tbuckley/cabot-search huggingface dataset:
Treatment burden following standard of care open versus robotic D2 gastrectomy plus neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC).
Authors: Mariana Juanita Rodriguez, Ana Sofia Ore, Khoschy Schawkat, Kevin F. Kennedy, Andrea J. Bullock, Jonathan F. Critchlow, James Moser
Journal: Journal of Clinical Oncology (2020)

303 Background: Phase III trials demonstrate improved short-term outcomes after laparoscopic gastrectomy for LAGC compared to open. We hypothesized that robotic D2 gastrectomy after NAC (NAC/RG) yields benefits across multiple outcome domains vs standard of care treatment for LAGC. Methods: Single institution, interrupted time series comparing SOC plus open gastrectomy (OG,2008-2013) for LAGC (T 2-4 N any /T any N + ) vs universal neoadjuvant plus RG (2013-2018). Treatment burden was a composite of adverse events affecting: efficiency (postoperative length of stay, reoperation or 90 d readmission), oncology (positive margins, &lt; 16 resected nodes), cumulative major morbidity (90 d comprehensive complication index) and pain (narcotic consumption). Predictors were evaluated via multivariate modeling, and 2-year overall survival was estimated by Kaplan-Meier/log-rank tests. Results: After exclusions, 87 subjects underwent surgical resection (55 OG; 32 RG) with equivalent baseline characteristics: demographics, BMI, comorbidity (Charlson), tumor size, and clinical AJCC staging; male sex was more likely in RG (69% vs. 44%, p = 0.02). NAC administration increased from 35% in SOC/OG cohort to 100% in NAC/RG. All four domains of efficiency, oncologic efficacy, morbidity, and pain (narcotic use) improved. Treatment burden declined from 86% in OG to 56% after RG (p = 0.003). Multivariable modeling demonstrated OR 0.23 for treatment burden in RG compared to OG (95% CI 0.07-0.72, p = 0.012), whereas sex, extent of resection (total vs subtotal), tumor size, and T stage had no effect. These differences persisted in NAC subgroup (n = 51) comparisons between RG and OG treatment burden, as well as pathologic T stage, tumor size, and AJCC stage. No detriment in 2-year overall survival was observed after adoption of NAC/RG (80% RG vs. SOC 60%, p = 0.048). Conclusions: After NAC, robot-assisted D2 gastrectomy was associated with decreased treatment burden relative to OG. Frequencies of unfavorable hospitalization, adverse oncological outcomes, major morbidity, and narcotic consumption all improved after RG in this interrupted time series. Prospective trials are needed.
Development and validation of a pancreatic cancer prediction model from electronic health records using machine learning.
Authors: Limor Appelbaum, Jose Pablo Cambronero, Karla Pollick, George Silva, Jennifer P. Stevens, Harvey J. Mamon, Irving D. Kaplan, Martin Rinard
Journal: Journal of Clinical Oncology (2020)

679 Background: Pancreatic Adenocarcinoma (PDAC) is often diagnosed at an advanced stage. We sought to develop a model for early PDAC prediction in the general population, using electronic health records (EHRs) and machine learning. Methods: We used three EHR datasets from Beth-Israel Deaconess Medical Center (BIDMC) and Partners Healthcare (PHC): 1. “BIDMC-Development-Data” (BIDMC-DD) for model development, using a feed-forward neural network (NN) and L2-regularized logistic regression,randomly split (80:20) into training and test groups. We tuned hyperparameters using cross-validation in training, and report performance on the test split. 2. “BIDMC-Large-Data” (BIDMC-LD) to re-fit and calibrate models. 3. “PHC-Data” for external validation. We evaluate using Area Under the Receiver Operating Characteristic Curve (AUC) and compute 95% CI using empirical bootstrap over test data. PDAC patients were selected using ICD9/-10 codes and validated with tumor registries. In contrast to prior work, we did not predefine feature sets based on known clinical correlates and instead employed data-driven feature selection, specifically importance-based feature pruning, regularization, and manual validation, to identify diagnostic-based features. Results: BIDMC-DD included demographics, diagnoses, labs and medications for 1018 patients (cases = 509; age-sex paired controls). BIDMC-LD included diagnoses for 547,917 patients (cases = 509), and PHC included diagnoses for 160,593 patients (cases = 408). We compared our approach to adapted and re-fitted published baselines. With a 365-day lead-time, NN obtained a BIDMC-DD test AUC of 0.84 (CI 0.79 - 0.90) versus the previous best baseline AUC of 0.70 (CI 0.62 - 0.78). We also validated using BIDMC-DD’s test cancer patients and BIDMC LD controls. The AUC was 0.71 (CI 0.67 - 0.76) at the 365-day cutoff. NN’s external validation AUC on PHC-Data was 0.71 (CI 0.63 - 0.79), outperforming an existing model’s AUC of 0.61 (CI 0.52 - 0.70) (Baecker et al, 2019). Conclusions: Models based on data-driven feature selection outperform models that use predefined sets of known clinical correlates and can help in early prediction of PDAC development.
Impact of facility type, insurance status, and income on use of single agent chemotherapy (SACT) for advanced hepatocellular carcinoma (AHCC): Analysis of National Cancer Database (NCDB).
Authors: Richard T. Lee, Gino Cioffi, Aman Opneja, Asrar Alahmadi, Nirav Patil, Nelroy Jones, David Lawrence Bajor, Joel N. Saltzman, Amr Mohamed, Ankit Mangla, Jill Barnholtz-Sloan
Journal: Journal of Clinical Oncology (2020)

