A 62-year-old grandfather develops a cancerous mass on his ankle; it spreads to his lungs.
A football-sized abdominal tumor afflicts a 40-something ultramarathoner, threatening a kidney and leg.
A 9-year-old boy needs surgery to remove a tumor in his pelvic bone.
Different people, different ages, different symptoms, different tumor locations. What they have in common is a rare category of cancer known as sarcoma. It’s not nearly as well-known as the so-called “carcinomas” like lung cancer or breast cancer. But it can be just as dangerous. Here are some things you need to know.
What is sarcoma and how is it different from other cancers?
Sarcoma develops in the body’s connective tissues: bones, fat, muscles, nerves, cartilage and blood vessels. Other types of cancer typically appear in so-called epithelial cells (on an organ’s outer layers): the lung, kidney, stomach, colon, etc.
It can be challenging to diagnose sarcoma because it can resemble other tumors, including noncancerous lipomas, or fatty growths. A pathologist with sarcoma expertise will recognize the molecular differences in sarcoma tissue samples.
“Sarcoma has a different molecular profile and will ‘immuno-stain’ differently than other cancers,” explained pediatric hematologist-oncologist Janet Yoon, M.D., clinical professor and medical director of the Pediatric Musculoskeletal Tumor Program at City of Hope's® Children’s Cancer Center. Immunostaining identifies proteins found in specific cancers.
How many types of sarcoma are there?
Sarcoma is a very diverse category of cancer with at least 70, and possibly as many as 100, subtypes. Among the better known is osteosarcoma, cancer of the bone. Soft tissue sarcomas can show up in many places, like fat (liposarcoma) smooth muscle (leiomyosarcoma), nerve cells (neurosarcoma) and under the skin (Kaposi’s sarcoma, which was a common byproduct of AIDS).
How rare is sarcoma?
Sarcoma makes up less than 1% of all adult cancer diagnoses. It’s a different story with children. Sarcoma, especially when it appears in the bones or joints, comprises 20% of childhood cancers.
What are the symptoms of sarcoma?
It depends on where it is. A malignancy in the abdomen, for example, can grow for years without the patient knowing about it. These tumors eventually announce themselves at a late stage, when the patient feels bloated, or when the tumor presses against organs, like the bladder or kidneys, interfering with normal function.
A bone sarcoma can appear as a hard, painless mass. If it does cause pain, it’s likely because the tumor is touching some nerves. If located at the knee or ankle, it can also limit normal movement.
Although sarcoma can show up on an ultrasound or X-ray, it is often confused with other cancers and even benign tumors. “Sarcomas are best seen on CT or MRI,” Dr. Yoon said.
Who gets sarcoma and why?
We don’t know why one person may develop sarcoma while another does not. “There are no real risk factors,” said surgical oncologist William Tseng, M.D., “like smoking, obesity or alcohol, which do increase the risk of other cancers.” Dr. Tseng, associate clinical professor in the Division of Surgical Oncology, Department of Surgery, specializes in rare soft tissue sarcomas called retroperitoneal liposarcomas, which are found in the abdominal cavity and can grow to 50 pounds or more.
Nevertheless, there are some clues. People with the rare inherited condition known as Li-Fraumeni syndrome appear to be at greater risk. This genetic mutation damages a tumor suppressor protein, allowing sarcoma to develop. In addition, as many as 50% of patients with neurofibromatosis — another genetic disorder — may develop sarcoma. Exposure to radiation, especially high doses for treating other cancers, may also play a role.
Does sarcoma spread, and is it as dangerous as other cancers?
“Any sarcoma is life-threatening if not treated,” said orthopedic oncology surgeon John A. deVries, M.D. , M.S., assistant clinical professor and chief of the Division of Orthopaedic Surgery, Department of Surgery. “Some can take years. Others are more aggressive.” Many sarcomas are capable of spreading to other parts of the body. Cancerous cells can travel through the bloodstream and settle in the lungs, brain and other organs.
“Generally speaking, I would consider sarcomas as a group to be aggressive, but there is a wide range in terms of prognosis that includes some sarcoma types that are almost benign,” added Dr. Tseng. “Some almost always recur, even after repeated surgery.”
