tbuckley/cabot-search huggingface dataset:
Pancreatic cancer survival trends overall, by stage, and histologic sub-type: An analysis of Surveillance, Epidemiology and End Results (SEER) population-based data (2000-2015).
Authors: Parisa Karimi, Vanessa L Gordon-Dseagu, Pavel Chernyavskiy, Michael Goggins, Philip S. Rosenberg, Rachael Stolzenberg-Solomon
Journal: Journal of Clinical Oncology (2019)

e15772 Background: Pancreatic cancer (PC) is the third leading cause of cancer mortality in the United States, with an overall relative 5-year survival rate of 8.2%. We conducted a comprehensive evaluation of survival trends after PC diagnosis overall and by stage and histologic sub-type. Methods: We conducted a retrospective, population-based study of 91,234 PC cases using nationally representative data from the SEER program to evaluate 5-year survival trends by histologic sub-type from 2000 to 2015. Our model incorporated sub-type-specific random intercepts to effectively stabilize survival estimates by borrowing information across all sub-types. The estimation was performed in a fully Bayesian setting in R. Results: Adenocarcinoma, not otherwise specified (NOS) and ductal adenocarcinomas comprised 81% of PC. Cancer stage and histologic sub-type were both important factors in explaining variability in 5-year survival. We observed a consistent ordering of cancer stages within each histologic sub-type from highest to lowest survival for local, regional, and metastatic disease, respectively. Adenocarcinoma not otherwise specified, ductal adenocarcinoma, ductal specified as mucinous, and poorly specified type had the lowest 5-year survival with fitted ranges of 25-35% for localized, 5-19% for regional and &lt; 4% for metastatic disease. Ductal arising from intraductal papillary mucinous neoplasm, ductal specified as cystic, acinar cell, other adenocarcinoma, and non-carcinomas had intermediate 5-year survival of 54-75%; while endocrine non-secretory or neuroendocrine, endocrine secretory, carcinoid, and solid pseudopapillary cancers had the best survival (87-98%). On average, across histologic sub-types, PC survival improved by 0.5% (90% credible interval 0.01%, 1.0%) per year, or 5.1% (0.1%, 10.0%) per decade. Some improvement in fitted survival occurred across all stages and histologic sub-types. Conclusions: Overall survival for patients with PC has improved by around 5% per decade from 2000 to 2015, with significant heterogeneity by histologic sub-type.
Clinical impact of the Mexican healthcare system "Seguro Popular" on breast cancer survival.
Authors: Luis Antonio Cancel, Carlos Eduardo Salazar-Mejía, Francisco Emilio Vera Badillo, Juan Francisco Gonzalez Guerrero, Jackeline Grace Lara-Campos, Lorena Itzel González-Palau, Blanca Otilia Wimer-Castillo, Oscar Vidal-Gutiérrez, Jose Luis Gonzalez Vela, Diego A Jaime-Villalon
Journal: Journal of Clinical Oncology (2019)

6569 Background: Breast cancer (BC) is one of the leading issues in public health in low and middle-income countries. In Mexico, access to healthcare is fragmented according to the patient´s employment and not by its needs; IMSS and ISSTE (Social Security) provide access to prepaid medicine to those under the formal sector of the economy, leaving up to 50 million Mexicans without access to a prepaid scheme. In 2003, the Seguro Popular (SP) was created in order to bring universal access to prepaid medicine in Mexico, and in 2007 expanded its coverage for BC. Methods: Retrospective and comparative study. The primary endpoint was to determine the impact on survival of SP on BC. Records were obtained from the electronic database of the Hospital Universitario “Dr. José Eleuterio González”. We included patients with invasive BC stage I-IV. Patients with any other kind of healthcare schemes other than SP, patients who underwent treatment outside our institution, and those with a follow up no greater than 3 months were excluded. 104 patients from the period prior the implementation of the SP (2000-2007) met the criteria for evaluation; thereafter we randomly selected a second cohort with the same size from the period after the implementation of the SP (2008-2013). Results: Median age at diagnosis was 48 and 51 years, respectively, for the periods before and after the implementation of SP. Distribution by clinical stage (Non-SP vs SP): CS I, 4.8 vs 10%, CS II, 31 vs 44%, CS III, 52 vs 38%, and CS IV, 10 vs 6.7%. Molecular subtypes distribution (Non-SP vs SP): Luminal, 61 vs 62%, HER2 Positive (IHC+++/FISH+) 17 vs 22%, TNBC, 21 vs 18%, unknown 6.7 vs 5.7%. Regarding survival, we observed a statistically significant difference on progression-free survival and overall survival favoring the SP cohort; PFS at 5 years, 54 vs 81% (p = &lt; 0.0001) and OS at 5-year, 72 vs 86% (p = 0.01). Conclusions: We present evidence that the Mexican healthcare scheme SP, created to bring medical access to those patients without prepaid health protection, provides a significant clinical benefit on survival (PFS and OS) in women with breast cancer.
Single agent of apatinib in patients with recurrent or refractory cervical cancer: A real-world multicenter retrospective study.
Authors: Ning Li, Ziyi Wang, Jing Wang, Lingying Wu
Journal: Journal of Clinical Oncology (2019)

