This refers to a large group of malignant tumors arising embryonically from the primitive mesoderm. The primitive Mesenchyme within the Mesoderm differentiate into the various connective tissue of the body –Tendon, Ligament, muscle, and bone. Tumors of these tissues referred to as soft tissue sarcoma.

Summary: Sarcoma is malignant tumor that can be divided into 2 groups: bone sarcomas, arising from bone or cartilage, and soft tissue sarcomas, arising from tissues such as fat, muscle, and nerves.

Soft tissue sarcomas present unique challenges in detection and treatment. Sarcomas are unusual in that they can occur in any site of the human body, although about one-half occur in the limbs. There are more than 50 different types of soft tissue sarcomas and sarcoma-like growths.

Because treatment varies for the different subtypes, your cancer care team should include a pathologist who can determine the exact type of soft tissue sarcoma you have. The most common subtypes of soft tissue sarcoma are malignant fibrous histiocytoma, liposarcoma, leiomyosarcoma, unclassified sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor.

Exposure to ionizing radiation, usually given to treat other tumors, is a risk factor accounting for less than 5% of sarcoma diagnoses. The average time between the exposure and diagnosis of a sarcoma is about 10 years. However, advances in radiation therapy treatment are expected to reduce the number of related secondary malignancies.

Information on the following subtypes of soft tissue sarcoma is available:

The most common site for the development of a sarcoma is in the extremities (arms or legs), accounting for 50% of all soft tissue sarcomas. They occur more commonly in the legs and in persons between 30 and 60 years of age.

Amputation was once considered the standard treatment to achieve local control in patients with extremity sarcomas. In recent years, technical advancements in reconstructive surgical procedures, implementation of multimodality therapy and improved selection of patients for adjuvant therapy have minimized the functional deficits in patients who might otherwise require amputation. Limb-sparing techniques coupled with radiation therapy (intensely modulated or external beam radiation therapy, or brachytherapy) can often be an effective treatment in patients with high grade soft tissue sarcomas of extremities.

Evaluation for post-operative rehabilitation is recommended for all patients with extremity sarcomas. If indicated, rehabilitation should be continued until maximum function is achieved.

This category includes sarcomas that develop within the abdominal or pelvic cavity. It also includes retroperitoneal sarcomas, which are those that develop within the abdomen or pelvic cavity in a distinct area called the retroperitoneal space. This space holds the pancreas and a portion of the small intestine (called the duodenum), kidneys, adrenal glands, major blood vessels, lymph nodes, and nerve branches that are all embedded in a loose framework of connective tissue. The most common types of sarcoma occurring in the retroperitoneal space are liposarcoma, malignant fibrous histiocytoma, and leiomyosarcoma. Surgical resection of a localized tumor with grossly negative margins remains the standard, potentially curative treatment for retroperitoneal soft tissue sarcomas. Complete primary tumor resection is the most important factor contributing to long-term disease free survival.

Pre-operative radiation therapy is often preferred, because the primary tumor acts to displace some of the abdominal organs out of the radiation therapy fields and it may render unresectable tumors more amendable to removal. The use of intraoperative radiation therapy with or without external beam radiation therapy has provided encouraging results in clinical studies. In addition, post-operative radiation therapy using newer techniques such as intensely-modulated radiation therapy or proton beam radiation therapy may allow tumor target coverage and acceptable clinical outcomes within normal tissue dose constraints to adjacent organs at risk in some patients with retroperitoneal STS who did not receive pre-operative radiotherapy.

Choosing the best option for the management of desmoid tumors can pose difficult decisions for the patient due to their high recurrence rate. To achieve optimal control of the tumors, extensive surgery may be necessary, but often this may result in an undesirable outcome for the patient. While most people will not die from their tumors and they are usually slow-growing, they can limit function and cause symptoms that interfere with daily living.

Because of unique differences in the staging and the treatment options of the four major types of soft tissue sarcomas covered in this pamphlet, specific staging and “decision trees” will be incorporated into each of the four sections covered: soft tissue sarcoma of the extremity, GIST, retroperitoneal/intra-abdominal sarcoma, and desmoid tumors.
In sarcoma staging, pathologists and other cancer specialists examine the appearance of the tumor biopsy specimen. They determine the cell type of the tumor, how actively the cells are dividing, and how closely the cancer cells resemble normal tissue. Based on cell type and grade, doctors can estimate how rapidly a cancer will grow and spread.

In soft tissue sarcomas, another factor that is considered is histopathologic Grade (G), or the microscopic appearance of the tumor compared to the normal tissue from which it originated.

To assign a stage, information about the tumor, lymph nodes, metastasis, and the tumor grade is combined by a process called stage grouping (see Table 1). The stage is described by Roman numerals from I to IV.

Primary Tumor (T)
TX Primary tumor cannot be assessed
TO No evidence of primary tumor
T1 Tumor is 5 cm or less in greatest dimension
a: The tumor is superficial (near the surface of the body)
b: The tumor is deep in the limb or in the abdomen
T2 Tumor is more than 5 cm in greatest dimension
a: The tumor is superficial
b: The tumor is deep in the limb or the abdomen

Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph nodes have sarcoma cells
N1 Regional lymph node metastasis

Distant Metastasis (M)
MO No distant metastasis
M1 Evidence of distant metastasis

Histopathologic Grade (G)
GX - Grade cannot be assessed
G1
Looks like normal tissue
Tends to grow slowly
(low grade, well-differentiated)
G2
Looks less like normal tissue
Faster growing
(low grade, moderately differentiated)
G3
Does not look like normal tissue
Fastest growing
(high grade, poorly differentiated)

For a more detailed Staging System, please refer to the NCCN Clinical Practice Guidelines in Oncology, Soft Tissue Sarcoma V.2.2010. This can also be found on the NCCN website (www.nccn.org).

Since staging is important in determining the most effective treatment for your sarcoma, be sure that you have discussed this process in depth with your doctor. Ask your doctor to explain what stage has been assigned to your sarcoma and how it was determined. If your treatment differs from those suggested in the NCCN Clinical Practice Guidelines, ask your doctor to explain the rationale for a different course of treatment.

It is often a good idea to seek a second opinion. Second opinions can provide you with additional information and treatment options or reinforce the one that has been recommended to you. Also, insurance companies may require a second opinion before consenting to a treatment.

Because the side effects of chemotherapy can be harsh, recommendations for chemotherapy should take into account a patient’s overall well-being or general health status, quantified by something called a performance status. NCCN physicians use precise definitions of “good health” or “poor health” based on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2
Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours
3
Capable of only limited self care, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any self care. Totally confined to bed or chair
5
Dead

As published in Am. J. Clin. Oncol.: Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982.

Surgery has been the preferred primary treatment for soft tissue sarcoma for decades, and surgical techniques have ranged throughout that time from simple wide excision (removal of the tumor and a margin of normal tissue around it) to radical amputation (the removal of a body extremity by surgery). The earliest surgeries often consisted of amputations because limited resections (less extensive surgeries to remove tumors) frequently resulted in high recurrence rates. However, with new and advanced combination treatment options, less extensive surgery is now more common.

The aim of surgery is to completely remove or excise the tumor. A border or margin of 2-3 cm of normal tissue around the tumor is also desirable to minimize the chance that tumor cells have been left behind. This margin of normal tissue is called a negative or clean margin. If there is evidence of tumor cells in the margin around the tumor, this is called positive margins. Positive margins may be associated with a higher rate of disease recurrence in some patients with soft tissue sarcomas. If resection with positive margins is anticipated, surgical clips can be left in place to identify high-risk areas for recurrence, particularly for retroperitoneal or intra-abdominal sarcomas to help guide future radiation therapy.

