tbuckley/cabot-search huggingface dataset:
The association between volumetric breast density and breast cancer subtypes among women newly diagnosed with breast cancer.
Authors: Wintana A. Balema, Tanya W. Moseley, Olena Weaver, Kenneth R. Hess, Abenaa M. Brewster
Journal: Journal of Clinical Oncology (2019)

e13115 Background: Increased breast density is a strong risk factor for breast cancer, women with high breast density have a four to six-fold increased risk of breast cancer compared to those with low density. This study explores breast density as a risk factor for specific breast cancer subtypes in order to improve risk assessment and screening recommendations for the general population. Methods: 790 women ≥ 18 years with breast cancer were evaluated who had volumetric percent density and volumetric density grade (VDG) assessed from diagnostic mammograms obtained within 9 months of diagnosis. Breast cancer subtypes were approximated based on the estrogen receptor (ER), progesterone (PR) and Her2neu status; ER and/or PR positive/Her2 negative or positive (HR+), ER and PR negative and Her2 positive (Her2-positive) and ER, PR and Her2 negative (TN). A linear model on a log scale was conducted to evaluate the associations between percentage volumetric breast density and VDG and breast cancer subtypes and race. Results: 36% of women were &lt; 50 years and 64% ≥50 years, 76% were white, 12% Black and 12% other race. There was no significant association between breast cancer subtype with age ( P = 0.068), BMI ( P = 0.81) or race ( P = 0.11). Women with VDG 1 or 2 were more likely to have HR+ (81.3%) than Her2-positive (5.1%) or TN subtypes (13.6%) (P = 0.024). There was no significant association between the percent volumetric breast density and breast tumor subtype or race. Conclusions: We found a significant association between lower breast density measured using VDG and the HR+ breast cancer subtype. This suggests a potential opportunity for assessing volumetric density grade for the development of individualized risk prediction models and for the identification of women who may benefit from preventive therapy to reduce HR+ breast cancer risk.
Chemotherapy-induced neuronal dysfunction in the absence of axon degeneration.
Authors: Stephen Nick Housley, Ann Marie Flores, Allison B. Wang, Eric J. Perreault, Paul Nardelli, Dario Carrasco, Lilya Matyunina, John F. McDonald, Timothy C. Cope
Journal: Journal of Clinical Oncology (2019)

