<div>AbstractPurpose:<p>Cardiac toxicity is a serious potential complication of HER2-directed therapies and anthracyclines. <i>HER2</i> codon 655 and <i>SLC28A3</i> gene polymorphisms have been reported to be associated with cardiac toxicity from anti-HER2 and anthracycline therapy, respectively. Association of the polymorphism at HER2 codon 655 with prognosis has also been reported.</p>Experimental Design:<p>Whole blood samples from patients treated on a randomized adjuvant breast cancer trial (BCIRG-006) that compared chemotherapy with or without trastuzumab plus either anthracycline or nonanthracycline chemotherapy were tested for genetic polymorphisms in <i>HER2</i> codon 655 and <i>SLC28A3</i>. Genotypes were correlated with cardiac function and disease-free survival (DFS) outcomes.</p>Results:<p>Of 3,222 patients enrolled in BCIRG-006, 662 patient samples were successfully genotyped for the rs1136201 allele in <i>HER2</i> (codon 655): 424 (64%) were AA, 30 (4.5%) were GG, and 208 (31%) were AG genotype. In addition, 665 patient samples were successfully genotyped for the rs7853758 allele in the <i>SLC28A3</i> gene: 19 (3%) were AA, 475 (71%) were GG, and 171 (26%) were AG genotype. Follow-up time was 10 years. No correlation between DFS, cardiac event rate, or mean left ventricular ejection fraction (LVEF) and rs1136201 genotype was seen in the trastuzumab-treated or non–trastuzumab-treated patients. Moreover, mean LVEF and cardiac event rates were similar in all rs7853758 genotype groups treated with anthracycline-based therapy.</p>Conclusions:<p>In the largest study to date to evaluate whether two polymorphisms are associated with DFS and/or cardiac toxicity in HER2-positive breast cancer treated with trastuzumab and/or anthracyclines, we observed no correlation.</p></div>
Abstract Purpose: Colon cancer is the most common malignant tumor in the intestine. Abnormal Carboxylesterases 3 (CES3）expression had been reported to be correlated to multiple tumor progression. However, the association among CES3 expression and prognostic value and immune effects in colonic adenocarcinoma (COAD) were unclear. Patients and methods: The transcription profile of CES3 were downloaded from The Cancer Genome Atlas (TCGA). The CES3 protein expression and the prognostic value were verified based on tissue microarray data. The Cancer immune group Atlas (TCIA), Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the GSE78220 immunotherapy cohort were used to forecast immunotherapy efficacy. Finally, a prognostic immune signature was constructed and verified. Results: Compared with normal colon tissues, the expression of mRNA and protein levels of CES3 were downregulated in tumor tissues. CES3 expression was associated with TIICs. Hihg-CES3 COAD patients had better efficacy of concurrent immunotherapy. CES3-related immune genes (CRIs) were identified and were then used to construct prognostic immune signature and had been successfully verified in GES39582. Conclusion: CES3 might be a potential immune-related gene and promising prognostic biomarker in COAD.
Background Accurate diagnosis of pancreatic lymphoma is crucial for clinical management. We evaluate the role of fine‐needle aspiration (FNA) in the diagnosis of pancreatic lymphoma with the aid of flow cytometry and/or immunohistochemistry on the cell block. Methods Cases of pancreatic lymphoma were collected by searching our pathology laboratory information system over a period of 16 years. The clinical findings, cytologic features, and immunophenotypic results were reviewed. The diagnoses of FNA were correlated with surgical specimens in a subset of FNA cases. Results A total of 25 FNA cases of pancreatic lymphoma were included. The most common type of pancreatic lymphoma was large B cell lymphoma followed by follicular lymphoma. With the aid of flow cytometry and immunohistochemical work‐up on cell block, 72% (18/25) of the cases were diagnosed as lymphoma and 16% of the cases (4/25) were diagnosed as suspicious for lymphoma by FNA. Only two cases (8%) including one false negative and one nondiagnostic aspirate missed the lymphoma diagnosis and 1 case (4%) was indeterminate by FNA evaluation. Conclusion FNA demonstrated high accuracy in rendering diagnosis of pancreatic lymphoma. The overall sensitivity is 88% and the false negative and nondiagnostic rates are 4%, respectively. Further subtyping of certain lymphomas can be difficult due to the lack of architectural features of FNA specimens.
Abstract The data directly comparing the spatial pattern of VF defects between primary angle-closure glaucoma (PACG), high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) is not available. We aim to compare the asymmetric patterns of VF defects in patients with PACG, NTG and HTG across different severity levels. A total of 162 eyes of 114 patients with PACG, 111 eyes of 74 patients with HTG and 148 eyes of 102 patients with NTG were included. VF examinations were performed with standard automated perimetry (HFA, SITA-standard strategy, 24-2), and defects were categorized into 3 stages (early, moderate, and advanced) and each hemifield was divided into 5 regions according to Glaucoma Hemifield Test (GHT). The mean total deviation (TD) of each GHT region was calculated. The relationship between the values of pattern standard deviation (PSD) and mean TD was assessed. In the early stage, nasal region of PACG, central region of HTG and all five regions of NTG in the superior hemifield had significantly worse mean TD than their counterparts in the inferior hemifield. In the moderate stage, three regions of NTG in the superior hemifield had significantly worse mean TD than their inferior counterparts. In the advanced stage, central region of PACG, and central and paracentral regions of HTG in the superior hemifield had significantly worse mean TD than their inferior counterparts. When participants were matched by age, sex and mean deviation, in PACG and HTG eyes, all 5 GHT regions in the superior hemifield had worse mean TD than that that of their inferior-hemifield counterparts; however, the differences were not statistically significant. In NTG eyes, the paracentral, nasal, arcuate 1 and arcuate 2 regions in the superior hemifield had significantly worse mean TDs than their inferior counterparts. The superior hemifield is affected more severely than the inferior hemifield in all 3 subtypes of primary glaucoma. This asymmetric tendency was more pronounced in NTG compared to PACG and HTG.
