An approach for improvement of the accuracy of cancer gene panel testing.

BACKGROUND: Tissue-based comprehensive genomic profiling (CGP) is increasingly being employed for genotype-directed therapies in patients with advanced cancer. However, tissue availability may limit their potential applications. In Japan, the cost of cancer gene panel tests is covered by public insurance for patients diagnosed with advanced solid tumors once in their lifetime. Therefore, it is essential to improve the success rate (reportability) and accuracy of CGP tests. The purpose of this study was to identify the factors associated with efficient and accurate CGP testing using relevant information obtained from real-world data. METHODS: This study included 159 samples analyzed using tumor-only panel FoundationOne® CDx cancer genome profiling (F1CDx) and 85 samples analyzed using matched-pair panel OncoGuide™ NCC Oncopanel system (NCCOP) at St. Marianna University Hospital. Sample characteristics (fixation conditions, storage period, histology, tumor cell ratio, and genomic tumor cell content), CGP performance, and quality control status were evaluated across all 244 tested samples. RESULTS: In 237/244 samples (97.1%), CGP testing results were successfully obtained [F1CDx, 99.4% (158/159) and NCCOP, 92.9% (79/85)]. An increased number of fibroblasts, inflammatory cells, and necrotic tumor cells, long-term storage, and/or prolonged fixation of tissue sections were involved in the unreported results and/or qualified CGP results. In addition, a negative correlation between median insert size values and ΔΔCq was observed in the NCCOP system. CONCLUSION: We identified various factors associated with efficient and accurate CGP testing using relevant information obtained from real-world data, suggesting that thorough selection and preparation of tissue sections could optimize CGP and maximize useful information.

Antiemetic Efficacy of Adding Olanzapine 5 mg to Aprepitant, Palonosetron and Dexamethasone-Sparing After Day Two for Cancer Patients Receiving Anthracycline and Cyclophosphamide.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) decrease patient quality of life (QOL). We evaluated the efficacy of adding 5 mg Olz to a three-drug steroid-sparing antiemetic regimen (aprepitant, palonosetron, and dexamethasone-sparing after day two) for breast cancer (BC) patients receiving anthracycline plus cyclophosphamide (AC) chemotherapy. PATIENTS AND METHODS: We retrospectively reviewed the records of 177 BC patients with no previous highly emetogenic chemotherapy history receiving AC plus the steroid-sparing three-drug regimen or the steroid-sparing four-drug regimen including Olz 5mg at our hospital between January 2012 and December 2018. The primary endpoint was complete response (CR), defined as no vomiting and no usage of rescue medication during the first AC cycle. We analyzed the odds ratio (OR) of the CR with 95% confidence interval (CI) in the three-drug group against the four-drug group. The OR was adjusted for types of anticancer drugs by the Cochran-Mantel-Haenszel (CMH) test. Secondary endpoints were incidences of nausea, anorexia, fatigue, and somnolence during the first cycle. RESULTS: Compared to the three-drug group, the four-drug group demonstrated high incidence of no vomiting (71% vs 95%), a similar incidence of no rescue medication usage (50% vs 51%), and a similar CR rate (45% vs 49%). The OR of the CR rate in the three-drug group against the four-drug group after CMH adjustment for drug type was 0.958 (95% CI, 0.46-1.98). Compared to the three-drug group, the four-drug group demonstrated identical incidence of nausea (66%), but lower incidences of anorexia (78% vs 35%) and fatigue (86% vs 73%). The incidence of somnolence in the four-drug group was 49%. We did not have data of somnolence for the three-drug group in the records. CONCLUSION: Adding 5 mg Olz to the steroid-sparing three-drug combination can reduce vomiting, anorexia, and fatigue, although there was no difference in CR rate.

Effects of proton pump inhibitors on severe haematotoxicity induced after first course of pemetrexed/carboplatin combination chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: Pemetrexed/carboplatin combination chemotherapy has shown efficacy as a first-line treatment for advanced non-small-cell lung cancer. However, severe haematotoxicity is often observed during this combination chemotherapy. Some studies have suggested that concomitant drugs may be the risk factors for severe adverse events. However, those studies identified the predictive risk factors without paying attention to the relative dose intensities (RDIs) of the anticancer drugs. The objective of this study was to clarify the effects of concomitant drugs on the severe haematotoxicity induced by pemetrexed/carboplatin combination chemotherapy using multiple logistic regression analysis incorporating RDIs of the anticancer drugs. METHODS: We retrospectively reviewed the records of 61 patients who had received first-line treatment with this combination chemotherapy at Yamato Municipal Hospital between April 2011 and May 2017. Severe haematotoxicity was defined as grade 3 or 4 according to the Common Terminology Criteria for Adverse Events, version 4.0. To clarify the influence of concomitant drugs on haematotoxicity, we performed multiple logistic regression analysis. RESULTS: Among the 61 patients, 18 (29.5%) developed grade 3 or 4 haematotoxicity. Multiple logistic regression analysis showed that body weight <54.5 kg [odds ratio: 5.21, 95% confidence interval (CI): 1.17-23.08, P = 0.030], haemoglobin <12.0 g/dL [odds ratio: 7.13, 95% CI: 1.54-33.11, P = 0.012], and coadministration of proton pump inhibitors (PPIs) [odds ratio: 5.34, 95% CI: 1.06-26.94, P = 0.042] were significantly associated with severe haematotoxicity in patients receiving pemetrexed/carboplatin combination chemotherapy after adjustment using non-steroidal anti-inflammatory drugs and RDIs of the anticancer drugs. WHAT IS NEW AND CONCLUSION: Multiple logistic regression analysis incorporating RDIs of the anticancer drugs revealed that low baseline body weight, low baseline haemoglobin level, and coadministration of PPIs were the independent risk factors for predicting severe haematotoxicity induced by pemetrexed/carboplatin combination chemotherapy.