504 Background: This study analyzes the pattern of use of SACT in the treatment and survival of AHCC before and after sorafenib was FDA approved in late 2007. Methods: Adult patients diagnosed with HCC and treated with only chemotherapy (CT) from 2004 – 2014 were identified in NCDB database. Patients were analyzed during 3 time frames: 2004–2006 (pre-sorafenib (PS), 2007–2011 (early sorafenib (ES) and 2012–2014 (late sorafenib (LS)). Cox proportional hazards models and Kaplan-Meier method were used for analyses. Results: The NCDB contained 31,107 patients with HCC diagnosed from 2004–2014 and treated with CT alone. Patients were generally men (77.3%), &gt;50 years of age (92.5%), and with a variety of T-stages - T1 (31.0%), T2 (23.9%), T3 (28.3%), and T4 (16.9%). The use of SACT was only 6.2% in the PS period, increased to 15.5% in the ES period, and to 22.3% in the LS period (p&lt;0.0001). During this later period, the highest proportion of SACT is among academic and integrated network facilities (23.4%) as compared to community facilities (16.4%, p&lt;0.0001). The MS of patients with AHCC treated only with CT has improved significantly over the study periods from 10 months (m) (95% CI: 9.5-10.6) to 12.5m (12.0-12.9) to 16m (15.6-16.4, p&lt; 0.001). Significant differences in MS were found between facility types in all time frames (Table). Multivariate analysis indicates worse outcomes for patients treated at community cancer programs (HR 1.66, 1.53-1.79) as compared to academic programs as well as for no insurance (HR 1.13, 1.05-1.22) and estimated household income of &lt;$63,000 (HR 1.09, 1.05-1.13). Conclusions: Despite an overall improvement in survival for AHCC patients treated with only CT, significant differences in the utilization of SACT and survival exist by facility type, insurance status, and income. [Table: see text]
Efficacy of second-line chemotherapy after standard combination chemotherapy in patients with metastatic pancreatic cancer: The results from the NAPOLEON study.
Authors: Masaru Fukahori, Yoshinobu Okabe, Mototsugu Shimokawa, Taiga Otsuka, Futa Koga, Yujiro Ueda, Junichi Nakazawa, Azusa Komori, Shiho Arima, Akitaka Makiyama, Hiroki Taguchi, Takuya Honda, Tomoyuki Ushijima, Keisuke Miwa, Taro Shibuki, Kenta Nio, Yasushi Ide, Norio Ureshino, Kenji Mitsugi, Tsuyoshi Shirakawa
Journal: Journal of Clinical Oncology (2020)

