bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemotherapy to induce T-cell subpopulation changes in advanced breast cancer patients.
Authors: Comolli Giuditta , Torchio Martina , Franceschetti Benvenuto , Cassaniti Irene , Rapposelli Ilario , Marone Piero , Bertolini Alessandro , Baldanti Fausto , Danova Marco
Published: September 2018

e12562

Background: Recent data suggest that some anti-cancer agents may generate a stimulation of the immune system that can account for additional clinical responses. In breast cancer (BC) the immunomodulation via chemotherapy (CT) opens possible clinical applications, but: a) the variability in the immune response requires a careful pt selection and b) monitoring immunocompetence in clinical routine still represents a technical challenge.Changes in sub-populations of cytotoxic (CD8+) T-cells (as reported in aging) are not well documented in cancer pts. Methods: We utilized multi-color immunophenotyping by flow cytometry (FCM) using a high-resolution whole-blood assay in 39 pts (median age 53; 34 - 74 yrs) with advanced BC undergoing first-line, standard-dose anthracycline/taxane-based CT and in 12 older healthy women, during a 6-months study, to analyze variations in CD8+ T-cells and the effects of CT on different T-cell sub-populations. Results: In all BC pts there was a consistent decrease in absolute numbers of lymphocytes, T-cells and CD8+ T-cells, starting from the first course and persisting during all the CT program. Among the T-cells, there was a lower CD8-/CD8+ ratio, persisting over 6 months, in pts compared to controls. The proportion of CD28-CD57+ cells also remained higher among pts throughout the sampling duration. The number of CD28+CD57- and CD28-CD5- cells decreased faster during CT than CD28+CD57+ and CD28-CD57+ cells, while only CD28-CD57- cells showed a significant reconstitutive capacity after 6 months.Anti-tumor CT in BC pts can produce clinical benefits also by restoring the responsiveness of T cells and by increasing the frequency and activation of tumor specific T-cells already present in blood before CT. Conclusions: Anthracycline/taxane-based CT is able to elicit changes in the pts immune system. These changes appeared to be pronounced in BC pts, with senescent CD8+ T-cells playing an important role. The pre-treatment condition was not restored after 6 months of CT. Multi-parameter FCM is a powerful tool for detailed analysis of the immune dysfunctions during CT and it will also help the development of combined schedules of CT plus new immunotherapeutic agents.
Association of clinicopathological parameters with outcome in patients with metastatic breast cancer treated with eribulin in South East London.
Authors: Li Su , Agorastos Antonios , Kristeleit Hartmut
Published: September 2018

e12567

Background: Eribulin is licensed for the ≥2-line treatment of patients with metastatic breast cancer. We assessed outcome of eribulin treatment in real world patients. Methods: We conducted a retrospective analysis of consecutive patients treated with eribulin for metastatic breast cancer at Guys Cancer Centre and affiliated units in South East London between Oct 2011 and Nov 2016. All data was extracted from electronic patient records. Results: We identified 158 patients with a median age of 55.8 years (range 30-94). Median WHO performance status (PS) was 1 (0-4). 68% were of white ethnicity, 23% black and 5% other. 67% were ER+, 13% Her2+ and 26% triple negative breast cancer (TNBC). 96% had visceral disease and 15% of patients had CNS involvement. Eribulin was given in 1% of patients as 1st line, 10% as 2nd, 51% as 3rd, 21% as 4th and 17% as 5thline treatment or beyond. Patients received a median of 4 cycles of eribulin (range 1-35). Median overall survival (OS) was 9.3 months and progression free survival (PFS) 3.4 months. A response was seen in 34% of patients, disease stability in 19%. OS was significantly better for patients > 60 years of age compared to < 60 years (10.3 vs 8.3 months, HR 1.45, 95% CI 1.04-2.10). OS for ER+ was 10.2 vs 7.6 months for ER- and for TNBC. OS for white patients was 9.4 months vs 8 months for black ethnicity. Black patients were younger (median age 50.5 vs 59.9). We observed that amongst TNBC patients black ethnicity had a trend towards longer survival (9.1 months for black vs 7.7 months for white). Due to the retrospective nature of this study toxicity was not well documented. Dose reductions were required in 35% of patients and 3% experienced neutropenic fever. Conclusions: OS was inferior to documented outcome in the EMBRACE trial (9.3 vs 13.1 months). This is despite a lower median number of previous lines of chemotherapy. Our cohort had a poorer baseline PS (20% PS2, 3% PS3 and above vs 8% PS2 in EMBRACE) and a higher proportion of black patients (23% vs 4% in EMBRACE). 15% had known CNS disease. The observation that triple negative patients of black ethnicity fare better than white patients treated with eribulin warrants further exploration.
Outcomes in BRCA1/2 breast cancer patients treated with everolimus followed by chemotherapy+/- PARP inhibitors.
Authors: Soliman Hatem Hussein , Anderson Matthew , Han Hyo S.
Published: September 2018

