Childhood Soft Tissue Sarcomas Soft tissue sarcomas are cancerous tumors that arise in various soft tissues of the body. Soft tissues connect, surround, and support other body structures and organs. They include muscles, tendons, fibrous tissues, fat, nerves, blood vessels, and synovial tissues. The most prevalent of all childhood soft tissue sarcomas is rhabdomyosarcoma. Other rare soft tissue sarcomas include fibrosarcoma, neurofibrosarcoma, leiomyosarcoma, liposarcoma, synovial sarcoma, hemangiopericytoma, alveolar soft part sarcoma, and malignant fibrous histiocytoma. Muscles and connective tissues Skeletal muscles are attached to bones by tendons. These cords of tissue are flexible and very strong. Their primary purpose is to move the force of muscular action to the bone to cause movement. For example, the Achilles tendon connects the calf muscles to the bone in the heel and allows the foot to push against the ground when walking. Another important feature of the musculoskeletal system is the joint. Its main function is to connect bone to other bone and to allow movement where it is needed. Joints and tendons are surrounded by synovial tissue--a sheath which secretes a clear, thick lubricating fluid. Ligaments cross over joints and help join bone to bone. The ligaments strengthen joints and provide support to prevent dislocation. The muscular system is a network of complex tissues working together, much like levers and fulcrums, which enables the body to move. Soft tissue sarcomas can arise at any point within this system. Rhabdomyosarcoma Childhood rhabdomyosarcoma is a soft tissue cancer that arises in the muscles. It accounts for approximately 4 percent of all cases of childhood cancer. Rhabdomyosarcoma can start anywhere in the body; however, the point of tumor origin is often associated with age at diagnosis. Most head and neck tumors occur in children under the age of eight, whereas extremity tumors are most commonly found in adolescents. Less common primary sites for this cancer are the genitourinary tract, including the bladder and prostate in the male and the vagina in the female. There are distinct histologic types (referring to how the cells look under a microscope) of rhabdomyosarcoma: Embryonal. This type accounts for approximately 60 to 70 percent of all childhood rhabdomyosarcomas. Tumors with this histology usually arise in the head, neck, and genitourinary areas. Botryoid. Botryoid tumors are a variant of the embryonal type and account for 10 percent of rhabdomyosarcoma cases. They are most commonly found in the genitourinary region and occur most often in infants. Alveolar. These tumors are usually found in the trunk or limbs. They are a more aggressive form of rhabdomyosarcoma and occur most often in adolescents. Rare forms. Pleomorphic and undifferentiated tumors are rarely found in childhood rhabdomyosarcomas. Who gets rhabdomyosarcoma? Rhabdomyosarcoma is the most common childhood soft tissue sarcoma. Approximately 250 children are diagnosed with rhabdomyosarcoma in the United States each year. Two-thirds of these cases are diagnosed in children under the age of six. The disease has a slightly higher incidence in males than in females. The occurrence of disease found in white and black males is very similar; however, the incidence in black females is only half of that in white females. The disease is more common in industrialized Western nations than in Asia. A parent describes the shock of diagnosis: In December 1996, my two-year-old son Kenny was diagnosed with stage IV rhabdomyosarcoma. Needless to say, our lives have changed. We were told a year earlier that Kenny had a cytoma and that it would get bigger and bigger, then eventually go away. Over the course of the year, the mass did grow larger. Little did I know that the "boo boo" I touched every day was in actuality trying to kill my son. Genetic factors Most rhabdomyosarcomas occur sporadically; however, certain familial syndromes are associated with this form of childhood cancer. Children with Li-Fraumeni syndrome, neurofibromatosis, or Beckwith-Wiedemann syndrome have a higher chance of developing rhabdomyosarcoma than do children who do not have these congenital disorders. Environmental factors No known environmental factors cause rhabdomyosarcoma in children. Rhabdomyosarcoma signs and symptoms The signs and symptoms of rhabdomyosarcoma depend very much on the location of the primary tumor and whether or not the disease has metastasized (spread) to other areas. Generally, the child will develop a lump or mass that is not related to trauma to the area. Sometimes a normal body function is disrupted by a growing tumor. For example, large masses in the genitourinary system can cause difficulty with urination. Symptoms may initially be attributed to noncancerous causes, like the pain this mother describes: Cassandra had been complaining of pain in her left knee while sleeping at night for one month previous to her diagnosis. I brought this to the attention of her pediatrician at a well child visit. The doctor looked her over and said that it was probably growing pains, and to elevate her leg in the evening and see if that might help. Following his advice, I began to elevate her leg at night with a pillow--a practice that my mother used when I had similar pains in my legs as a child. This