661 Background: Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) have been established as standard first-line combination chemotherapy (CTx) for patients with metastatic pancreatic cancer (MPC). However, the efficacy of second-line CTx and the significance of combination CTx in clinical practice are unclear. We therefore investigated the efficacy of second-line CTx in patients with MPC. Methods: Data were collected from CTx-naive MPC patients treated with first-line combination CTx at 14 hospitals in the Kyushu area of Japan from December 2013 to June 2018. The median overall survival (mOS) from second-line treatment was compared between patients who received second-line CTx (CT group) and those who received best supportive care (BSC group). Furthermore, in the CT group, the mOS was compared between the patients who received combination CTx and those who received mono-CTx. To control potential bias in the selection of second-line treatment, we also conducted a propensity score-adjusted analysis. Results: A total of 255 patients received GnP or FFX as first-line CTx. Of these, there were 156 (61%) in the CT group and 77 (30%) in the BSC group. The number of patients who received FFX/GnP as first-line CTx was 79 (51%)/77 (49%) in the CT group and 15 (20%)/62 (80%) in the BSC group, respectively (P &lt; 0.01). The mOS in the CT group was significantly longer than that in the BSC group (5.2 vs. 2.7 months; hazard ratio [HR] 0.42; 95% confidence interval [CI] 0.31-0.57; p &lt; 0.01 and 5.2 vs. 2.6 months; adjusted HR 0.39; 95% CI 0.28-0.55; p &lt; 0.01). In the CT group, 89 (57%) patients received combination CTx, and 67 (43%) received mono-CTx. There was no significant difference in the mOS between the combination CTx and mono-CTx patients (5.5 vs. 4.4 months; HR 0.88; 95% CI 0.62-1.26; p = 0.88 and 5.6 vs. 4.4 months; adjusted HR 0.85; 95% CI 0.56-1.30; p = 0.47). Conclusions: Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination CTx conferred no improvement in the survival duration compared with mono-CTx.
Over-detection of colonic abnormalities on CTAP and a decrease with experience: A simulation of machine learning.
Authors: John Chang, Ryan Brooks, Zachary Gibson, Phillip Koo∗∗, Tomislav Dragovich, Madappa N. Kundranda
Journal: Journal of Clinical Oncology (2020)

68 Background: Artificial intelligence (AI) can potentially improve patient care by assisting physicians as demonstrated with the recent approvals for technologies that detect intracranial hemorrhage on CT exams of the head. AI also has potential for assisting early detection of colorectal cancer (CRC) on routine CT abdomen and pelvis (CTAP). We assessed the difference in detection of abnormal colonic findings between an expert reader (JC) and amateur readers (ARs). Methods: ARs consisting of two third year medical students (RB - AR1, ZG - AR2) studied 20 CTAP for tracing the colon and identifying pathology. Their search pattern and assessment of the colon was then evaluated by an expert radiologist (JC). They then spent two hours reviewing abnormalities in 10 scans with JC, who highlighted suspicious neoplastic findings such as colonic wall thickening, fat stranding, edema, masses, and abnormal lymph nodes. The ARs then individually read 203 CTAP scans to assess for these suspicious findings. The studies were from a single institution and were reported in a prior study in 2019 GI-ASCO. The findings of the ARs were then compared to those of the expert reader and the initial reader for each study. Data was analyzed using t-test with 2 tails. Results: The incidence of suspicious neoplastic findings was 87% and 81% for AR1 and AR2, respectively, compared to 18% in the initial reads and 33% for expert reader (p=0.01). Greatest discordance were 94% and 87% between AR1 and AR2 to the initial reads. Additionally, the incidence of suspicious findings between the first and last 20 cases (p=0.03 and 0.17) examined by ARs declined from 79 to 40% for AR1 and 69 to 55% for AR2. Conclusions: ARs are capable of detecting CRC features on CTAP from ED, but with higher false-positive (FP) rate than trained experts. The FP rate decreases with increasing experience. ARs learning course simulates AI which will likely yield high FP rate with initial training, but with improving FP with deep training, especially with larger volume of normal variants.
Retrospective comparison of neoadjuvant chemoradiation (nCRT) +/- surgery using the CROSS trial regimen and definitive chemoradiation (dCRT) with carboplatin (C) and paclitaxel (P) in esophageal (EC), and gastroesophageal junction cancer (GEJC) in Canada.
Authors: Sidra Khalid, Wilma M. Hopman, Kiran Virik
Journal: Journal of Clinical Oncology (2020)