The evaluation of the margins is done in the laboratory by a pathologist, who examines the tumor sample carefully under the microscope to see how close tumor cells are found in relation to where the surgeon removed the tumor. At times, more than one surgery may be needed to achieve negative margins and may be rather extensive (called a re-resection).

Definition

Radiation therapy uses ionizing radiation to kill cancer cells and shrink tumors. Radiation therapy destroys cells in the area being treated by damaging their genetic material, making it impossible for these cells to continue to grow and divide, and killing them when they try. Advances in radiation therapy technology have led to the improvement of treatment outcomes in patients with soft tissue sarcoma.

Types of Radiation Therapy

Radiation can be delivered externally (external beam radiation) or internally (brachytherapy).

Linear Accelerator (LINAC): The linear accelerator produces x-rays , which are gathered and then shaped to form a beam that will be used to treat the tumor. Radiation can be delivered to the tumor from any angle by rotating the machine and moving the table the patient lies on.

Radiation given prior to surgery may have advantages. For instance, preoperative treatment involves a smaller area of the body than treatment after surgery, because radiation treatment after surgery should reach the entire operative field (the area surrounding the removed tumor). Preoperative radiation may make the removal of the tumor easier and decrease the risk of recurrence after surgery.
However, preoperative external radiation may pose a higher risk of complications following surgery, in certain cases,specifically in regards to wound healing. To allow time for healing and reduce the risk of wound complications, radiation given before surgery may occur 3 to 6 weeks before the operation. A longer interval between therapy and surgery is not recommended. Your cancer health care team will determine whether preoperative external radiation is right for you.
If wide margins are obtained after preoperative radiotherapy and surgery, additional radiation therapy may not be needed. Intraoperative radiation therapy (IORT) is the delivery of radiation to the cancer during surgery, externally or internally. The decision to include this type of therapy and at what dose after surgery depends on margin status. It is often combined with radiation treatment given before or after the operation. IORT is recommended for surgery with close or positive margins, which are associated with a higher rate of recurrence. Normal tissue can be moved out of the way and protected during surgery, reducing the total amount of tissue exposed to the radiation and allowing a higher dose to reach the tumor. IORT is delivered in a special operating room lined with radiation-shielding walls.

Single agents used include:
- doxorubicin - ifosfamide - epirubicin
- gemcitabine - dacarbazine - liposomal doxorubicin
- temozolamide

Combination regimens include (but are not limited to):
- (AD) doxorubicin and dacarbazine
- (AIM) doxorubicin, ifosfamide, and mesna
- (MAID) mesna, doxorubicin, ifosfamide, and dacarbazine
- gemcitabine and docetaxel
- gemcitabine and vinorelbine
- ifosfamide, epirubicin, mesna



Angiosarcomas

- paclitaxel - docetaxel - vinorelbine
- sorafenib - sunitinib – bevacizumab

Desmoid Tumors

- methotrexate and vinblastine
- toremifene - doxorubicin-based regimens - tamoxifen
- imatinib mesylate - low dose interferon
- sulindac or other non-steroidal anti-inflammatory drugs (NSAIDS) including celecoxib


GIST

- imatinib mesylate - sunitinib - sorafenib
- nilotinib – dasatinib

Radiofrequency Ablation (RFA)

Embolization
This is another treatment for tumors in the liver that cannot be surgically removed. An object is put into the artery that carries blood to the tumor, preventing the blood from reaching the tumor making it harder for the tumor to grow.

Conclusion
There are a variety of treatment options for sarcoma, including clinical trials. Many different types of treatment can be administered in the preoperative phase (neoadjuvantly) to help achieve better surgical outcomes. These therapies can also be given in the postoperative phase (adjuvantly) to decrease the chance of the cancer returning locally or in a different location, called distant spread or metastasis.
There seem to be advantages and disadvantages for any combination and sequence of therapy and surgery. These can be discussed with your cancer care team to determine what is best for you. Some therapies may be available for patients who are enrolled in a clinical trial. Your

Recurrent Disease and Follow-Up
When sarcoma cells can no longer be detected in the body, a patient is considered to be disease free or in remission. A recurrence is defined as the return of sarcoma after a period of remission.

Because doctors cannot guarantee a sarcoma will not return even if it appears the disease is completely gone, patients are given a plan for follow-up care and surveillance after successful treatment ends. This is done to help monitor recovery and check for the presence of recurrent disease, and usually involves periodic doctor’s visits and a schedule for tests or scans. The chance of recurrence is different for each person and depends on the type of sarcoma, the treatment received, and the length of time since treatment ended. For sarcomas that more commonly recur, the schedule for follow-up tends to be more rigorous.

Recurring disease is classified by its location and can be either a local recurrence (developing at or very close to the site of the original tumor) or a distant recurrence (also called metastatic disease, in which the tumor spreads to organs or tissues distant from the primary sarcoma, such as the lungs or liver). Soft tissue sarcomas have a somewhat predictable pattern of distant recurrence and most commonly spread to the lungs via the bloodstream. However, tumors arising in the abdominal cavity more commonly spread to the liver and peritoneum.
A recurrent sarcoma starts with malignant cells that treatment did not fully remove and were too small to be detected. Over time, these cells grow and multiply into tumors large enough to be detected as a recurrence.

After recurrence is detected, additional tests, scans, and blood work may be done to determine if it is the same type as what was there before. Even when sarcoma has spread to a new location, it is still named after the part of the body where it started. For example, if a GIST spreads from the stomach to the liver, it is still called GIST (with liver metastases).

Clinical Trials Phases
Before cancer treatments can be generally prescribed, the treatment is tested in various types (or phases) of clinical trials. A treatment must pass through a number of steps before it can be approved by the Food and Drug Administration (FDA) for widespread use.

Generally, subjects in Phase I trials are divided into small groups of patients (cohorts) which usually include approximately between three to five people. The first cohort receives a low, introductory dose of the new drug. Usually, researchers periodically conduct various tests throughout the trial to measure drug levels in the patients. If no severe side effects are detected, a second cohort receives the same drug in higher doses. The dose increases with each subsequent cohort until an optimum dosage is determined or too many adverse effects occur.

Phase II clinical trials test the treatment to see if it will work against a certain kind or subtype of cancer. This phase of cancer research, usually involves less than 100 patients. Side effects are monitored and recorded by doctors.

If this treatment is effective against cancer in a certain percentage of patients, the treatment may move on to phase III.  The goal of phase III trials is to compare the new treatment to the most effective currently known treatment. This phase of cancer research involves hundreds, sometimes thousands, of people. Researchers observe whether a new treatment is better, the same as, or less effective than the standard treatment. Phase III clinical trials usually consist of two or more groups (arms), and a patient has equal opportunity of participating in any one of these (called randomization, used to avoid statistical bias). One group usually receives a standard treatment – known as the control group; and the other receives the experimental treatment – known as the investigational or experimental group.

Deciding to Enter a Clinical Trial
If you are offered a clinical trial as a treatment option, you will go through a process called informed consent, in which you will learn about the specific trial, including information about purpose, the treatment procedures, potential risks, and explains your rights as a participant. All patients in clinical trials are volunteers. They are free to stop their participation in the trial at any time and for any reason.

Palliative and Supportive Care

Cancer-related fatigue, or a persistent sense of physical or emotional tiredness, is another common distressing side effect of the disease or its treatments. This fatigue is intense, it interferes greatly with typical daily activities, and it is not relieved by any amount of rest or sleep.

Complementary and Alternative Therapies
There is a great deal of interest today in complementary and alternative treatments for cancer–treatments that are not used in conventional medicine in the United States. Examples include special supplements or herbs, acupuncture, massage, and several other types of treatment.