e12569

Background: Research demonstrates blocking mTOR signaling can suppress homologous DNA repair pathways. Use of drugs like everolimus can sensitize cancer cells to DNA damaging agents, particularly if they already harbor defects in DNA repair, such as mutations in BRCA1/2 genes. We sought to analyze our Total Cancer Care (TCC) dataset including BRCA1/2 germline mutation carrier patients who were enrolled on a completed randomized phase 2 trial (NCT01506609) of carboplatin/taxol (CT) or temozolimide (TEM) +/- veliparib (PARPi) at Moffitt Cancer Center (MCC). Time on study treatment (TOT) for patients who received everolimus (EVE+) prior to study enrollment was compared to those who did not (EVE-). Methods: We identified MCC patients treated on trial who were TCC consented to provide clinicopathologic and treatment data. Information on prior treatments, EVE exposure, Estrogen receptor (ER) status, unblinded trial treatment if known, and TOT were collected. Summary statistics and comparison of median TOT in EVE+ vs. EVE- pts using a two tail Mann-Whitney test (significance p < .05), and Wilcoxon Signed Rank Test of TOT EVE+ vs. reported PFS of CT+PARPi arm were performed. Results: Fourteen pts (6 EVE+, 8 EVE-) were identified with clinical data described in Table 1. Median TOT for EVE+ = 25.1 mos (95% CI 19.5-29.8), EVE- = 7.4 mos (95% CI 3.9-15.4) with p = .002. EVE+ TOT was significantly higher than median PFS of 14.1 mos for CT+PARPi arm (p = .03). Median TOT on EVE was 4.3 mos (95% CI 2.7-16.3). In EVE+ 5 pts discontinued for progression, 1 for toxicity. In EVE- 5 pts discontinued for progression, 3 for other causes. Conclusions: Significantly better TOT on DNA damaging therapy was observed in a small group of ER+ BRCA1/2 mutated breast cancer pts previously exposed to EVE compared to EVE- pts. This observation requires further study in the entire study population and confirmation in prospective trials with sequenced EVE-CT+/-PARPi for ER+ BRCA1/2 pts. [Table: see text]
Retrospective review of steroid-induced acne in patients with breast cancer.
Authors: Krishnasamy Shalini R , Jung Jae
Published: September 2018

e12570

Background: With the rapid development of targeted inhibitors, the incidence of cutaneous chemotoxicities is rising and represents a significant cause of morbidity in cancer patients. Therefore, rapid recognition of rashes that warrant dose reduction or discontinuing treatment is critical. Unfortunately, the concomitant use of systemic steroids with chemotherapeutics that can produce acneiform eruptions, make it difficult to distinguish a cutaneous chemotoxicity from systemic steroid induced acne (SSIA). Although SSIA is a well known complication of systemic steroid administration, there are few published studies regarding this condition, none of which have been done in cancer patients. In this study, we sought to examine the incidence of SSIA, the patient and tumor characteristics as well as the chemotherapy regimen most commonly associated with SSIA in breast cancer patients treated with chemotherapy at the City of Hope National Comprehensive Cancer Center. Methods: We performed a retrospective study. Using the institutional registry of patients, we identified 3,848 patients that received a diagnosis of breast cancer between 1/2009-6/2015, 1,991 (51%) of which received at least one cycle of chemotherapy. 61 of these patients received a ICD-9 billing code for “acne” or “ steroid acne”, 10 of whom had explicit documentation of acne or acneiform eruption in their chart. Results: All 10 patients were female with a median age of 49 (range 36-56). 50% of patients had ER+/PR+ disease and 30% had ER-/PR-/HER2- breast cancer. 90% of patients had stage I or II disease. 70% of patients developed steroid induced acne after the 1st cycle of chemotherapy. All regimens contained either docetaxel or paclitaxel. Dexamethasone was implicated in all but one case. We report an overall incidence of SSIA of 0.05% among breast cancer patients treated with at least once cycle of chemotherapy at our institution. Conclusions: These results suggest that breast cancer patients at highest risk for SSIA are on taxane-based regimens with early stage disease and are most likely to develop the reaction after their first cycle of chemotherapy. This study however is limited by the retrospective design, the reliance on ICD 9 billing codes, and the limited sample size.
Safety and efficacy of eribulin in combination with gemcitabine in patients with advanced triple negative breast cancer.
Authors: Michalaki Vasiliki , Fragulidis Georgios , Kondis Ioannis , Karvouni Eleni , Dafnios Nikolaos , Kotsiou Antonia , Vassiliou Ioannis , Papadimitriou Christos
Published: September 2018

e12578

Background: Triple negative breast cancer (TNBC) characterized by aggressive tumor behavior with very poor prognosis following progression after standard chemotherapeutic regimens.The combination of Gemcitabine, a nucleoside analogue, and eribulin a microtubule-targeting agent exhibited synergistic cytotoxic effects in pre-clinicall and clinical setting . Thus, eribulin combined with gemcitabine may synergistically induce tumor cell death, especially in tumors like TNBC. Based on this rationale, we conducted a phase II study evaluating this combination either in first- or in second-line treatment for advanced TNBC.Methods: Females with locally advanced or metastatic TNBC who had received previous chemotherapy , with an ECOG (PS) ≤ 1, and adequate hematological, renal and hepatic function. Patients received eribulin (1mg/m2) plus gemcitabine (1000 mg/m2) on day 1 and 8, q21 until disease progression. CT scans were performed every 12 weeks. The main objective of this trial was to evaluate the overall response rate (ORR) and secondary were Feasibiliy, safety and clinical benefit rate (CBR ). Results: Thirty –two females (median age: 62 years, median ECOG performance status (PS) 1) were enrolled the study. The majority had visceral disease (78.5%). A median of 9 (range:4–18) treatment cycles was administered (69% of patients received ≥ 6 cycles), .All patients were evaluable for response. We did observe 12 partial responses for an overall response rate of 37.5% (95%CI,26.1-57.0). A stable disease was observed in 15 patients (46.8%). Clinical benefit, was observed in 21 patients (65.6%; 95%CI,48.1-76.6). The most common grade 3 or 4 toxicities were haematologic . The main grade 3 or 4 non-hematolgic toxicities were fatigue, diarrhoea, nausea and vomiting. Of the 32 patients in total 7 patients had dose reductions and 14 patients had dose delays. Conclusions: Resistance to current standard therapieslimits the available options for previously treated patients with metastatic TNBC and there is currently no preferred standard chemotherapy. This study demonstrated that the combination of eribulin and gemcitabine was efficacious, feasible and toxicity was generally manageable
Long term follow up of patients with locally advanced triple negative breast cancer treated with adjuvant high dose chemotherapy and autologous stem cell transplantation: A single center experience.
Authors: Bukari Sani Mohammed , Usman Muhammad , Abrams Judith , Ratanatharathorn Voravit , Uberti Joseph P. , Deol Abhinav , Bhutani Divaya , Alavi Asif , Ayash Lois Jeanne ,   Blood and Marrow Transplant Program, Wayne State University/Karmanos Cancer Institute
Published: September 2018

