Targeted therapy for soft tissue sarcomas in adolescents and young adults

Abstract

Soft tissue sarcomas (STSs) are a heterogeneous group of tumors originating from the mesenchyme. Even though they affect individuals in all age groups, the prevalence of subtypes of STSs changes significantly from childhood through adolescence into adulthood. The mainstay of therapy is surgery, with or without the addition of chemotherapy and/or radiation therapy. These treatment modalities are associated, in many cases, with significant morbidity and, given the heterogeneity of tumor histologies encompassed by the term “STS”, have not uniformly improved outcomes. Moreover, some subgroups of STSs appear to be more, and others less, responsive to conventional chemotherapy agents. Over the last two decades, our understanding of the biology of STSs is slowly increasing, allowing for the development of more targeted therapies. We review the new treatment modalities that have been tested on patients with STSs, with a special focus on adolescents and young adults, a group of patients that is often underrepresented in clinical trials and has not received the dedicated attention it deserves, given the significant differences in biology and treatment response in comparison to children and adults.

Optimal cancer drug dosing in adolescents: new issues and the old unaddressed ones

“…‘Precision medicine’ or molecular targeting of cancer cells aims at delivering drugs to specific cancer genes or proteins to increase effectiveness and decrease the toxicity of therapy. However, in the absence of clinical trials, it can be unclear if response to therapy is the same in AYA as in adults and may be worse . Furthermore, the relationship of dose to activity at the cancer cell is unknown in AYA, as are the off‐target effects.…”

“…Mental health issues are on the rise for young people, both in Australia and around the world. 12,13 The Mission Australia Youth Health report demonstrated a rise in the number of [15][16][17][18][19] year olds who met the criteria for a serious mental illness from 18.7% in 2012 to 22.8% in 2016. 12 The second Australian Child and Adolescent Survey of Mental Health and Wellbeing survey demonstrated that 14% of children and adolescents had mental health problems, and 16.7% of those young people with a mental health issue were taking medication.…”

“…However, in the absence of clinical trials, it can be unclear if response to therapy is the same in AYA as in adults and may be worse. 17 Furthermore, the relationship of dose to activity at the cancer cell is unknown in AYA, as are the off-target effects. These effects may be particularly problematic for late toxicity, including effects on endocrine, immune and bone organs.…”

OncoKids

“…Because treatment protocols are increasingly focused on precise diagnosis for soft tissue tumors/sarcomas, broad molecular profiling of pediatric malignancies will become ever more critical as a diagnostic tool. 15 In addition to improved diagnosis, routine application of the OncoKids panel can improve therapy by identifying targetable mutations in the front-line setting. Of note, imatinib has been incorporated into current treatment algorithms for Philadelphia (Ph) chromosomeepositive acute lymphoblastic leukemia (ALL).…”

Canine Soft Tissue Sarcomas: Can Being a Dog’s Best Friend Help a Child?

“…They arise from the tissues that emerge from the embryonic mesoderm and therefore are all mesenchymal. The WHO defines STSs as soft tissue tumors with malignant potential, that is, a propensity for locally destructive growth, risk of recurrence, and risk of distant metastasis ( 1 , 2 ).…”