tbuckley/cabot-search huggingface dataset:
Influence of organ location and sex of patient on pancreatic neuroendocrine tumor 5-year survival.
Authors: Gregory P. Botta, Munveer Singh Bhangoo, Darren Sigal
Journal: Journal of Clinical Oncology (2017)

e15713 Background: Pancreatic neuroendocrine tumors (PNET) represent a rare tumor histology among patients diagnosed with pancreatic cancer (less than 2% incidence). These tumors arise from the endocrine tissues of the pancreas and can present with a variable clinical course. We sought to examine the overall survival (OS) of patients based upon sex and anatomic location via the SEER database. Methods: Accessing the SEER-Medicare database, we identified 3,242 patients with both Pancreatic Cancer and Neuroendocrine Tumor (NET) histologic validation using ICD-O-3 Codes while excluding Large Cell, Small Cell, and Mixed Endocrine-Exocrine tumors. We then sub-stratified the data to male (N = 1816) and female (N = 1426) sex as well as pancreatic location: Head (Male = 831; Female = 657), Body (Male = 283; Female = 258), or Tail (Male = 701; Female = 510). We excluded PNETs of the pancreatic duct as there were only 2 cases (Male = 1; Female = 1). All comparison tests were run with SEER*STAT 8.3.2 via a Two-Sample t-Test Assuming Equal Variances. OS was analyzed using the Kaplan–Meier method. Results: Overall, both Male and Female patients with PNET have significantly improved 5-Year survival compared with those patients with Pancreatic Adenocarcinoma ((47.47% (n = 3242) vs 6.6% (n = 117,204), p &lt; 0.05). There is no difference in 5-Year OS between Male (44.9%) and Female (50.5%) patients with PNET accounting for all locations. There is a trend towards significance in improved 5-Year OS in Female patients with Tail PNET versus Male patients with Tail PNET (55.8% (n = 510) vs 48.6% (n = 701), p &lt; 0.06). Significantly, Female patients with Tail PNET have a significantly higher 5-Year OS compared to Female patients with Head PNET (55.8% (n = 510) vs 46.9% (n = 657), p &lt; 0.05). There was a trend towards improved 5-Year OS in Female patients with Tail PNET versus those within the Body (55.8% (n = 510) vs 48.6% (n = 258), p &lt; 0.01). Conclusions: Based upon this population study, Female patients with PNET localized to the Tail have a significantly higher 5-Year OS than Female patients with PNET localized to the Head of the Pancreas. These same patients trend towards improved survival when compared with Female patients with Body PNET as well as Male patients with Tail PNET.
TCT-231 An artificial intelligence based solution for fully automated cardiac phase and end-diastolic frame detection on coronary angiographies
Authors: Costin Ciusdel, Alexandru Turcea, Andrei Puiu, Lucian Itu, Lucian Calmac, Emma Weiss, Cornelia Margineanu, Elisabeta Badila, Tiziano Passerini, Mehmet Gulsun, Puneet Sharma
Journal: Journal of the American College of Cardiology (2018)
Metastatic disease representation: An analysis of 148 paired colorectal cancer lymph node metastatic tumour deposits.
Authors: Lennard YW Lee, Joanna Anderson, Roland Arnold, Luke Freeman Mills, Lai Mun Wang, Ian Tomlinson
Journal: Journal of Clinical Oncology (2018)

e15595 Background: Metastasis is a key hallmark of cancer and the principal cause of death of patients with colorectal cancer (CRC). Lymph node metastatic tumour deposits (LNMTD) are of interest as its presence is a histological feature that defines colorectal cancer stage and closely linked to patient survival. There have been no studies looking at the transcriptional profiles of LNMTD in CRC. Methods: A prospective cohort of 148 stage III CRC patients was assembled and paired RNA sequencing performed of the primary tumour and LNMTD. Results: LNMTD gene expression profiles were markedly different from the primary tumour and we identified and validated 95 genes that were differentially expressed in the LNMTD with changes in expression of ZEB2, DOCK10, MRC2. A number of gene sets, such as “MYC” and “MTORC1” signalling were linked with patient prognosis and we demonstrated that these could be successfully incorporated into predictive machine learning algorithms for stage III CRC. Conclusions: This study has highlighted the presence of intra-patient heterogeneity between the LNMTD and primary tumour and our results supports the importance of understanding metastatic disease representation as a means to increase our understanding of cancer biology and personalised therapies.