At this time, we have limited knowledge about the use of complementary and alternative methods. To learn more, there are currently several ongoing studies rigorously evaluating their safety and benefits in much the same manner conventional therapies are studied.
Currently there is published information available for only a few therapies that have already been evaluated in clinical studies. Some have been found to be ineffective or potentially harmful. However, a few therapies found to be helpful in making patients feel better and recover faster are now being accepted and incorporated into the realm of conventional medicine. One example is acupuncture, which has been proven to be effective in the management of chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery.

Decision Trees

Extremity Soft Tissue Sarcomas
Evaluation and Work-Up of Extremity Soft Tissue Sarcomas
Your first symptom might be a lump or swelling in your arm or leg. This lump may or may not be painful and may be either fast or slow growing. If you have more than one lump, all suspicious or unexplained lumps in the extremities should be evaluated. Your physician will take a complete history and perform a physical examination. Imaging studies, such as MRI or CT scan, may be used to assess tumor characteristics and to determine whether the tumor is close to important internal organs, major nerves, or blood vessels. Because sarcomas sometimes spread to the lungs, imaging studies of the chest are recommended. Under certain circumstances, a PET scan may be useful in determining prognosis, tumor grade and response to chemotherapy. Adequate and high-quality imaging studies are crucial to good clinical management, because the presence of metastatic disease may change the management of the primary tumor and the overall approach to a patient’s disease management. Your doctor will choose the best method or test for you, based on the location of the mass and which study will give the best image of the tumor.

If imaging studies show that a sarcoma may be present, a carefully planned biopsy will be done (usually a core needle or incisional biopsy). An experienced pathologist will examine the tissue sample under a microscope to determine if the mass is a sarcoma and which subtype it is, and to establish the tumor grade. If necessary, other diagnostic techniques might be used to identify the tumor type and subtype. Treatment is generally based on the stage of the sarcoma .

Treatment of Extremity Soft Tissue Sarcomas by Stage
For stage I (low grade) sarcomas, surgery to remove the tumor is considered to be the primary therapy.


If the tumor is smaller than 5 cm (2 inches), surgery may be the only treatment necessary. If the tumor is removed and examination by the pathologist confirms wide negative margins were obtained, then no further treatment will generally be recommended because these tumors are less frequently associated with local recurrence. You will need to see your doctor for regular follow-up to evaluate for return of the disease.

If the clean margins obtained during surgery are less than 1 cm, postoperative radiation therapy may be suggested to reduce the risk of recurrence. If there are positive margins after initial surgery, a re-resection may be done. If achieved after re-resection, then the patient may enter the follow-up phase to monitor for recurrence.

For stage II and III (high grade) extremity soft tissue sarcomas, a multidisciplinary team will determine treatment options based on your performance status, your age, the location of your tumor, the histological subtype of your tumor, and the experience of the institution at which you are being treated. Surgical removal of the tumor is still the primary goal. The ideal surgical treatment is removal of the tumor and at least 2 cm (over an inch) of normal tissue around the tumor in all directions. In such cases, surgery may be the only treatment needed.

If it appears that the tumor can be removed with little or no effect on the function of the affected arm or leg, your cancer care team might recommend surgery with postoperative chemotherapy or radiation. In some cases, preoperative therapy (radiation therapy, chemotherapy, or chemoradiation) is also recommended. Preoperative chemoradiation (generally using doxorubicin) along with postoperative therapy has been shown to improve local control rates in patients with stage II or III soft tissue sarcomas of the extremity. These preoperative therapies are used in many centers for high grade tumors to downstage a large tumor (greater than 10 cm) and enable effective surgical resection.

Sometimes, the tumor simply cannot be removed surgically at the time of diagnosis because it lies very close to important organs or its removal is likely to cause unacceptable damage to the affected arm or leg (the tumor is then considered unresectable). In these cases, radiation therapy, chemotherapy, and chemoradiation can be administered in attempts to shrink the tumor, making it possible and easier to remove or making less extensive surgery possible. If therapy is successful and the tumor becomes resectable, surgery can be done, followed by postoperative radiation therapy, chemotherapy, or chemoradiation. If the tumor remains unresectable, your doctor might recommend additional chemotherapy or radiation, palliative surgery, or best supportive care. Simple observation may also be considered if you have no symptoms.

For stage IV sarcomas of the extremity, treatment recommendations are based on the degree of metastasis.

If the sarcoma has spread to a single distant location, the primary tumor will be treated as described for stage II or III sarcomas. The area to which the sarcoma has spread may also be treated with surgery, radiation, or chemotherapy. Single agents (doxorubicin, ifosfamide, or dacarbazine) or anthracycline-based combination regimens (doxorubicin or epirubicin with ifosfamide and/or dacarbazine) have been widely used for metastatic disease. Other chemotherapeutic agents have also been tested in clinical trials (mentioned below). Embolization and RFA techniques may also be considered.

If the sarcoma has spread to multiple distant sites, there are several options. In some patients, the main tumor and all of their metastases can be removed by surgery, particularly when the spread is only to the lungs. For patients whose primary tumor and all metastases cannot be completely removed by surgery, any of the above treatment options (chemotherapy, radiation therapy, palliative surgery, RFA, embolization) or best supportive care all may be used to control or relieve symptoms. Stereotactic radiosurgery/radiotherapy may also be an option for patients with disseminated metastasis. Simple observation may suffice if you have no symptoms. Participation in available clinical trials may also be encouraged at this point.

Isolated limb perfusion techniques may be used to treat unresectable intermediate or high-grade extremity soft tissue sarcomas. This procedure delivers anticancer drugs directly to an arm or leg. A tourniquet (a tight band around the limb) will temporarily stop the flow of blood to and from the limb, and then anticancer drugs are administered. This allows a high dose of drugs to be delivered directly to the cancerous area.

Your cancer treatment will be tailored for you. You and your cancer care team will weigh the risks and benefits of each treatment option while also considering your individual performance status, your personal preferences, and your specific symptoms related to the metastases. Actively participate in your cancer treatment. Ask questions, and be sure you understand the risks and benefits of your treatment plan.

There is always a possibility that a soft tissue sarcoma will recur. Disease which recurs after primary therapy is again treated with a multi-disciplinary approach. If there is a limited local recurrence, treatment options will be similar to those for a new primary tumor.
Surgery may be possible if it is a limited recurrence. It may be difficult to give additional radiation if the tumor recurs in an area that has already received maximum radiation in the past. However, newer targeted radiation therapy may be possible (for example, brachytherapy) despite past treatments. Chemotherapy is often offered and the specific agents chosen will depend on the period of time that has elapsed since primary therapy and the doses given initially, if any.

Retroperitoneal/Intra-Abdominal
Evaluation and Work-Up of Retroperitoneal/Intra-Abdominal Sarcoma
In many cases, a retroperitoneal or intra-abdominal sarcoma is not noticed until it grows large enough to compress or invade normal tissue, organs, blood vessels, or nerves. Many patients have no symptoms up to that point. About 40% of patients experience abdominal pain. Other less common symptoms depend on location of the tumor and specific organs involved and include gastrointestinal bleeding, nausea or vomiting, weight loss, swelling of the lower legs, or symptoms related to nerve compression such as numbness in the lower legs and partial paralysis.
Your doctor will begin with a physical examination and an accurate medical history. Imaging studies, such as CT or MRI scans, of the primary tumor and the surrounding area will be used to assess tumor location and size. Chest imaging, usually an x-ray, may also be done to determine if the sarcoma has spread to the lungs. It is important that a medical center or clinic specializing in sarcoma treatment evaluate these imaging studies. Endoscopy may also be necessary in some cases.

Treatment of Retroperitoneal/Intra-Abdominal Sarcoma

Once the primary treatment is completed, follow-up care is recommended and is very important to assess for any tumor recurrence (return of the tumor). Imaging may include CT scans, MRI scans, or x-rays of the abdomen and chest.

