tbuckley/cabot-search huggingface dataset:
Duloxetine (DL) in treatment of oxaliplatin-induced peripheral neuropathy (PN).
Authors: Jeffrey Chi, Fatima Fayyaz, Su Yun Chung, Jyothi Jose, Anna W. Komorowski, Maura Dillon, Patnita Shepherd, Kenneth D. Gold, Wasif M. Saif
Journal: Journal of Clinical Oncology (2021)

195 Background: Oxaliplatin is commonly used to treat many GI cancers, especially colorectal (CRC), pancreatic (PC), and gastric (GC); however, peripheral neuropathy (PN) is the dose-limiting toxicity. Duloxetine (DL) is a second-generation selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of depression, anxiety, PN-associated with diabetes or ongoing pain due to medical conditions such as fibromyalgia. In this retrospective study, we evaluated the role of DL in reduction of oxaliplatin-induced neuropathy. Methods: Patients with GI cancers receiving oxaliplatin-based chemotherapy regimens from Nov 2016 to Nov 2019 were included. Patients with pre-existing PN from other etiologies such as diabetes, alcoholism, autoimmune disease, infections, hereditary, etc. were excluded. Neurological evaluations were performed serially before initiating DL and every 4 weeks thereafter according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DL was given at 30 mg by mouth (PO) once daily and if tolerated after 3 days, was escalated to 60 mg once daily. Response was calculated to include number of patients with stable PN, improved PN, or no benefit. Adverse toxicities were graded. Results: 53 patients with median age of 53 years (range: 38 – 72) received DL for oxaliplatin-induced PN during treatment of GI cancers (CRC: 40%, PC:30%, GC: 10%, others: 10%). Improvement in PN from higher to lower grades was witnessed at 2 weeks in only 4 patients. At 4 week of DL, 3/53 (6%) patients improved from G3 PN to G2, 6/53 (11%) from G3 to G1, and 28/53 (52.8%) from G2 to G1, 14/53 (26%) and 2/53 (4%) had stable G3 and G2 PN respectively. At 8 week of DL, 10/53 (19%) of patients improved from G3 to G2, 3/53 (6%) from G2 to G1, 23/53 (43%) from G1 to G0, while 11/53 (21%), 2/53 (4%) and 4/53 (8%) remained stable at G1, G2 and G3 respectively. Overall DL resulted in a response rate of 89% and stable PN in 11%. 5 patients had to stop DL due to G3 drowsiness, insomnia, dry mouth and headache. Overall, DL was well-tolerated with majority of toxicities in G1-2 grade: dizziness (15%), drowsiness (11%), sexual side effects (11%), dry mouth (11%), insomnia (8%), headache (8%). In addition to PN, DL helped in improving depression in 50% of these patients and decreased the pain score in an additional 23%. Conclusions: DL resulted in a clinically significant improvement in PN-induced by oxaliplatin with manageable toxicity profile. Additionally, DL also improved depression and pain score. DL may be considered as an option in ameliorating PN in these patients, however, caution must be taken about DL and other drugs interaction. Our study warrants a prospective randomized trial to study the effectiveness of DL in treating oxaliplatin-induced PN. Moreover, cost effectiveness of DL in concurrently improving PN, depression and pain needs to be studied as well.
FRI0141 Prevalence of thyroid disease in systemic lupus erythematosus and primary sjÖgren syndrome
Authors: M Alexandre, A Braña, A Barcelos, MJ Salvador, C Silva, L Inês, D Nour, P Reis, JA Pereira da Silva, A Malcata, A Porto
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Thyroid dysfunction (hypo and hypertiroidism) has been described among patients with connective tissue diseases, particularly in patients with systemic lupus erythematosus (SLE) and primary Sjögren syndrome (PSS). Also a high prevalence of anti-thyroid antibodies (ATA) has been found in these patients. <h3>Objectives</h3> To study:1) Thyroid function and morphology in a population of SLE and PSS patients; 2) To evaluate the prevalence of ATA in these patients; 3) To correlate clinical manifestations with laboratory data. <h3>Methods</h3> We studied serum levels of thyroid hormones, TSH, anti-thyroglobulin and anti-microssomal antibodies in 70 consecutive patients (50 with SLE and 20 with PSS), followed in our department. We performed thyroid ultrasound in all patients. Patients were asked about signs and symptoms related to the manifestations of thyroid dysfunction. <h3>Results</h3> <h3>Conclusion</h3> In this group of patients we found a high prevalence of thyroid morphology abnormalities and thyroid dysfunction. In both groups less than half of the patients with thyroid dysfunction presented related symptoms. These results suggest that all SLE and PSS patients should be routinely screened for thyroid disease even in the absence of clinical manifestations.
Texting to Improve Colonoscopy Preparation and Adherence Needs More Study
Authors: Carolyn M. Clancy, Jason A. Dominitz
Journal: JAMA Network Open (2021)