didn't help alleviate the pain, though, and in fact, it seemed to intensify as days went by. One week later we were at a local Starbucks and Cassandra had to go to the bathroom. I went in with her, and while I was helping her with her tights I noticed a large lump on her left buttock. Primary tumors located in the head or neck region can cause many different signs and symptoms. Orbit tumors can cause eyelid swelling or drooping, called ptosis. The eye may appear to protrude or bulge, and the muscles surrounding the eye may be weakened. The child may also complain of double vision. Tumors that arise in the sinus area or the middle ear can cause nasal obstruction, sometimes with discharge and intermittent bleeding. The child may have a nasal voice. Rhabdomyosarcomas are often found in the bladder and prostate. Symptoms include blood in the urine, difficulty passing urine, urinary obstruction, and pain. Prostate tumors tend to be found as a large mass, sometimes accompanied by constipation. A painless scrotal enlargement may be found in boys with tumors in the paratesticular area (the areas next to the testicles). Vaginal tumors generally present with a mass that looks like a bunch of grapes at the vaginal opening, often accompanied by a vaginal discharge. Tumors originating in the cervix or uterus are diagnosed more frequently in older girls, and may present with a mass and sometimes discharge. Tumors that occur in the extremities and trunk most often will cause swelling, pain, tenderness, and redness in the affected area. Diagnosis of rhabdomyosarcoma Many tests are performed to diagnose rhabdomyosarcoma as well as to distinguish it from several other childhood cancers that can appear very similar. First, the doctor obtains the child's medical history and performs a physical examination. Usually, he orders a complete blood count (CBC). A computed tomography (CT) scan or magnetic resonance imaging (MRI) may reveal a mass. The lump will then be sampled, either with open or needle biopsy. Rhabdomyosarcoma can appear very similar to other childhood cancers at the microscopic level, and extra tests may be needed to help differentiate between malignancies and establish the proper diagnosis. An imaging test was needed to clarify the following child's diagnosis: At the end of all the tests, the ophthalmologist asked me to come back into his office alone to speak with him. He told me that Joseph had some kind of growth pressing out on his eyeball from above and behind. I looked down at the notes he had in front of him and I saw the word "TUMOR." He told me that Joseph would need further testing in the form of an MRI to tell what the growth was, and gave me a list of possibilities, at the bottom of which (and "highly unlikely") was a cancerous tumor. Staging Once rhabdomyosarcoma has been diagnosed, more tests are done to determine if the cancer has spread to other parts of the body. Bone marrow aspiration and biopsy may be performed to see if disease has spread to the bone marrow. Ordinary x-rays are used to detect disease that has spread to the bone or lungs. More specialized imaging techniques used to evaluate the extent of the disease include CT, MRI, and bone scans. If the mass is located within the pelvic area, ultrasonography may be done along with CT. This process is called staging, and it helps the doctor choose the most appropriate treatment for the child. This parent describes a workup for rhabdomyosarcoma: Cassandra had to undergo a myriad of tests and procedures when she was initially diagnosed. The CT scans showed that the tumor in her bottom had spread to the lungs, so we knew that first night that she was fighting a malignant cancer. The second day at the hospital she had an MRI. While she was under anesthesia for that procedure, the doctors implanted a Hickman line in her chest that would be used for administering chemo, antibiotics, fluid, food, etc. over the next eight months. They also took samples of her bone marrow to see if the cancer had spread there--it hadn't. The next day she had a bone scan to detect any bone involvement, of which there was none. They also ran tests on her kidney function to use as a baseline to see how the treatment would affect her kidneys. An ultrasound of her heart was done as well, also to use as a baseline, since one of the chemo drugs, Adriamycin, can cause heart problems. The Intergroup Rhabdomyosarcoma Study Group (IRSG) currently bases treatment protocols on the following staging system: Stage 1. The tumor is localized to the orbit and head or the genitourinary region (excluding the bladder and prostate). Stage II. The tumor is localized to any primary site not included in stage I. Primary tumors must be less than 5 cm in diameter, and there must be no regional lymph node involvement. Stage III. The tumor is localized to any primary site not included in stage I. Primary tumors are greater than 5 cm and/or there is regional lymph node involvement. Stage IV. The tumor has spread to distant sites. Another system is called the TNM system. The T represents tumor, and takes into consideration its size and location. The N represents nodes, and is used to indicate the presence or absence of lymph node involvement. The M represents metastases, indicating whether the disease has spread beyond the primary site to distant areas. The TNM