disease, type of STS involved, patient’s age and overall health, side effects associated with the treatment approach, and the patient’s preference. Based on the results obtained from various clinical research studies carried out so far, following are the preferred treatment approach for different STSs:

Treatment of Sarcoma of the Trunk, Extremities (limbs), Head and Neck, Abdominal or Thoracic Visceral Organs, and Retroperitoneum

Stage I

Stage I sarcomas are low-grade tumors of any size. If possible, surgical resection with negative margins is considered as the standard treatment.

In a case when negative margins were not obtained, further surgical resection to remove all cancerous tissue is the preferred approach. If further surgery is not possible, radiotherapy may be employed to decrease the chances of disease recurrence. 

If the tumor is present at such a location (e.g. retroperitoneum, trunk, and head and neck,) that it cannot be entirely removed without functional disability, radiotherapy may be employed as the first-line treatment. This may cause the tumor to shrink sufficiently that it can be removed surgically.

The patient should be followed-up closely after treatment for any sign of recurrence.

Stage II or III

Most Stage II and III sarcomas are high-grade tumors that tend to spread quickly and some of them has already spread to nearby lymph nodes. If possible (without any significant functional disability), surgical resection with negative margins is considered as the standard treatment. Any lymph node with the sign of disease spread should also be removed. In case of the positive margin, further surgical resection to remove all cancerous tissue is the preferred approach. If further surgery is not possible, radiotherapy may be employed to decrease the chances of disease recurrence.

Sarcoma cancer treatment in gurgaon: If tumor is too large or present at such a location (e.g. retroperitoneum, trunk, and head and neck), that it cannot be entirely removed without functional disability, or if surgery is not possible due to overall health of the patient, radiotherapy with or without chemotherapy may be employed as the first-line treatment. This may cause the tumor to shrink sufficiently that it can be removed with surgery. Further treatment, such as more radiotherapy/chemotherapy and/or supportive care or any other treatment may be provided based on the response to initial treatment.

The patient should be followed-up closely after treatment for any sign of recurrence.

Stage IV

Stage IV sarcomas are cancers that have spread to a distant body part and are very hard treat. For patients with a single site of disease-spread and a small primary tumor that can be entirely removed with surgery, a surgical resection with the negative surgical margins for the primary tumor and the distant site is considered as the preferred treatment. As appropriate, tumor ablation, embolization, or radiotherapy may be employed instead of surgical resection for the secondary tumors. 

For patients with a widespread disease or when the primary and secondary tumors cannot be removed by surgery, chemotherapy with or without radiotherapy is usually employed. Any other suitable treatment may be employed as palliative treatment.

Treatment of Gastrointestinal Stromal Tumors (GISTs)

Localized, resectable tumors

For some very small GISTs that are not causing any symptom and are assessed to be low-grade tumors based on diagnostic tests, observation is considered as the preferred approach. Active treatment will only be required in case of the disease progression.

For small, resectable, low-grade tumors, surgical resection to remove all cancerous tissue is the preferred approach. Targeted drug (e.g. Imatinib) should be employed after surgical resection to prevent disease recurrence in case of a high-risk disease. 

Localized, marginally resectable tumors

For localized GISTs that cannot be completely removed with surgery (marginally resectable tumors), targeted therapy should be considered as the first-line treatment. This should be continued until the cessation of clinical benefit. In case of a good response to treatment (sufficient shrinkage to resectable disease), surgical resection to remove all cancerous should be attempted. After surgery, a continuation of the targeted drug for at least 1 year is generally recommended to prevent disease recurrence in case of a high-risk disease.  In case of the cessation of clinical benefit and unresectable disease, the dose of the targeted drug should be increased or a different drug may be employed.

Disseminated, unresectable tumors

For disseminated GISTs that cannot be removed with surgery (unresectable tumors), targeted therapy should be considered as the first-line treatment. This should be continued until the cessation of clinical benefit. In case of a good response to treatment (sufficient shrinkage to resectable disease), surgical resection to remove all cancerous should be attempted. After surgery, a continuation of the targeted drug for at least 1 year is generally recommended to prevent disease recurrence in case of a high-risk disease.

In the case of the cessation of the clinical benefit and unresectable disease, the dose of the targeted drug should be increased or a different drug may be employed. Surgical resection of the primary and secondary tumor to an extent possible may be employed as per discretion of the treating physician. Any other treatment may be employed as palliative treatment.

Treatment of Rhabdomyosarcoma

The standard treatment approach for RMS is not yet established and it is still evolving with the availability of new treatment options. Pleomorphic RMSs are usually treated with a treatment approach similar to that for other STSs. For the treatment of embryonal and alveolar RMS, patients should refer to institutions with experience in treating RMS.

All children and adults with RMS are treated with a multimodality treatment approach. Chemotherapy along with surgery and/or radiotherapy is usually the part of the multimodality treatment approach. The surgery may be performed before chemotherapy, if possible, without any significant functional disability or other major cosmetic issues. Otherwise, chemotherapy and/or radiotherapy are employed as first-line treatment. In case of the sufficient shrinkage in the tumor to render it resectable, surgery may be employed to remove all cancerous tissue.

RMS has a very high tendency to reoccur, and thus, almost always require chemotherapy after surgical resection (whether complete or incomplete). All these treatments may be employed separately or in combination when the tumor continues to grow or comes back after the initial treatment. Supportive care is usually provided to minimize the side-effects of the primary treatment employed.

Treatment of Kaposi sarcoma

Epidemic/AIDS-related KS

For patients with AIDS-related KS, treatment of the HIV infection with highly active antiretroviral therapy (HAART) is considered the primary treatment. Treatment of AIDS lead to better immune function and relieve symptoms of KS as well. Prophylactic treatment for opportunistic infection or immediate treatment of any infection should be provided as supportive care. 

