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Purpose@#K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. @*Materials and Methods@#Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). @*Results@#In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. @*Conclusion@#The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.
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Purpose@#We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations. @*Materials and Methods@#In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1. @*Results@#The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths. @*Conclusion@#Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.
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Purpose@#The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication. @*Materials and Methods@#Surgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites. @*Results@#A total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases. @*Conclusion@#Driver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.
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BACKGROUND/AIMS@#We investigated the efficacy and toxicity of a weekly schedule of docetaxel and cisplatin as a first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).@*METHODS@#In this study, 18 patients with previously diagnosed R/M HNSCC were treated with combination chemotherapy of weekly docetaxel 35 mg/m² (day 1 and 8) and cisplatin 70 mg/m² (day 1) as first-line chemotherapy, repeated every 3 weeks.@*RESULTS@#Partial response and stable disease were observed in six patients (33.3%; 95% confidence interval [CI], 11.1% to 55.6%) and six patients (33.3%; 95% CI, 11.1% to 55.6%), respectively. The median overall survival and progression-free survival were 11.26 months (95% CI, 8.87 to 15.83) and 5.68 months (95% CI, 4.80 to 6.51), respectively. The major toxicity was grade 1/2 anemia (50%). Grade 3/4 neutropenia was observed in one patient (5.6%). Among the non-hematologic toxicities, grade 1/2 hepatotoxicity was most common (22.2%), and grade 3/4 infection was observed in one patient (5.6%). There was no treatment-related mortality.@*CONCLUSIONS@#For patients with R/M HNSCC, a cisplatin and weekly docetaxel regimen showed high efficacy with tolerable toxicity as a first-line treatment.
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PURPOSE: KRAS mutations have been used widely as prognostic or predictive marker in patients with advanced colorectal cancer (CRC). However, it may be difficult to obtain a tumor tissue for analyzing the status of KRAS mutation in large proportion of patients with advanced disease. MATERIALS AND METHODS: We obtained pairs of tumor and serum samples from 65 patients with advanced CRC, between March 2008 and July 2011. KRAS mutation status from the tumor samples was analyzed by genomic polymerase chain reaction and direct sequence, and KRASmutation status from the serum samples was determined by a genomic polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: KRAS mutations were detected in the serum samples of 26 patients and in the tumor samples of 31 patients. KRAS mutation status in the serum and tumor samples was consistent in 44 of the 65 pairs (67.7%). There was a significant correlation between the mutations detected in the serum sample and the mutations detected in the matched tumor sample (correlation index, 0.35; p 0.05). In a multivariate analysis, liver metastasis and no cytoreductive operation were independent prognostic factors for decreased OS. CONCLUSION: The serum sample might alternatively be used when it is difficult to obtain tumor tissues for analyzing the status of KRAS mutation in patients with advanced CRC.
Subject(s)
Humans , Colorectal Neoplasms , Liver , Multivariate Analysis , Neoplasm Metastasis , Polymerase Chain ReactionABSTRACT
Interdigitating dendritic cell sarcoma (IDCS) is a very rare and aggressive neoplasm that arises from antigen presenting cells. IDCS usually involves lymph nodes; however, extra-nodal involvement has also been reported. Because a consistent standard therapy for IDCS has not been established to date, we report a case of the successful treatment of disseminated IDCS using ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine). A 64-year-old man was diagnosed with IDCS on the basis of immunohistochemical findings of a biopsy specimen of the inferior nasal concha. Immunohistochemical staining showed a positive reaction for CD68, leukocyte common antigen, and S-100 protein, but a negative reaction for CD34, CD1a, and CD21. Imaging studies showed cervical and axillary lymphadenopathies, subcutaneous nodules, and a soft tissue lesion in the nasal cavity. Treatment with the ABVD regimen resulted in complete remission after 8 cycles of chemotherapy.
Subject(s)
Humans , Middle Aged , Antigen-Presenting Cells , Leukocyte Common Antigens , Biopsy , Bleomycin , Dacarbazine , Dendritic Cell Sarcoma, Interdigitating , Dendritic Cells , Nasal Cavity , S100 Proteins , Turbinates , VinblastineABSTRACT
BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been widely performed. However, procedure related-complications and the risk of tumor recurrence are limitations. We analyzed the clinicopathological characteristics of patients who underwent curative additional gastrectomy (gastrectomy) after ESD. METHODS: The clinical characteristics of cases underwent gastrectomy after ESD were retrospectively analyzed. RESULTS: Between January 2002 and August 2010, 1,512 cases underwent ESD for early gastric cancer (n=511) or adenoma (n=1,001). Thirty-two cases (2.1%) underwent gastrectomy after ESD. Thirty cases (2.0%) were EGC and 2 cases (0.1%) were adenoma. Extended indication, larger tumor size and piecemeal resection were risk factors for gastrectomy after ESD. According to the causes of gastrectomy, 13 cases underwent gastrectomy due to complications (40.6%; bleeding in 9, perforation in 4), and 19 cases based on pathological results (incomplete resection in 13, lymphatic invasion in 6). In cases with incomplete resection, the rate of residual tumor and lymph node metastasis after gastrectomy was 69.2% (75% lateral margin, 60% deep and 75% both) and 7.7%, respectively. Three (50%) of the 6 cases with lymphatic invasion had lymph node metatstasis. CONCLUSIONS: The causes of gastrectomy after ESD were the procedure-related complications, the incomplete resection and lymphatic invasion. For complete and curative ESD, endoscopists should try to minimize complications and determine the depth of invasion accurately before ESD.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Adenoma/pathology , Gastrectomy , Gastric Mucosa/pathology , Gastroscopy , Lymphatic Metastasis , Neoplasm Staging , Neoplasm, Residual , Retrospective Studies , Risk Factors , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is accepted as a standard treatment of early gastric cancer (EGC) and gastric adenoma. Occasionally, tumorous lesion is not found and pathologic discrepancies can occur after ESD. The aim of this study was to analyze the factors affecting the negative pathologic results after ESD. METHODS: We retrospectively reviewed the data from all patients with gastric neoplasm (276 EGC and 516 gastric adenomas) who were treated with ESD during past 3 years and enrolled the patients who had negative pathologic results. RESULTS: Out of 792 patients treated with ESD, 27 patients (3.4%) were eligible for inclusion. Among the 27 patients, factors affecting the negative pathologic results were, most commonly, the focal lesion (n=13, 48.2%) which was small enough to be removed completely during pre-ESD biopsy, followed by pathologic discrepancies (n=11, 40.7%) between pathologists and lastly the operator factor (n=3, 11.1%) dissecting incorrect lesions. Of the focal lesions, the initial pathologic diagnoses were adenocarcinoma in 11 cases (84.6%). In cases with pathologic discrepancies, all the pretreatment diagnoses were adenoma with low grade dysplasia. In cases caused by operator factors, intestinal metaplasia was accompanied by elevated adenoma in all cases. CONCLUSIONS: To decrease negative pathologic results after ESD, an endoscopist should perform ESD after sufficient communication with pathologists, especially for adenoma with low grade dysplasia, and choose correct lesion, especially located at the antrum and associated with intestinal metaplasia. The possibility of total removal of small lesions even by forcep biopsy should be considered.