Soft Tissue Sarcoma Synopsis

In 2024, approximately 13,590 cases of soft tissue sarcoma will be reported. Because sarcomas are difficult to distinguish from other cancers when they are found within organs, their incidence is probably underestimated, according to the National Cancer Institute.

Soft tissue sarcoma is a rare but common type of cancer that develops in the body's soft tissues, such as muscles, fat and blood vessels. Sarcoma tumors can grow slowly over months or years and are often painless, but they can also cause pain or trouble breathing as they get bigger. They can be superficial or in tissue and can form almost anywhere in the body, but are most common in the arms, legs, abdomen and retroperitoneum. Soft tissue sarcomas form in cartilage, fat, muscle, blood vessels, tendons, nerves and around joints. Osteosarcomas develop in bone, liposarcomas form in fat, rhabdomyosarcomas form in muscle and Ewing sarcomas form in bone and soft tissue.

Sarcomas are especially prevalent in children—pediatric cases add up to 15% in childhood. Risk factors for soft tissue sarcomas include past treatment with radiation therapy for certain cancers; exposures to chemicals, such as thorium dioxide, vinyl chloride, or arsenic. Patients with long-term lymphedema in the arms or legs are at risk for development of sarcoma.

Sarcomas that begin in the abdomen may not cause signs or symptoms until they get very big. A sarcoma may appear as a painless lump under the skin, often on an arm or a leg. As the sarcoma grows and presses on nearby organs, nerves, muscles or blood vessels, signs and symptoms may include pain or trouble breathing1.

Almost 55% of sarcoma patients survive their cancer for five years or more after diagnosis. 45 out of 100 people (45%) survive their cancer for 10 years or more after diagnosis2. The statistics are based on standard of care oncology treatment plans.

A major focus in functional medicine and for oncology patients is on the G.I. microbiome. In January 2023, the Journal of Immunotherapy published research linking the tumor’s microbiome with the immune system and the immune response in sarcoma. Natural killer (NK) infiltration was associated with superior metastasis-free and overall survival. A higher rate of NK cell infiltration in a tumor can increase the chances that the sarcoma won't spread to other parts of the body3. NK cells are a group of cytotoxic lymphocytes that are essential for host immunity against cancer. The G.I. microbiome can impact NK cells in several ways, including:

  • Gut microbiota composition: The composition of gut microbiota can affect resistance to immunotherapy. For example, higher diversity in the G.I. microbiome is associated with more NK cells in the peripheral blood and better responses to immunotherapy4.
  • Early-life antibiotic treatment: Antibiotic treatment in early life can alter the gut microbiota, which can impair the maturation of NK cells5
  • A high abundance of the bacteria Fusobacterium nucleatum (F. nucleatum) in the gastrointestinal tract could cause reduced NK cell activity6
  • Short-chain fatty acids in the GI microbiome can boost antitumor NK cell activity7

For patients undergoing cancer treatment, the gut microbiota has been shown to modulate anticancer drug efficacy. Altered gut microbiota is associated with resistance to chemotherapy drugs or immune checkpoint inhibitors (ICIs), whereas supplementation of distinct bacterial species restores responses to the anticancer drugs. Studies have shown that altered commensal bacteria in the G.I. microbiome leads to cancer susceptibility and progression in diverse pathways. The microbiome disturbance in the G.I. tract is known as dysbiosis. Dysbiosis is associated with a variety of pathological conditions, such as neurological and behavioral disorders, diabetes, obesity, rheumatic and inflammatory diseases, metabolic syndrome, liver cirrhosis and various cancers8. Regarding the development of cancer, it is believed that dysbiosis should be considered for promoting and/or sustaining various cancer types9. Well-balanced gut microbiota plays a crucial role in a healthy life, while dysbiosis can have inflammatory consequences that aggravate the development of cancer. The gut microbiome can affect the treatment of soft tissue sarcomas by influencing the immune system. The gut microbiome's composition can limit or promote the effectiveness of cancer immunotherapy, which can impact tumor clearance, survival, and treatment response10.