e15091 Background: Colorectal cancer is one of the three most prevalent cancers. Mortality rates have largely decreased due, in part, to advanced treatments such as platinum-based chemotherapy (e.g. oxaliplatin – OX). Unfortunately, OX induces severe off-target, neurotoxic side-effects in the sensory nervous system that can limit or end treatment and diminish patient quality of life for years. Patient symptoms are often attributed to dying-back degeneration of primary sensory axons despite the absence of conclusive evidence. We tested the hypothesis that proprioceptive disorders persisting after chemotherapy result solely from axon degeneration of muscle proprioceptors. Methods: We used a rat model to test our hypothesis. In a rodent model of OX clinical cancer treatment, one that exhibits sensorimotor deficits in a test of proprioceptive behavior, we performed single-neuron in vivo electrophysiological and immunohistological experiments. We then profiled transcriptomes of sensory neurons to gain unbiased insight into molecular evidence of degeneration. We compared the OX group of rats (n = 18) to healthy, control rats (n = 6) using hierarchical Bayesian analysis. Results: We found no evidence for sensory axon degeneration in electrophysiologic measures of axon conduction or in immunohistochemical analysis of the axon terminals of sensory neurons, OX and control rats were indistinguishable by these measures. Unbiased transcriptional profiling gave little evidence of neuronal degeneration, although genes related to axon transport showed signs of dysregulation. Structural degeneration was also ruled out by finding that all sensory neurons fired in response to stretch. Nonetheless, anomalous firing patterns were observed, e.g. decreased spike activity in response to mechanosensory stimulation, consistent with changes in ion channel physiology. Conclusions: Our findings reject the hypothesis that nerve degeneration is required to explain OX-related sensorimotor disorders. Our research suggests biological mechanisms that are alternative to axon degeneration in explaining sensorimotor changes due to OX.
AB0054 SEQUENTIAL INTRA-ARTICULAR INJECTIONS OF LINEAR AND CROSS-LINKED HYALURONIC ACIDS IN THE TREATMENT OF GONARTHROSIS
Authors: Elena Barbieri
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Sequential intra-articular injections of linear and cross-linked hyaluronic acids in the treatment of gonarthrosis <h3>Objectives:</h3> This study evaluates clinical and biochemical effects of sequential intra-articular (IA) injections of two different formulations of hyaluronic acid (HA) in gonarthrosic (GA) patients. The first formulation consists in linear HA (LHA, MW 800-1200kDa; Regenflex Starter, Regenyal Labs, Italy) and the second in an intercalated mixture of cross-linked and linear HAs (CL-LHA, MW 1-2 MDa the crosslinked form and 500kDa the linear, intercalated one; Regenflex BioPlus). <h3>Methods:</h3> 39 knee GA patients, 19 adults (50–65 years) and 20 elderly (&gt;65 years), underwent two IA injections, i.e. LHA only at baseline and CL-LHA after 1 week. The same injections were repeated after 6 months. Clinical assessment - visual analogic scale (VAS) for pain, range of motion (ROM) and WOMAC index for knee functional limitation - was performed at baseline and after 3, 6, 9, 12 months. Blood, collected at baseline, after 1 week and 3 months, was analysed for relevant cytokines and collagen telopeptide II (CTX-II). Synovial fluid (SF) from patients with recurrent knee effusion (GA worse group) was biochemically analysed at baseline and 1 week. SF proteomic analysis was also carried out at specific time points. <h3>Results:</h3> This HA-regimen improved joint pain and function independently from the age; plasma and synovial biochemical analyses indicate the attenuation of inflammatory cytokines (IL-1β, IL-9 and IL-17) and the stabilization of CTX-II; ultrasonograph data show an improvement of cartilage conditions and thickness at 12 months. <h3>Conclusion:</h3> Sequential IA injections of LHA and CL-LHA represent a highly effective treatment especially in low degree GA patients and produce a significant and perduring improvement also in the GA worse group. The efficacy is likely dependent on the sequential administration of LHA and CL-LHA: the pharmacokinetic rationale of this combination will be discussed. <h3>References:</h3> E. Barbieri<sup>1,2*</sup>, P. Sestili<sup>1</sup>, F. Mannello<sup>1</sup>, G. Annibalini<sup>1</sup>, S. Contarelli<sup>1</sup>, L. Vallorani<sup>1</sup>, A. M. Gioacchini<sup>1</sup>, D. Ligi<sup>1</sup>, L. Croce<sup>1</sup>, Tung Tran Dang Xuan<sup>3</sup>, C. Bartolucci<sup>1</sup> V. Stocchi<sup>1</sup> and I. Capparucci<sup>1</sup> <sup>1</sup>Department of Biomolecular Sciences, University Urbino Carlo Bo, via A. Saffi 2, 61029 Urbino, Italy <sup>2</sup>Interuniversity Institute of Myology <sup>3</sup>Stem Cells Center, Van Hanh Hospital, Hochiminh City, Viet Nam <h3>Disclosure of Interests:</h3> None declared
Description of Restrictively Defined Acute Flaccid Myelitis
Authors: Pin Fee Chong, Ryutaro Kira, Keiko Tanaka-Taya
Journal: JAMA Pediatrics (2019)

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Prognostic value of lymph node positivity and number of lymph nodes required for accurate staging of pancreatic neuroendocrine tumors.
Authors: Jie Hua, Si Shi, Miaoyan Wei, Yiyin Zhang, Chen Liang, Qingcai Meng, Jiang Liu, Bo Zhang, Jin Xu, Xianjun Yu
Journal: Journal of Clinical Oncology (2019)