e17011 Background: Few effective treatment strategy has been established for patients with recurrent or refractory cervical cancer. The present study evaluates the efficacy and safety of apatinib single agent in Chinese patients with recurrent or refractory cervical cancer. Methods: Records of patients with cervical cancer treated from October 1, 2016 to December 31, 2017 in Cancer Hospital, Chinese Academy of Medical Sciences and Hunan Cancer Hospital were reviewed. Patients who met the following criteria were included: 1) patients had pathologically confirmed cervical cancer; 2) patients who experienced progression within 6 months or during previous treatment; 3) patients were given 250 mg apatinib daily for the present recurrence; 4) medical records were complete for evaluation of efficacy and toxicity. Tumor response was determined according to RECIST 1.1. The toxicity was determined according to CTCAE 4.0. SPSS 20.0 was adopted for statistic analysis. The primary endpoint was progression-free survival (PFS). Results: Twenty-nine patients were enrolled in our retrospective study. The clinical characteristics were shown in table 1. Thirteen patients (44.8%) had persistent disease and the other 16 patients (55.2%) had recurrent disease less than 6 months after the last treatment. Up to February 1, 2018, the median follow-up time was 8 months. Five (17.2%) patients achieved partial response, and 11 (37.9%) achieved stable disease, representing a disease control rate of 55.1%. The median PFS was 4 months (1-16 months). Nine patients were still on medication. The reasons of discontinued intervention were disease progression (80.0%, 16/20), toxicity (10.0%, 2/20) and other events unrelated with apatinib (10.0%, 2/20). Common adverse events were hypertension (G1, 65.5%), mucositis (G1, 55.2%), hand-foot syndrome (G1-2, 44.8%) and proteinuria (G1-2, 20.7%). Grade 3 proteinuria occurred in 1 patient (3.4%,). Conclusions: Apatinib single agent might be an effective and tolerable choice for patients with recurrent or refractory cervical cancer. Further study is warranted.[Table: see text]
Outcome of children with malignant germ cell tumors by response status at the end of induction chemotherapy.
Authors: Adriana Fonseca, Doojduen Villaluna, Mark D. Krailo, A. Lindsay Frazier, Furqan Shaikh
Journal: Journal of Clinical Oncology (2019)