It is recommended that patients with low-grade tumors that have been successfully resected have a follow-up physical examination with imaging every 3 to 6 months for 2 to 3 years and then annually. Patients with high-grade tumors that have been successfully resected need more frequent surveillance: physical examination with imaging every 3 to 6 months for 2 or 3 years, every 6 months for the next 2 years, then annually.

Chemotherapy agents for retroperitoneal sarcoma may include but are not limited to:
Cisplatin Cyclophosphamide Dacarbazine
Vincristine Doxorubicin (Adriamycin®) Etoposide
Ifosfamide Gemcitabine (Gemzar®)

There is always a possibility a soft tissue sarcoma will recur. Local recurrence occurs in about half of the patients who have undergone complete resection. Recurrent disease is treated the same as primary disease. Enrollment in a clinical trial may be considered if an appropriate trial is available.

Gastrointestinal Stromal Tumor (GIST)

Evaluation and Work-Up of GIST
GIST tumors often grow quite large before they are diagnosed because patients with GIST may have non-specific symptoms or even none at all. In patients with symptoms, the most common include abdominal discomfort, abdominal pain, and bleeding into the intestinal tract. Usually the bleeding appears as dark or black bowel movements. Intestinal bleeding can lead to anemia (low red blood cell counts), which can cause fatigue. Loss of appetite and bloating are also possible symptoms.

It is recommended patients with these symptoms receive a complete history, physical examination, and appropriate imaging with either a CT scan (with contrast) or an MRI to evaluate the mass and get a better idea of the size and extent of the tumor. Imaging of the chest may also be needed. An endoscopy may be completed in some cases of primary gastric masses.

A PET scan may help differentiate active tumor from necrotic or inactive scar tissue, malignant from benign tissue and recurrent tumor from nondescript benign changes. PET provides valuable info because changes in metabolic activity often precede anatomic changes on a CT, and may also be used to clarify ambiguous findings on a CT/MRI.

If the CT or MRI shows an abdominal mass that appears to be localized and can be easily removed, your doctor will likely recommend that the tumor be removed and analyzed by a pathologist with expertise in sarcoma. The pathologist will identify the type of tumor after it has been surgically removed.

If the tumor is not completely removable or if preoperative therapy is being considered, a biopsy will be necessary to confirm the diagnosis of GIST (ruling out another type of cancer or intra-abdominal sarcoma). Because GISTs are soft and fragile tumors, a biopsy could rupture and possibly spread the cancer cells to other parts of the body. Therefore, the biopsy should be completed by someone with extensive experience in dealing with these types of tumors.

Molecular analysis using various immunohistochemistry tests should be considered to determine the subtype of the biopsy sample. This involves part of the sample being treated (or stained) with special manmade antibodies that will attach only to the KIT protein. If the KIT protein is present, the antibodies cause color changes seen under a microscope (the sample is said to be CD117 positive). Because most GIST cells contain KIT but cells of most other types of cancer do not, this test can be useful in determining whether the tumor is a GIST. Additionally, a pathologist with expertise in sarcoma should carefully review the sample of the tissue to provide detail regarding the size of the tumor and the rate at which it is dividing. Determination of the actual mutation present in the GIST cells may also be helpful.

Treatment for Gastrointestinal Stromal Tumor (GIST)

Targeted Chemotherapy for GIST

Imatinib mesylate (Gleevec®) has produced reliable, objective reduction in tumor size and relief of symptoms in patients with GIST. In clinical trials, the tumors shrunk by at least half in about 2/3 of patients treated. Other patients had mild shrinkage or disease stabilization (no further growth of their tumor). Response to treatment with imatinib differs based on the type of mutation associated with the GIST. In some cases, imatinib stops working and the GIST begins to grow again.
Switching to a higher dosage of imatinib or another drug may be effective if imatinib stops working. Most patients experience some side effects with imatinib. Side effects are usually mild and quite manageable, and there are many options to minimize or prevent them.

Surgery for GIST

If the margins after surgery were positive, therapy with imatinib may be started or continued. Sometimes more surgery may an option to achieve a complete resection, called a re-resection. Treatment with imatinib may begin after re-resection and continued until disease progression.

Follow-Up (Surveillance) of GIST

NOTES
45

Recurrence
There is always a possibility a soft tissue sarcoma will recur and, unfortunately, in GIST patients it is not uncommon. GIST may spread from the primary site, usually to the liver or the peritoneum. It is rare for a GIST to spread to the lymph nodes or metastasize to the lungs. After two years, the risk of recurrence decreases.

The treatment options depend on the nature and location of the recurrence. If it is isolated and potentially easily resectable, surgical resection or chemotherapy may be considered. Best supportive care is also an option at this point. For unresectable disease with only a liver recurrence, a local ablative procedure such as RFA, embolization, or other local therapy may be considered. The NCCN guidelines also have included sorafenib or nilotinib as options for patients who are no longer received clinical benefit from imatinib or sunitinib.

46
Desmoid Tumors

Evaluation and Work-Up of a Desmoid Tumor

After imaging has been obtained and reviewed, a biopsy may be performed. This should be done by an expert pathologist to rule out other conditions, such as a type of sarcoma, malignant carcinoma, or another type of benign tumor. However, if complete resection is feasible, then biopsy may not be necessary.

Treatment of Desmoid Tumors

The primary treatment of desmoid tumors is surgery. The goal of surgery is to remove the mass and a wide margin or area of normal tissue around it. This is generally done to improve the chance that any tiny or microscopic tumor cells that cannot be seen by the surgeon are removed. If the tumor is removed and examination by the pathologist confirms that there are no desmoid cells within the margin of normal tissue (negative margins), then no further treatment is generally recommended. Regular follow-up to evaluate for return of the disease is advisable.

If the tumor is surgically removed and the margin has desmoid tumor cells present, the next step might be a wider surgical resection or radiation therapy, with the intent to reduce the risk of return of the disease. However, depending on the location of the tumor, surgery or radiation may cause loss of function or other undesirable symptoms. Therefore, each situation is evaluated and plans for treatment will take into account all these factors. The goal of treatment is to remove the tumor with minimal symptoms or loss of function.
If a significant amount of tumor remains after surgery, and more extensive surgery is not possible, your doctor may recommend radiation therapy or treatment with certain medications (systemic therapy).

Desmoid tumors generally respond slowly to radiation. It may be up to 2 years following radiation treatment before the maximum benefit of the radiation can be evaluated.

Systemic therapy is indicated as a treatment option for unresectable desmoids or for patients who had residual disease after resection. Studies looking at the use of type of therapy for use in patients with desmoid tumors have shown promising results. Both cytotoxic and cytostatic therapies have been evaluated.

The word “cytotoxic” means toxic to cells, or cell-killing. Chemotherapy is a “cytotoxic” therapy. ”Cytostatic” treatments do not kill cancer cells but work by suppressing cellular growth and multiplication.

Tamoxifen is an example of a “cytostatic” therapy. This drug blocks the actions of estrogen and is primarily used to treat and prevent some types of breast cancer. Anti-hormonal therapy medications such as tamoxifen are used as a form of treatment because some hormones seem to increase the growth of desmoid tumors.

Cytostatic drugs such as tamoxifen (Nolvadex®)and nonsteroidal anti-inflammatory agents such as sulindac (Clinoril®) and celecoxib (Celebrex®) have been reported to halt the growth of desmoid tumors. The risk of cardiovascular events may be increased in people taking celecoxib. Studies using a combination of high doses of tamoxifen with sulindac showed promising results. Interferon-alpha and tretinoin have also been used. Imatinib has shown some activity against desmoids as well. If these cytostatic therapies do not elicit a response, then cytotoxic therapy with low toxicity regimens, including methotrexate with vinblastine or doxorubicin-based regimens, may be considered.
If removing the entire tumor will cause disability, unacceptable loss of function, or damage to vital structures, then surgery is not the treatment of choice. Treatment options for unresectable disease include radiation, systemic therapy, or observation for a stable (not growing or spreading) desmoid tumor. Sometimes, radiation therapy shrinks the tumor enough that surgery can be considered. Enrollment in a clinical trial should also be considered.

