Identifying Opportunities and Challenges for Patients With Sarcoma as a Result of Comprehensive Genomic Profiling of Sarcoma Specimens

Abstract

PURPOSE Comprehensive genomic profiling (CGP) of sarcomas is rapidly being integrated into routine clinical care to help refine diagnosis and prognosis and determine treatment. However, little is known about barriers to successful CGP or its clinical utility in sarcoma. We set out to determine whether CGP alters physician treatment decision-making, and whether sarcoma subtypes influence the frequency of successful technical performance of CGP. METHODS A single-institution study evaluated profiling outcomes of 392 samples from patients with sarcoma, using a commercially available CGP panel. Of this group, 34 patients were evaluated prospectively (Decision Impact Trial) to evaluate the utility of CGP in physician decision-making. All cases were retrospectively analyzed to identify causes of CGP failure. RESULTS CGP successfully interrogated 75.3% (n = 295 of 392) of patients with sarcoma. Bone sarcomas had lower passing rates at 65.3% (n = 32 of 49) compared with soft tissue sarcomas at 76.7% (n = 263 of 343; P = .0008). Biopsy location also correlated with profiling efficiency. Bone biopsy specimens had a 52.8% (n = 19 of 36) passing rate versus lung (61.1%; n = 33 of 54) and abdomen (80.1%; n = 109 of 136) specimens. CGP altered physician treatment selection in 25% of evaluable patients (n = 7 of 28) and was associated with improved progression-free survival. CONCLUSION To our knowledge, this is the largest technical evaluation of the performance of CGP in sarcoma. CGP was effectively performed in the vast majority of sarcoma samples and altered physician treatment selection. Tumor location and tissue subtype were key determinants of profiling success and associated with preanalytic variables that affect DNA and RNA quality. These results support standardized biopsy collection protocols to improve profiling outcomes.

Clinical utility of comprehensive genomic profiling tests for advanced or metastatic solid tumor in clinical practice

“…This is the first report to show that the proportion of patients receiving genomically matched therapy was significantly higher among those with common cancers (16.2%) than non‐common cancers (9.4%) ( p = 0.0365), which confirmed our hypothesis that the clinical utility of CGP tests might differ between patients with common and non‐common cancers. Current CGP tests are primarily based on DNA sequencing that cannot detect all gene fusions, which could have significant clinical implications for diagnosis and treatment‐related decisions in patients with non‐common cancers, such as sarcoma and pediatric cancer 16,17 . Additionally, patients with non‐common cancers have less opportunity to participate in IND trials than those with common cancers (Figure S2A–C).…”

“…Performing CGP tests earlier in the course of the disease could minimize the attrition of patients qualifying for IND trials. To a High tumor mutation burden corresponding to ≥10 mutations per megabase.treatment-related decisions in patients with non-common cancers, such as sarcoma and pediatric cancer 16,17. Additionally, patients with non-common cancers have less opportunity to participate in IND trials than those with common cancers (FigureS2A-C).…”

Pulmonary thromboembolic disease or pulmonary artery intimal sarcoma: Case report and literature review

“…In addition, comprehensive genomic profiling (CGP) is the sequencing of DNA and RNA from tumor samples, which enables the identification of known and novel alterations that may drive oncogenicity. Therefore, it is not surprising that CGP is increasingly being used in the evaluation and management of sarcomas ( 12 ). For instance, Wu et al ( 13 ) reported a case of disseminated primary pulmonary artery sarcoma achieving clinical tumor response to olaparib based on genetic alterations detected by CGP, which involved the DNA repair pathway.…”

Pharmacogenomics and Pharmacogenetics in Osteosarcoma: Translational Studies and Clinical Impact

“…Very recently, the results of the Sarcoma Decision Impact Clinical Trial study have been published by the Foundation Medicine group [ 164 ]. This study applied the strategy of comprehensive genomic profiling to sequence both DNA and RNA from sarcoma tumor samples, with the aim to identify known and novel alterations that may drive oncogenicity and potentially impact on physicians’ treatment decision-making.…”