10023 Background: The management of pediatric malignant germ cell tumors (MGCTs) includes induction therapy with 3-4 cycles cisplatin, etoposide, bleomycin (PEb). The current practice recommends 2-3 cycles of PEb (total 6 cycles) as consolidation therapy if response is not complete at the end of induction, a significantly different approach than that used in adult patients who receive a standard number of cycles. Furthermore, there is no evidence supporting the addition of a consolidation phase with PEb in pediatric patients with MGCTs. Methods: We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs (AGCT0132). All patients received 3 cycles of PEb and underwent response assessment at the end of induction. Complete Response (CR) was defined as negative tumor markers and no viable residual lesion. Patients in CR were not to receive any further chemotherapy. Patients not in CR were prescribed 3 additional cycles of PEb as consolidation. Event-free survival (EFS) and Overall survival (OS) was calculated using the Kaplan-Meier method. Results: Among 210 patients enrolled, 193 patients had CR after 3 cycles of induction chemotherapy, and their post-induction 4yr-EFS and OS was 93% and 99%. Fifteen patients were not in CR at the end of the first 3 cycles and received additional chemotherapy, and their 4yr-EFS and OS was 51% and 60%. Conclusions: Children with MGCTs who have a partial response after the first 3 cycles of chemotherapy had an inferior outcome compared to those with a CR, despite receiving additional cycles of PEb chemotherapy. Thus, we conclude that consolidation is of unclear benefit. Although our results are limited by small sample size and lack of comparator, we propose that pediatric MGCT patients who fail to achieve a CR after standard induction chemotherapy should receive a salvage regimen with different agents rather than consolidation with more cycles of the same chemotherapy.
A genomic atlas of systemic interindividual epigenetic variation in humans
Authors: Chathura J. Gunasekara, C. Anthony Scott, Eleonora Laritsky, Maria S. Baker, Harry MacKay, Jack D. Duryea, Noah J. Kessler, Garrett Hellenthal, Alexis C. Wood, Kelly R. Hodges, Manisha Gandhi, Amy B. Hair, Matt J. Silver, Sophie E. Moore, Andrew M. Prentice, Yumei Li, Rui Chen, Cristian Coarfa, Robert A. Waterland
Journal: Genome biology (2019)

DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample. We describe an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is not tissue-specific. For each of 10 donors from the NIH Genotype-Tissue Expression (GTEx) program, CpG methylation is measured by deep whole-genome bisulfite sequencing of genomic DNA from tissues representing the three germ layer lineages: thyroid (endoderm), heart (mesoderm), and brain (ectoderm). We develop a computational algorithm to identify genomic regions at which interindividual variation in DNA methylation is consistent across all three lineages. This approach identifies 9926 correlated regions of systemic interindividual variation (CoRSIVs). These regions, comprising just 0.1% of the human genome, are inter-correlated over long genomic distances, associated with transposable elements and subtelomeric regions, conserved across diverse human ethnic groups, sensitive to periconceptional environment, and associated with genes implicated in a broad range of human disorders and phenotypes. CoRSIV methylation in one tissue can predict expression of associated genes in other tissues. In addition to charting a previously unexplored molecular level of human individuality, this atlas of human CoRSIVs provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease.
Trends in pancreatic cancer chemotherapy treatment in the United States from 2008 through 2016.
Authors: Shirley Hui, David Bernstein, Vinod P. Balachandran, Henry J. Henk
Journal: Journal of Clinical Oncology (2019)

e15734 Background: Pancreatic cancer is the third leading cause of cancer death in the United States. 55% of patients present with advanced disease at diagnosis and are treated with chemotherapy, with gemcitabine and 5FU-backbone based therapies both demonstrating efficacy. However, data on the adoption of these of therapies in academic and non-academic centers is scarce. The goal of this study is to examine the aggregate adoption of these therapeutic regimens in widespread clinical practice from 2008 through 2016 using health plan claims data. Methods: Privately insured and Medicare patients with advanced pancreatic cancer treated with chemotherapy from 2008 through 2016 were identified from the OptumLabs Data Warehouse. First-line treatment regimen and duration were correlated with age, sex, race, Charlson Comorbidiy Index (CCI) score, and opioid use measured by morphine milligram equivalents (MME) (as a proxy for pain) in the 6 months prior to starting chemotherapy. Disease status was classified as advanced, adjuvant or neo-adjuvant. Results: For 14,301 patients treated with chemotherapy primarily, the use of monotherapy has significantly decreased from 73% to 27% (p &lt; 0.001) between 2008 and 2016, while combination therapy using two antineoplastic agents (20% to 41%; p &lt; 0.001) and three or more agents (6% to 32%; p &lt; 0.001) increased. Since 2013, patients receiving combination therapy vs. monotherapy are significantly younger (mean 66 vs. 70; p &lt; 0.001), have higher CCI (6.3 vs. 6.1; p = 0.002), and have similar daily opioid dose prior to chemotherapy (5.2 vs. 3.8 MMEs; p = 0.086). Duration on first-line regimen was greater in patients receiving combined therapy, compared to those on gemcitabine monotherapy (median 130 vs. 119 days; p &lt; 0.001) after adjusting for CCI, disease status, and demographics. Conclusions: The use of combined therapy for the treatment of pancreatic cancer has increased over time, with patients on combined therapy appearing to be younger. [Table: see text]
Lenvatinib for the treatment of HCC: A single institute experience.
Authors: San-Chi Chen, Yee Chao, Ming Huang Chen
Journal: Journal of Clinical Oncology (2019)