e12590

Background: Adjuvant high dose chemotherapy (HDC) with Autologous Hematopoietic Stem Cell Transplantation (AuSCT) as part treatment of high risk locally advanced breast cancer has remained controversial. Multiple trials reported disease free survival (DFS) without Overall survival (OS) resulting in its abandonment in early 2000s. However, post hoc analysis of these trials consistently reported DFS and OS benefit in young and triple negative breast cancer (TNBC) subgroups. This has not been re-evaluated till date. Recent European registry reports coupled with improved transplant related mortality (TRM) and still poor out-come of standard of care in TNBC subgroup has generated renewed interest. We report long term out-come of locally advanced high risk TNBC treated with HDC and AuSCT treated in Karmanos Cancer Institute from 1995 to 2001 Methods: Majority of the patients were treated with Adriamycin and Taxane based induction chemotherapy. Patients without evidence of metastatic disease proceeded to HDC and AuSCT using Carmustine 600mg/sqm Cyclophosphamide 5.6gm/sqm and Cisplatin 165mg/sqm (STAMP 1 regimen). This is followed with loco- regional radiation per protocol. Results: 72 hormone negative patients with Lymph Node(LN) > 4 or inflammatory breast cancers were selected from 576 treated for advanced or metastatic breast cancer. 33 patients were TNB with HER2 status of 39 patients unknown. Median time from diagnosis to stem cell transplantation was 6 months. Median age at diagnosis was 47yrs. Mean LN involvement was 9 with 90% having (4-20) LN positivity. With median follow up of 16 years,10yrs DFS and OS were both 62.5%. Median follow up for DFS and OS was not reached.TRM was 9% mostly from pulmonary toxicity. Conclusions: This study of locally advanced high risk TNBC treated with adjuvant HDC and AuSCT have high 10yr OS of 62.5% compared to current standard of care. With the current improvement in TRM, reevaluation of this strategy through clinical trials in this subgroup whose outcome remain poor is reasonable.
Risk evaluation about genetic screening among ovary cancer with regard to Lynch syndrome.
Authors: Kim Min Kyu
Published: September 2018

e13000

Background: Hereditary cancer syndrome about ovary cancer is mostly BRCA related. But mismatch repair genes related Lynch syndrome is also associated with it.There is not much study about risk evaluation about this among Korean population. We investigate this. Methods: A retrospective review of ovary cancer patients who was counseled about Lynch syndrome in Department of Obstetrics and gynecology, Samsung Changwon Hospital by single surgeon was done. Clinical information was extracted from the medical record including age, family and personal history of cancer, immunohistochemistry (IHC) of MLH1/MSH2, microsatellite instability test (MSI). Results: Total test was 26.mean age was 54(16~75) and fifty percent was serous type (13/26).There were 2 patients with Lynch syndrome related cancer family history (stomach and ovary) among their 1st degree relatives. Only one patient has abnormal MLH1 IHC.There were three unstable MSI patients (BAT26, D2S123, D55346, and NR21). Conclusions: We found three abnormal MSI patients among this population. Cost effective algorithm using multiple genetic testing to find Lynch syndrome associated ovary cancer patients should be developed through large population study.
A novel approach to detect large indels from targeted sequencing data in clinical cancer setting.
Authors: Chen Lijuan , Chen Caiping , Chen Dongling , Zou Qiuyi , Qin Gungwei , Kang Hui , Yao Ming , Wang Kai
Published: September 2018

e13002

Background: Next generation sequencing (NGS) technologies have already shown numerous advances to revolutionize our understanding of cancer genomic profiling and improve cancer treatments. There have been many NGS data analysis tools available for identification of different genomic alternations including short insertion and deletion (short indel, < 25 bp in general). However, detection of > 100 bp large indel (L-indel) from short reads (generally < 200 bp) remains a huge challenge. L-indels identified in genes like MET and FLT3 have proven a critical implication in cancer treatments. Moreover, there is an urgent need for an algorithm to validate L-indels generated by genomic modification systems like ZFN, TALENs and CRISPR/Cas9. Methods: A novel algorithm was developed for calling L-indels in targeted sequencing data as following: raw reads were first filtered by selecting high-quality ones and correcting wrong bases; a chunk of contig (unitig) was then assembled and aligned to reference genome; lastly, break point information was collected and L-indels were calculated. The algorithm was applied on the reads generated from NA12878 cell line and FFPE samples collected in our lab respectively on the Illumina platform. Validation were performed by PCR and Sanger sequencing. Results: 22 novel exonic L-indels (17 deletions and 5 insertions) were identified with a median size of 1,616 bp (range: 25-6,684 bp) from NA12878 sequencing data and 100% successfully confirmed by Sanger sequencing. In addition, 6 out of 9 reported L-indels were also found with the rest awaiting for further exploration. Strikingly, a 2,446 bp deletion on MSH6, encodes an important component in mismatch repair (MMR) system, was detected on a FFPE sample of a lung cancer adenocarcinoma, which prompted to consideration of MMR deficiency otherwise. Conclusions: We have developed and validated a novel and accurate method for NGS large indels detection dedicated for targeted sequencing data in clinical cancer setting. Equipment of this method will greatly increase the capability of comprehensively understanding genomic alterations from a single NGS-based assay, and provide more information for potential clinical use.
Identification of genes with clonal mutations for the tumorigenesis of breast cancer subtypes.
Authors: Cheung Yee Him , Wu Jie , Dimitrova Nevenka
Published: September 2018

