A Rare Cancer 'Sarcoma' & the Need for a Multimodal Treatment Approach

A cancer that can develop anywhere in the body is sarcoma. Sarcomas disease is an uncommon type of cancer that appears in soft tissues and bones. About 12,000 soft tissue sarcomas and 3,000 bone sarcomas are diagnosed in the United States annually, according to the National Cancer Institute (NCI). In the UK, 15 new cases of sarcoma are diagnosed every day. That's almost 5,300 individuals annually. Soft tissue sarcoma (STS) and bone sarcoma (BS), also referred to as primary bone malignancy, are two of the over 100 molecular subtypes of sarcoma that have been identified due to its diverse character. [1]

Common types of Sarcoma

The most common varieties of STS are liposarcoma, leiomyosarcoma, and undifferentiated pleomorphic sarcoma (UPS), while the most common types of BS are osteosarcoma, chondrosarcoma (CS), and Ewing sarcoma (ES). There are over 70 histologic subtypes known to exist. Any age can be affected by sarcoma. Although it is more prevalent in middle-aged or older adults, it is the third most frequent cancer in youngsters. BS is most commonly reported in children and STS being more common in adults. Sarcoma accounts for about 1% of all cancer diagnoses in the United States. [2]

Signs of Sarcoma

A developing or shifting lump is the most typical sign of sarcoma. Additional symptoms may include stomach pain, nausea, loss of appetite or feeling full after a small quantity of food, blood in your stool or vomit, and bone swelling, soreness, or pain that may be worse at night. The cause of sarcomas is not supported by any evidence. [3]

Risk factor associated with Sarcoma

To completely comprehend how sarcoma develops, more research is required. Although sarcoma can strike at any age, there are a few factors that can raise the risk as we age. As with other cancers, sarcoma risk rises with age. Certain uncommon genetic abnormalities may raise your risk of developing sarcoma. Examples include Li-Fraumeni syndrome and neurofibromatosis. Rarely, years after receiving radiation treatment for another kind of cancer, some patients may develop STS. Chemical exposure has been linked to higher incidences of STS. These chemicals include vinyl chloride, dioxins, and phenoxyacetic herbicides. Bone disorder as Paget's disease is one illness that can raise the chance of BS. [4]

Current treatment to Sarcoma

Patients with resectable sarcoma are initially treated with surgery, but advanced sarcoma (unresectable) necessitates other treatments. For unresectable or metastatic STS, conventional chemotherapy (CT) is currently the accepted standard of care. While other cytotoxic medications are typically employed in subsequent lines (gemcitabine plus docetaxel, trabectedin, eribulin, or dacarbazine), anthracycline-based regimens, typically adriamycin plus ifosfamide, continue to be the initial treatment. Anaplastic lymphoma kinase (ALK) inhibitors for myofibroblastic tumors with ALK fusions, cediranib for alveolar soft part sarcoma (ASPS), and multi-TKI pazopanib for non-adipocytic STS are among the oral tyrosine–kinase inhibitors (TKI) that have also shown activity for STS. It is advised to treat BS using a multimodal approach that includes CT, radiation therapy (RT), and radical surgery. Preoperative CT combined with a MAP regimen (doxorubicin, cisplatin, and high-dose methotrexate) is typically the first line of treatment for young patients with high-grade osteosarcoma. Conventional CT with ifosfamide or cyclophosphamide plus carboplatin or etoposide is frequently used in progressing disease. There is less evidence to support the use of alternative medications like gemcitabine and docetaxel. Perioperative CT is recommended in ES, typically in conjunction with an interval VDC/IE regimen (etoposide, vincristine, doxorubicin, cyclophosphamide, and ifosfamide). The best choices for additional lines are topotecan with cyclophosphamide and high-dose ifosfamide, followed by irinotecan plus temozolomide and docetaxel plus gemcitabine. A number of multi-TKI, namely regorafenib, cabozantinib, and apatinib for osteosarcoma, have also demonstrated effectiveness in advanced BS. [5]

Challenges with current Sarcoma treatments

The effectiveness of existing therapies, including as radiation therapy, chemotherapy, and surgery, is limited, particularly for advanced or recurrent disease. Sarcomas frequently resemble benign disorders, which causes advanced disease and delayed diagnosis. Although early discovery is essential for effective treatment, misdiagnosis and treatment delays may result from the absence of particular symptoms and their resemblance to non-cancerous illnesses. It is challenging to identify individuals who would benefit from particular (personalized) medications when biomarkers and genomic profiling are not available in the healthcare space. Patients' quality of life (QoL) may be negatively impacted by significant side effects from conventional treatments. Although they can be beneficial in certain situations, chemotherapy and radiation therapy can have serious adverse effects such exhaustion, nausea, hair loss, and an elevated risk of infection. A patient's quality of life and capacity to manage the illness may be greatly impacted by these adverse effects. Despite these obstacles, there is optimism for better outcomes for sarcoma patients due to continued research and developments in immunotherapies and targeted medicines. In order to overcome the drawbacks of existing medicines and enhance the quality of life for sarcoma patients, researchers are striving to create more potent and focused treatments. Minimally intrusive clinical trials for cryoablation, a relatively novel treatment for sarcoma, are still ongoing. But first findings are encouraging, and it might be a good choice for some sarcoma patients. [6]

Immunotherapies in Sarcoma treatment

A promising new field of study for the therapy of sarcoma is immune treatments. They function by assisting the immune system in identifying and combating cancerous cells. Checkpoint inhibitors are one of numerous immune therapy types being investigated in sarcoma clinical studies.

