Comprehensive tumor molecular profile analysis in clinical practice

Abstract

Background Tumor molecular profile analysis by Next Generation Sequencing technology is currently widely applied in clinical practice and has enabled the detection of predictive biomarkers of response to targeted treatment. In parallel with targeted therapies, immunotherapies are also evolving, revolutionizing cancer therapy, with Programmed Death-ligand 1 (PD-L1), Microsatellite instability (MSI), and Tumor Mutational Burden (TMB) analysis being the biomarkers employed most commonly. Methods In the present study, tumor molecular profile analysis was performed using a 161 gene NGS panel, containing the majority of clinically significant genes for cancer treatment selection. A variety of tumor types have been analyzed, including aggressive and hard to treat cancers such as pancreatic cancer. Besides, the clinical utility of immunotherapy biomarkers (TMB, MSI, PD-L1), was also studied. Results Molecular profile analysis was conducted in 610 cancer patients, while in 393 of them a at least one biomarker for immunotherapy response was requested. An actionable alteration was detected in 77.87% of the patients. 54.75% of them received information related to on-label or off-label treatment (Tiers 1A.1, 1A.2, 2B, and 2C.1) and 21.31% received a variant that could be used for clinical trial inclusion. The addition to immunotherapy biomarker to targeted biomarkers’ analysis in 191 cases increased the number of patients with an on-label treatment recommendation by 22.92%, while an option for on-label or off-label treatment was provided in 71.35% of the cases. Conclusions Tumor molecular profile analysis using NGS is a first-tier method for a variety of tumor types and provides important information for decision making in the treatment of cancer patients. Importantly, simultaneous analysis for targeted therapy and immunotherapy biomarkers could lead to better tumor characterization and offer actionable information in the majority of patients. Furthermore, our data suggest that one in two patients may be eligible for on-label ICI treatment based on biomarker analysis. However, appropriate interpretation of results from such analysis is essential for implementation in clinical practice and accurate refinement of treatment strategy.

Digging into the NGS Information from a Large-Scale South European Population with Metastatic/Unresectable Pancreatic Ductal Adenocarcinoma: A Real-World Genomic Depiction

“…With a failure rate of 2.2%, the used approach was successful in obtaining accurate results in 97.8% of analyzed cases, highlighting the significance of employing appropriate techniques even for low-quality DNA, such as that obtained from FFPE tissues. These results are comparable to the findings of previous studies employing the same platform in various histological types [ 35 , 36 , 37 ].…”

CNV and RNA analysis reveal a germline pathogenic duplication of MSH2 exon 15 in a family with Lynch syndrome: A case report

“…Since MSI-high status did not predict unresponsiveness to chemotherapy in stage III colon cancer, the patient was administered 12 courses of adjuvant FOLFOX [19,20]. Adjuvant treatment was completed in six months and clinical follow-up was initiated.In addition, since MSI-high was observed during MSI analysis of the patient's tumor tissue, the patient is eligible for immunotherapy administration [21].…”

How aging of the global population is changing oncology

“…The spectrum of tumors in physiologically older patients tends to be more responsive to immunotherapies [ 94 ], even if only in a minority [ 95 ], whereas those in the physiologically younger group more often respond to hormonal or targeted drug therapies [ 96 ]. The higher educational profile of physiologically younger patients [ 97 , 98 ] will likely favor interest in personalized oncology – i.e., targeted ‘smart drugs’ which are scientifically plausible [ 99 ] but not always empirically testable [ 100 , 101 ]. So-called theranostic use of 177 Lu-PSMA-617 radionuclide therapy to treat prostate cancer [ 102 ] is one example of a targeted treatment modality that may in future become more widely sought by some older patients – for example, when standard options are exhausted, or are anticipated to be poorly tolerated [ 103 ].…”