system has several benefits. It is the method used for staging rhabdomyosarcoma in many other counties, and its use allows direct comparison between studies. The system has also been shown to be very predictive of long-term outcome because location of the tumor has been found to be the most important prognostic factor--regardless of whether the surgeon achieves an excision. Prognosis Since the 1970s, the treatment of rhabdomyosarcoma has dramatically improved. The majority of children and teens diagnosed with non-metastatic rhabdomyosarcoma now survive the disease. The prognosis and best treatment for each child is determined by analysis of several clinical and biologic features. The histology of the tumor is important, with alveolar tumors tending to behave more aggressively. Within any given histologic type, localized tumors respond better to therapy than do those that have metastasized. Tumors that are completely resected have the best prognoses. The degree to which resection can be achieved is determined by the size of the tumor and its closeness to vital structures. The importance of these determinants is that the aggressiveness of treatment can be increased for those with adverse features to improve their prognosis. Treatment of rhabdomyosarcoma At diagnosis, many parents are confused about how to find the best doctors and treatments for their child. State-of-the-art care is available from physicians who participate in Intergroup Rhabdomyosarcoma Study Group (IRSG), the Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG). These study groups, composed of pediatric surgeons and oncologists, urologists, radiation oncologists, researchers and nurses, establish the standard of care for patients worldwide, conduct new studies to discover better therapies, and establish follow-up for survivors. They are in the process of merging into one entity called the Children's Oncology Group (COG). If the treatment center you are referred to is a member of one of these groups, you can rest assured that your child will have access to the best thinking on the treatment of pediatric cancers. The oncologist will choose the best treatment or clinical trial based on many factors. For most patients with rhabdomyosarcoma, treatment usually includes surgery, chemotherapy, and radiation, as was the case for this child: Cassandra was started on a pilot study put together by Children's Cancer Group (CCG), with which our hospital was affiliated. We didn't have time to look into alternatives. Our surgeon told us that this was fast growing and very dangerous, and we wanted to start fighting immediately. The protocol involved using multiple drugs together on an aggressive treatment plan consisting of one week of treatment, then two weeks off, then another week of treatment, etc. She would have six rounds of chemo, and then surgery to remove any residual tumor in the buttocks, have two more rounds of chemo, and finally she would end with six weeks of daily radiation. The drugs dripped into her for 24 hours a day for six days. She was hospitalized for the treatment and then released until her immune system, so weakened by the treatment, would give in, and she would get an infection. This began to happen like clockwork. She would be admitted for treatment on Tuesday, let out on Sunday and readmitted by Thursday with neutropenia and a fever. We would then spend about a week in the hospital until her blood counts recovered, go home for a few days and then start the next round of chemo. This was our life from November 1995 until May 1996. Surgery All children diagnosed with rhabdomyosarcoma will have surgery, either to remove all or part of the primary tumor, or to perform an incisional biopsy to reach a definitive diagnosis. Surgery is used as early as possible in the course of treatment and is the quickest method to reduce the amount of the disease. However, complete resection may not be possible, particularly if the mass is located near vital blood vessels, if it deeply invades surrounding normal tissue, or if there are functional or cosmetic reasons for preventing such a procedure. The doctor showed us the MRIs, and we got to see the monster in Joseph's head. It was a creepy top-down view, and we could see a big white blob behind his right eyeball, pushing it much farther out and down than the left one. Still no one used the word cancer. He explained how he would do the biopsy, cutting across the width of the whole eyelid to retrieve a bit of the mass, leaving packing and stitches that would make the eye look puffy and scary for a few days, but which would retreat into invisibility within a few months. During surgery the doctor removes as much of the tumor as he can and then samples surrounding tissues which are later examined by a pathologist. The pathologist determines whether all of the tumor has been removed, or whether some cells remain behind. If the surgeon is able to remove the entire tumor, it is referred to as a total gross resection. If there is evidence of remaining disease, it is referred to as residual disease. If it is visible to the naked eye or can be felt by the surgeon's hand, it is called gross residual disease. If it is only visible under the microscope, it is called microscopic residual disease. Second-look surgical procedures, done after chemotherapy, remove any remaining