Inhibitors of immune checkpoints function by preventing checkpoint proteins from attaching to their partner proteins. By doing this, the "off" signal is not sent, enabling the T cells to destroy cancer cells. One such medication targets the CTLA-4 checkpoint protein. The checkpoint protein PD-1 or its companion protein PD-L1 is the target of several immune checkpoint inhibitors. Some cancers produce large amounts of PD-L1, which suppresses the T cell response. These medications stop the proteins that cancer cells use to avoid detection by the immune system. Some sarcoma forms, including dedifferentiated liposarcoma and alveolar soft part sarcoma (ASPS), have responded well to checkpoint inhibitor treatment. There is just one FDA-approved checkpoint inhibitor designed especially to treat sarcoma with Roche's Tecentriq, or atezolizumab. This medication is authorized to treat ASPS. Other checkpoint inhibitors have not yet been fully approved for these uses, despite promising clinical trials for a variety of sarcoma subtypes. The potential of immune checkpoint inhibitors in conjunction with other treatments to enhance the prognosis of sarcoma patients is still being investigated. Although the FDA has approved Merck's Keytruda (pembrolizumab) as a checkpoint inhibitor, it is not expressly authorized to treat all forms of sarcoma. Its usage in other sarcoma forms is frequently regarded as off-label, despite the fact that clinical trials have demonstrated promise for specific sarcoma subtypes, such as alveolar soft part sarcoma. An alternative is adoptive cell therapy, which entails taking immune cells out of a patient's body, altering them so they can more effectively identify and combat cancer cells, and then reintroducing them into the patient. Clinical trials are being conducted to investigate adoptive cell treatment for various kinds of sarcoma. The FDA has approved one adoptive cell therapy to treat sarcoma of Adaptimmue's Autoleucel Afamitresgene (Tecelra) use in adults with metastatic synovial sarcoma who express the MAGE-A4 antigen and have previously received chemotherapy can be treated with this T-cell receptor (TCR) therapy. This approval demonstrates the potential of adoptive cell therapy to target certain disease antigens and represents a major advancement in the treatment of sarcoma. Vaccines against cancer are also being developed to encourage the immune system to combat cancerous cells. The development of cancer vaccines for sarcoma is still in its early phases. Although they have showed potential in treating sarcoma, immune treatments are not yet a cure. They are a valuable new weapon in the fight against this illness, nevertheless. Although there are currently no FDA-approved cancer vaccines for sarcoma, research in this field is ongoing and shows promise. [7] [8]

In conclusion, despite ongoing difficulties, there remains hope for the treatment of sarcoma. To create more potent treatments and enhance the quality of life for sarcoma patients, additional research, clinical trials, and cooperation between scientists and medical professionals are essential.

References:

1. John Hopkins Medicine, Sarcoma. Accessed on: 01 Dec, 2024

URL: https://www.hopkinsmedicine.org/health/conditions-and-diseases/sarcoma

2. Burningham Z, Hashibe M, Spector L, Schiffman JD. The epidemiology of sarcoma. Clin Sarcoma Res. 2012 Oct 4;2(1):14. 

3. Mayo clinic, Sarcoma. Published on : December 28, 2022; Accessed on: December 01, 2024

URL: https://www.mayoclinic.org/diseases-conditions/sarcoma/symptoms-causes/syc-20351048

4. Cancer research UK, Risks and causes of soft tissue sarcomas. Reviewed on: April 23, 2024; Accessed on: December 01, 2024

URL: https://www.cancerresearchuk.org/about-cancer/soft-tissue-sarcoma/risks-causes

5. Demetri GD, Baker LH, Beech D, Benjamin R, Casper ES, Conrad EU 3rd, DeLaney TF, Ettinger DS, Heslin MJ, Hutchinson RJ, Kiel K, Kraybill WG, Letson GD, Neff J, O'Donnell RJ, Paz IB, Pollock RE, Randall RL, Schupak KD, Tyler DS, von Mehren M, Wayne J; National Comprehensive Cancer Network. Soft tissue sarcoma clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2005 Mar;3(2):158-94.

6. Salerno KE. Radiation Therapy for Soft Tissue Sarcoma: Indications, Timing, Benefits, and Consequences. Surg Clin North Am. 2022 Aug;102(4):567-582. doi: 10.1016/j.suc.2022.04.001. Epub 2022 Jun 24. PMID: 35952688; PMCID: PMC9372474.

7. Klemen ND, Kelly CM, Bartlett EK. The emerging role of immunotherapy for the treatment of sarcoma. J Surg Oncol. 2021 Mar;123(3):730-738.

8. Hoang NT, Acevedo LA, Mann MJ, Tolani B. A review of soft-tissue sarcomas: translation of biological advances into treatment measures. Cancer Manag Res. 2018 May 10;10:1089-1114.

About the author 

Shruti Talashi

boasts a dual mastery of lab research and writing. Her doctoral study outcome as M.Phil in biomedical science while studying breast cancer and an extraordinary masters degrees dissertation work on exploring role of Gal-lectin in cancer metastasis fuels her extensive research interests. She has gained few publication in journals. Bridging the science-public gap is her passion, aided by expertise in diverse techniques. From oncology to antibiotic/drugs production, she's led and managed complex projects, even clinical trials. Now, as a freelance Content Coordinator for Sinoexpo Pharmasource.com, her industry knowledge shines through valuable insights on cutting-edge topics like GMP, QbD, and biofoundry.