tbuckley/cabot-search huggingface dataset:
Differences in the immune microenvironment between early and late-onset colon and rectal cancer.
Authors: Ivy Hernandez Gardner, Ragavan Siddharthan, Kate Watson, Rebecca Ruhl, Sudarshan Anand, Vassiliki Liana Tsikitis
Journal: Journal of Clinical Oncology (2020)

214 Background: Over the past 35 years, there has been a significant increase in the number of patients below the recommended initial screening age (50 years old) diagnosed with colorectal cancer (CRC). Early onset colorectal cancer is more likely to occur in non-white patients, be located in the rectum, be diagnosed at a more advanced stage, and have concerning pathological features. The immune microenvironment in CRC is a key player in disease progression, therapy response, and overall survival. However, the role of the immune microenvironment in early onset CRC, particularly in rectal cancer has not been investigated. This study aims to characterize the immune microenvironment of early onset ( 50 years old) and late onset ( 65 years old) colon and rectal cancer patients. Methods: We used Nanostring immune profiling to analyze FFPE surgical specimens and identified genes that were differentially expressed between early and late onset colon and rectal cancer groups. We validate our results with qPCR. The differentially expressed genes in the rectal cancer cohort were compared to our analysis of a publically available database (GSE8721) of gene expression profiles for 203 rectal cancer and 160 matched normal mucosa samples. Immunohistochemistry (IHC) was performed on FFPE colorectal specimens for CXCL3. Results: Using Nanostring, we identified two genes that were differentially expressed between early and late onset colon cancer (IFITM1, CXCL3) and two genes in the rectal cancer cohort (FLT3, SAA1). CXCL3 has increased expression in late onset colon cancer utilizing qPCR and IHC. High expression of CXCL3 in both IHC and qPCR is associated with improved disease free survival. Analysis of the GSE8721 database also showed that FLT3 and SAA1 were differentially expressed in early versus late onset rectal cancer. Using qPCR, FLT3 is increased in early onset rectal cancer specimens compare to late onset rectal cancer, early and late onset colon cancer, and normal colon. Conclusions: There are distinct differences in the immune microenvironment between early and late onset colon and rectal cancer that may hold the potential for targeted therapeutics.
The economic impact of violence perpetration in severe mental illness: a retrospective, prevalence-based analysis in England and Wales
Authors: Morwenna Senior, Seena Fazel, Apostolos Tsiachristas
Journal: The Lancet Public Health (2020)

BackgroundCalls for increased funding for mental health services require many lines of evidence in support, including estimates of economic impact. One understudied source of cost is violence perpetrated by individuals with severe mental illness. Estimating this economic impact can inform budget planning across several government sectors and emphasise the importance of violence prevention. Therefore, we aimed to provide a comprehensive estimate of the economic costs of violence perpetrated by people with severe mental illness.MethodsFor this retrospective analysis, we used a prevalence-based modelling approach to estimate the annual economic cost of violent incidents committed by people with severe mental illness in England and Wales during 2015–16. The model was based on secondary data, including the association between violence and severe mental illness, illness prevalence, recidivism, absolute numbers of violent incidents in 2015–16, and costs to society per violent crime, by area of spending. Uncertainty was addressed with probabilistic and deterministic sensitivity analyses that tested the effect of underreporting of domestic violence and distributions of crime types in individuals with severe mental illness.OutcomesThe estimated annual economic impact of violence perpetrated by people with severe mental illness was £2·5 (95% CI 1·4–4·5) billion in England and Wales in 2015–16, or 5·3% of the total estimated societal cost of violence. The largest contributors to the cost of violent crime perpetrated by individuals with severe mental illness were the cost of physical and emotional harm to victims (£1·4 [95% CI 0·8–2·5] billion), followed by lost productivity of victims (£348.0 [190·0–628·8] million), while the combined cost to the police and criminal justice system was £561·3 (305·9–1009·2) million and the cost to health services was £136·7 [74·3–246·3] million. The additional cost to secure forensic care was estimated to be £487·7 (302·0–709·1) million.InterpretationThe economic impact of violence perpetrated by individuals with severe mental illness is potentially important. Preventing violence, especially through services for individuals with comorbid substance misuse, and reducing recidivism might lead to cost savings at a governmental and individual level, in addition to the clinical and societal benefits.FundingWellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, and NIHR Applied Research Collaboration Oxford and Thames Valley.
Reply To Kenneth B. Yatai, Mark J. Dunning, Dennis Wang. Consensus Genomic Subtypes of Muscle-invasive Bladder Cancer: A Step in the Right Direction but Still a Long Way To Go. Eur Urol 2020;77:434–5
Authors: Aurélie Kamoun, Aurélien de Reyniès, Yves Allory, Gottfrid Sjödahl, A. Gordon Robertson, Roland Seiler, Katherine A. Hoadley, Clarice S. Groeneveld, Hikmat Al-Ahmadie, Woonyoung Choi, Mauro A.A. Castro, Jacqueline Fontugne, Pontus Eriksson, Qianxing Mo, Jordan Kardos, Alexandre Zlotta, Arndt Hartmann, Colin P Dinney, Joaquim Bellmunt, Thomas Powles, Núria Malats, Keith S Chan, William Y Kim, David J McConkey, Peter C Black, Lars Dyrskjøt, Mattias Höglund, Seth P Lerner, Francisco X Real, François Radvanyi, Mattias Aine, Isabelle Bernard-Pierrot, Bogdan Czerniak, Ewan A Gibb, Jaegil Kim, David J. Kwiatkowski, Thierry Lebret, Fredrik Liedberg, A Arlene Siefker-Radtke, Nanor Sirab, Ann Taber, John N. Weinstein
Journal: European Urology (2020)
A phase II study of enterade in neuroendocrine tumor (NET) patients with quality-of-life limiting bowel movement frequency.
Authors: Satya Das, Tatsuki Koyama, Laura Luque, Samuel Cheuvront, Jordan Berlin
Journal: Journal of Clinical Oncology (2020)