Association of androgen receptor (AR) gene status in plasma DNA with outcome on enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC): Exploratory results from the PREMIERE trial—On behalf of SOGUG.
Authors: Enrique Grande, Albert Font Pous, Natalia Fernández Núñez, Aranzazu Gonzalez del Alba, Begoña Mellado, Ovidio Fernandez Calvo, Maria Jose Mendez, Miguel Ángel Climent, Ignacio Duran, Enrique Gallardo, Angel Rodriguez Sanchez, Carmen Santander, M Isabel Sáez, Javier Puente, Maria Piedad Fernandez Perez, Vincenza Conteduca, Daniel Wetterskog, Gerhardt Attard, Daniel Castellano, Enrique Gonzalez-Billalabeitia
Journal: Journal of Clinical Oncology (2017)

5016 Background: Building on previous discoveries studying AR status in plasma (Carreira S, Sci Transl Med 2014, Romanel A, Sci Transl Med 2015) and following a road-map for biomarker development, we aimed to clinically qualify AR status in chemotherapy-naïve mCRPC using an optimized multiplex droplet digital PCR (ddPCR) assay (Condeduca et al.;ASCO2017;Abstract#). Methods: Between February and November 2015, 98 asymptomatic or oligo-symptomatic chemotherapy-naïve mCRPC patients were recruited in 16 Spanish hospitals. Tissue and blood samples were required at study entry. Although initially designed to study the predictive value of TMPRSS2-ETS, data emerging after the trial was initiated led the group to prioritize alternative predefined exploratory biomarkers, including plasma ARand CTC characterization (Grande E. ESMO 2016 &amp; Font A. et al; ASCO2017; Abstract #). Outcome measures included PSA-progression-free survival (sPFS), radiographic progression-free survival (rPFS) and overall survival (OS). Cox regression was used for survival analyses and Fisher’s exact test for PSA response. Results: Ninety-four patients had plasma DNA available for analysis. At baseline, AR gain was present in 11 pts (12%) and CTCs in 35 (37%). AR gain in CTC-positive and negative patients was 20% and 7%, respectively. At first interim analysis and with a median follow-up of 10.6 months, detection of AR gain was associated with worse sPFS (median, 3.60 versus 15.5 m, HR, 4.33; 95% CI 1.94-9.68; P &lt; 0.001), rPFS (median, 3.90 m versus not reached HR, 8.06; 95% CI, 3.26-19.93; P &lt; 0.001) and OS (medians not reached, HR, 11.08; 95% CI, 2.16-56.95; P = 0.004). These results were independently associated in multivariate analysis including cfDNA and CTCs for all described endpoints. AR gain patients were less likely to have a ≥50% decline in PSA (OR, 4.93; 95% CI, 1.30-18.75; P = 0.025). Conclusions: Detection of AR gain in plasma using a robust multiplex ddPCR method predicts an adverse outcome in chemotherapy-naïve mCRPC. Further prospective randomized studies are warranted. Clinical trial information: NCT02288936.
CDC Grand Rounds: Promoting Well-Being and Independence in Older Adults
Authors: Benjamin S. Olivari, Matthew Baumgart, Sarah L. Lock, C. Grace Whiting, Christopher A. Taylor, John Iskander, Phoebe Thorpe, Lisa C. McGuire
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Healthy aging is not merely the absence of disease or disability, but requires physical and mental health and ongoing social engagement (1). As the average U.S. life expectancy increases, recognition that public health can play a vital role in promoting healthy, successful aging even in the face of increased prevalence of chronic diseases, including types of dementia, among older adults (i.e., aged ≥65 years) has grown. Furthermore, actively engaging adults in prevention and wellness along with involving their caregivers (i.e., the family and friends of older adults who provide them with unpaid and informal support and services) can serve to prevent or delay the onset of physical disabilities and cognitive decline. Adults often are reluctant to discuss their concerns about worsening memory with their health care providers although such discussions can lead to earlier diagnosis and better care, planning, and support. As advances in public health and health care have helped increase life expectancy, public health professionals and health care providers have the opportunity to improve the quality of life for older adults and their caregivers and reduce the burdens associated with aging.
Clinical utility of reflex testing using focused next generation sequencing for management of patients with advanced lung adenocarcinoma.