“There are many variables involved,” said Dr. Yoon. “It depends on the sarcoma subtype and whether it is localized or metastatic at diagnosis.” This makes prognosis and treatment highly individualized.
How is sarcoma treated?
The No. 1 treatment for sarcoma, in almost all cases, is surgery. Removing the tumor with enough (but not too much) healthy tissue around it to create clear margins is the best path to a cure, if possible. In children with bone cancer, the results can be profound. “We can see survival rates of 70 years or more, something you never see in, say, breast cancer,” Dr. deVries said.
In some cases, surgery is all that’s needed, because that particular type of sarcoma does not tend to invade other organs. But some sarcomas may “micro-metastasize,” sending invisible numbers of cancerous cells elsewhere, even when it looks like the entire tumor has been removed. That’s when drug therapy and radiation become important to eradicate any remaining cancer cells.
How well does sarcoma respond to chemotherapy, targeted therapy or immunotherapy?
With so many different varieties of sarcoma out there, as yet there’s no “magic bullet” drug or combination of drugs capable of arresting and eliminating sarcoma across the board.
According to the American Cancer Society, some of the most commonly used chemotherapies for sarcoma, given before and/or after surgery, are ifosfamide (Ifex) and doxorubicin (Adriamycin). Several other drugs are also used, either individually or in combination.
Deciding which drug should be employed depends on the data, especially in the case of targeted therapies that seek out and derail a tumor’s molecular drivers. Some sarcomas may be susceptible to so-called tyrosine kinase inhibitors or gamma secretase inhibitors — each designed to block a particular cellular function. Some targeted drugs may work only on very rare, specific forms of sarcoma. Others have been found to be effective in all soft tissue sarcomas except one. This is both the frustration and the promise of such novel treatments. Researchers keep finding new targets in sarcoma cells, but matching them up with the appropriate drug is not easy.
The news is less promising for most immunotherapy drugs, which train the body’s immune system to fight the cancer. Part of the problem here is the tumor’s microenvironment.
“The tumor microenvironment for sarcoma is adversarial,” explained Dr. Yoon. “It gets in the way, preventing treatment through immunotherapy.”
Have there been any breakthroughs in sarcoma treatment?
Researchers are looking for ways around that microenvironment obstacle. Many clinical trials are underway at City of Hope, and Dr. Yoon is excited about one involving “adoptive” T cell therapy. A virus is added to patients’ immune cells, depositing a specific protein on them. That surface protein directs the T cells to the cancer cells, which are then destroyed. “We may even have a commercial product available by the end of 2024,” she said.
Surgical techniques continue to improve, with a big assist from 3D printing technology. For excising bone tumors, surgeons can create a 3D model of the tumor and surrounding bone to aid in visualizing and planning the removal procedure. A customized 3D “jig” can be created, which surgeons can then follow during the actual cutting. 3D technology also makes it possible to fabricate custom implants to replace what’s been removed.
In addition, to better “see” the tumor site, surgeons are injecting a fluorescent dye that “lights up” areas of poor blood flow, indicating tumor tissue that needs to be removed.
There is much more on the horizon, giving encouragement to sarcoma specialists.
“We’re getting closer and closer to more personalized, genetic-based treatments,” said Dr. deVries. “We’ll be able to dial in treatments that are more precise and less invasive.”
One tool that will be part of that mix is the so-called “liquid biopsy,” which measures circulating tumor DNA in the bloodstream. “Right now, we rely on imaging [to detect cancer], which is not perfect,” said Dr. Yoon. “The DNA method will do a better job, especially when it comes to catching relapses.”
And as we learn more about sarcoma, it will be possible to fine-tune and personalize combination treatments for each patient. “The best advance in this field is our improving understanding of the disease,” said Dr. Tseng.
All agree that it is imperative to seek out sarcoma specialists for diagnosis and treatment.
“This is a rare disease best handled by a specialized center,” said Dr. Yoon. “You need an experienced, knowledgeable team. And we at City of Hope have such a team, along with researchers pushing the boundaries.”
And in case you were wondering, those three sarcoma patients — the grandfather, the ultramarathoner and the 9-year-old — were all successfully treated at City of Hope.