TPS634 Background: BM frequency in NET pts is a major cause of morbidity. Though typically associated with serotonin excess in pts with carcinoid syndrome (CS), it can also occur in pts without CS due to etiologies such as short bowel syndrome, bile acid malabsorption, steatorrhea from somatostatin analogs (SSAs) and complications from chemotherapy/immunotherapy/biologics. Enterade is an oral rehydration solution, comprised of 5 amino acids, which has demonstrated pre-clinical and clinical potential to improve small intestinal resorption, thereby offering a potential treatment for limiting BM frequency in NET pts. Methods: We are conducting a phase II parallel cohort study in CS and non-CS NET pts (NCT 4073017). To be eligible, pts must be experiencing an average of ≥ 4 daily BM while on standard-of-care (SOC) therapies (SSAs, anti-diarrheals). Pts will be categorized into CS or non-CS cohorts based upon biochemical evaluation which includes plasma 5-HIAA/24-hour urine 5-HIAA, VIP or gastrin levels. Eligible pts will undergo observation during weeks 1-4 (baseline period). During weeks 5-8, pts will consume Enterade twice per day (Enterade period) while during weeks 9-12, pts will stop Enterade and resume observation. Daily stool diaries for each pt will be assessed to compute differences in mean bowel movement number between baseline and Enterade periods. Endpoints: The primary endpoint of the study is reduction in BM frequency in individual pts between baseline and Enterade periods. Based on parameters utilized in a prior study, we will assume that the mean daily reduction in bowel movements from baseline is equal to 1.5 (standard deviation of change = 1.5) representing a large effect size = 1.0. A sample of 12 pts in each cohort will provide nearly 90% power to detect this effect size based on a one-sample t-test (α = .05). An additional 3 pts will be added to each cohort to account for potential dropouts. Key secondary study endpoints include differences in pt-reported QOL outcomes (FACIT-D), pt weight, intravenous fluid requirement and utilization of SOC anti-diarrheals between baseline and Enterade periods. Accrual for the study will be ensuing shortly. Clinical trial information: NCT04073017.
Perioperative complication rates following neoadjuvant therapy in pancreatic adenocarcinoma.
Authors: Christopher R. Deig, Blake Beneville, Amy Liu, Aasheesh Kanwar, Alison Grossblatt-Wait, Brett C. Sheppard, Erin W. Gilbert, Charles D. Lopez, Kevin G. Billingsley, Nima Nabavizadeh, Charles R. Thomas, Aaron Grossberg
Journal: Journal of Clinical Oncology (2020)