Authors: Navid Sadri, Tyler E Miller, Michael Yang, Afshin Dowlati, Judah D. Friedman, David Lawrence Bajor, Richard Y. Chang, Joseph E Willis
Journal: Journal of Clinical Oncology (2018)

e24199 Background: Genomic testing is an increasingly important part of directing therapy for cancer patients, especially in lung cancer where there are an increasing number of genomically-directed therapies. However, testing failure, costs, and long turn-around times can be barriers to treatment. Effective approaches to reduce these barriers are needed. Methods: Over 14 months, starting in December 2016, 282 tumors from patients seen at University Hospitals Cleveland Medical Center (UHCMC) or UH affiliated community hospitals with advanced lung adenocarcinoma were tested in-house using the Oncomine™ Focus Assay. Sample testing was reflexed from pathology for all stage III or IV tumors. Genomic alterations were tiered according to their clinical relevance and reported. Clinical implications of genomic testing was assessed by manual chart review. Results: With a sample cohort consisting of 63% biopsies, 19% fine-needle aspirations, and 18% resections, the assay was reliable with a 93% success rate. The average turn-around time from receipt of FFPE slides to reporting was 5.0 ± 2.1 days, half of the recommended 10 days. Genomic alterations were found in 79% of cases. KRAS mutations made up 41% of these alterations, consistent with a higher smoking population. Alterations with FDA-approved or NCCN guideline-recommended targeted therapies were found in 19% of cases. Within this group, 56% of patients went on genomically-driven therapies (see table). Conclusions: Incorporation of reflex and in-house testing with a reliable and cost effective NGS assay can led to an expansion of successful genomic profiling for advanced lung adenocarcinoma patients in a timely fashion. This approach has the potential to increase the utilization of genomically-driven targeted therapy and reduce time to treatment. Clinical Action EGFR mutation ALK fusion BRAF V600E MET ex.14 skip ERBB2 mutation RET fusion Total (%) Genomic-driven therapy 18 4 3 2 27 (50.9) Immunotherapy (PD-L1+) 1 2 3 (5.7) Chemo-radiation 3 1 2 2 2 10 (18.9) Hospice (no therapy) 4 1 5 (9.4) Lost to follow-up 3 1 1 1 2 8 (15.1) Total (% of all tumors) 28 (9.9) 5 (1.8) 5 (1.8) 8 (2.4) 3 (1.1) 4 (1.4) 53 (18.8)
Integration of lymphocyte ratios (LRs) and circulating tumor cells (CTCs) characterization: The interplay between immunity and metastatic breast cancer (MBC).
Authors: Lorenzo Gerratana, Michela Bulfoni, Debora Basile, Giacomo Pelizzari, Marta Bonotto, Antonio Paolo Beltrami, Qiang Zhang, Alessandro Marco Minisini, Carla Di Loreto, Gianpiero Fasola, Massimo Cristofanilli, Daniela Cesselli, Fabio Puglisi
Journal: Journal of Clinical Oncology (2018)

12039 Background: The detection of CTCs in MBC is associated with worse prognosis and metastases development. We evaluated the integration of immunity biomarkers such as monocyte, neutrophil and platelets LRs (MLR, NLR, PLR) with CTCs data to identify new clues about the interaction between MBC and the immune system. Methods: The study enrolled 44 MBC patients (pts) at the University Hospital of Udine, Italy, between 2013 and 2015, regardless of the line of treatment. CD45neg circulating cells (CC) were sorted through the DEPArray microfluidic system, based on a multiparametric fluorescence analysis. The CD45neg CC phenotypes were defined as epithelial (E CTC), mesenchymal (MES) and transitional (EM CTC). MLR, NLR and PLR cut-offs were previously obtained through ROC analysis using propensity score-matched healthy controls (Gerratana et al 2018). The association between LRs and CD45neg CC was explored through Kruskal Wallis test. CC subtypes were analyzed both as a percentage of total CD45neg CCs and as absolute values. Results: In luminal-like MBC pts, both NLR and PLR were significantly associated with EM CTC (P = 0.016), while a trend was observed in respect to MLR. In pts with HER2 positive MBC, PLR was significantly associated with E CTC (P = 0.042). Notably, only MLR was associated with EM CTC in the total population (P = 0.02). Pts with visceral involvement had higher EM CTC and E CTC when MLRhigh (P = 0.036 and P = 0.031, respectively) and E CTC when PLRhigh (P = 0.025), while MES was significantly lower when MLRhigh (P = 0.001). In particular, in case of liver localizations, the MLRhigh subgroup showed higher E CTC (P = 0.022) and lower MES (P < 0.001). Pts with bone localizations had lower MES when MLRhigh (P = 0.004). Interestingly, MLRhigh pts with 2 or more sites of distant involvement, had higher EM CTC and lower MES (P = 0.015 and P < 0.001, respectively). Conclusions: MLR is associated with CD45neg CC subtypes proportions. Particularly intriguing is the direct correlation with EM CTCs suggesting an interlink between CTC and immunity in MBC pathogenesis and progression. Moreover, these findings highlight the need to explore more granular classifications for CD45neg CC.