e15611 Background: Lenvatinib, a multiple kinase inhibitor, is an emerging for the treatment of advanced HCC. In REFLECT study, lenvatinib demonstrated higher ORR and longer PFS than sorafenib as the first line treatment for patients with Child-Pugh score A and tumor less than 50% of liver occupation. However, the efficacy for patients failed with sorafenib, with Child-Pugh score B and C, tumor more than 50% of liver occupation is not clear. Methods: A retrospective clinicopathological analysis was performed on 70 patients with HCC who received lenvatinib in our institute between 2017 and 2018. Lenvatinib was given orally 10 mg once daily. Treatment response, progression-free survival, overall survival and prognostic factors were explored. Results: Among 70 patients in this cohort, the mean age was 59.7 year-old and 78.6% were male, 58.6% were HBV(+) and 18.6% HCV(+). Among these patients, 65.7% had experienced sorafenib and 57.1% anti-PD-1. Patients who were not eligible for REFLECT study including having tumor more that 50% of liver occupation (40%), main portal vein invasion (34.3%) and Child-Pugh Score B and C (30.0% and 21.4%) were also enrolled. Treatment response was evaluable in 51 patients. Best responses were CR in 1 patients (2%), PR in 21 (41%), SD in 23 (45%) and PD in 6 (12%) by mRECIST criteria. Tumor with &gt; 50% of liver occupation has higher ORR. However, no significant difference of response was observed regarding etiologies, AFP levels, tumor types, Child-Pugh Score, main portal vein thrombosis, sorafenib and anti-PD-1 experienced. The median PFS was 5.3 months and OS 8.5 months. Regression analysis showed AFP &gt; 20 and Child-Pugh score B and C were poor prognostic factors for survival. Conclusions: Lenvatinib is potent drug for both treatment naïve and sorafenib-resistance HCC. Lenvatinib is also effective for patients with Child-Pugh Score B and C, tumor &gt; 50% of liver occupation who were ineligible to REFLECT study.
Genomics and data science: an application within an umbrella
Authors: Fábio C. P. Navarro, Hussein Mohsen, Chengfei Yan, Shantao Li, Mengting Gu, William Meyerson, Mark Gerstein
Journal: Genome biology (2019)

Data science allows the extraction of practical insights from large-scale data. Here, we contextualize it as an umbrella term, encompassing several disparate subdomains. We focus on how genomics fits as a specific application subdomain, in terms of well-known 3 V data and 4 M process frameworks (volume-velocity-variety and measurement-mining-modeling-manipulation, respectively). We further analyze the technical and cultural "exports" and "imports" between genomics and other data-science subdomains (e.g., astronomy). Finally, we discuss how data value, privacy, and ownership are pressing issues for data science applications, in general, and are especially relevant to genomics, due to the persistent nature of DNA.
Toxicity of chemotherapy in patients with colorectal cancer: The role of age in the Latin American setting.
Authors: Fernando Namuche, Paola Catherine Montenegro, Jorge Leon, Claudio J. Flores
Journal: Journal of Clinical Oncology (2019)