e15736 Background: The prognostic role of the number of positive lymph nodes (PLNs), as well as the minimum number of lymph nodes needed to accurately stage patients with pancreatic neuroendocrine tumors (pNETs), remain controversial. The aim of this study was to assess the effect of the number of PLNs on prognosis in pNETs and to determine the ideal number of examined lymph nodes (ELNs) for accurate staging of pNETs. Methods: The SEER database was reviewed from 2004 to 2014 for pts with surgically resected, pathologically confirmed pNETs. Pts with missing data for pathological stage, tumor size, ELNs or PLNs were excluded. Kaplan-Meier survival analysis was used to evaluate the association between lymph node involvement and disease-specific survival (DSS). The optimal number of ELNs was identified using the log odds of positive lymph nodes (LODDS). A large single institutional cohort with 203 patients was used for validation. Results: Of the 1,813 patients included, 686 (37.8%) had lymph node-positive disease. Patients with lymph node-positive disease had a significantly worse DSS than those with lymph node-negative disease (Log-rank P &lt; 0.001). Patients with 4 or more positive lymph nodes had a worse DSS compared with those with 1 to 3 positive lymph nodes (Log-rank P &lt; 0.001). In order to capture 95% of pNETs with PLNs at the time of surgery, 12 lymph nodes need to be examined (LODDS: -2.344). Findings were reproducible with the validation cohort. Conclusions: The number of PLNs leads to better prognostic discrimination of lymph node-positive patients with pNETs. The current staging systems may include an N-stage that distinguishes lymph node-positive disease into N1 (1 to 3 PLNs) and N2 (4 or more PLNs) categories. The minimum number of ELNs for accurate staging of pNETs is 12. [Table: see text]
Survival by stage and tumor measurability in metastatic melanoma patients treated with autologous dendritic cell tumor cell vaccines.
Authors: Robert O. Dillman, Andrew N Cornforth, Edward Francis McClay, Carol DePriest
Journal: Journal of Clinical Oncology (2019)

2637 Background: Survival of cancer patients is greatly affected by stage and tumor burden. The purpose of this study was to determine survival for melanoma patients who were treated with patient specific vaccines in the context of prospective clinical trials, by cohorts defined by stage and tumor measurability. Methods: Metastatic melanoma patients were treated with autologous dendritic cells loaded with antigens from irradiated cells from short-term autologous tumor cell lines (DCV). All patients had a metastatic melanoma lesion surgically resected, from which a tumor cell line was established. Irradiated tumor cells (ITC) were incubated with autologous dendritic cells (DC) to produce the DCV, which were injected s.c. in 500 micrograms GM-CSF weekly x 3 weeks, then monthly for 5 months. Data was pooled for DCV-treated patients enrolled in either of two phase II trials: one single-arm (NCT00948480), one randomized (NCT00436930). Patients were assigned to one of three cohorts based on their most advanced stage of disease prior to treatment, and whether they had measurable disease at the time of treatment. Survival was determined per Kaplan and Meier. Results: The final therapeutic products consisted of autologous DC with non-phagocytosed ITC making up 0% to 20% of cells in the final product. There were 45 men and 27 women. Median age was 52 years (range 17 to 83). Tumor sources were 37-lymph node, 20-viscera, and 15-soft tissue. No patients were lost to follow up; all surviving patients were followed 5 years. Toxicity was minimal. Median overall survival (OS) for all 72 patients was 49.4 mos; 5-year OS 46%. There was no correlation between survival and the number of DC or ITC in the first three injections. Patients with recurrent stage 3 disease that had not recurred (n=18) had a 72% 5-year OS; patients with non-measurable stage 4 (n=30) had a 53% 5-year OS. Patients with measurable stage 4 (n=18) had received an average of four prior therapies. They had a median OS of 18.5 months, and 2-year OS of 46%. Conclusions: This patient-specific DCV was associated with encouraging survival in all three clinical subsets. Because of its mechanism of action and absence of toxicity, it should be evaluated further. Clinical trial information: NCT00948480, NCT00436930.
Safety and antitumor activity of accelerator-based boron neutron capture therapy in patients with inoperable recurrent and locally advanced head and neck cancer: A phase II study.
Authors: Katsumi Hirose, Akiyoshi Konno, Seiichi Yoshimoto, Koji Ono, Naoki Otsuki, Jun Hatazawa, Junichi Hiratsuka, Yoshihiro Takai
Journal: Journal of Clinical Oncology (2019)