Nadim Mahmud, MD, MS, MPH, MSCE; David A. Asch, MD, MBA; Jessica Sung, BA; Catherine Reitz, MPH; Mary S. Coniglio, MBA; Caitlin McDonald, MPH; Donna Bernard, MSN; Shivan J. Mehta, MD, MBA, MSHP
A phase IIb, open-label, single-arm study of zanidatamab (ZW25) monotherapy in subjects with advanced or metastatic HER2-amplified biliary tract cancers.
Authors: Shubham Pant, Michel Ducreux, James J. Harding, Milind M. Javle, Do-Youn Oh, Harpreet Singh Wasan, Allison Fortenberry, Neil C. Josephson, Anthony Mwatha, Kui Wang, Jia Fan
Journal: Journal of Clinical Oncology (2021)

TPS352 Background: Advanced biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CC), have a poor prognosis. Zanidatamab (ZW25) is a novel bispecific antibody that targets HER2 domains ECD2 and ECD4, resulting in increased antibody binding density and improved receptor internalization and downregulation relative to trastuzumab. In an ongoing phase I trial (ZWI-ZW25-101; NCT02892123), single-agent zanidatamab was well tolerated and showed promising anti-tumor activity across HER2-expressing solid tumors, including BTCs. These results formed the basis for a phase IIb study of zanidatamab in patients with BTC. Methods: Study ZWI-ZW25-203 (NCT04466891) is a global, multicenter, open-label, single-arm, phase IIb trial designed to evaluate the anti-tumor activity of zanidatamab monotherapy in patients with HER2-amplified, inoperable and advanced or metastatic BTCs, including GBC and CC. Patients must have received at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease and have experienced disease progression after (or developed intolerance to) their most recent prior therapy. New or archival tumor tissue is required from all patients for HER2 amplification and protein expression testing at a central lab using in situ hybridization (ISH) and immunohistochemistry (IHC) assays. Approximately 100 patients with HER2 amplification by ISH will be enrolled. Zanidatamab 20 mg/kg will be administered intravenously every 2 weeks until one of the treatment discontinuation criteria is met. The primary endpoint of the study is the confirmed objective response rate (ORR) by independent central review per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Secondary endpoints include duration of response (DOR), proportion of patients with DOR ≥ 16 weeks, disease control rate, progression-free survival, overall survival, safety, quality of life, and disease-related pain. The safety and tolerability of zanidatamab will be assessed by recording the frequency and severity of adverse events, serious adverse events, and laboratory abnormalities, as well as the frequency of zanidatamab dose modifications. The study is currently open for enrollment. Clinical trial information: NCT04466891.
Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).
Authors: Daisuke Takahari, Manabu Ohashi, Atsuo Takashima, Takuro Mizukami, Naoki Ishizuka, Hitoshi Katai, Shinya Mikami, Takeru Wakatsuki, Keisho Chin, Satoshi Ida, Koshi Kumagai, Souya Nunobe, Satoru Iwasa, Miki Ito, Takeyuki Wada, Yukinori Yamagata, Takashi Ogura, Takeshi Sano, Narikazu Boku, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2021)

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m 2 , intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in &lt; 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.
Real-world effectiveness of lenvatinib monotherapy among unresectable hepatocellular carcinoma patients treated in United States clinical practices.
Authors: Amit G. Singal, Saurabh P Nagar, Abigail Hitchens, Shrividya Iyer
Journal: Journal of Clinical Oncology (2021)

