By Swetha Babu
Raising awareness about sarcoma is crucial due to its rarity and the challenges associated with its diagnosis and treatment, so we at Pharmora have decided to put together a blog detailing what Sarcoma is, and what the landscape of treatment looks like. Pharmora would like to bring awareness to the various breakthroughs and advances in understanding and treating Sarcoma Cancer, and celebrate these incredible breakthroughs which were made possible by research.
The Bone Cancer Research Trust and Sarcoma UK have teamed up to support the National Sarcoma Awareness Project (NSAP) – an initiative to educate medical students and post-graduate doctors about sarcoma. This is vital, considering a key issue for correct and accurate diagnosis of sarcoma cancer is that many sarcoma symptoms resemble those of benign conditions, causing patients to often endure months of treatment for other ailments before receiving the appropriate tests and treatments. NSAP includes an e-learning course, free resources and educational webinars for healthcare professionals, and awareness packs.
Various organizations and communities often participate in activities, events, and campaigns to increase visibility and support for those affected by sarcoma with the goal of educating the public, improving early detection, and supporting research efforts to find better treatments and ultimately a cure for these rare cancers.
What is Sarcoma?
Sarcoma is a type of cancer that originates in the bones and soft tissues of the body, including fat, muscle, blood vessels, deep skin tissues, and nerves. It is clearly malignant, more than just a “flesh tumor.” In fact, compared to the more common cancers, sarcoma can be just as aggressive, if not more so, and can affect any part of the body thus making it harder to diagnose and treat. Therapies that have gained traction for the treatment of other cancer types encounter challenges in sarcoma due to:
- a lack of well-established antigens in subtypes that can be targeted by vaccines, therapeutic antibodies or chimeric antigen receptors (CAR) therapy
- presence of extensive tumor heterogeneity
- a lack of characterization of the tumor microenvironment (TME) in unique subtypes.
There are two main categories of sarcoma: bone sarcomas and soft tissue sarcomas.
Soft tissue sarcomas are more common than bone sarcomas, accounting for about 1% for all cancers in the UK. In the UK, approximately 3,300 new cases of soft tissue sarcomas and 580 cases of bone sarcomas are diagnosed annually.
Soft tissue sarcomas may present as painless lumps, whereas bone sarcomas often cause bone pain and swelling.
Sarcomas are relatively rare compared to other cancers, but they can occur at any age, affecting both children and adults. Treatment plans are often personalized and may involve a combination of therapies to effectively target the tumour, which may include radiotherapy, chemotherapy, immunotherapy, targeted therapy or surgery.
What are some of the symptoms, causes and risk factors?
Symptoms include a noticeable lump or swelling, pain (which may be worse at night), weight loss, and fatigue. In some cases, there may be no symptoms until the tumour is large.
Although the exact cause is unknown, certain genetic mutations and inherited conditions, such as Li-Fraumeni syndrome or neurofibromatosis, can increase risk. Other factors include exposure to certain chemicals and radiation as well as lymphedema (swelling caused by lymph fluid).
Clinical trials and ongoing research
Joint effort has been made on researching various therapies for sarcoma, mostly focusing on targeted therapies or immunotherapies. Below is a list of the most recent clinical trials:
– A Phase Ib/II single arm study to determine the dose level and to evaluate the efficacy of sunitinib (targeted drug) combined with nivolumab for sarcoma, measured by progression-free survival rate (PFSR). Participants aged between 12-80, with recurrent soft tissue sarcoma or bone sarcoma were recruited. Based on the interim analysis, results showed that the PFSR at 6 months were 48%, with a median overall survival of 24 months. (Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial – PMC)
– Comparing the effectiveness of trabectedin versus dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma. This multicentre study, to our knowledge, is the first Phase III trial to compare these agents in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen. A total of 518 patients were enrolled and randomly assigned to either one of the arms. Results showed a significant reduction in risk of disease progression (p<0.001) for treatment with trabectedin, with a median PFS of 4.2 months versus 1.5 months for dacarbazine. The median Overall Survival (OS) showed a trend in favour of trabectedin, although results were not statistically significant (p=0.37).
– A randomised Phase II trial evaluating the safety and efficacy of neoadjuvant radiotherapy (RT) and surgery with or without an immunotherapy drug for soft tissue sarcoma. This trial was based on the hypothesis that neoadjuvant immunotherapy with concurrent RT followed by surgery and adjuvant immunotherapy for stage III undifferentiated pleomorphic sarcoma (UPS), including myxofibrosarcoma, or LPS would stimulate an anti-tumour immune response to eliminate micrometastatic disease & improve disease-free survival (DFS). Participants were aged 12 or above. Results showed that there was a significant improvement in DFS for this group of patients.
– A Phase II single arm open-label ongoing clinical trial of ADP-A2M4 SPEAR™ T Cells in Subjects with Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma. Participants were aged between 16 and 75 were selected for the study. This study is measuring overall response rate ORR) as a primary outcome, evaluating safety and efficacy.
– CAR T-Cell Therapy: Investigating the use of genetically modified T-cells to treat sarcomas. Early studies have shown encouraging results for some sarcoma subtypes.
Research is ongoing to identify and develop drugs targeting other specific molecules and pathways involved in sarcoma growth and progression, utilising advanced imaging and liquid biopsies.
One such area of research is Genetic and Molecular Research, which shows interesting and exciting potential in identifying genetic mutations and alterations in sarcoma tumours, through advances in genomic sequencing, which allows for more precise identification of such mutations. This helps tailor treatments to individual patients’ tumour profiles. Another is the gene-editing CRISPR Technology, which is being explored to understand better and potentially correct genetic mutations driving sarcoma.
Advances in supportive care are helping to improve the quality of life for sarcoma patients, addressing pain, mobility, and emotional well-being. These advances, while promising, are often still in the experimental stage and may not yet be widely available. However, they represent significant steps forward in the fight against sarcoma and hold the potential to improve patient outcomes in the near future.