e15095 Background: The incidence of colorectal cancer (CRC) in Peru has increased in the last decades. In our country, the toxicities of systemic treatment have not been analyzed in a large population in the different disease settings. Numerous clinical studies have shown an association between toxicities and age, type of chemotherapy, number of courses, and others. Our objective was to explore the toxicities presented in our population and find if any variables could help us predict these toxicities. Methods: We retrospectively reviewed the electronic medical records of 371 patients with CRC from one specialized Peruvian cancer center between 2006 and 2016. Descriptive results for numeric variables were presented as means with standard deviation (SD) or medians with interquartile range (IQR), depending on their distributions; otherwise, we expressed the qualitative variables as numbers with percentages. The primary outcome measure was if the patient developed toxicity ≥3 assessed with multiple variables: age, sex, tumor location, NLR, PLR, pathological stage group (PSG), type of chemotherapy (CT), liver metastases, metastasectomy performed, albumin level, CEA, nodal involvement, time to CT, number of CT courses. Multivariable analysis in logistic regression model was adjusted for the factors statistically significant in the univariable analysis. Results: A total of 371 patients were included, of which 95 (25.6%) developed a ≥3 grade toxicity. The more frequent toxicity was neuropathy (30.5%). Univariate logistic regression analysis showed that age, albumin level, PSG, time to CT, number of CT courses, type of chemotherapy (CT), tumor location and liver metastases were associated with a ≥3 grade toxicity. Furthermore, multivariate regression analysis demonstrated that stage IV [OR, 0.012; 95% CI, 0.002-0.078; p &lt; 0.001], age ≥70 [OR, 3.475; 95% CI,1.818-6.643; p &lt; 0.001], number of courses [OR, 0.839; 95% CI, 0.763-0.922; p &lt; 0.001] and albumin levels [OR, 0.391; 95% CI,0.257-0.596; p &lt; 0.001]were independently risk factors for ≥3 grade toxicity. Conclusions: Stage IV, age ≥70, a greater number of CT courses and lower albumin levels were independently associated with a ≥3 grade toxicity.
Primary Immunodeficiency, a Possible Cause of Neutrophilic Necrotizing Dermatosis—Reply
Authors: Sara A. Hylwa, Alex G. Ortega-Loayza, Kanade Shinkai
Journal: JAMA Dermatology (2019)

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Comparison of tumor characteristics and survival between esophageal and other gastroenteropancreatic neuroendocrine neoplasms.
Authors: Mehran Taherian, Shabnam Samankan, Adrienne Groman, Saikrishna S. Yendamuri, Amarpreet Bhalla
Journal: Journal of Clinical Oncology (2019)

e15556 Background: Neuroendocrine neoplasms (NEN) of esophagus are extremely rare. Limited information is available on survival of these tumors. The objective of this study was to define the clinicopathologic predictors of overall survival (OS) in esophageal NEN, and to compare them with the other gastroenteropancreatic NEN (GEP-NEN). Methods: Esophageal NEN were selected from the National Cancer Database (2004–2013). Multivariable analysis and Kaplan–Meier method were performed. The prognostic factors for GEP-NEN were derived from literature including WHO classification and AJCC TNM classification. Results: Of 802 selected patients with esophageal NEN, 97.5% were NEC and only 2.5% typical NET. The median age for NET was 58 vs. 66 for NEC (p = 0.007). NET more commonly presented in females (60%) compared to NEC wherein 68% patients were male. Most of the NEC were grade III/IV and &gt; 4 cm, while most NET were grade I/II and &lt; 4 cm. They most frequently metastasized to the liver. 10.7% of patients with esophageal NEN underwent esophagectomy while 86.5% had no surgery; 68.5% had adjuvant and 6.6% neoadjuvant therapy. Multivariable analysis showed that tumor &gt; 4 cm (hazard ratio (HR) 1.45; P = 0.013), stage III and IV (HR 2.27; p = 0.030, and HR 4.02; P &lt; 0.001, respectively) were associated with significantly worse OS, while esophagectomy (HR 0.30; P = 0.019) and neoadjuvant therapy (HR 0.35; p = 0.006) were predictors of better OS. The 5-year OS rate was 12% for all esophageal NEN (95% CI, 10-15): 89% for NET and 9% for NEC. Pancreatic NET are generally &gt; 2 cm and NEC have an average size of 4 cm. The factors associated with worse prognosis in pancreatic NEN include positive surgical resection margins, lymph node metastases, advanced TNM stage, vascular invasion and distant metastasis. The 5-year OS for patients with pancreatic NET and NEC is 65% and 16%, respectively. NET of ileum are &lt; 2 cm in 47% of cases, and the 5-year OS is about 60%. Tumor stage is the most important predictor of survival. The malignant potential is retained for ileal NET &gt; 1 cm. Only Stage III vs. Stage IV has a better OS. The G3 NEC and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) have poor OS and variable median survival time reported up to 40 months. Conclusions: Using the largest dataset of esophageal NEN to date, the major independent predictors of OS include tumor size, stage, esophagectomy, and chemotherapy. The majority of esophageal NEN are NEC. Their OS is similar or slightly higher in comparison to ileal NEC but poor in comparison to similar tumors presenting in the pancreas.