Follow-up (Surveillance) for Desmoid Tumors

Once the primary treatment is completed, follow-up care is recommended and is very important to assess any tumor recurrence. If a tumor has been completely surgically removed, then baseline x-rays are taken. This is usually done after sufficient time for healing and resolution of any swelling has passed. A baseline x-ray documents the appearance of the area from which the tumor was removed. Follow-up x-rays taken later will be compared to the baseline x-rays to find changes or areas of concern.

It is recommended a history and physical examination, along with x-ray imaging studies be done every 3 to 6 months for 2 to 3 years, then annually. The length of time between follow-up visits will be determined by the doctor based on the risk of recurrence and any complications that may have occurred following treatment.
The follow-up phase for patients with desmoid tumors may also include evaluation for rehabilitation, occupational therapy, and physical therapy. If necessary, these therapies should be continued until maximal function is regained.

Recurrent Desmoid Tumors
Recurrent disease is treated the same as primary disease, discussed previously. For recurrent tumors that are stable (not growing or spreading), observation alone may be considered. Also consider enrolling in a clinical trial, if an appropriate trial is available.

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Glossary of Sarcoma Subtypes

Atypical fibroxanthoma is an unusual and relatively less aggressive form of sarcoma that shows features of both fibroblasts and cells that retain fat (xanthomas). The primary treatment is surgical. Radiation is occasionally used to try and prevent tumor recurrence, and chemotherapy is largely ineffective for this diagnosis. These tumors metastasize very rarely.

Bone and cartilage sarcomas of soft tissue arise in soft tissue but mimic sarcomas that typically arise in cartilage or bone. Many of these sarcomas have some (but not all) features in common with their bone tumor equivalents, and each has unique characteristics that should be considered in their treatment.

Extraskeletal osteosarcoma (also called extraskeletal osteogenic sarcoma) arises in soft tissue but looks just like its counterpart in bone. It typically arises in older adults, not in children like conventional osteogenic sarcomas. It does not respond very well to the chemotherapy drugs used in osteogenic sarcoma of bone, and is more commonly treated like another soft tissue sarcomas.

(Extraskeletal) myxoid chondrosarcoma is an unusual form of chondrosarcoma that shows a wide variety of features under the microscope, and arises in people typically from 20-40 years of age. It grows relatively slowly but has a high risk of recurrence elsewhere in the body, such as the lung. It is largely insensitive to standard chemotherapy drugs.

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Clear cell sarcoma (melanoma of soft parts) is an unusual hybrid tumor that appears to be biologically related to alveolar soft part sarcoma. It is one of the rare tumors with features of both sarcoma and melanoma, including the ability to travel to lymph nodes (typical of melanoma) and to lung (more common for sarcomas). Surgery and radiation of the primary tumor site provide the best chance for cure.

Dermatofibrosarcoma protuberans is another form of tumor with some kinship to fibroblasts. This tumor typically arises in the skin, and should be excised by an appropriate expert, as less extensive resections often fail. These tumors only rarely (5-10%) travel to lungs, even many years after removal of the initial tumor. The mild chemotherapy drug imatinib shows surprising usefulness for this diagnosis, and should be considered a standard of care per members of SARC.

Desmoplastic small round cell tumor (DSRCT) is a sarcoma distantly related to Ewing’s sarcoma that starts and travels in the abdominal cavity long before it is recognized clinically in the majority of patients. It typically arises in young men 15-35 years old. The tumor can travel not only elsewhere in the abdominal or pelvic cavity where it starts, but it can also spread to liver, lung, or the space between the lungs (mediastinum). Though cure is infrequent because of the early spread of this form of sarcoma, the people who do the best are those who both have a good response to chemotherapy and can have all visible sign of their tumor removed.

Epithelioid sarcoma is another form of sarcoma that typically affects the extremities (arms and legs) and tends to travel early to other sites of the body. Similar to people with alveolar soft part sarcoma, people can live for a long time with epithelioid sarcoma, despite metastatic disease. Unlike other sarcomas, epithelioid sarcoma can travel to lymph nodes and cause side effects from involving multiple lymph nodes in a given area of the body.

Even rarer tumors can arise from the sensory organs that regulate blood flow to different parts of the body. These are termed glomus tumors, and they can be painful. Surgery is usually the best way to treat this rare form of sarcoma. Another group of tumors that were once thought to arise from cells around blood vessels, hemangiopericytoma, is now termed solitary fibrous tumor/hemangiopericytoma, since the tumors all appear to be very similar in terms of their biology.

Ewing’s sarcoma / primitive neuroectodermal tumor (PNET) is another family of sarcomas. This group of sarcomas typically occurs in children or young adults, although cases in people up to age 80 or more are occasionally seen. We estimate there are fewer than 500 cases a year in the United States. Without chemotherapy, the cure rate is at best 10%, but with chemotherapy a cure rate of up to 75% in children and 50-60% in adults is seen. Surgery and radiation are also commonly used as treatment for the primary tumor in order to try to achieve the highest cure rate possible. Ewing’s sarcomas appear to affect bone in children and soft tissue in adults, and can be seen in any site of the body. They commonly recur in the lungs and bones.

Fibrosarcoma arises from fibroblasts or their precursors, and form a group of tumors that are difficult to diagnose correctly, given their relative scarcity. In decades past, fibrosarcoma was a common name given to sarcomas, but now a true fibrosarcoma is only infrequently diagnosed. These tumors affect the extremity and trunk most frequently, and can metastasize to the lungs, like other sarcomas. There is an "inflammatory" version of this tumor, which appears to have white blood cells coursing throughout the tumor, for unclear reasons. Inflammatory myofibroblastic tumor is a similar tumor to inflammatory forms of fibrosarcoma in which the tumor cells have both features of connective tissue cells (fibroblasts) and muscle.

Gastrointestinal stromal tumor (GIST): Some people do not consider this a sarcoma, while others do. If it is considered a sarcoma, it is the most common type. It appears to arise from the interstitial cells of Cajal (or its precursors), which are the pacemaker cells of the intestines. In other words, they are responsible for the peristaltic wave that pushes food through the intestines. There may be as many as 4,000 new GIST patients per year in the United States. About 2/3 of GISTs arise in the wall of the stomach, 20% in the small intestine, and the remainder from other places within the abdomen. The common places that GIST recur are in the abdominal cavity or in the liver. GIST tumor cells nearly always show evidence of the c-kit molecule or PDGFR molecule being activated. This is the means by which the imatinib (Gleevec®) and sunitinib (Sutent®) appear to function, the two FDA-approved drugs for metastatic GIST.

Giant cell tumors (GCT) of tendon sheath and pigmented villonodular synovitis (PVNS) are very rare connective tissue tumors that arise nearly exclusively from cells near the knee joint. They are initially removable with surgery but have a high risk of recurrence. Occasionally, GCT of tendon sheath and PVNS can become more aggressive and travel to other organs, such as the lung.

Leiomyosarcoma, a tumor of smooth muscle (or its precursors), it can arise anywhere in the body. There are about 2,500 cases a year of this diagnosis in the United States. Roughly 60% of leiomyosarcomas occur in women with an average age of 60 years (usually with the primary site in the uterus). Other common sites for this tumor to start are the small intestine or stomach, or the wall of a blood vessel in the abdomen, an arm or leg, or the skin. These sarcomas have a highly variable behavior, but when they metastasize they characteristically travel to the lungs, and less commonly to the liver, bone, and soft tissues.