6028 Background: To assess safety and efficacy of accelerator-based boron neutron capture therapy (AB-BNCT) using cyclotron-based neutron generator, BNCT30, and 10 B-boronophenylalanine (borofalan(10B)) agent, SPM-011, in patients with recurrent squamous cell carcinoma (R-HNSCC) or recurrent/locally advanced non-squamous cell carcinoma (R/LA-HNNSCC) of the head and neck. Methods: The multi-institutional open-label, a world-first phase II trial of AB-BNCT in patients with inoperable R-HNSCC which present resistance to platinum-based chemotherapy, or with inoperable R/LA-HNNSCC, was conducted to assess safety and antitumor activity of AB-BNCT with BNCT30 and SPM-011. SPM-011 was administered at 200 mg/kg/h intravenously for 2 hours, followed by neutron irradiation with continuous infusion of SPM-011 at 100 mg/kg/h. The irradiated dose for tumor was determined passively as a mucosal maximum dose was given 12 Gy-Eq in calculation with a blood boron concentration measured just before the start of neutron irradiation. Primary endpoint was objective response rate (ORR) by central review. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) ver 1.1 every 4 weeks for the first 3 months and every 12 weeks thereafter. Results: Eight R-HNSCC and thirteen R/LA-HNNSCC patients were enrolled and received AB-BNCT. All R-HNSCC patients had prior radiotherapy with a median dose of 65.5 Gy (range 59.4–76.0). The median irradiation time was 43 min (range 26–65). The median tumor minimum dose was 31.0 Gy-Eq (range 16.1–42.6). For adverse event, nausea (81%), dysgeusia (71%), parotitis (67%) were observed more frequently. The ORR for all patients were 71.4%, and CR/PR were 50.0%/25.0% in R-HNSCC and 7.7%/61.5% in R/LA-HNNSCC. At a median follow up of 18.8 months (range 9.2–29.0), 1-year PFS and OS by investigator assessment were 70.6% and 100%, respectively. The data for antitumor activity is still immature and will be further updated. Conclusions: AB-BNCT for R-HNSCC and R/LA-HNNSCC demonstrated an acceptable safety profile and a promising antitumor activity.
Frequency of somatic mutations in the KRAS gene in patients of the South Russia diagnosed with colorectal cancer.
Authors: Dmitry Yu. Gvaldin, Oleg I. Kit, Ekaterina P. Omelchuk, Dmitry O. Kaymakchi, Sergey I. Poluektov, Dmitry Sergeevich Petrov, Vladimir E. Kolesnikov, Liubov Yu Vladimirova
Journal: Journal of Clinical Oncology (2019)

e15081 Background: Colorectal cancer (CRC) is a common pathology in the world; the annual incidence rate reaches 1 million cases, and the annual mortality rate exceeds 500,000. The target therapy of EGFR with monoclonal drugs improves the survival of patients with this pathology. However, the effectiveness of therapy depends on the presence of mutations in genes involved in the EGFR signaling cascade, in particular KRAS. The purpose of this study was to determine the frequency of somatic mutations in the KRAS gene in tumor samples of patients from the South Russia diagnosed with colorectal cancer, as well as to analyze the effect of point mutations G12A, G12C, G12D, G12R, G12S, G12V and G13D on tumor metastasis. Methods: 744 patients diagnosed with colorectal adenocarcinoma were examined for mutations in 12th and 13th codons of KRAS. Somatic mutations in the KRAS gene were detected with reagent kit Biolink (Russia) using FFPE DNA samples of tumor tissues. Statistical analysis was performed using the method of binary logistic multiple regression and χ2-test. Results: Mutations in the KRAS gene were found in 32% of patients in the pooled sample; the most common mutation was the replacement of G12D in the KRAS gene (36%). Less common detectable mutations in the KRAS gene were G13D (18%), G12V (16%), G12A (10%), G12C (8%), G12S (10%), G12R (2%). Metastatic CRC was found in 86% of carriers of the wild-type allele and in 88% of carriers of the mutant allele. The presence of a G12V substitution almost 6 times increased the risk of metastasis in patients with CRC (OR = 5.89; 95% CI: 0.8-43.45; p = 0.049). Conclusions: Mutations in the KRAS gene were found in 32% of patients with CRC in the South of Russia. A significant association of G12V replacement with a high risk of metastasis was established. Further study of somatic mutations in the KRAS gene will allow to choose the most effective therapeutic strategies in the presence of one or another of the studied mutations.
Visceral adiposity as a predictor of survival in patients with epithelial ovarian cancer receiving platinum and taxane-based chemotherapy.
Authors: Stuart-Allison Moffat Staley, Katherine Tucker, Jorge Oldan, Dominic T. Moore, Meredith Newton, Michelle Ertel, Lindsay West, Victoria Bae-Jump
Journal: Journal of Clinical Oncology (2019)