e13006

Background: Current analyses on somatic mutations mainly involve counting samples as either carriers or non-carriers. Such a binary approach misses to take into account the fraction of tumor cells that carry a mutation, which is a significant measure of the influence of a mutation on the overall phenotype, such as gene expressions, subtype and pathway activity. Methods: In this study, we re-analyzed the 72,084 non-synonymous somatic mutation in 16,164 genes of 817 TCGA breast cancer samples (HER2+: 65, Luminal A: 415, Luminal B: 176, Basal: 136 and Normal-like: 25) using variant allele frequency (VAF) adjusted by sample purity derived from multiple methods. We obtained a gene-based VAF by choosing the maximum VAF among all mutations found in each gene for each sample. For each breast cancer subtype, we filtered for top 100 genes with highest number of mutation carriers and then ranked them by decreasing average VAF across all samples. We assume genes with higher average VAF are more likely to harbor clonal mutations in early tumor progression. We further evaluated the Pearson correlation between VAF of genes having at least ten mutation carriers and the expression levels of ESR1, PGR and ERBB2 in Luminal A subtype. Results: The top two genes with highest VAF for each of the four subtypes are as follows: (a) HER2+: ERBB2 (VAF = 0.39 ± 0.21, n = 4), KAT6A (0.31 ± 0.09, 4), (b) Luminal A: CTCF (0.41 ± 0.19, 13), MAP2K4 (0.37 ± 0.14, 24), (c) Luminal B: MAP2K4 (0.46 ± 0.11, 5), TP53 (0.46 ± 0.17, 64), and (d) Basal: SCN10A (0.46 ± 0.29, 5), MYH9 (0.43 ± 0.16, 5). The strongest correlations for Luminal A are: (i) SPEN (corr. = 0.85, n= 14), KMT2C (0.73, 24) and DMD (0.73, 11) with ESR1, (ii) DMD (0.69, 11) and NBL1 (0.67, 10) with PGR, and (iii) TBX3 (-0.51, 12) and MUC12 (0.47, 14) with ERBB2. Conclusions: While carrier count is effective for identifying genes prone to mutations, average VAF opens another perspective for uncovering genes that tend to harbor clonal mutations. Our work shows the potential of VAF analysis for identifying driver genes, understanding tumor progression and evaluating the impact of a mutation on a patient. As future work, we may improve the VAF estimates by adjusting for copy number variations and weight each variant by pathogenicity.
MFN2 might be a risk factor for lung adenocarcinoma.
Authors: Lou Yuqing , Zhang Yanwei , Xu Jianlin , Gu Ping , Zhang Wei , Zhang Xueyan , Zhong Hua , Jiang Liyan , Han Baohui
Published: September 2018

e13007

Background: Genetic mutations in Mitofusin-2(MFN2) interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition Charcot-Marie-Tooth disease type 2A( Nature, December 2016). MFN2 was initially identified as a hypertension-associated gene and implicated in the pathogenesis of multiple cancer types. However, underlying mechanisms of MFN2 in lung adenocarcinoma was unclear. Methods: MFN2 expression at protein level was examined in 30 pair lung adenocarcinoma/adjacent normal lung samples with immunohistochemistry staining. Then MFN2 knocked down in human lung adenocarcinoma cells A549 with lentiviral-mediated shRNA strategy. The effects of MFN2 knockdown on cell proliferation, cell cycle process, cell migration and invasion was investigated in A549 cells. MFN2-knockdown induced gene expression changes was analyzed by microarray assay and then functional pathway enrichment analysis was performed to identify critical pathways involved in MFN2-mediated lung adenocarcinoma development. The expression changes of downstream factors were determined by western blot. Furthermore, tumor models in nude mice were generated. Tumor formation and progression in these mice were analyzed. Results: As compared to adjacent normal lung tissues, MFN2 expression was significantly higher in lung adenocarcinoma tissues with positive MFN2 signals in 90% (27/30) lung adenocarcinoma tissues and only in 26.7% (8/30) adjacent normal tissues. Furthermore, MFN2 knockdown inhibited cell proliferation, induced cell cycle arrest and blocked invasion behavior in A549 cells. MFN2-knockdown induced gene expression changes in A549 cells was analyzed by microarray assay. Functional pathway enrichment analysis revealed that 6 pathways were enriched in deregulated genes including Cell cycle, DNA replication, ECM-receptor interaction, Focal adhesion, MAPK signaling pathway and Chemokine signaling pathway. Downregulation of RAP1A and upregulation of RALB and ITGA2 identified in MFN2-knockdown cells by microarray analysis were confirmed by western blot. In vivo, tumor formation and progression in nude mice showed that MFN2 knockdown reduced tumorigenesis of A549 cells. Conclusions: MFN2 overexpression run a risk of lung adenocarcinoma.
Effectiveness of tablet family history collection in a multidisciplinary pancreatic tumor clinic in identifying patients with risk factors for hereditary cancer.
Authors: Everett Jessica , Schradle Kara , Cameron Heather , Patel Anisha , Koeppe Erika , Stoffel Elena Martinez , Simeone Diane M.
Published: September 2018

