ABSTRACT: BACKGROUND:Patients with rare tumors may lack approved treatments and clinical trial access. Although each rare tumor is uncommon, cumulatively they account for approximately 25% of cancers. We recently initiated a Rare Tumor Clinic that emphasized a precision medicine strategy. MATERIALS AND METHODS:We investigated the first 40 patients presenting at the Rare Tumor Clinic. Next-generation sequencing (NGS) of tissue and plasma-derived, circulating-tumor DNA (ctDNA), and protein markers were assessed. RESULTS:Median age was 58 years (range, 31-78 years); 70% (28/40) were women; median number of previous systemic therapies was 2 (range 0-7). The most common diagnoses were sarcoma (n?=?7) for solid tumors and Erdheim-Chester disease (n?=?5) for hematologic malignancies. Twenty distinct diagnoses were seen. Examples of ultrarare tumors included ameloblastoma, yolk sac liver tumor, ampullary cancer, and Castleman's disease. Altogether, 32 of 33 patients (97%) with tissue NGS and 15 of 33 (45%) with ctDNA sequencing harbored ?1 alteration. Overall, 92.5% of patients (37/40) had ?1 actionable target based on either genomic (n?=?32) or protein (n?=?27) markers. In total, 52.5% (21/40) received matched therapy; 52.4% (11/21) achieved stable disease (SD) ?6 months (n?=?3), partial remission (PR; n?=?6), or complete remission (CR; n?=?2). Matched therapy resulted in significantly longer progression-free survival compared with last prior unmatched therapy (hazard ratio 0.26, 95% confidence interval 0.10-0.71, p?=?.008). CONCLUSION:Identifying genomic and protein markers in patients with rare/ultrarare tumors was feasible. When therapies were matched, >50% of patients attained SD ?6 months, PR, or CR. Further precision medicine clinical investigations focusing on rare and ultrarare tumors are urgently needed. IMPLICATIONS FOR PRACTICE:Although rare tumors are infrequent by definition, when all subtypes of rare cancers are combined, they account for approximately 25% of adult malignancies. However, patients with rare tumors may lack approved treatments and clinical trial access. This paper describes an institutional a Rare Tumor Clinic focused on a precision medicine strategy. Performing genomics and protein analyses was feasible amongst patients with rare cancers. Over 50% of patients attained SD ?6 months, PR, or CR when they received matched therapy (genomically targeted and/or immunotherapy). Further studies investigating the efficacy of the precision therapy approach among rare tumors are warranted.