e17031 Background: Obesity has been linked to worse outcomes in epithelial ovarian cancer (EOC), due to underlying metabolic dysfunction. Visceral fat (i.e. central obesity) compared to subcutaneous fat is more metabolically active and has been linked to higher rates of obesity-related comorbidities such as hypertension and diabetes, but less is known of the impact of increased visceral adiposity on EOC outcomes. Thus, our goal was to evaluate if visceral adiposity, as determined by computed tomography (CT) morphometric measurements, was associated with worse outcomes in EOC patients undergoing platinum and taxane-based chemotherapy. Methods: EOC patients diagnosed between 12/2004 and 5/2016 who received neoadjuvant or adjuvant treatment with platinum and taxane-based chemotherapy were included. Data on age, stage, grade, histology, BMI, comorbidities, treatment approaches and outcomes were collected. CT images closest to the time of diagnosis were retrospectively evaluated for mid-waist visceral fat volume (VFV), mid-waist subcutaneous fat volume (SFV) and the ratio of mid-waist VFV/SFV. Visceral adiposity is commonly defined as a VFV/SFV ≥ 0.4. Cox regression models were used to analyze time-to-event outcomes. Results: Two hundred fifty-eight EOC patients were evaluated. Seventy-five percent of patients were diagnosed with Stage III or IV disease, with high grade serous as the most common histology (72%). Median age at diagnosis was 62.4 years. Approximately 65% were obese; the median BMI was 26.8 (IQR 23.1 – 32.6). The median VFV/SFV ratio was 0.46 (IQR 0.32 – 0.70). Patients were categorized into those with a VFV/SFV ratio greater than 0.4 or a ratio less than 0.4. When comparing these two groups, there was no difference in progression free survival (PFS) for women with a VFV/SFV ratio greater or less than 0.4 (p = 0.22). However, a VFV/SFV ratio of greater than 0.4 was associated with worse overall survival (OS) (p = 0.01). Conclusions: We found that visceral adiposity, defined as a VFV/SFV ratio greater than 0.4, appeared to be associated with decreased OS, but not PFS. These findings suggest that body fat distribution may be an important prognostic factor for EOC and should be further explored as we expect the obesity epidemic to continue and influence EOC oncologic outcomes.
Patient Eligibility for Transoral Endocrine Surgery Procedures in the United States
Authors: Raymon H. Grogan, Insoo Suh, Kate Chomsky-Higgins, Salman Alsafran, Elya Vasiliou, Christopher R. Razavi, Lena W. Chen, Ralph P. Tufano, Quan-Yang Duh, Peter Angelos, Jonathon O. Russell
Journal: JAMA Network Open (2019)

Transoral endocrine surgery (TES) allows thyroid and parathyroid operations to be performed without leaving any visible scar on the body. Controversy regarding the value of TES remains, in part owing to the common belief that TES is only applicable to a small, select group of patients. Knowledge of the overall applicability of these procedures is essential to understand the operation, as well as to decide the amount of effort and resources that should be allocated to further study the safety, efficacy, and value of these operations.To determine what percentage of US patients undergoing thyroid and parathyroid surgery are eligible for TES using currently accepted exclusion criteria.Cross-sectional study of 1000 consecutive thyroid and parathyroid operations (with or without neck dissection) performed between July 1, 2015, and July 1, 2018, at 3 high-volume academic US thyroid- and parathyroid-focused surgical practices (2 general surgery, 1 otolaryngology-head and neck endocrine surgery). Eligibility for TES was determined by retrospectively applying previously published exclusion criteria to the cases.The primary outcome was the percentage of thyroid and parathyroid cases eligible for TES. Secondary outcomes were a subgroup analysis of the percentage of specific types of cases eligible and the reasons for ineligibility.The mean (SD) age of the 1000 surgical patients was 53 (15) years, mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 29 (7), and 747 (75.0%) of the patients were women. Five hundred fifty-eight (55.8%) of the patients were eligible for TES. Most patients with thyroid nodules with cytologically indeterminate behavior (165 of 217 [76.0%]), benign thyroid conditions (166 of 240 [69.2%]), and primary hyperparathyroidism (158 of 273 [57.9%]) were eligible for TES, but only 67 of 231 (29.0%) of patients with thyroid cancer were eligible. Among all 1000 cases reviewed, previous neck operation (97 of 441 [22.0%]), nonlocalized primary hyperparathyroidism (78 of 441 [17.7%]), and need for neck dissection (66 of 441 [15.0%]) were the most common reasons for ineligibility.More than half of all patients undergoing thyroid and parathyroid surgery in this study were eligible for TES. This broad applicability suggests that a prospective multicenter trial is reasonable to definitively study the safety, outcomes, and cost of TES.