688 Background: Whether upfront resection or total neoadjuvant therapy is superior for the treatment of potentially resectable pancreatic adenocarcinoma (PDAC) remains controversial. The impact of neoadjuvant treatment on major perioperative complication rates for patients (pts) undergoing resection for PDAC is commonly debated. We hypothesized that rates would be comparable among patients receiving neoadjuvant chemoradiation (neo-CRT), neoadjuvant chemotherapy alone (neo-CHT), or upfront surgery. Methods: This is a retrospective study of 208 pts with PDAC who underwent resection within a multidisciplinary pancreatico-biliary program at an academic tertiary referral center between 2011-2018. Data were abstracted from the medical record, an institutional cancer registry and NSQIP databases. Outcomes were assessed using χ 2 , Fisher’s exact test and two-tailed Student’s t-tests. Results: 208 pts were identified: 33 locally advanced, borderline or upfront resectable pts underwent neo-CRT, 35 borderline or resectable pts underwent neoadjuvant-CHT, and 140 resectable pts did not undergo neoadjuvant therapy. There were no statistically significant differences in major perioperative complication rates between groups. Overall rates were 36.4%, 34.3%, and 26.4% for pts who underwent neo-CRT, neo-CHT alone, or upfront resection, respectively (p = 0.38). No significant difference were observed in complication rates (35.3% v. 26.4%; p = 0.19) or median hospital length of stay (10 days v. 10 days; p = 0.87) in pts who received any neoadjuvant therapy versus upfront resection. There were two perioperative deaths in the neo-CRT group (6.1%), zero in the neo-CHT group, and four in the upfront resection group (2.9%); p = 0.22. Conclusions: There were no significant differences in major perioperative complication rates, hospital length of stay, or post-operative mortality in pts who underwent neoadjuvant therapy (neo-CRT or neo-CHT alone) versus upfront surgery. Notably, neo-CRT had comparable perioperative complication rates to neo-CHT alone, which suggests neoadjuvant radiation therapy may not pose additional surgical risk.
Correlation of mesothelin (MSLN) expression with future peritoneal metastases (PM) in colorectal cancer (CRC).
Authors: Midhun Malla, Noah Rozich, Ayesha Hassan, Maham Hayat, Sixia Chen, Sanober Nusrat, Richard M. Goldberg, Katherine Teresa Morris
Journal: Journal of Clinical Oncology (2020)

176 Background: CRC patients with PM have a significantly worse median overall survival (OS) when compared to those with liver and lung metastases. We studied MSLN protein expression using immunohistochemistry (IHC) on primary resected CRC (PRC), its correlation with future development of PM and its effect on OS. Our hypothesis is that PRC tumors from patients who later developed PM will have an increased proportion of positive MSLN scores based on IHC. Methods: We performed a retrospective case control study of all localized CRC (Stage I, II, III) patients who underwent curative resection from 2000- 2017 at the University of Oklahoma. The target population consisted of PRC patients who had distant recurrence during surveillance. Control group comprised of patients who never recurred after a minimum of 5 years of surveillance. MSLN score was calculated by the sum of staining percentage and intensity scores on each MSLN stained slide. Kaplan-Meier method was used to estimate OS and differences in survival were estimated using log-rank test. Results: Among 100 patients with recurrent CRC, 19 patients had PM, 51 had solid organ only metastases (SOM) and 66 are in the control group. MSLN staining results by IHC were satisfactory in 87 patients (Table). 91%, 46% and 21% of the patients in PM, SOM, and control groups had a positive MSLN score on PRC respectively. A significant association between MSLN score and future development of PM was observed (p&lt;0.001) based on Fisher’s exact test. Sensitivity of MSLN as a marker for future PM was 93% and specificity was 58%. Patients with a positive MSLN score had a poor OS when compared to those with a negative MSLN score on univariate analysis (95% CI: 4.1-NR (not reached), p &lt;0.001), which lost significance on multi-variable cox proportional analyses. Conclusions: A higher proportion of patients in the PM group had a positive MSLN score on PRC when compared to the SOM and control groups. MSLN was found to be a highly sensitive marker for future PM in CRC. We intend to expand this work by examining an additional cohort to validate these findings. [Table: see text]
Impact of <i>CDKN2A/b</i> status in pancreatic cancer (PC).
Authors: Kaitlin Annunzio, Claire Griffiths, Igli Arapi, Matthew Lasowski, Arun K. Singavi, Kulwinder Dua, Abdul H. Khan, Paul S. Ritch, Mandana Kamgar, James P. Thomas, William Adrian Hall, Beth Erickson, Susan Tsai, Kathleen K. Christians, Douglas B. Evans, Raul Urrutia, Aniko Szabo, Ben George
Journal: Journal of Clinical Oncology (2020)