Liposarcoma arises from fat cells or its precursors. It is also fairly common for a sarcoma, with about 2,000 cases per year in the United States. There are three families of liposarcoma: (1) well-differentiated and/or dedifferentiated (~50%); (2) myxoid and/or round cell (~40%); and (3) pleomorphic (10%). Each has its own specific biology and risk of recurrence or spread.

Well-differentiated and/or dedifferentiated liposarcoma typically arises in the abdominal cavity or in an arm or leg. It presents as a large painless mass. Primary therapy is surgical, although the recurrence risk in the abdomen is very high, at least 70-80% over 10 years. The less aggressive form of this tumor is termed "well-differentiated". The more aggressive version of this sarcoma is called "dedifferentiated", but is oftentimes less aggressive than other so-called "high-grade" sarcomas.
Myxoid and/or round cell liposarcoma is the second most common family of liposarcomas. Both forms carry the same translocations (abnormal joining) between two chromosomes, numbers 12 and 16. These tumors typically arise in the leg, with an unusually high risk of recurring in other soft tissue sites or in bones such as the spine and pelvis. Myxoid and/or round cell liposarcoma appears to be sensitive to the presently experimental agent ET-743 (ecteinascidin 743, also known as trabectedin or Yondelis®). This type of sarcoma is otherwise relatively chemotherapy sensitive.

Pleomorphic liposarcoma is the least common form of liposarcoma, and also tends to affect an arm or leg. It is often more aggressive than other liposarcomas, and can spread to other sites of the body such as lung and soft tissue.

Malignant extrarenal rhabdoid tumor is a very aggressive form of sarcoma that nearly always arises in childhood. It affects the kidneys and other structures in the abdomen, and has a high risk of early spread to liver, lung, and other sites.

Malignant fibrous histiocytoma (MFH) is now termed high-grade undifferentiated pleomorphic sarcoma (HGUPS) by pathologists. There are about 2,000 cases a year of this type of sarcoma in the United States. It tends to affect the leg, trunk, or arm of people over 50 years of age. MFH does not have particular distinguishing characteristics, besides appearing as a relatively aggressive tumor by microscopic examination, with a modest degree of architecture. The cell of origin of such a tumor is unclear. Sarcomas that express no evidence of architecture, looking to be sheets and sheets of aggressive looking sarcoma cells, are often termed "high grade sarcoma, not otherwise specified (NOS)". The most common place for MFH to recur is in the lungs.

Malignant peripheral nerve sheath tumors (MPNST) are sarcomas that arise from the insulating cells that surround nerve endings. They can arise in people who have a familial disposition to forming benign versions of these tumors called neurofibromas or schwannomas. This condition is called neurofibromatosis type I, and carries with it the risk of developing MPNSTs and other tumors, such as relatively less aggressive tumors that affect the brain or nerve sheaths of nerve endings as they leave the brain, but within the skull (acoustic neuromas). Both MPNSTs that arise in people with neurofibromatosis type I and spontaneously have mutations in a gene called neurofibromin (NF1), thus linking these tumors together through a common pathway of activation of the tumor cell. A cousin of this tumor, which appears to arise purely from the neuronal insulating cell called a Schwann cell, is the malignant granular cell tumor, which mimics the behavior of an MPNST.

Paraganglioma is not a sarcoma itself, but is a soft tissue tumor, and is sometimes treated by sarcoma specialists. It is mentioned here for completeness. It is a tumor of remnants of cells related to the adrenal gland (specifically adrenal medulla) and specific types of nerve bodies found throughout the body. Treatment is primarily surgical, with chemotherapy and radiation typically held in reserve for any form of later metastatic disease.

Rhabdomyosarcoma is a rare sarcoma that typically affects children. Only 20% of rhabdomyosarcomas occur in adults. There are only about 250 cases a year in the United States. It is a heterogeneous type of sarcoma, with several recognized subtypes, including embryonal, botryoid, alveolar, and pleomorphic as its principal types. Treatment for these sarcomas nearly always involves surgery, radiation, and chemotherapy. Cure rates are better for children than for adults, for unclear reasons. This is one form of sarcoma that can travel to lymph nodes, though it can also travel to lungs and other sites.
Sarcomas of blood vessels comprise an uncommon group of sarcomas that appear to arise from the lining of blood vessels (endothelial cells) or their precursors. There are less aggressive (epithelioid hemangioendothelioma or EHE) and more aggressive (angiosarcoma) members of this family of sarcomas. Some blood vessel sarcomas can affect the lymphatic system, which carries fluid from soft tissue to lymph nodes. The vessels of the lymphatic system are lined with cells very similar to those found in blood vessels, and give rise to what is termed lymphangiosarcoma. Kaposi sarcoma is a form of blood vessel sarcoma that is caused by a virus, HHV-8 (also called KSHV), both in people with HIV disease, as well as a group of typically older persons who have intact immune systems. These tumors have a high risk of recurring where they start and can also travel to liver, bone, lung, and other sites.

Solitary fibrous tumor, which also encompasses the diagnosis hemangiopericytoma, is an uncommon tumor that is found in the chest cavity, orbit (which contains the eye), coverings of the brain (dura mater), or from the pelvis. There are less aggressive and more aggressive versions of this tumor, which can easily grow to a size of 6-10 inches or more before they cause symptoms of compression of other organs. The more aggressive form of this tumor is termed malignant solitary fibrous tumor, and is associated with metastatic disease to the lungs or to bone, among other sites.

Synovial sarcoma is common between ages 15 and 35, and often affects the leg, foot, and hand, although other unusual sites such as chest cavity are seen. It is often a chemotherapy sensitive form of sarcoma. It contains an abnormal joining of two chromosomes in each cell, between chromosomes X and 18. There are two principal forms of synovial sarcoma: monophasic and biphasic. Biphasic tumors have what appear to be glands on microscopic examination, and can appear more like more typical cancers (carcinomas) rather than sarcomas on this basis. We do not have different therapies based on the type of synovial sarcoma, and therapy for a primary leg tumor often involves surgery, radiation, and sometimes chemotherapy. The lungs are the most common site of recurrence for synovial sarcomas.

Abdomen

The part of the body between the chest and the pelvic bones. It contains the stomach, small and large intestines, liver, gallbladder, spleen, and pancreas.

Adjuvant Therapy
Treatment used in addition to the main treatment. This usually refers to treatment given postoperatively, either chemotherapy or radiation therapy, with the intent of destroying any cancer cells that may not have been removed during surgery but cannot be detected.

Aggressive Fibromatosis
(See Desmoid Tumor)

Alternative Therapy

Alternative therapies are defined as those that are used instead of your standard medical care. They are generally not recognized by the medical community as standard or conventional therapies. The American Cancer Society recommends that patients considering the use of any alternative or complementary therapy discuss this with their health care team. See also Complementary Therapy.

Anemia

Anemia occurs when the blood has too little hemoglobin, the part of the red blood cell (RBC) that carries the oxygen needed by your body. The normal level of hemoglobin is generally different in males and females. For men, anemia is typically defined as hemoglobin level of less than 13.5 gram/100ml and in women as hemoglobin of less than 12.0 gram/100ml.

Autonomic Nervous System

The part of the nervous system that controls body processes outside conscious control, stimulating cardiovascular, digestive, reproductive and respiratory organs.

Benign

Not cancerous; not malignant.

Biopsy

The removal of a sample of tissue for analysis. There are several types of biopsies. In an excisional biopsy, the whole tumor including some surrounding normal cells is removed. An incisional biopsy removes only a portion of the tumor. Another type of biopsy is fine needle biopsy which involves a needle removing tissue sample. Core needle biopsy is similar.

