e24045 Background: The cell-free DNA (cfDNA) exists in very small amount and fragmented in the bloodstream. It is well known that cfDNA contains tumor-derived DNA(tDNA) in malignant patients Therefore, cfDNA has been clinically applied to oncogene testing as a liquid biopsy We hypothesised that cfDNA has a potency to alternate the whole state and heterogeneity of lung cancer. The purpose of this study is 1) to evaluate the cfDNA as a marker to evaluate inter-tumor heterogeneity in each patient, and 2) to evaluate the characteristics of tDNA found in cfDNA. Methods: The patients with primary lung cancer who died due to cancer progression and autopsies were obtained from September 2011 April to 2017 were entered in the study. It was also necessary that there is cfDNA sample one month before the death. Informed consent was obtained from substitute. The gene alterations detected from each lesion including metastases using next generation sequencing (NGS) were compared with those derived from cfDNA of own patient. Results: The seven patients were entered in this study. Seven primary lesion and XX metastatic tumor were analyzed. The mean number detectable gene alterations from per patient is 253 (range 99-1918) from tDNA samples and 218 (range 56-362) from cfDNA sample, respectively. Although not all gene alterations detected from tDNA samples derived from all lesions were found out in cfDNA sample, the truncal gene alterations that involved in carcinogenesis could be detected in cfDNA. The gene alterations detected in at least two tumor samples were detected in cfDNA more frequently, than those in one sample. Furthermore, gene abnormalities in with high allele frequencies in tumor DNA tended to be easily found abnormal with cfDNA. Conclusions: In conclusion, cfDNA have a great potency because it includes the essential gene alterations which were characterized as the broad range among the tumor extent and the deep variant frequency in certain lesion.
A 50-year-old man presented to our hospital in 1995. Invasive thymoma was diagnosed and extended thymectomy and left upper lobe partial resection were performed. In 2013, he complained of dyspnea. Chest computed tomography showed postoperative recurrence of invasive thymoma. Several chemotherapies were administered. Severe anemia and an increase in the total bilirubin level were observed with chemotherapies. In additional, an examination showed that the direct Coombs test was positive. Cold agglutinin was also high. We herein experienced a rare case of postoperative recurrence of invasive thymoma with cold agglutinin disease and autoimmune hemolytic anemia.
e20602 Background: The EGFR T790M mutation is the most common mechanism about drug resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in EGFR-mutated lung cancer. The third generation EGFR TKI has been reported a good efficacy to the patient who has a non small cell lung cancer harvouring the EGFR T790M mutation. On the other hand, several highly sensitive assays can already detect this mutation in pretreatment tissue biopsy. This study aim to evaluate a correlation the EGFR T790M mutation dominancy about the EGFR-mutated lung cancer which was not until exposed EGFR TKI therapy and actual resistance mechanism. Methods: We assessed the 26 EGFR TKI-free samples from EGFR-mutated non-small cell lung cancer by droplet digital PCR (ddPCR). T790M mutation dominancy ratio was calculated from isolated two PCR data about common mutation and T790M mutation and was estimated according to the following various clinical characteristics, that is actual T790M mutation using standard clinical method, age, sex, smoking status, PFS and treatment response of EGFR-TKIs. Results: We can detect the T790M mutation in 19 cases (73%) in initial biopsy tissue by ddPCR. The mean value of T790M mutation dominancy ratio was 0.48% (0.00-69.09%) and it is not difference in this ratio between T790M-positive and –negative cases, using standard clinical method (p = 0.92). The other clinical characteristics were not related with T790M mutation dominancy at all. Conclusions: T790M mutation was detected in most of the EGFR TKI-free sample, however the T790M mutation dominancy in pretreatment may not be related to actual post-treatment resistant mechanism whether EGFR T790M mutation was found.
Abstract Background: The detection of circulating cell free DNA (cfDNA) has been examined as a predictor of postoperative recurrence and survival in lung cancer patients. Extracellular vesicles (EVs) have potent for searching a new target to cancers. Objective: To analyze the association between cfDNA/EVs and prognosis after lung cancer surgery. Methods: We retrospectively examined patient background, disease-free survival, overall survival, and preoperative cfDNA in lung cancer patients who underwent surgery at Kanazawa University Hospital between January 2017 and May 2020, in whom preoperative chemotherapy was not administered. We extracted cfDNA from 4 ml plasma within 7 days before surgery and measured its concentration. EVs were extracted from 500 μl serum via Tim4 protein. Proteins included in EVs were analyzed by mass spectrometry. Results: 285 patients were included, 179 males and 106 females, median age 71(36-88) years, and 8 patients had SCLC. EGFRm- positive lung cancer was included in 93 cases (32.6%). The pStage0/l/ll/lll/lV of NSCLC was 7/187/42/36/6 respectively, and the pStagel/ll/lll of SCLC was 4/1/3 respectively. The mDFS of NSCLC was 14.6 (7.8-29.7)/21.5 (8.5-NA) months in pStage lll/lV, respectively. mOS was 53.3 (28.7-NA) months in pStage lll and was not achieved in other stages. The mDFS of SCLC was 19.8 (1.9-NA)/NA/5.7 (1.9-NA) months in pStage l/ll/lll, respectively. mOS was NA/NA/9.3 (9.3-NA) months, respectively. cfDNA was detected in 283 (99.2%) patients, with a concentration of 4.7 (0-60.0) ng/μl. The correlation coefficient between cfDNA concentration and DFS/OS in NSCLC was -0.023 (P=0.70)/-0.014 (P=0.81). The correlation coefficient between cfDNA concentration and DFS/OS for SCLC was -0.86 (P=0.024)/-0.89 (P=0.012). No recurrence was observed in patients in whom cfDNA was not detected.EVs were detectable from pre-operative serum samples, and the proteins included in these were different, whether disease was recurrent or not. Conclusion: The cfDNA concentration did not correlate with DFS/OS in post-operative NSCLC, whereas it correlated negatively with DFS/OS in SCLC. In the presentation, we will further discuss about the concrete genetic alterations and protein expression, based on the cfDNA sequencing and proteomics analysis. Citation Format: Hayato Koba, Hideharu Kimura, Seiji Yano. Genomic and proteome analysis using preoperative cell free DNA and extracellular vesicles of lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6596.
Three COVID-19 patients who were received lopinavir/ritonavir plus favipiravir got to improved without any severe adverse events. Two patients harboring high fever, severe pneumonia and respiratory failure obtained dramatic improvement. The combination therapy might be a treatment option; earlier therapy onset may have needed to avoid lung sequela.
Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)