313 Background: Trimodality therapy using the CROSS trial protocol is an accepted standard of care for locally advanced EC and GEJC. For medically inoperable patients (pts), CRT has been a standard. CRT with C and P is an option in the definitive setting. This single institution review aims to assess the application and outcomes of the CROSS trial protocol in our real world population. Methods: From June 2012 until June 2018, a retrospective review was undertaken of 83 pts who underwent CRT with C and P with trimodaility or upfront definitive intent. 65 pts underwent nCRT; 40 proceeded to surgery. 18 had upfront dCRT. Pt demographics, clinical, pathological, treatment and surgical characteristics were assessed. These factors and outcomes were analyzed in exploratory analyses. Results: Of the 83 pts: median (m) age was 69 yrs (range 48-82), 34% were ≥ 75 yrs, 80% were male, 21% had CAD, 43% GERD, 23% Barrett’s, 77% adenocarcinoma, m tumor length was 5 cm, 36% had BMI &gt; 30 and 80% were Siewert I tumors. The m RT dose was 50.4 Gy, m chemo doses were 5, m time to CRT was 69 days and m time from CRT to surgery was 66 days. 23% nCRT pts and 72% dCRT pts were ≥ 75 yrs and 49% and 33% of these respectively had no interruptions to CRT. Pts who underwent surgery were younger (p = 0.04) and weighed more (p = 0.05). Pts ≥75 yrs were likely to have dCRT (p = 0.001). For nCRT and surgery, nCRT only and dCRT respectively, median overall survival (mOS) was 35.5, 12.1 and 17.1 months (M) (log rank p = 0.08), PFS was 32.2, 10 and 9.6M (log rank p = 0.01). Compared to the other 2 groups, pts who underwent surgery had: no COPD (p = 0.004), less CAD (p = 0.003), less renal impairment (p = 0.023) and had lower esophageal tumors (p = 0.027). mOS for pts who had nCRT was 28.9M and 17.1M for dCRT (log rank p = 0.70). Further correlative outcome data will be presented. Conclusions: Despite the broadening of CROSS trial eligibility criteria in our real world data, there appears to be a survival benefit with trimodality therapy. The use of C and P in dCRT may be of value especially in the elderly, and requires further study.
Clinical utility of the systemic inflammatory response (SIR) in identifying high-risk stage II colon cancer.
Authors: Allan Matthew Golder, Donald C. McMillan, David Mansouri, Paul G. Horgan, Campbell SD Roxburgh
Journal: Journal of Clinical Oncology (2020)

220 Background: Surgery for TNM Stage II colon cancer is considered curative however approximately 20% of patients will have recurrence of their disease. A number of high risk pathological features guide the use of adjuvant chemotherapy. More recently the preoperative SIR has been consistently shown to have prognostic value but to date has not been utilised clinically as a high risk feature. The present study compared the influence of the SIR versus established high-risk clinical features on overall/cancer specific survival (OS/CSS). Methods: Patients in the West of Scotland undergoing curative resection for Stage II colon cancer from 2011-2015 were identified with survival updated until December 2018. Additional data was obtained from online records. Through uni/multivariate analysis (UVA/MVA) we compared the effect on survival of the SIR measured using the modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) when entered individually into a multivariate model alongside established high-risk features. Results: 982 patients were identified having had a curative resection of Stage II colon cancer. Median follow up was 61 months and there were 307 deaths during follow up. For OS: emergency presentation, T stage, adjuvant chemotherapy, nodal harvest, margin involvement, mGPS, LMR, NLR (all p≤0.001) and EMVI (p &lt; 0.05) were significant on UVA. On MVA: age (HR 1.51), T stage (HR 1.59), nodal harvest (HR 1.67), margin involvement (HR 1.94), adjuvant chemotherapy (HR 0.47), mGPS (HR 1.38), NLR (HR 1.35) and LMR (HR 1.50) remained significant (all p &lt; 0.05). For CSS: age, emergency presentation, T stage, margin involvement, mGPS, NLR, LMR (all p &lt; 0.001), nodal harvest and adjuvant chemotherapy (both p &lt; 0.05) remained significant on UVA. On MVA emergency presentation (HR 1.88), T stage (HR 2.02), margin involvement (HR 2.98), adjuvant chemotherapy (HR 0.51) and mGPS (HR 1.34) remained significant (all p &lt; 0.05). Conclusions: The present study suggests that the SIR is an independent predictor of worse OS/CSS in Stage II colon cancer and should be considered a high risk feature in future prospective studies.
Exploring the epidemiology of gastric cancer in a Tibetan population.
Authors: Krisha K. Mehta, Tsetan D. Sadutshang, Tenzin Namdon, Tenzin Woesal, Arthur P. Grollman, Kathleen G. Dickman, Kunchok Dorjee
Journal: Journal of Clinical Oncology (2020)