The identification of KRAS mutations in patients with certain types of cancer, including colonic adenocarcinoma and non–small cell lung carcinoma, has become increasingly important as these patients are contraindicated from receiving epidermal growth factor receptor-targeted therapies. Several polymerase chain reaction (PCR)-based tests are commercially available for KRAS mutation testing including Applied Biosystems KRAS Mutation Analysis on the ABI3130xl, Qiagen therascreen KRAS RGQ PCR on the Rotor-Gene Q MDx, and Qiagen KRAS Pyro on the PyroMark Q24; however, these tests have not been compared side by side. The purpose of this study was to evaluate the performance characteristics and workflow for 3 PCR-based methods of detecting KRAS mutation status. We evaluated the performance characteristics and workflow for 3 commercially available KRAS mutation detection platforms. All of the 188 samples run were successful, with 29% being positive for the KRAS mutation. Of the positive tests, Applied Biosystems detected 84% of the positive cases, whereas Qiagen therascreen RGQ and Qiagen KRAS Pyro detected 100% of the positive cases. In cases of discrepancy between Applied Biosystems and therascreen RGQ, Pyro agreed with therascreen RGQ 95% of the time. Qiagen therascreen RGQ and Pyro were comparable in terms of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy, with all values being 100%. All 3 techniques accurately identified the appropriate mutation in the known control specimens. In summary, all 3 tests are relatively comparable for detecting the KRAS mutation, with Applied Biosystems having a slightly lower sensitivity, negative predictive value, and accuracy than therascreen RGQ and Pyro.
African–American (AA) cancer patients have long-experienced worse outcomes compared to non-Hispanic whites (NHW). No studies to date have evaluated the prognostic impact of sickle cell trait (SCT) and other inherited haemoglobinopathies, of which several are disproportionately high in the AA population. In a cohort analysis of treated patients diagnosed with breast or prostate cancer in the linked SEER-Medicare database, the relative risk (RR) for ≥1 serious adverse events (AEs), defined as hospitalisations or emergency department visits, was estimated for 371 AA patients with a haemoglobinopathy (AA+) compared to patients without haemoglobinopathies (17,303 AA−; 144,863 NHW−). AA+ patients had significantly increased risk for ≥1 AEs compared to AA− (RR = 1.19; 95% CI 1.11–1.27) and NHW− (RR = 1.23; 95% CI 1.15–1.31) patients. The magnitude of effect was similar by cancer type, and in analyses of AA+ with SCT only. Our findings suggest a novel hypothesis for disparities in cancer outcomes.
55 Background: The therapy with tyrosine kinase inhibitors changed the prognosis of patients with advanced GIST. Unfortunately, most of the tumors become resistant to therapy and patients succumb to the disease. New therapies for this patient population are needed. Here we report interim analyses of safety and efficacy in advanced GIST patients treated with immunotherapy. Methods: Patients with advanced/metastatic GIST progressing on at least imatinib were enrolled on a randomized, parallel group, unblinded phase 2 trial of either nivolumab(nivo) (240 mg Q2wks) or nivo (240 mg Q2wks) with ipilimumab(ipi) (1mg/kg Q6wks) for up to 2 years. The primary endpoint was the objective response rate (ORR) of nivo alone or nivo + ipi by RECIST 1.1 criteria. Patients were randomized 1:1 and the response was assessed every 8 weeks. With a sample size of 20 per group, an exact binomial test with a nominal 0.050 one-sided significance level will have 82% power to detect the difference between the null hypothesis response rate 1.5% and the alternative response rate of 15%. Secondary objectives are to ascertain the PFS, CBR, RR by Choi criteria and safety. Blood and biopsies are also being collected. Results: To date, 14 patients (median # of prior therapies: 4) have started on trial and 8 remain on treatment. In the nivo only arm, 3/7 patient had SD for a CBR of 42.8 %. The median PFS of the nivo arm was 8 weeks. In the nivo + ipi arm, 1/5(20%) patients had a PR and 1/5 have SD for a CBR of 40%; 2 patients were censored. The median PFS of the nivo + ipi arm was 8.43 weeks. 1 patient in the nivo arm had grade 3 fatigue and 1 patient in the nivo + ipi arm had grade 3 diarrhea. Pretreatment biopsies have been obtained in all patients and blood has been collected on all patients for correlative analysis. Conclusions: In a heavily pretreated GIST population, durable responses and disease control were observed. To date, the drugs have been well tolerated and no new safety signals have been observed in this disease state. Clinical trial information: NCT02880020.
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