273 Background: In the United States (U.S.), lenvatinib monotherapy was approved in August 2018 for first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC) based on the pivotal trial, REFLECT. Real-world data are essential to assess if this efficacy translates into effectiveness in clinical practice. The main objective of our real-world data (RWD) study was to assess clinical characteristics and effectiveness of lenvatinib among patients treated in U.S. clinical practices. Methods: A retrospective patient chart review study was conducted among adult patients (≥18 years) in the U.S. initiating lenvatinib monotherapy as first-line (1L) systemic therapy for uHCC between Aug 2018 and Sept 2019 and with ECOG status of 0 or 1. Data were extracted from individual patients’ electronic health records and captured in electronic case report forms. Clinical outcomes assessed include provider-reported best response, progression-free survival (PFS) and overall survival (OS). PFS and OS were estimated using Kaplan-Meier methods. For PFS, patients were censored at end of treatment or end of follow-up in case of ongoing treatment, while censoring occurred at end of follow-up for OS. Results: Among 233 patients treated with 1L lenvatinib monotherapy, majority were male (68%) and most were Caucasian (52%) or African American (25%). Median age was 63 years and median body weight was 76 kg. The most common etiologies of liver disease were hepatitis C (36%), alcohol-related liver disease (28%), hepatitis B (16%) and non-alcoholic steatohepatitis (14%). Most patients had compensated cirrhosis, with 49% Child Pugh A and 43% Child Pugh B. All patients had uHCC, with most having Barcelona Clinic Liver Cancer stage B (29%) or C (44%) disease. Portal vein invasion was reported in 19%, of whom7% had main portal vein involvement. The median starting dose of lenvatinib was 12 mg daily. Over a median follow-up period of 9 months from HCC diagnosis, median PFS and OS were not reached. At 6 and 12 months landmark PFS was 85% and 65%, respectively and landmark OS was 92% and 73%, respectively. In the overall cohort, provider-reported best response was complete response (CR): 21%, partial response (PR):44% and stable disease (SD): 26%. Based on RECIST 1.1 (n = 125) CR:16%, PR:54%, SD:26% and mRECIST (n = 11) CR:73%, PR:0% and SD:18% were reported. Average duration of lenvatinib treatment was 7.4 months (median: 6.7 months) with 61% of patients remaining on lenvatinib at end of follow-up. Second-line (2L) treatment was initiated in 32 patients, with immunotherapy (50%), sorafenib (31%) and regorafenib (9%) being most common. Median time to 2L treatment from initiation of lenvatinib was about 8 months. Conclusions: Results from this retrospective real-world study in an U.S. population affirm the clinical effectiveness of 1L lenvatinib monotherapy among patients with uHCC.
Impact of socioeconomic status (SES) on colorectal cancer patient survival: An analysis of 890,867 patients in the National Cancer Database (NCDB).
Authors: Mohamed E. Salem, Sally Jeanne Trufan, James Thomas Symanowski, Kunal C. Kadakia, Alberto Puccini, Laura W. Musselwhite, Kristi D Graves, Marion L. Hartley, Edward S. Kim, Jimmy J. Hwang, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2021)

19 Background: SES has been associated with outcomes in cancer patients (pts). We examined associations between SES and survival of pts with colorectal cancers (CRC). Methods: The NCDB was used to examine the association of SES status with clinicopathological features and outcomes of colorectal cancer pts, categorized by the income and education level of their area of residence. Logistic regression, Cox proportional hazard model, and chi-square test were used to examine the differences between groups. Results: A retrospective analysis of 890,867 pts with CRC (right-sided 34.1%, transverse 11.9%, left-sided 46.2%, and rectal 7.8%) diagnosed between 2004 and 2016, was conducted. About half the pts were male (51.4%); 84.3% were white, 11.2% black, and 4.5% of other races. Overall, 30.8% of pts lived in the highest and 18.4% in the lowest income areas. Twenty-three percent lived in areas comprising the highest high school graduation rate areas (&gt;93%), while 17.4% lived in the lowest (&lt; 79%). Compared to pts living in high-income areas, pts living in the lowest income areas were more likely to be black (OR 6.2, 6.1-6.3), present at a younger age (18-30 yrs vs. &gt;70 yrs; OR 1.28, 1.18-1.39), have T3/T4 disease at presentation (OR 1.03, 95%CI 1.02-1.04), left-sided tumors (OR 1.05, 1.04-1.06), higher Charlson-Deyo score (OR 1.34, 1.33-1.36), and have Medicaid (OR: 3.9, 3.8-4.0) or no health insurance (OR: 2.9, 2.8-3.0). Tumor location and grade, stage, age, sex, race, ethnicity, income, education, insurance status, Charlson-Deyo score, and type of treatment center were independent predictors for survival in the multivariate analysis. Pts living in the lowest income and lowest education areas had a 13% and 4% higher risk of death, respectively, compared to pts in the highest income areas and education areas. Black pts had a 7% increased risk of death. Pts with Medicaid and no insurance coverage had a 44% and 29% increased risk of death, respectively, compared to pts with private insurance. Conclusions: CRC pts living in areas of low income and low education had worse survival. Insurance status and type of treatment center also have a strong impact on survival. Sociodemographic characteristics need to be taken into account and studied further, with the aim of improving outcomes for all pts. [Table: see text]
SOX2-dependent expression of dihydroorotate dehydrogenase regulates oral squamous cell carcinoma cell proliferation
Authors: Xuemei Qiu, Sheng Jiang, Yanxuan Xiao, Yumin He, Tao Ren, Lu Jiang, Rui Liu, Qianming Chen
Journal: International Journal of Oral Science (2021)

