Detection of NTRK fusions by RNA-based nCounter is a feasible diagnostic methodology in a real-world scenario for non-small cell lung cancer assessment.

NTRK1, 2, and 3 fusions are important therapeutic targets for NSCLC patients, but their prevalence in South American admixed populations needs to be better explored. NTRK fusion detection in small biopsies is a challenge, and distinct methodologies are used, such as RNA-based next-generation sequencing (NGS), immunohistochemistry, and RNA-based nCounter. This study aimed to evaluate the frequency and concordance of positive samples for NTRK fusions using a custom nCounter assay in a real-world scenario of a single institution in Brazil. Out of 147 NSCLC patients, 12 (8.2%) cases depicted pan-NTRK positivity by IHC. Due to the absence of biological material, RNA-based NGS and/or nCounter could be performed in six of the 12 IHC-positive cases (50%). We found one case exhibiting an NTRK1 fusion and another an NTRK3 gene fusion by both RNA-based NGS and nCounter techniques. Both NTRK fusions were detected in patients diagnosed with lung adenocarcinoma, with no history of tobacco consumption. Moreover, no concomitant EGFR, KRAS, and ALK gene alterations were detected in NTRK-positive patients. The concordance rate between IHC and RNA-based NGS was 33.4%, and between immunohistochemistry and nCounter was 40%. Our findings indicate that NTRK fusions in Brazilian NSCLC patients are relatively rare (1.3%), and RNA-based nCounter methodology is a suitable approach for NRTK fusion identification in small biopsies.

Cost-effectiveness of hypofractionated versus conventional fractionated radiotherapy for the treatment of men with early glottic cancer: a study in the Brazilian public and private health system.

BACKGROUND: This study aims to evaluate whether hypofractionated radiotherapy (HYPOFRT) is a cost-effective strategy than conventional fractionated radiotherapy (CFRT) for early-stage glottic cancer (ESGC) in the Brazilian public and private health systems. METHODS: Adopting the perspective of the Brazilian public and private health system as the payer, a Markov model with a lifetime horizon was built to delineate the health states for a cohort of 65-year-old men after with ESGC treated with either HYPOFRT or CFRT. Probabilities of controlled disease, local failure, distant metastasis, and death and utilities scores were extracted from randomized clinical trials. Costs were based on the public and private health system reimbursement values. RESULTS: In the base case scenario, for both the public and private health systems, HYPOFRT dominated CFRT, being more effective and less costly, with a negative ICER of R$264.32 per quality-adjusted life-year (QALY) (public health system) and a negative ICER of R$2870.69/ QALY (private health system). The ICER was most sensitive to the probability of local failure, controlled disease, and salvage treatment costs. For the probabilistic sensitivity analysis, the cost-effectiveness acceptability curve indicates that there is a probability of 99.99% of HYPOFRT being cost-effective considering a willingness-to-pay threshold of R$2,000 ($905.39) per QALY (public sector) and willingness-to-pay threshold of R$16,000 ($7243.10) per QALY (private sector). The results were robust in deterministic and probabilistic sensitivity analyses. CONCLUSIONS: Considering a threshold of R$ 40,000 per QALY, HYPOFRT was cost-effective compared to CFRT for ESGC in the Brazilian public health system. The Net Monetary Benefit (NMB) is approximately 2,4 times (public health system) and 5,2 (private health system) higher for HYPOFRT than CFRT, which could open the opportunity of incorporating new technologies.

Cost-effectiveness of stereotactic body radiotherapy versus conventional radiotherapy for the treatment of surgically ineligible stage I non-small cell lung cancer in the Brazilian public health system.

Background: The Brazilian public health system does not pay for the use of Stereotactic body radiotherapy (SBRT) due to its costs and the absence of cost-effectiveness analysis showing its benefit. The present study aims to evaluate whether the SBRT is a more cost-effective strategy than the conventional fractionated radiotherapy (CFRT) for surgically ineligible stage I non-small cell lung cancer (NSCLC) in the Brazilian public health system. Methods: Adopting the perspective of the Brazilian Unified Healthcare System (SUS) as the payer, a Markov model with a lifetime horizon was built to delineate the health states for a cohort of 75-years-old men with medically inoperable NSCLC after treatment with SBRT or CFRT. Transition probabilities and health states utilities were adapted from the literature. Costs were based on the public health system reimbursement values and simulated in the private sector. Findings: The SBRT strategy results in more quality-adjusted life-year (QALYs) and costs with an incremental cost-effectiveness ratio (ICER) of R$ 164.86 (U$ 65.16) per QALY and R$ 105 (U$ 41.50) per life-year gained (LYG). This strategy was cost-effective, considering a willingness-to-pay of R$ 25,000 (U$ 9,881.42) per QALY. The net monetary benefit (NMB) was approximately twice higher. The outcomes were confirmed with 92% of accuracy in the probabilistic sensitivity analysis. Interpretation: Using a threshold of R$25,000 per QALY, SBRT was more cost-effective than CFRT for NSCLC in a public health system of an upper-middle-income country. SBRT generates higher NMB than CFRT, which could open the opportunity to incorporate new technologies. Funding: Varian Medical Systems.