335 Background: Gastric cancer is the 3rd leading cause of death from cancer and the 5th most common cancer world-wide. It is the primary cause of death for people of Tibetan origin in the Himalayan belt, with incidence (and death) rates between 60-140/100,000 people per year. Despite such a high disease burden, the epidemiology of gastric cancer has not been studied in this population. In this study, we explore gastric cancer risk factors among Tibetan refugees residing in India. Methods: Patients diagnosed with gastric cancer were identified by reviewing admission, discharge and out-patient endoscopy records between 2013-2019 at the Tibetan Delek hospital in Dharamshala, India. Risk factors not captured in the records were collected through interviews of patients or their relatives. Results: A total of 52 gastric cancer cases were identified, mostly males (77%). Median age was 78 (range: 30-91 years). Of the gastric cancer cases, 32% (n = 12/37) were retired military, 19% (n = 7/37) were monks or nuns, and 95% (n = 36/38) were born in Tibet. Sixty-five percent (n = 34/52) of the cases had histories of dyspepsia, 49% (n = 21/43) had used alcohol, and 40% (n = 17/43) were past smokers. Ninety-five percent (n = 20/21) of cases had been treated with traditional Tibetan medicines for various reasons in the past. Of the 17 patients (or relatives) interviewed for dietary risk factors, 76% (n = 13) reported frequent ingestion of stale and unrefrigerated food, 30% (n = 5) did not eat fresh fruit, and 47% (n = 8) reported intake of fresh fruit &lt; 3 times per month. Most (83%, n = 24/29) patients had non-cardia cancers located in the fundus/body (n = 12) and antrum/pylorus (n = 12). Fifty-two percent (n = 16/31) had been treated with either chemotherapy, radiotherapy, or surgery, and 34% (n = 11/32) of the patients were receiving traditional Tibetan medicine as treatment for gastric cancer. Conclusions: Tibetan people have socio-cultural, behavioral and dietary risk factors that may be associated with gastric cancer. Investigations of causal factors (genetic, infective ( Helicobacter pylori), environmental) with possible synergistic interactions could inform clinical and public health practice for this population and globally.
ACE and Type 2 Diabetes Risk: A Mendelian Randomization Study
Authors: Marie Pigeyre, Jennifer Sjaarda, Michael Chong, Sibylle Hess, Jackie Bosch, Salim Yusuf, Hertzel Gerstein, Guillaume Paré
Journal: Diabetes Care (2020)

OBJECTIVE To determine whether ACE inhibitors reduce the risk of type 2 diabetes using a Mendelian randomization (MR) approach. RESEARCH DESIGN AND METHODS A two-sample MR analysis included 17 independent genetic variants associated with ACE serum concentration in 4,147 participants from the Outcome Reduction with Initial Glargine INtervention (ORIGIN) (clinical trial reg. no. NCT00069784) trial, and their effects on type 2 diabetes risk were estimated from 18 studies of the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. A genetic risk score (GRS) underpinning lower ACE concentration was then tested for association with type 2 diabetes prevalence in 341,872 participants, including 16,320 with type 2 diabetes, from the UK Biobank. MR estimates were compared after standardization for blood pressure change, with the estimate obtained from a randomized controlled trial (RCT) meta-analysis of ACE inhibitors versus placebo (n = 31,200). RESULTS Genetically lower ACE concentrations were associated with a lower risk of type 2 diabetes (odds ratio [OR] per SD 0.92 [95% CI 0.89–0.95]; P = 1.79 × 10−7). This result was replicated in the UK Biobank (OR per SD 0.97 [0.96–0.99]; P = 8.73 × 10−4). After standardization, the ACE GRS was associated with a larger decrease in type 2 diabetes risk per 2.4-mmHg lower mean arterial pressure (MAP) compared with that obtained from an RCT meta-analysis (OR per 2.4-mmHg lower MAP 0.19 [0.07–0.51] vs. 0.76 [0.60–0.97], respectively; P = 0.007 for difference). CONCLUSIONS These results support the causal protective effect of ACE inhibitors on type 2 diabetes risk and may guide therapeutic decision making in clinical practice.
Correction: Androgen Receptor Is the Key Transcriptional Mediator of the Tumor Suppressor SPOP in Prostate Cancer
Authors: Chuandong Geng, Kimal Rajapakshe, Shrijal S. Shah, John Shou, Vijay Kumar Eedunuri, Christopher Foley, Warren Fiskus, Mahitha Rajendran, Sue Anne Chew, Martin Zimmermann, Richard Bond, Bin He, Cristian Coarfa, Nicholas Mitsiades
Journal: Cancer Research (2019)
The Mental Health Hazards of Reading About Physician Suicide
Authors: Kayla H. Isaacs
Journal: JAMA Internal Medicine (2020)

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