For patients with localized disease (good risk patients) and presence of symptoms, besides HAART, a local treatment is usually employed, which may include radiation therapy, cryosurgery, a topical retinoid, intralesional chemotherapy, or local excision.
For patients with widespread disease (patients with poor risk), lymphedema, or other serious complications, HAART and systemic chemotherapy are usually employed to control disease symptoms. Targeted drugs or immunotherapeutic agents may be employed alone or in combination with chemotherapy to slow down or delay the progression of the disease. HAART should be continued with the cessation of chemotherapy and/or targeted therapy upon resolution of skin lesions. 

Classic/Mediterranean KS

Classic KS grow and spread very slowly and do not cause any symptom unless has spread to vital body parts. These patients are also at a high risk of developing secondary cancer and should be followed-up closely to monitor the same.

For patients with localized disease, surgery, radiotherapy, or intralesional chemotherapy is considered as the preferred treatment. For patients with disseminated disease, chemotherapy is usually employed to control disease symptoms. Radiotherapy may be added to chemotherapy for local/superficial disease control.

Endemic/African KS
Endemic Ks is usually observed in poor countries where treatment options are limited. When possible treatment similar to that f classic KS should be employed for endemic KS. 

Iatrogenic/transplant-related KS
For patients with transplant-related KS, cessation or dose reduction of the immunosuppressive agents is recommended to ease the disease symptoms. In place of conventional immunosuppressive drugs, angiogenesis inhibitor (e.g. sirolimus) may be employed as anti-rejection treatment. This enables the immune system to recover and fight against the KS cells. Radiotherapy and other local treatments can be employed to relieve the local disease symptoms. 

Role of Surgery

Surgery is the treatment of choice for most early-stage and some higher stage STSs that have not spread to distant body parts and can be completely removed. The goal of surgery is to remove entire cancerous tissue along with some healthy tissue to ensure no cancer cell is left behind. This is possible for some early-stage disease where the tumor is confined to a specific area, and complete resection can be performed with ease. However, a complete resection is not always possible, such as in the case of advanced-stage disease, the disease involving a vital organ/structure, or when a surgical resection will lead to a significant functional disability. In such cases, surgery may still be employed with an objective to remove maximum possible cancerous tissue along with the administration of other treatment to kill the remaining cancer cells in the body. Surgery may also be performed to collect biopsy sample in some cases. Sometimes, a reconstructive surgery is required to improve/restore lost organ function due to the primary surgical procedure employed to treat STS. Modified surgical procedures, like an endoscopic or laparoscopic surgery, may be employed in selected cases.
Relative to the site of disease, surgery is generally associated with the risk of loss of function and other associated complications, such as infection, bleeding, leakage from the surgical sites, pneumonia, rupture of arteries, nerve damage leading to loss of function, and common post-surgical problems, like nausea, vomiting, change in bowel habit etc. Thus, surgery may not be employed in old-aged or otherwise frail individuals. In such case, other suitable treatments are usually employed.

Role of Radiation Therapy

Radiation therapy uses high-energy x-rays or other high-energy radiations which are directed to the affected area to kill cancerous cells. Radiotherapy can be employed either by using an external radiation source (external beam radiation therapy) or by directly placing the source of radiation near the cancer tissue (brachytherapy). Radiotherapy can be employed alone as the first-line treatment for certain early-stage STSs or can be combined with other treatment options, such as surgery and chemotherapy for some advanced-stage STSs. Radiotherapy may be considered in some patients who cannot tolerate surgery or in case of disease recurrence after primary treatment. It is sometimes used for palliation of symptoms of the disease such as pain, bleeding, and obstructive problems. It is generally associated with several side effects like skin reactions, nausea, vomiting, loss of appetite, dry mouth/eyes, Sores in the mouth/throat, problem in swallowing, loss of hearing, altered speech, bone pain, low blood cells count, and accidental damage to nearby organs.

Role of Chemotherapy

Chemotherapy means treatment with anti-cancer drugs that kill or decrease the growth of rapidly growing cancer cells. Chemotherapy is generally employed for the treatment of advanced stage STS that has spread to distant body parts and cannot be removed completely with surgical resection. Depending on the physician’s preference and patient’s condition, it may also be combined with other treatment options, like radiotherapy, to accelerate the benefit achievement. Many pharmaceutical companies are conducting a number of clinical trials to find out new drugs and drug-combinations with increased efficacy and specificity to target cancer cells. Chemotherapy is generally associated with several side effects due to its effect on normal body cells apart from cancerous cells. Common side effects of chemotherapy include nausea, vomiting, hair-loss, diarrhea, mouth ulcers, increased chances of infection, fatigue, and a decrease in the number of blood cells.

Role of Targeted Therapy

Targeted drugs work differently than chemotherapy drugs that they target a specific gene or protein characteristic of the cancer cells that help them to divide and grow indefinitely. For example, Olaratumab targets PDGFR-alpha; Pazopanib targets tyrosine kinases; and Imatinib targets both the KIT and PDGFRA proteins. They are generally used alone or in combination with chemotherapy for the treatment of advanced-stage STSs or STSs that possess specific proteins. The side effects of targeted therapy are generally mild, but these can be severe in some cases, for example, autoimmune reactions.

Where can I find the best specialists for Sarcoma treatment in Gurgaon?

Dr. Sunny Garg is a renowned Medical Oncologist in Gurgaon with an experience of more than 10 years of treating sarcoma patients. He has treated sarcoma patients with Chemotherapy, Targeted Therapy and Personalized Cancer Treatment. He is currently practicing at Sanar International Hospital, Golf Course Road, Gurgaon.

Call Or Whatsapp +91 9686813020 For Appointment.