Phase II study of stereotactic radiosurgery or other local ablation followed by erlotinib for patients with EGFR mutation who have previously progressed on an EGFR tyrosine kinase inhibitor (TKI).
Authors: Jared Weiss, Brian D. Kavanagh, Allison Mary Deal, Timothy Zagar, Lawrence Bruce Marks, Tom Stinchcombe, Hossein Borghaei, Howard Jack West, David E. Morris, Liza Cosca Villaruz, Nathan A. Pennell
Journal: Journal of Clinical Oncology (2017)

e20623 Background: For patients with metastatic EGFR mutated NSCLC, 1 st line treatment with EGFR TKIs such as erlotinib result in a median PFS of about 10 months. In patients with a limited number of progressing lesions, local ablation therapy (LAT) of progressive lesions followed by re-initiation of TKI has shown promise in retrospective studies but to date this strategy has not been testing in prospective fashion. Methods: As part of an IRB approved open label prospective phase II trial (NCT01573702), patients with EGFR mutated NSCLC and immediate progression on a TKI in &lt; 5 locations were treated with stereotactic radiosurgery (SRS) to progressing lesions followed by re-initiation of erlotinib. Our primary endpoint is PFS, and we hypothesize that it will be at least 3 months. Results: 25/40 planned patients have been enrolled and data is available on 23. By local reporting, 14 had exon 19, 5 had exon 21, 1 had compound exon 18 and exon 20, 1 had compound exon 19 and EML4/ALK and 2 were unknown. 65% were female, all were non-Hispanic white, median age 62.5 (range 43-85), PS0 65.2%/PS1 34.8%, median Charlson Comorbidity Index 6, and 71.4% were never smokers. Median number of lesions treated was 1 (range 1-3). Treated lesions included lung (14), bone (6), liver (3) and brain (2). There were no G3-4 AEs to SRS. Two subjects had grade 3 rash on erlotinib. Median PFS post treatment was 5.8 months (95% CI, 2.5 to 11.3) and median OS was 2.9 years (95% CI 1.1 to 2.9). Conclusions: LAT resulted in a modest extension in the duration of targeted therapy, supporting retrospective data in this population. Accrual to this study has been challenging due to the availability of 3 rd generation EGFR TKIs and because LAT is often done outside of a clinical trial. Clinical trial information: NCT01573702.
AGO-OVAR 16: A phase III study to evaluate the efficacy and safety of pazopanib (PZ) monotherapy versus placebo in women who have not progressed after first line chemotherapy for epithelial ovarian, fallopian tube, or primary peritoneal cancer—Overall survival (OS) results.