e13020

Background: A substantial percentage of patients with pancreatic adenocarcinoma (PDAC) harbor pathogenic germline variants in known cancer risk genes, some with relevance for treatment options. Robust collection of relevant personal and family cancer history risk factors for all patients with PDAC is needed to optimize identification of those who could benefit from genetic counseling and testing (GC/GT). Methods: 464 adult patients (≥18 years of age) presenting to a multi-disciplinary pancreatic tumor clinic were invited to complete a tablet based family cancer history survey prior to their clinic appointments. Standard family history entry into electronic medical record (EMR) was reviewed for comparison. Eight GC/CT referral criteria were developed based on existing guidelines for known syndromes associated with PDAC, reported findings from studies of GC/GT outcomes in patients with PDAC, and expert opinion. Presence of any of the 8 criteria were documented for both tablet and EMR collection methods in the subset of patients with PDAC (n = 230). Results: Completion rate for the tablet survey was high (87%). 78% of users completed the survey in ≤15 minutes (x̄ = 12 minutes). 202 patients with PDAC (88%) completed the tablet survey, and 100 (50%) met ≥1 GC/GT criteria. Most frequent criteria identified were: ≥2 relatives with related cancers (28%); ≥1 relative with PDAC (12.9%); personal history of related cancer (12.9%). Tablet data collection improved identification of relatives with breast cancer ca < age 50 from 1.5% to 5.5% due to missing ages at diagnosis in the EMR. The tablet survey also identified 12 patients with Ashkenazi Jewish (AJ) ancestry (6%), a risk factor not accounted for in EMR. Conclusions: Tablet based family cancer history collection is well accepted by patients and easily integrated into clinic work flow. The tablet survey found GC/GT criteria in 50%, and improved identification of key risk factors for BRCA1/2 mutation (AJ ancestry, relative with breast ca < age 50). Further work should focus on integration of tablet based survey data into EMR, and decision support tools to optimize referral and follow through with genetic services.
Implementation and outcomes of lung cancer screening in a community health care system.
Authors: McCabe Vita , Raleigh Ruth , Pichan Alice , Lavasseur Beth Irene , Swarup Rajeev , Fugenschuh David , Ferguson Eric , Stella Philip J. , Griggs Jennifer J.
Published: September 2018

e13035

Background: Lung cancer screening using low dose computed tomography (LDCT) in patients meeting criteria is a covered preventative service under the Affordable Care Act and policies of CMS. The purpose of this study is to describe implementation and results of a lung cancer screening program in a community health care system. Methods: We prospectively collected data on all patients obtaining a baseline LDCT scan who enrolled beginning February 2015. Referring provider, smoking history, demographics, comorbidity, findings, and, in those found to have an abnormality, diagnosis were collected. The study was reviewed by the St Joseph Mercy Health System Institutional Review Board and was considered exempt. Results: Over the course of 18 months, 955 patients were referred for a baseline LDCT. 57% were current smokers, 53% were male, and 38% had no comorbid conditions. The mean number of pack-years was 50 (range 6 to 160). 76% of patients were referred by primary care providers. The number of new patients referred per month increased from 8 to 89, largely due to outreach and education directed at primary care physicians and office staff. Of the 955 patients screened, we identified cancer in 2% overall (small cell cancer in 0.2% patients and non-small cell lung cancer (NSCLC) in 1.6%). Among those with NSCLC, 60% had Stage I disease, 20% had Stage II, 13% had Stage III, and 7% had Stage IV disease. Compared to the stage distribution of lung cancer patients identified before the implementation of the screening program, there was significant down-staging in those with NSCLC. Barriers to implementation have included lack of clear smoking history documentation and billing code release delays which led to reimbursement difficulties. Conclusions: Successful implementation of a LDCT lung cancer screening program in a community setting. Improving patient/provider education and documentation of tobacco use in electronic medical records will streamline the referral process and increase screening among eligible patients. Outreach to practices that serve minority and other medically-underserved populations will require specific efforts to achieve health equity in the area of lung cancer screening.
Precision prostate cancer chemoprevention with gamma-tocotrienol.
Authors: Moore Christine Ann , Palau Victoria , Lightner Janet , Brannon Marianne , Stone William , Krishnan Koyamangalath
Published: September 2018