residual disease and determine if remission has been reached. This can be especially important for choosing appropriate further treatment, such as the amount of radiotherapy to be given. Approximately 10 percent of newly diagnosed children have tumors that can be completely removed. In most cases, residual disease is present. For this reason, chemotherapy is used in all treatment protocols and radiation in most. To judge from imaging conducted afterward, this little boy's extensive surgery appears to have removed the entire tumor. Sean had a ten-hour surgery during which they removed a three-pound tumor from his shoulder. He was cut from the top of his ear down to his midchest area. I believe they could not find the point of origin of the tumor and cut to the top of his ear searching for it. I have been told by the MRI technicians that the surgeon must have been a magician to leave the area so incredibly clean. Two MRIs since surgery have showed the site remains tumor-free. Chemotherapy All children diagnosed with rhabdomyosarcoma receive chemotherapy, with the quantity and duration dependent on risk factors. Without chemotherapy, the majority of children with rhabdomyosarcoma would die of metastases which are usually present at diagnosis, even though they are too small to appear on scans. Giving several anticancer drugs in combination has markedly improved the survival rate for this disease. The most commonly used drugs include cyclophosphamide, vincristine, ifosfamide, etoposide, dactinomycin, and doxorubicin. These parents describe their children's responses to chemotherapy: Sean's treatment included 14 rounds of chemotherapy and 30 radiation treatments. He had every side effect imaginable. Aside from very low counts, he also had raised liver counts and had jaundice a few times. He has had pneumonia and klebsiella when neutropenic. His eyes were blood red from capillaries breaking. Amazingly, with all of the side effects he experienced, he had very little nausea during and after chemotherapy. I have seen him sit and eat greasy fried chicken and fries during chemo. •  •  •  •  •   Kenny started off on the VACIME protocol. After each round of chemo, his counts would bottom out and we would do G-CSF, a white blood cell booster, for up to ten days. Sometimes we would be home for one day and have to go back in for fever and neutropenia. Clinical trials are also evaluating melphalan, topotecan, and taxol for their efficacy against rhabdomyosarcoma. The use of higher doses of chemotherapy, followed by autologous bone marrow transplantation. Radiation Radiotherapy is an important tool used to treat children with rhabdomyosarcoma. The Intergroup Rhabdomyosarcoma Study Group has designed radiation therapy guidelines for treating this disease. Generally, children with stages I and II disease do not receive radiation therapy if their tumors are able to be completely resected. However, the need for radiation also depends on the histology of the tumor. Current protocols give patients with residual disease external beam radiation in fractions of 180 cGy a day, for up to six weeks. Total radiation may reach 4000 to 5500 cGy. Most often, radiation is given approximately nine weeks after chemotherapy has begun. However, children with tumors in the skull, meninges (lining of the brain), or spinal cord may start radiation therapy soon after diagnosis. A parent describes radiation therapy: Our son Joseph had roughly 5000 Gy delivered to his right orbit. His radiation was "hyperfractionated"--a method of giving smaller doses more often in the hopes that the patient can receive a larger total amount with fewer long-term side effects. In Joseph's case, this meant two treatments per day over six weeks. His treatments began three weeks before his fifth birthday. The radiotherapy staff handled him with patience, affection, and respect from the first day they met him, and gave us a lot of support as a family. They invited him in for a couple of trips to their treatment rooms to get used to the equipment and meet all the people before they did any of the preliminary measurements or scans. He got all the time he wanted to ride up and down on the tables and ask questions about the machines. Using me as a sample patient, they made a mold of the type of plastic mesh mask Joseph would need for his treatments so he could see what it would be like. Having my head screwed down to that table was NOT FUN! I'm glad I did it, though, because just as I tasted all his medicines, this gave me a chance to try a physical experience from his perspective, too. Other soft tissue sarcomas Childhood soft tissue sarcoma is a disease in which cancer arises in soft tissue somewhere in the body. Soft tissues include muscles, tendons, fat, blood vessels, nerves, and synovia (tissues around joints). Forty-seven percent of all childhood soft tissue sarcomas have a histology (how the cells look under a microscope) that is different from rhabdomyosarcoma. As a group, these soft tissue sarcomas comprise only 3 percent of all malignant tumors in children. They include the following: Synovial sarcoma. The most common non-rhabdomyosarcoma soft tissue sarcoma in childhood. Synovial sarcoma is found most often in older children and is very rarely diagnosed in those under ten years of age. The disease occurs most frequently in the