Authors: Ignace Vergote, Lars Christian Hanker, Anne Floquet, Joern Rau, Jae-Weon Kim, Eugenia Ortega Izquierdo, Michael Friedlander, Sandro Pignata, Keiichi Fujiwara, Nicoletta Colombo, Mansoor Raza Mirza, Bradley J. Monk, Manfred Mörtl, Paula Calvert, Thomas J. Herzog, Christian Jackisch, Jérome Meunier, Jung-Yun Lee, Antje Kristina Belau, Andreas Du Bois
Journal: Journal of Clinical Oncology (2018)

5518 Background: AGO-OVAR 16 study investigated PZ, an oral multi-kinase inhibitor of VEGFR-1, -2, -3, PDGFR-α and -β and c-Kit. This study was designed to test efficacy, safety and tolerability of PZ maintenance after first-line chemotherapy in newly diagnosed advanced ovarian cancer (AOC). The results of final analysis of OS following last patient last visit (LPLV) after prespecified futility criteria were met during 3rd OS interim analysis (IA) are reported. Methods: Inclusion criteria: Patients with histologically confirmed AOC; prior treatment of surgical debulking and at least five cycles of platinum-taxane chemotherapy with no evidence of progression; and no bulky disease or disease requiring imminent therapy. Nine hundred and forty patients were randomized in a 1:1 ratio to receive either 800 mg PZ once daily or placebo for up to 24 months unless disease progression, toxicity, withdrawal of consent, or death. The Primary endpoint (investigator assessed progression-free survival (PFS) was met (J Clin Oncol. 2014 Oct 20; 32:3374-82). The 3rd IA of OS (key secondary endpoint) confirmed futility (conditional power < 1%), and led to study closure and a final analysis after LPLV. Results: The final OS analysis was conducted after 494 (89.7% of the planned 551) events occurred. No difference was observed in OS between PZ and placebo. The HR was 0.960 (95% CI: 0.805, 1.145), and the median OS was 59.1 months in PZ and 64.0 months in placebo. For the East Asian patients, similar to the first three OS IA, a numerical negative trend was observed favoring placebo (HR = 1.332, 95% CI: 0.863, 2.054). Exploratory analyses showed a trend for a longer time to first subsequent anticancer therapy or death with PZ over placebo (HR = 0.829, 95% CI: 0.713, 0.965) with a median estimate of 19.0 and 14.5 months, respectively, suggesting that the PFS benefit remained with additional data maturity. Conclusions: Although PZ prolonged PFS, OS benefit was not demonstrated. Clinical trial information: NCT00866697.
Mucinous colorectal carcinoma to predict poor outcome in young patients.
Authors: Basem Gamal Abdelghany Soliman, Gamal Amira, Hesham Mohamed Hamza, Hamza Abbas Hamza, Ahmed Salem, Ashraf Elyamany, Ali Zedan, Mahmoud Elshoieby, Hussein Fakhry, Murad Ali Jabir, Kareem Abu-Elmagd
Journal: Journal of Clinical Oncology (2016)

e15076 Background: The prognostic significance of mucinous colorectal carcinoma (MC) is controversial, potentially due to heterogonous nature of populations studied. Clinically, we noticed that the young MC patients had more frequent and earlier recurrence compared to nom-mucinous colorectal cancer patients (NMC). We performed this study to compare the oncological outcome in young patients with MC and NMC. Methods: A single-institution prospectively maintained colorectal cancer database was queried for patients with colorectal adenocarcinoma (CRC) less than 40 years of age. Medical records were reviewed for clinicopathological characteristics, treatment, and oncologic outcomes. Patients with inflammatory bowel disease and hereditary colorectal cancer syndromes were excluded. The population was categorized as MC or NMC according to the presence of mucinous histology (extracellular mucin over 50%) on pathology reports. Results: We identified 84 patients who were younger than 40 years-old and underwent resection for CRC between 2003 and 2011. The mean age was 30 years and 50% were female. 44 patients (52.4%) had rectal cancer. 41 patients (48.8%) had MC histology and 43 (51%) had NMC histology. MC patients were younger (28 ± 6 years vs. 31.5 ± 6 years, p = 0.01), and MC occurred more often in men (65% vs 35%, p = 0.02). The MC and NMC study populations were not statistically different in terms of tumor site, pathological stage, T stage, N stage, m stage, differentiation degree, or the use of neoadjuvant and adjuvant therapy. MC tumors were larger in size (4.9 ± 2.8 cm vs. 3.4 ± 2.7 cm, p = 0.01) and were more likely to have angiolymphathic invasion (27.8% vs. 7.7%, p < 0.001). Five-year disease free survival (DFS) was (20.2% vs. 38.3%, p = 0.006) and five-year overall survival (OS) was (24.7% vs 47.8%, p = 0.002) for young patients with MC compared to NMC. Multivariate analysis revealed that the mucinous pathology was independent negative prognostic factor for both DFS and OS. Conclusions: Mucinous differentiation in young CRC patients is an independent poor prognostic factor predicting more frequent and earlier recurrence and reduced overall survival. Physicians need to be attentive of this association and possible novel treatment options should be explored.
TCT-266 OCT and Histopathological Assessment of Coronary Plaque Obtained by Directional Coronary Atherectomy
Authors: Hiroshi Okamoto, Teruyoshi Kume, Tomoko Tamada, Terumasa Koyama, Koichiro Imai, Ryotaro Yamada, Yoji Neishi, Shiro Uemura
Journal: Journal of the American College of Cardiology (2018)