Alex's Lemonade Stand Foundation for Childhood Cancer

Sarcomas are cancers that form in the connective tissues of the body—the bone, cartilage, fat, muscle, and other supporting tissues.¹²⁶ There are more than 70 different types of sarcomas.¹²⁷ Osteosarcoma and Ewing sarcoma are two common types that arise from bone cells.¹²⁸ Soft tissue sarcomas, like rhabdomyosarcoma, form in the muscles and other connective tissue in the body. Bone sarcomas tend to spread to the lungs, and when they do, the chances of survival drop to 30% or lower.¹²⁹

Encouragingly, some investigations into the genetic causes of specific types of sarcomas have led to breakthroughs, identifying clear disease drivers that can be targeted using FDA-approved treatments.

Childhood Bone Sarcomas

*Bone sarcoma cases among children under 1 are extremely rare and the sample size is too small to produce a reliable survival estimate.

Childhood Soft Tissue Sarcomas

Breakthroughs and Research Milestones:

Amputation used to be more prevalent, but recent technologies have improved the ability of surgeons to preserve limb function. Such examples include expandable implants using a magnetic coil and even 3D printing techniques.¹³⁶

As with neuroblastoma and brain tumors, proton therapy is commonly used to treat pediatric sarcoma patients, with a goal of reducing toxicities associated with radiation.¹³⁷

Immune checkpoint inhibitors, such as atezolizumab, nivolumab, and pembrolizumab, are undergoing testing for various types of pediatric sarcomas, with atezolizumab approved by the FDA for children and adults with alveolar soft part sarcoma. An additional type of immunotherapy called CAR T-cell therapy is currently being explored as a potential treatment option in sarcomas. Cancer vaccines are also being tested in treating pediatric sarcomas, in combination with targeted therapies or other immunotherapy agents, such as immune checkpoint inhibitors.¹³⁸

• Surgical Breakthroughs (1970s-present)
  Amputation used to be more prevalent, but recent technologies have improved the ability of surgeons to preserve limb function. Such examples include expandable implants using a magnetic coil and even 3D printing techniques.¹³⁶
• Proton therapy (2010)
  As with neuroblastoma and brain tumors, proton therapy is commonly used to treat pediatric sarcoma patients, with a goal of reducing toxicities associated with radiation.¹³⁷
• Immunotherapy (2017-present)
  Immune checkpoint inhibitors, such as atezolizumab, nivolumab, and pembrolizumab, are undergoing testing for various types of pediatric sarcomas, with atezolizumab approved by the FDA for children and adults with alveolar soft part sarcoma. An additional type of immunotherapy called CAR T-cell therapy is currently being explored as a potential treatment option in sarcomas. Cancer vaccines are also being tested in treating pediatric sarcomas, in combination with targeted therapies or other immunotherapy agents, such as immune checkpoint inhibitors.¹³⁸
• Targeted therapy (2018-present)
  Targeted therapy agents that can help treat sarcomas:
  • Larotrectinib is effective against sarcomas with a type of alteration in the NTRK gene called a fusion. This includes infantile fibrosarcoma, for which larotrectinib is now a standard treatment, often making surgery and chemotherapy unnecessary. Relative to chemotherapy, this drug has very few side effects, even in small infants.
  • Tazemetostat works by blocking EZH2, an enzyme that regulates the machinery controlling patterns of gene expression within cells. Tazemetostat has been FDA-approved in patients 16 and older with epithelioid sarcoma, and studies are ongoing to assess this drug in younger patients.¹³⁹
  • Cabozantinib works by blocking processes that are essential for tumor cell growth and survival. Cabonzantinib is currently used in the treatment of osteosarcoma and Ewing sarcoma.¹⁴⁰ Anlotinib, regorafenib, and pazopanib, like cabozantinib, simultaneously target multiple pathways that promote tumor growth. Each of these drugs exerts anti-tumor activity in ways that are complex, diverse, and not yet well-understood. However, their proven clinical activity has fueled widespread use in patients with high-risk sarcomas.^141,142
  • Entrectinib and Repotrectinib are tyrosine kinase inhibitors that block fusion proteins containing ROS1 or NTRK domains—mutations that drive cancer. Numerous types of sarcomas have these fusion proteins and the FDA has approved these drugs for the treatment of NTRK fusion sarcomas.^143,144
  • Crizotinib is an ALK inhibitor that has been FDA-approved for the treatment of children with a rare sarcoma called an inflammatory myofibroblastic tumor.