e13043

Background:  A goal of precision chemoprevention is to prevent or delay cancer progression by using minimally toxic agents guided by knowledge of alterations in oncogenic molecular pathways and signaling cascades. Indolent prostate cancer can benefit from chemopreventive agents by delaying growth. Vitamin E is not a single compound and refers to four tocopherols and four tocotrienols. The use of all-racemic-alpha tocopheryl acetate in preventing cancer was studied in the SELECT clinical trial. This trial found it was not chemopreventive and could promote prostate cancer. We compared the abilities of RRR-alpha-tocopherol (AT), RRR-gamma-tocopherol (GT), and gamma-tocotrienol (GT3) in preventing growth of two prostate cancer cell lines (LNCaP and PC-3) and a control prostate cell line (RWPE-1) by quantifying their effects on two signaling pathways known to be pivotal in prostate carcinogenesis, AKT and MAP Kinase (pERK). Methods:  LNCaP, PC-3, and RWPE-1 cell lines were treated with increasing concentrations of AT, GT and GT3 in DMEM, and cytotoxicity determined by MTS cell culture experiments. We determined the effect of GT3 on signaling pathways by analyzing B-actin, P-AKT and p-ERK in combination with AKT and/or MEK inhibitors via Western immunoblot and PCR analysis. Results:  Initial experiments with LNCaP and PC-3 cells showed GT3 induced the expression of pERK and p-c-JUN, inhibited cell growth and promoted apoptotic cell death. Neither AT nor GT had these effects. AKT was not activated by AT, GT or GT3. Inhibition of AKT activation via MK-2206 did not block GT3 growth inhibition in LNCaP cells. No growth inhibition was found with RWPE-1 control cells in presence of AT, GT or GT3 yet GT3 induced pERK expression. AT did not interfere with cancer growth inhibition and did not block the anticancer effects of GT3. Conclusions: GT3 induces the activation of pERK but this effect is not sufficient to account for the in vitro chemopreventive effects of this form of vitamin E. The AKT pathway is not modulated by GT3 and does not appear to be relevant to GT3 killing of PC-3 or LNCaP. Of five signaling pathways implicated in prostate carcinogenesis, we explored AKT and pERK. Future research will explore B-catenin, mTOR and PI3K.
Identifying women at high-risk for breast cancer using data from the electronic health record compared to self-report.
Authors: Li Xinyi , McGuinness Julia E. , Vanegas Alejandro , Colbeth Hilary , Vargas Jennifer , Sandoval Rossy , Kukafka Rita , Crew Katherine D
Published: September 2018

e13044

Background: One of the barriers to chemoprevention uptake among high-risk women is the lack of routine breast cancer risk assessment in the primary care setting. We calculated breast cancer risk using the Breast Cancer Surveillance Consortium (BCSC) model, which accounts for age, race/ethnicity, first-degree family history of breast cancer, benign breast disease, and mammographic density, using data collected from the electronic health record (EHR) compared to self-report. Methods: Among women undergoing screening mammography, we collected breast cancer risk information from the EHR and a self-administered survey. Eligibility criteria for calculating 5-year invasive breast cancer risk using the BCSC model included age 35-74, no prior history of breast cancer, mastectomy, or breast augmentation. We extracted data on demographics, structured first-degree family history, breast radiology and pathology reports from the EHR. We assessed agreement in breast cancer risk information between the EHR and self-report data. Results: Among 13,735 women with EHR data for BCSC risk calculation, 2708 women (20%) met high-risk criteria, based upon a 5-year breast cancer risk ≥1.67%. Among high-risk women, 2% were age 40-49, 23% age 50-59, 48% age 60-69, and 26% age 70-74. From the EHR, data was missing on 31% for race/ethnicity and 85% for family history. Among 2320 women with both EHR and self-report data, more complete information was available for race/ethnicity, family history, and breast biopsies in the surveys. More first-degree family history (14% vs. 3%) and prior breast biopsies (18% vs. 11%) were identified by self-report vs. EHR, respectively. However, more women with atypia and lobular carcinoma in situwere identified from the EHR. More high-risk women (20% vs. 16%) were identified with EHR vs. survey data, respectively, with correlation of 0.82. Conclusions: Among women undergoing screening mammography, we identified 20% who met high-risk criteria according to the BCSC model based upon EHR data, despite missing information on race/ethnicity, family history, and prior breast biopsies. This may serve as an initial screen for identifying women eligible for breast cancer chemoprevention.
National trends in cholangiocarcinoma in the United States (US): 2000-2014.
Authors: Lee Ru Min
Published: September 2018

e13056

Background: Cholangiocarcinoma (CCA) arise from the epithelial cells of the intrahepatic and extrahepatic bile ducts. Although rare in the US, they are highly lethal because most are locally advanced at presentation. The incidence of CCA has increased over time. This study aims to estimate the characteristics, outcomes, and cost burden of patients hospitalized for CCA by using a large national database. Methods: The Nationwide Inpatient Sample (NIS) database was used to obtain data from 2000-2014. The NIS contains data from over 7 million hospital stays in the US per year generalizable to the American population. The NIS was queried for ICD-9 codes for primary diagnosis of CCA with 155.1 [Malignant Neoplasm of Intrahepatic Ducts (MNID)] and 156.1 [Malignant Neoplasm of Extrahepatic ducts (MNED)]. Information for total number of hospitalizations, mortality, and hospital charges was evaluated. Results: The number of hospitalizations for MNID increased from 2,599 in to 4,840 (p < 0.001) from 2000 to 2014. The number of hospitalizations for MNED decreased from 2,529 to 2,350 but was not statistically significant. Inpatient mortality of MNID decreased from 12.98% to 8.57% (p < 0.05%). Inpatient mortality of MNED decreased from 7.46% to 5.11% but was not statistically significant. Mean charges for MNID increased from $27,779 to $79,096 (p < 0.001). Mean charges for MNED increased from $34,212 to $89,852 (p < 0.001). Conclusions: This study demonstrates that the number of hospitalizations for MNID has increased by 86% from 2000 to 2014. This number continues to rise. However, inpatient mortality of MNID is decreasing. These findings show that the incidence of cholangiocarcinoma of the intrahepatic subtype is increasing and more study is required to investigate why this is so.
Epidemiology and outcomes of bloodstream infections in patients with solid tumors in a Latin American population at Mexico Hospital, San Jose, Costa Rica.
Authors: Calvo Jorge , Villalobos Juan , Ramos-Esquivel Allan , Landaverde Denis Ulises
Published: September 2018