In functional oncology, we use stool testing to identify the root cause of symptoms and disease and define the health of the microbiome. All patients are offered a research-based stool analysis to identify dysbiosis, inflammation, immune dysfunction, and diversity of microbes. Cancer prevention and ceasing progression is a priority for all cancer patients, we know the role of probiotics can be essential in creating a healthy microbiome for all. All probiotics are not the same. Specific probiotics that have been found to be beneficial in cancer patients are Lactobacillus acidophilus, Streptococcus, Bifidobacterium, Propionibacterium and Enterococcus, as well as beneficial yeasts such as Saccharomyces boulardii. But every cancer is different and not all probiotics work the same. Through stool studies, patients can have a well-defined microbiome to guide prescriptions for specific probiotics needed to optimize the microbiome and the prescriber needs to have knowledge of their type of cancer and use the research defining the impact of bacteria in microbiota in the G.I tract. In many cancers, probiotics have been shown to decrease cancer cell proliferation, decrease inflammation, induce cancer cell death and produce important anticancer substances such as short chain fatty acids .

Contact Hyperion Functional Medicine to learn more about soft tissue sarcoma.

 

1 https://www.cancer.gov/types/soft-tissue-sarcoma/patient/adult-soft-tissue-treatment-pdq

2 https://www.cancerresearchuk.org/about-cancer/soft-tissue-sarcoma/survival#

3 Perry LM, Cruz SM, Kleber KT, Judge SJ, Darrow MA, Jones LB, Basmaci UN, Joshi N, Settles ML, Durbin-Johnson BP, Gingrich AA, Monjazeb AM, Carr-Ascher J, Thorpe SW, Murphy WJ, Eisen JA, Canter RJ. Human soft tissue sarcomas harbor an intratumoral viral microbiome which is linked with natural killer cell infiltrate and prognosis. J Immunother Cancer. 2023 Jan;11(1):e004285. doi: 10.1136/jitc-2021-004285. PMID: 36599469; PMCID: PMC9815021.

4 Kang X, Lau HC, Yu J. Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy. Cell Rep Med. 2024 Apr 16;5(4):101478. doi: 10.1016/j.xcrm.2024.101478. PMID: 38631285; PMCID: PMC11031381.

5 Borbet TC, Pawline MB, Li J, Ho ML, Yin YS, Zhang X, Novikova E, Jackson K, Mullins BJ, Ruiz VE, Hines MJ, Zhang XS, Müller A, Koralov SB, Blaser MJ. Disruption of the early-life microbiota alters Peyer's patch development and germinal center formation in gastrointestinal-associated lymphoid tissue. iScience. 2023 May 4;26(6):106810. doi: 10.1016/j.isci.2023.106810. PMID: 37235047; PMCID: PMC10206152.

6 Kim YJ, Kim BK, Park SJ, Kim JH. Impact of Fusobacterium nucleatum in the gastrointestinal tract on natural killer cells. World J Gastroenterol. 2021 Aug 7;27(29):4879-4889. doi: 10.3748/wjg.v27.i29.4879. PMID: 34447232; PMCID: PMC8371507.

7 Pérez M, Buey B, Corral P, Giraldos D, Latorre E. Microbiota-Derived Short-Chain Fatty Acids Boost Antitumoral Natural Killer Cell Activity. J Clin Med. 2024 Jul 2;13(13):3885. doi: 10.3390/jcm13133885. PMID: 38999461; PMCID: PMC11242436.

8 Liu Y, Baba Y, Ishimoto T, Gu X, Zhang J, Nomoto D, Okadome K, Baba H, Qiu P. Gut microbiome in gastrointestinal cancer: a friend or foe? Int J Biol Sci. 2022 Jun 21;18(10):4101-4117. doi: 10.7150/ijbs.69331. PMID: 35844804; PMCID: PMC9274484.

9 Scott AJ, Alexander JL, Merrifield CA. et al. International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis. Gut. 2019;68:1624–32.

10 Khan MAW, Ologun G, Arora R, McQuade JL, Wargo JA. Gut Microbiome Modulates Response to Cancer Immunotherapy. Dig Dis Sci. 2020 Mar;65(3):885-896. doi: 10.1007/s10620-020-06111-x. PMID: 32067144; PMCID: PMC7678709.
Sankarapandian V, Venmathi Maran BA, Rajendran RL, Jogalekar MP, Gurunagarajan S, Krishnamoorthy R, Gangadaran P, Ahn BC. An Update on the Effectiveness of Probiotics in the Prevention and Treatment of Cancer. Life (Basel). 2022 Jan 2;12(1):59. doi: 10.3390/life12010059. PMID: 35054452; PMCID: PMC8779143.