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Chemotherapy

Treatment with drugs to destroy cancer cells. It is called systemic treatment because the drug(s) travels throughout the body and kills cancer cells. Chemotherapy is often used in addition to surgery and/or radiation to treat cancer. Chemotherapy may be taken by mouth (pill) or given intravenously.

Chromosomal Translocation

Translocations are a type of DNA abnormality that can lead to many different disorders. Human DNA is packaged in 23 pairs of chromosomes. A translocation means that DNA from one chromosome breaks off and becomes attached to a different chromosome. The point at which the break occurs can affect genes - for example, it can cause oncogenes to be turned on.

Cisplatin

A chemotherapy drug used to treat various cancers including sarcomas.

Clean Margins

Surgical report completed by a pathologist showing no cancer cells are visible at the outer edges or borders of a tumor that is surgically removed. It is also known as Clear or Negative Margins.

Clinical Trial

Studies of promising new or experimental treatments.
Complementary Therapy

Therapies used to complement or enhance standard therapy. They generally are not recognized by the medical community as conventional approaches to care. See also Alternative Therapy.

Computed Tomography (CT Scan)

An imaging test in which many x-rays are taken from different angles of a part of the body. A computer combines these images to produce cross-sectional pictures of internal organs.

Connective Tissue

That material made up of fibers that creates a framework to support and connect body tissues and organs. Connective tissue surrounds many organs. Cartilage and bone are forms of connective tissue.

Cytogenetics

A branch of biology that deals with heredity and cellular components, particularly chromosomes, associated with heredity.

Cytostatic Agent

A drug that inhibits or suppresses cellular growth and multiplication.
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Cytotoxic Agent

A drug that is lethal to cancer cells. It works by inhibiting or preventing the normal functioning of cells.

Cyclophosphamide

A cytostatic drug used for the treatment of cancer, also called Cytoxan®. It works by slowing the growth of tumor cells. It is often used in combination with other drugs.

Desmoid Tumor

A benign nodule or relatively large mass consisting of firm, scar-like connective tissue. These tumors are locally aggressive, meaning they can grow into or destroy nearby normal tissue.

Doxorubicin

A cytotoxic drug, also called Adriamycin®. It may be used in combination with other drugs.

Emesis

Vomiting.

Endoscopy

A technique to examine the inside of a canal in the body or hollow space using an instrument called an endoscope. It can be used to see a cancer mass and estimate its size and location.

Epidermis

The superficial (outer) portion of the skin.

Etoposide

A chemotherapy drug (also called Etopophos®, VePesid®, or VP-16) used for certain cancers including sarcomas.

Extra-abdominal Desmoid Tumors

Desmoid tumors outside the abdominal cavity.

Familial Adenomatous Polyposis (FAP)

A genetically inherited disorder characterized by the presence of many polyps throughout the colon.

Fibroma

A benign neoplasm derived from fibrous connective tissue.

Gardner’s Syndrome

A rare, hereditary disorder inherited as an autosomal dominant. It is a variant form of familial adenomatous polyposis in which polyps in the colon are associated with fibromas and osteomas.
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Gastrointestinal Tract (GI Tract)

The system in your body that digests food, absorbs nutrients, and expels waste. The gastrointestinal tract starts with the mouth and proceeds to the esophagus, stomach, duodenum, small intestine, large intestine (colon), rectum, and ends with the anus.

Gross

Large, bulky enough to be visible to the naked eye.

Gross Residual Disease

When visible cancer cells remain after a surgical procedure.

Growth Factor

A naturally occurring protein capable of stimulating cellular growth, proliferation, and differentiation. Growth factors typically act as signaling molecules between cells. Examples are cytokine and hormones that bind to specific receptors on the surface of their target cells.

Histology

The field of medicine that studies tissue under the microscope.

Ifosfamide
A cytostatic chemotherapy drug, also called Ifex®.
Imaging Studies
Methods used to produce a picture of internal body structures. Some imaging studies used to help diagnosis cancer include x-rays, CT scans, magnetic resonance imaging (MRI), and ultrasound.

Infusion
In cancer treatment, it refers to the intravenous (through a vein) administration of chemotherapy drugs.

Intra-abdominal Desmoid Tumors
Desmoid tumors that develop in the muscular tissue of the abdominal cavity.

KIT
A protein, expressed on interstitial cells of Cajal, which regulates their replication; GIST cells usually express a mutated form of KIT

Laparoscopy
A technique used to look inside the abdomen or pelvic area to diagnose certain conditions. It requires a small incision to be made in the skin, through which a thin tube called a laparoscope is inserted.

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Leiomyosarcoma
A malignant tumor originating in smooth muscle, the major structural component of most hollow internal organs and walls of blood vessels.

Li-Fraumeni Syndrome (LFS)
Li-Fraumeni syndrome is an inherited cancer predisposition syndrome associated with osteosarcoma, soft-tissue sarcoma, and many other types of cancer. Individuals with LFS are at increased risk for developing multiple primary cancers. More than 50% of individuals diagnosed clinically have an identifiable disease-causing mutation in the TP53 gene.

Limb Sparing Surgery
Also known as limb salvage surgery. This is performed to remove bone and soft-tissue cancers occurring in the limbs in order to avoid amputation. It involves three steps: 1) removal of the tumor; 2) reconstruction of the limb by means of a prosthesis or bone graft; 3) transfer of soft tissue and muscle to close the site and restore motor power.

Liposarcoma
A sarcoma that develops in fat or adipose tissue.

Localized
Sarcoma cells have not spread beyond the site where they started growing. Localized sarcoma may be curable with adequate surgery and other treatments.

Magnetic Resonance Imaging (MRI)
An imaging process that uses radio waves to create cross-sectional pictures of the body. MRI uses a powerful magnet and transmits radio waves through the body; the images appear on a computer screen as well as on film.

Malignant Fibrous Histiocytoma (MFH)
MFH is the most common malignant sarcoma of older adults, occurring in the deep soft tissue of the extremities and the retroperitoneum.

Margin
A boundary, edge or border

Medical Oncologist
A physician who specializes in the treatment of cancer using drug therapy.

Metastasis

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Methotrexate
A type of chemotherapy drug used to treat cancers. It may also be used in other conditions that are not cancer.

Microscopic Residual Disease
When a small number of cancer cells, visible only under a microscope, remain after a surgical procedure.

Necrotic
Necrotic tissue is dead tissue.

Negative Margins
(See Clean Margins)

Neoadjuvant Therapy
Therapies, such as chemotherapy, hormone therapy, or radiation therapy, that are given before surgery. Preoperative therapy may be used to shrink cancer in order to remove the tumor with less extensive surgery than would otherwise be needed.

Neurofibromatosis
A genetic disease in which patients develop multiple soft tumors (neurofibromas). These tumors occur under the skin and throughout the nervous system.

Oncogene
A gene that contributes to the production of a cancer. Oncogenes are generally mutated forms of normal cellular genes (proto-oncogenes).

Orthopedic Oncologist
A physician who specializes in the diagnosis and treatment of malignant primary bone tumors.

Palliative Treatment
Forms of medical care or treatment that concentrate on reducing the severity of disease symptoms, rather than striving to halt, delay, or reverse disease progression or provide a cure. The goal is to prevent and relieve suffering and to improve quality of life for people facing serious, complex illness.

Pathologist
A physician who specializes in diagnosis and classification of diseases by laboratory tests (such as examination of tissue and cells under a microscope). The pathologist determines whether a tissue sample is benign or cancerous.

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Pediatric Oncologist
A physician who specializes in the treatment of children with cancer and incorporates all three primary oncology disciplines (medical, surgical, and radiation oncology) in the care of their young patients.