Oral squamous cell carcinoma (OSCC) become a heavy burden of public health, with approximately 300 000 newly diagnosed cases and 145 000 deaths worldwide per year. Nucleotide metabolism fuel DNA replication and RNA synthesis, which is indispensable for cell proliferation. But how tumor cells orchestrate nucleotide metabolic enzymes to support their rapid growth is largely unknown. Here we show that expression of pyrimidine metabolic enzyme dihydroorotate dehydrogenase (DHODH) is upregulated in OSCC tissues, compared to non-cancerous adjacent tissues. Enhanced expression of DHODH is correlated with a shortened patient survival time. Inhibition of DHODH by either shRNA or selective inhibitors impairs proliferation of OSCC cells and growth of tumor xenograft. Further, loss of functional DHODH imped de novo pyrimidine synthesis, and disrupt mitochondrial respiration probably through destabilizing the MICOS complex. Mechanistic study shows that transcriptional factor SOX2 plays an important role in the upregulation of DHODH in OSCC. Our findings add to the knowledge of how cancer cells co-opt nucleotide metabolism to support their rapid growth, and thereby highlight DHODH as a potential prognostic and therapeutic target for OSCC treatment.
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats
Authors: Robin Mesnage, Maxime Teixeira, Daniele Mandrioli, Laura Falcioni, Quinten Raymond Ducarmon, Romy Daniëlle Zwittink, Francesca Mazzacuva, Anna Caldwell, John Halket, Caroline Amiel, Jean-Michel Panoff, Fiorella Belpoggi, Michael Nicolas Antoniou
Journal: Environmental Health Perspectives (2021)

There is intense debate on whether glyphosate can inhibit the shikimate pathway of gastrointestinal microorganisms, with potential health implications.
Optimal Time for 124I PET/CT Imaging in Metastatic Differentiated Thyroid Cancer
Authors: Di Wu, Donika Plyku, Kanchan Kulkarni, Carlos Garcia, Frank Atkins, Eshetu Tefera, Kenneth D. Burman, Leonard Wartofsky, Douglas Van Nostrand
Journal: Clinical Nuclear Medicine (2021)

Background The objective of this study was to determine the optimal time for 124 I PET/CT imaging to maximize the detection of locoregional and/or distant metastases of differentiated thyroid cancer. Methods Differentiated thyroid cancer patients suspected of having metastatic disease were prepared with low-iodine diet and appropriate thyroid-stimulating hormone stimulation. 124 I PET and low-dose localization CT were performed over 4 days after oral administration of 31.5 or 62.9 MBq (0.85 or 1.7 mCi) of 124 I. Each scan was independently reviewed by 2 nuclear medicine physicians. All foci of activity were categorized, and the visual intensity of uptake was scored by a semiquantitative 3-point grading system (1: mild uptake, 2: moderate uptake, 3: intense uptake). Lesion volumes were determined on the CT image or on the PET images. Background (bkg) was also measured for each lesion and on each individual PET image. For each lesion, the mean activity concentration rate per unit administered activity (ACR mean /AA) and lesion-to-bkg ratios were compared across the 5 different time points. The semiquantitative grade and the quantitative measurements were compared. Results A total of 45 124 I PET/CT scans were reviewed for 9 patients. In the visual assessment, a total of 31 foci suggestive for or highly suggestive of metastasis were identified on 124 I PET/CT. Of these, 6 were seen on the 2-h, 18 on the 24-h, 27 on the 48-h, 24 on the 72-h, and 20 on the 96-h scan. There was a significant difference between the 24- and 48-h scans in the total number of foci (ie, locoregional and distant metastasis) ( P &lt; 0.05) and in the number of distant metastases ( P &lt; 0.05). The 24-, 48-, and 72-h scans identified the same number of locoregional foci. The 48-h scan visualized more of the distant metastases than any other time point. 124 I PET/CT with dual-time-point imaging was superior to single-time-point imaging (97% vs 87%). In the quantitative analysis, the median ACR mean /AA was highest at 24 and 48 h, and the median lesion-to-bkg ratio was variable for different lesion locations. For lung metastases, the highest median lesion-to-bkg ratio was at 72 and 96 h. Conclusions 124 I PET/CT with dual-time-point imaging was superior to any single-time-point imaging ( P &lt; 0.10). Based on the visual assessment, dual time points at 48 + 72 h or 48 + 96 h yielded the highest lesion detection rate, whereas for single-time-point imaging, the 48-h images had the highest lesion detection rate. If the 48-h scan is completely negative or has negative 124 I uptake in the region of interest, then a 72- or 96-h scan may be valuable. If lung metastases are suspected, then one should consider additional imaging at 72 or 96 h.