e13057

Background: Bloodstream infections (BSI) are an important cause of mortality in patients with solid tumors. We decided to conduct a retrospective study to evaluate the epidemiological profile and mortality of BSI in admitted patients with solid tumors at Mexico Hospital, being the first study in Costa Rica and also Central America describing our current epidemiological situation. Methods: We analyzed the infectious disease database for BSI in patients with solid tumors admitted in our Institution from January 2012 to December 2014. Epidemiology and mortality was obtained according to microorganism, antibiotic sensitivity, tumor type and presence of central venous catheter (CVC). Descriptive statistics were used. Results: A total of 164 BSI were recorded, the median age was 58 years, 103 cases (63%) were males, 128 cases (78%) were due to gram-negative bacilli (GNB), K. pneumoniae (21%), E. coli (21%) and P. aeruginosa (15%) were the most common microorganisms isolated. Gram-positive cocci (GPC) were found in 36 cases, being the most frequent S. aureus (10%) and S. epidermidis (6%). In respect to tumor type, BSI were more frequent in the gastrointestinal tract, as follow: gastric 43 (27%), colorectal 23 (14%), pancreatic 9 (6%), but also 7 cases (4%) in breast cancer and lung cancer 6 (4%). In terms of antibiotic sensitivity only 17% (GNB) expressed extended spectrum beta-lactamase (ESBL) and 12% (GPC) had methicillin-resistance. Patients with CVC inserted (59 cases) were colonized by GNB (78%). In overall the mortality rate at 30 days was 30%. Conclusions: GNB are the most frequent cause of BSI in solid tumors, and in patients with CVC inserted. Gastrointestinal cancers reported more BSI than other sites. Mortality as well as antibiotic sensitivity remain stable and acceptable during the observational time, in this Latin American population.
A ten-year epidemiology of cancers managed at the hematology and oncology unit of a Haitian tertiary hospital from 2006 to 2015.
Authors: Jacques Flawendjee Djaweelentz , Bernard Joseph , Chalumeau Elsie Metellus
Published: September 2018

e13061

Background: The recent epidemiology of cancers in Haiti is poorly known, since there is no national cancer registry. The data from GLOBOCAN 2012 are estimations that do not reflect the real cancer epidemiology in countries such as Haiti. The aim of this study was to determine the ten-year epidemiology of cancer cases managed at a Haitian tertiary hospital. Methods: A retrospective study based on the chart review of cancer cases aged 18 years old or more with histologic diagnosis was conducted at the Hematology and Oncology Unit of the State University Hospital of Haiti (HUEH) from 2006 to 2015. Variables such as age, gender, year of diagnosis and cancer type were collected. Results: Eight hundred seventy-five cancer cases out of 1191 (73.47%) were selected for this study. The mean age of the study population is 51 years-old [18 – 91] and there were 13.6% males and 86.4% females. Breast cancer is the most common type (70.74% [95% CI, 67.58% - 73.71%]) followed by gastrointestinal cancers (5.6% [95% CI, 4.21% - 7.39%]), leukemias/multiple myeloma (4.69% [95% CI, 3.43% - 6.36%]), skin cancers (4.57% [95% CI, 3.32% - 6.23%]), gynecological cancers (4% [95% CI, 2.84% - 5.58%]), lymphomas (3.77% [95% CI, 2.65% - 5.31%]), sarcomas (3.31% [95% CI, 2.27% - 4.78%]) and ear, nose and throat (ENT) cancers (1.14% [95% CI, 0.58% - 2.16%]). Breast cancer is the most common type among women (80.6%) and the gastrointestinal cancers the most diagnosed among men (21.9%). Conclusions: Breast cancer is by far the most prevalent cancer in this retrospective cohort. Gynecological and lung cancers are underestimated and urology cancers not represented in this sample possibly because they are not systematically referred to the unit.This study can hopefully lead to more advocacy for all patients to be evaluated at the Hematology and Oncology Unit for a better management.
Sociodemographic factors associated with developing head and neck and esophageal cancers following breast cancer.
Authors: Tyker Albina , Dollar Krista , Simpson Matthew , Adjei Boakye Eric , Varvares Mark A , Osazuwa-Peters Nosayaba
Published: September 2018