Pelvis
The part of the body below the abdomen within the confines of the pelvic bones.

Peritoneum
The membrane that forms the lining of the abdominal cavity, covering and supporting most of the intra-abdominal organs. The peritoneum serves as a channel for the passage of fluids to and from the organs, via blood vessels, lymphatic vessels, and nerves.

Port
A device that can be implanted under the skin into a large vein to allow medication to be delivered without repetitive needle sticks in the arm/hand.

Positive Margins
After a surgical procedure, a pathologist examines the tumor specimen that was removed. When cancerous cells extend to the edges of the removed specimen, it is referred to as positive margins. This raises concerns that some cancerous cells may still be present at the surgical site.

Positron Emission Tomography (PET)
A scan that uses radioactive glucose. A scanner makes detailed, computerized pictures of areas inside the body where the glucose is used. Because cancer cells often use more glucose than normal cells, the pictures can be used to find cancer cells in the body.

Primary Cancer
The site where the cancer is thought to have started. For example, GIST that spreads to the liver is still called GIST, but with liver metastasis.

Primitive Neuroectodermal Tumor (PNET)
One group of cancers that develop from the same type of early cells, and share certain biochemical and genetic features. Some PNETs develop in the brain and central nervous system, and others develop in sites outside the brain such as the limbs, pelvis, and chest wall.

Radiation Oncologist
A physician who specializes in therapeutic radiation.
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Radiation Therapy
Treatment with high-energy rays (such as x-rays) to kill or shrink cancer cells. The radiation may come from outside the body (external radiation) or from radioactive materials placed directly in the tumor (internal or implant radiation).

Radiologist
A physician who specializes in reading and interpreting x-rays and scans.

Recurrence
Cancer that has come back after treatment. Local recurrence means that the cancer has come back at the same place as the original cancer. Regional recurrence means that the cancer has come back near the first site. Distant recurrence is when cancer metastasizes after treatment to organs or tissues (such as the lungs, liver, or brain) farther from the original site than the regional area.

Re-resection
A second surgery to remove cancer cells remaining after the first surgery.

Resectable
A term used to describe a tumor that can be surgically removed.

Retroperitoneum
The anatomical space behind the abdominal cavity is called the retroperitoneum.

Rhabdomyosarcoma
A type of sarcoma in which the cancer cells are thought to arise from skeletal muscle.

Staging
Performing examinations and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. It is important to know the stage of the disease in order to plan the best treatment.

Supportive Care
Treatment given to prevent, control, or relieve complications and side effects and to improve the patient’s comfort and quality of life.

Surgical Oncologist
A physician who specializes in surgical aspects of cancer including biopsy, staging, and surgical resection of the tumor.
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Surveillance
Follow-up of a patient after treatment for cancer to monitor his/her current status. Surveillance typically includes physical examination, blood tests, and x-rays. These examinations are typically ordered periodically for many years.

Systemic Therapy
Treatment that reaches cells throughout the body by traveling through the blood stream.

Vincristine
A type of chemotherapy drug, also called Oncovin®.

X-rays
High energy radiation that can be used at low levels to diagnose disease or at high levels to treat cancer.
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About SARC and the NCCN
SARC (Sarcoma Alliance for Research through Collaboration) is a 501(c)3 Michigan non-profit organization dedicated to the development and support of clinical trial research for the prevention, treatment, and cure of sarcomas. This organization facilitates dialogue and collaboration among sarcoma researchers and clinicians, assists in the development and dissemination of protocols for clinical trials and information relating to sarcoma research and the results of clinical trials, administers research grants and funding for clinical trials, and acts a resource to provide the most up-to-date information to physicians, patients, and caregivers. SARC member institutions are listed at www.sarctrials.org.

The National Comprehensive Cancer Network (NCCN) is composed of institutions with extensive experience in the diagnostic evaluation and treatment of sarcomas using a multidisciplinary approach, with various experts functioning as a team. This is especially important in the management of bone cancer (also known as a primary bone tumor, or sarcoma of the bone) where expertise in surgery, pathology, medical and pediatric oncology, and radiology all play a vital role in the combined treatment planning and delivery of state-of-the-art care tailored to your needs.

NCCN Clinical Practice Guidelines were developed by a diverse panel of experts to assist community based health care providers in the treatment of primary bone tumors. The guidelines are a statement of consensus of its authors regarding the scientific evidence and their views of currently accepted approaches to treatment. The NCCN guidelines are updated as new, significant data becomes available. See www.nccn.org to view NCCN Clinical Practice Guidelines in Oncology, Bone Cancer – v.1.2009. The patient Information version translated by SARC with NCCN permission will be updated accordingly and will be available on-line through the SARC website (www.sarctrials.org).

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This booklet, Soft Tissue Sarcoma Treatment Guidelines for Patients, was developed by a diverse group of experts and is based on the NCCN Clinical Practice Guidelines for Soft Tissue Sarcoma – v.2.2008. These guidelines were written for patients, reviewed, and published with help from staff at SARC and the following individuals from SARC’s member institutions.

Denise Reinke, APRN, BC, AOCN
Editor
Nurse Practitioner – Sarcoma Program
University of Michigan Comprehensive Cancer Center
President and COO, SARC
Monica Davey, RN, BSN, MEd, MBA
Assistant Editor
Clinical Research Nurse Coordinator-Sarcoma Program
Fox Chase Cancer Center
Jill E. Nelson APRN, BC. AOCNP
Hematology/ Oncology Nurse Practitioner
Massachusetts General Hospital
Joan Giblin, MSN, APRN-BC, AOCN
NP Coordinator Winship Cancer Institute at Emory University
Denise Parker, RN
Clinical Nurse Coordinator Sarcoma services
Seattle Cancer Care Alliance
Lisa Buchanan, RN
Clinical Nurse Coordinator
Seattle Cancer Care Alliance
Kelly Scheu, MS, NP - C
Nurse Practitioner
Hematology Oncology Program
Allegiance Health
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The original NCCN Soft Tissue Sarcoma Clinical Practice Guidelines were developed by the following NCCN Panel Members:
George Demetri, MD/Chair
Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center
Scott Antonia, PhD, MD
H. Lee Moffitt Cancer Center
& Research Institute
Robert S. Benjamin, MD
The University of Texas, M. D. Anderson Cancer Center
Ephraim S. Casper, MD
Memorial Sloan-Kettering Cancer Center
Ernest U. Conrad, III, MD
Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance
Thomas F. DeLaney, MD
Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center
Robert Heck, Jr., MD
University of Tennessee Cancer Institute
Martin J. Heslin, MD
University of Alabama at Birmingham Comprehensive Cancer Center
Raymond J. Hutchinson, MD
University of Michigan Comprehensive Cancer Center
Charlotte Jacobs, MD
Stanford Comprehensive Cancer Center
John M. Kane, III, MD
Roswell Park Cancer Institute
G. Douglas Letson, MD
H. Lee Moffitt Cancer Center & Research Institute
Sean V. McGarry, MD
UNMC Eppley Cancer Center at the Nebraska Medical Center
Richard J. O’Donnel, MD
UCSF Helen Diller Family Comprehensive Cancer Center
I. Benjamin Paz, MD
City of Hope Comprehensive Cancer Center
John D. Pfeifer, MD
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Raphael E. Pollock, MD
The University of Texas, M. D. Anderson Cancer Center
R. Lor Randall, MD
Huntsman Cancer Institute at the University of Utah
Karen D. Schupak, MD
Memorial Sloan-Kettering Cancer Center
Herbert S. Schwartz, MD
Vanderbilt-Ingram Cancer Center
Katherine Thornton, MD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Douglas S. Tyler, MD
Duke Comprehensive Cancer Center
Margaret von Mehren, MD
Fox Chase Cancer Center
Jeffrey Wayne, MD