Clinical Next-Generation Sequencing for Precision Oncology in Rare Cancers

Area of Science:

• Oncology
• Genomics
• Precision Medicine

Background:

• Rare cancers, defined as ≤5 cases per 100,000 people annually, often lack standard treatments.
• Targeted genomic alterations present a rational strategy to improve therapeutic options for rare tumors.

Purpose of the Study:

• To catalog genomic mutations in rare tumors.
• To assess the clinical utility of identified mutations for targeted therapy.

Main Methods:

• Retrospective analysis of rare tumor patients undergoing clinical tumor genomic profiling (sarcomas excluded).
• Review of genomic reports for cancer-associated gene and pathway mutations.
• Abstraction of clinical records to evaluate targeted therapy benefits.
• Actionable alterations defined as those targeted by available or investigational drugs.

Main Results:

• 95 patients with 40 rare tumor subtypes were analyzed; 92% had at least one genomic alteration.
• Common mutations included TP53 (23%), KRAS (10%), and PIK3CA (9%).
• 38% of patients had actionable alterations; 13 received targeted therapy with 4 partial responses and 6 stable disease outcomes.

Conclusions:

• Genomic profiling provides a potential therapeutic avenue for rare cancers lacking standard care.
• Targeted therapies, such as BRAF inhibitors for BRAF-altered tumors, can be effective.