e13063

Background: Breast cancer survivors may develop other primary malignancies due to several factors. However, sociodemographic factors associated with the development of head and neck (HN) and esophageal second primary malignancies (SPMs) following management of primary breast cancer (BC) have not been well studied. This study examined the association between BC patients’ sociodemographic characteristics and the development of an esophageal or HN SPM. Methods: Patients ( n= 505,641) diagnosed with breast cancer between 1973 and 2013 in the Surveillance, Epidemiology, and End Results (SEER) 9 program were used for this analysis. HN SPMs included oral cavity, pharynx, larynx, and sinuses. Cox proportional hazards regression was used to evaluate estimators of survival based on age at diagnosis, race, marital status, treatment type, and year of diagnosis. Results: A total of 284 BC patients developed an esophageal SPM, and 969 developed HN SPM. In the adjusted model, increased age at BC diagnosis was a significant predictor for developing both HN and esophageal SPMs. For every 1-year increase in age at diagnosis, the hazard of developing an esophageal SPM increased (HR: 1.05; 95% CI: 1.04-1.06) and HN SPM increased (HR: 1.02; 95% CI: 1.02 -1.03). Hispanic women had a decreased hazard (HR: 0.63; 95% CI: 0.47-0.85) of developing HN SPM compared to non-Hispanic White women, however there was no significant difference for esophageal SPM. Women that were married had a decreased hazard (HR: 0.70; 95% CI: 0.55-0.90) of developing esophageal SPM compared to unmarried women. Conclusions: Sociodemographic factors may be important in the development of SPMs after treatment for breast cancer. While older women with BC were more likely to develop SPMs of the HN and esophagus, Hispanic breast cancer survivors and married women were less likely to develop SPMs of the HN and esophagus. To optimize survival benefits in the breast cancer population, there is need to further explore these sociodemographic factors associated with developing SPMs.
Exploring the association between renal cell carcinoma (RCC) and myeloid malignancies.
Authors: Shenoy Niraj Konchady , Mudireddy Mythri , Leung Nelson , Costello Brian Addis , Leibovich Bradley C. , Thompson Robert Houston , Pagliaro Lance C. , Witzig Thomas E. , Ou Fang-Shu , Ordog Tamas , Patnaik Mrinal Mahesh , Tefferi Ayalew , Begna Kebede
Published: September 2018

e13073

Background: We observed several patients with a personal history of both RCC and myeloid malignancy, and aimed to explore a possible association, especially given the similarity in their epigenetic landscape, with both being characterized by widespread aberrant hypermethylation (Hu C et al, CCR 2014; Jiang Y et al, Blood 2009). Methods: Mayo Clinic’s ‘Advanced Cohort Explorer’ database was used to identify patients with a history of both RCC and a myeloid malignancy - Acute Myelogenous Leukemia (AML), Myeloproliferative Neoplasms (MPN), Myelodysplastic syndromes (MDS) - and to determine the clinical characteristics. The incidence of MDS in patients ≥65 years with a history of RCC was compared to that in the general population ≥65 years (SEER- Medicare database) as well as the general patient population at Mayo Clinic, using one sample test of proportions. Results: A total of 59 patients were identified, with both biopsy proven RCC and a myeloid malignancy during their life time (12 AML, 9 MPN, 9 low risk MDS and 29 intermediate- high risk MDS). The cohort was characterized by marked male predominance (4.4: 1). Median age at RCC diagnosis was 64 years (range 37-87) and myeloid malignancy was 75 years (range 44-90). 46/59 patients had the RCC antecedent, 10/59 concurrent and 3/59 subsequent to the myeloid malignancy with a median time of myeloid malignancy diagnosis after RCC diagnosis of 7.7 years. For patients ≥65 years, the risk of developing MDS with a history of stage I/II RCC and nephrectomy was 5.26 times that of the general population based on the SEER-Medicare database (Cogle, Blood 2011)(395/100,000 vs 75/100,000; p value < 0.001), and 3.07 times that of the general population at Mayo Clinic (395/100,000 vs 128.4/100,000; p value < 0. 001). Conclusions: We observed an association between RCC and myeloid malignancies, particularly MDS; with a history of RCC conferring a substantially increased risk of developing MDS. We hypothesize that the perturbation of epigenetic landscape in the form of widespread hypermethylation may explain, in part, the association between the two malignancies; and aim to explore the potential aberrancy of epigenetic regulators in our patient cohort with a genomic, epigenomic and transcriptomic analysis.
Prevalence of EGFR mutations in the Peruvian population: Study in a large cohort of patients with NSCLC.
Authors: Mas Luis , Piscocha Christian , Landa Jose , Roe Carlos , Roe Eduardo , Barletta Claudia , Velarde Raul E. , Larrabure Luis , Jauregui Sandra , Flores Christina , Gomez de la Torre Juan C
Published: September 2018

e13076

Background: The evaluation of EGFR mutational status of the EGFR in non-small cell lung cancer (NSCLC) is crucial to select the adequate targeted therapy and to know the outcome of patients. Previous studies in relative small sample sizes have described a higher prevalence of EGFR mutations in Peruvian population than other Latin American countries. Our aim in this study was to determine the prevalence of activating and resistance mutations of EGFR in a large cohort of Peruvian patients. Methods: We profiled metastatic tumor samples from 847 NSCLC patients for known EGFR mutations associated to sensitivity or resistance EGFR inhibitors, including exon 18 (G719X), exon 19 (deletions), exon 20 (T790M, S768I and insertions) and exon 21 (L858R). All samples were centrally tested in reference laboratory (Roe laboratory, Lima-Peru). Results: A total of 847 samples were profiled for EGFR mutational status. EGFR mutations were present in 32.9% of cases (n = 279). In regard to distribution of mutations in cases EGFR mutated, G719X (in exon 18) was present in 2.5% (n = 7); deletions in exon 19 had a frequency of 58.4% (n = 163). Mutations in exon 20 were present in 9.7% (n = 27). In patients with exon 20 mutated, 14 cases had insertions, 9 cases had the mutation T790M and 4 cases had the mutation S768I. Mutation L858R (exon 21) was present in 34.1% (n = 95) of cases. Coexistence of two mutations were present in exon 18/exon 20 (n = 1), exon 19/exon 20 (n = 7) and exon 20/ exon 21 (n = 5). In tumors with EGFR mutated. The sensible profile for EGFR tyrosine kinase inhibitors (TKI´s) was present in 96.8% of cases (n = 138). Conclusions: We have a high prevalence of EGFR mutations compared than Caucasian or other Hispanic cohorts. It has relevance in the Peruvian public health because more efforts should be done to screen NSCLC patients for EGFR mutations.