lower extremities, most often in the area of the thigh or knee. The second most common sites are the upper extremities, followed by the head, neck, and trunk. Fibrosarcoma. This soft tissue sarcoma is the most frequently occurring non-rhabdomyosarcoma soft tissue sarcoma in children under one year of age. The two incidence peaks that occur with this disease are in infants and children under five years of age, and children between ages ten and fifteen. These tumors occur most often in the extremities and the majority of children diagnosed have localized disease. Infants diagnosed with this disease tend to respond to treatment better than do older children. Malignant peripheral nerve sheath tumor (also known as neurofibrosarcoma or malignant Schwannoma). An aggressive malignancy that accounts for approximately 5 to 10 percent of all non-rhabdomyosarcoma soft tissue sarcomas of childhood. The disease often occurs in association with neurofibromatosis. The most common site of origin is the extremities. Malignant fibrous histiocytoma. This form of soft tissue sarcoma most frequently occurs in the lower extremities and the trunk area. Other sites include the upper limbs, scalp, and kidney. There are other extremely rare forms of childhood soft tissue sarcomas. Young children with these diseases are generally treated on protocols based on those used for childhood rhabdomyosarcoma. Teens are usually treated on protocols similar to those used for adults with soft issue sarcomas. These rare soft tissue sarcomas include: Leiomyosarcoma. Leiomyosarcoma, which arises from smooth muscle, most often occurs in the gastrointestinal tract, especially the stomach. Liposarcoma. Liposarcoma arises in fatty tissue and is found most frequently in early adolescents. The most common sites of origin are the legs or trunk. Hemangiopericytoma. Hemangiopericytoma is a tumor of the blood and lymph vessels that occurs most frequently in infants. Alveolar soft part sarcoma. This is a rare sarcoma found most often in older children. The tumor arises from skeletal muscle of the extremities, head, and neck, and presents as an asymtomatic, slow-growing mass. Signs and symptoms Typically, soft tissue sarcomas are first noticed as a painless mass, with symptoms, if present, caused by the tumor pressing on surrounding structures. For example, a soft tissue sarcoma in the head can cause paralysis of nerves. Invasion of the disease into peripheral nerves can cause pain or weakness in the pelvis and extremities. Tumors that arise on the chest wall can cause difficulty in breathing and an abdominal mass can block the gastrointestinal or genitourinary tract. Treatment overview Treatment for non-rhabdomyosarcoma soft tissue sarcomas is usually surgery and sometimes radiation therapy. Chemotherapy is sometimes used to shrink large tumors to make them operable. Surgery is the cornerstone of treatment for soft tissue sarcomas. Ideally, the surgeon will attempt to completely remove the mass with wide margins (portions of the surrounding tissue) to ensure that no microscopic disease remains. This is often followed by radiation, given every day for five to six weeks. The total dose is usually 4000 to 5500 cGy. Although medical science has made advances in treating soft tissue sarcomas while reducing the side effects and long-term impact to the child, amputation is sometimes necessary. Limb-sparing procedures have made this less common. Since these malignancies are so rare in children, treatments for non-rhabdomyosarcoma soft tissue sarcomas are based on experience with the adult population. Generally, the size and location of the tumor, as well as tumor histology, are more significant than the actual type of sarcoma when determining prognosis. The most important prognostic factor with each is the ability to completely remove the primary tumor. The Intergroup Rhabdomyosarcoma Study Group studies 3 and 4 demonstrated that children with non-rhabdomyosarcoma soft tissue tumors do as well on IRSG studies as do children with rhabdomyosarcoma. Since the number of children with these tumors is small, these results need to be verified with additional multi-institutional studies. Newest treatment options New treatments for rhabdomyosarcoma and other soft tissue sarcomas are being developed using immunotherapy and other biologic modifiers. These include antitumor immune responses and methods to interrupt specific growth factor loops. Research into the basic biology of soft tissue sarcomas has made these advances possible. To learn of the newest treatments available, call (800) 4-CANCER and ask for the PDQ (physicians data query) for "sarcoma, rhabdomyosarcoma, childhood" or "sarcoma, soft tissue, childhood." These free statements explain the disease, state-of-the-art treatments, and ongoing clinical trials. There are two versions available: one for patients, which uses simple language and contains no statistics, and one for professionals, which is technical, thorough, and includes citations to scientific literature. The PDQ can also be read on the Internet at http://cancernet.nci.nih.gov/. This fact sheet was derived from Childhood Cancer: A Parent's Guide to Solid Tumor Cancers, by Honna Janes-Hodder and Nancy Keene, © 2001 by Patient-Centered Guides. Inc. For more information, call (800) 998-9938 or see www.patientcenters.com.