759 Background: PC is a lethal disease with limited treatment options. We utilized Comprehensive Genomic Profiling (CGP) to identify putative prognostic and/or predictive biomarkers. Methods: We retrospectively reviewed PC patients (pts) at our institution who underwent CGP utilizing the Foundation One assay. CGP was performed on hybrid-capture, adaptor ligation-based libraries for up to 315 genes plus 47 introns from 19 genes frequently rearranged in cancer. PC pts were categorized by clinical stage – localized (resectable and borderline resectable PC; LPC), locally advanced (LAPC) and metastatic (mPC). Effect of gene alterations (GAs) with at least 10% prevalence were analyzed. The marginal effect of each gene on radiographic response and survival outcomes was estimated using proportional odds and multivariate Cox regression analysis, respectively, adjusting for stage. Results: Ninety-three pts were identified - median age was 63, 55% were male, and 50% were smokers. Clinical stage at diagnosis was LPC, LAPC and mPC in 42 (45%), 23 (25%) and 28 (30%) pts, respectively. The most commonly altered genes were KRAS (94%), TP53 (75%), CDKN2A (41.2%) and SMAD4 (32.9%). All patients were microsatellite stable and the median tumor mutational burden was 1.7. 5-FU (52%) or Gemcitabine (46%) based chemotherapy combinations were utilized as the first systemic therapy. Median overall survival for patients with LPC, LAPC and mPC were 30.7, 28.8 and 9.6 months respectively. Thirty-eight (91%) pts with LPC underwent curative intent surgery compared to 15 (65%) pts with LAPC (p = 0.019). Thirty-five (95%) pts with wild type (WT) CDKN2A and 47 (94%) pts with WT CDKN2B underwent curative intent surgery compared to 13 (65%) and 1(14%) pt(s) with GAs in CDKN2A and CDKN2B respectively (p = 0.003 and p &lt; 0.0001 respectively). The response to chemotherapy was statistically significantly higher in pts with WT CDKN2A (53%) and CDKN2B (48%) compared to pts with GAs in CDKN2A (19%) and CDKN2B (12%) (p = 0.03 and p = 0.05, respectively). Conclusions: GAs in CDKN2A/B may have a predictive and possibly a prognostic impact. The clinical validity and biological relevance of these findings need to be further explored in larger studies.
Randomized phase II trial of chemoradiotherapy with S-1 versus combination chemotherapy with gemcitabine and S-1 as neoadjuvant treatment for resectable pancreatic cancer (JASPAC 04).
Authors: Hirochika Toyama, Teiichi Sugiura, Akira Fukutomi, Hirofumi Asakura, Yuriko Takeda, Kouji Yamamoto, Satoshi Hirano, Sohei Satoi, Ippei Matsumoto, Shinichiro Takahashi, Soichiro Morinaga, Makoto Yoshida, Yasunaru Sakuma, Hidetaka Iwamoto, Yasuhiro Shimizu, Katsuhiko Uesaka
Journal: Journal of Clinical Oncology (2020)

724 Background: Although neoadjuvant treatment (NAT) has been widely employed for resectable pancreatic ductal adenocarcinoma (PDAC), it is still unclear what kind of regimen is recommended. The aim of the study is to investigate which chemoradiotherapy (CRT) with S-1 or combination chemotherapy with gemcitabine (GEM) and S-1 is more promising as NAT for resectable PDAC in terms of effectiveness and safety. Methods: Patients with resectable PDAC were enrolled and randomly assigned into either CRT group or chemotherapy group. In the CRT group, a total radiation dose of 50.4 Gy in 28 fractions was administered and S-1, at a dose of 30, 40 or 50 mg according to the body surface area, was orally provided twice a day on the same day of irradiation. In the chemotherapy group, GEM was intravenously administered at a dose of 1000 mg/m 2 on day 1 and 8 and S-1 was orally provided at a dose of 30, 40 or 50 mg according to the body surface area twice daily on day 1 to 14 followed by one week reset. Patients in the chemotherapy group received two cycles of this regimen. Surgery was performed between 15 and 56 days after the last day of NAT. The primary endpoint was 2-year progression-free survival (PFS) rate. With 50 patients in each group, the study had 80% power assuming a threshold 2-year PFS rate of 25% and an expected 2-year PFS rate of 40% at 0.05 one-sided alpha. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. Results: From April 2014 and April 2017, 103 patients were enrolled from 11 institutions in Japan. One was excluded because of ineligibility, therefore 51 patients in CRT group and 51 patients in chemotherapy group constituted the intention-to-treat analysis. The 2-year PFS rate was 45% (90% CI, 33-60%) in the CRT group and 55% (43-65%) in the chemotherapy group (p = 0.52). The hazard ratio for chemotherapy to CRT was 0.78 (0.46-1.31). The median survival time was 37.7 (95% CI, 30.3-NE) in the CRT group and NE (29.9-NE) in the chemotherapy group (p = 0.30). There was no treatment-related death in both groups. Conclusions: Combination chemotherapy with GEM and S-1 may be more promising compared with CRT with S-1 as NAT for resectable PDAC. Clinical trial information: UMIN000014894.
Burden of Complications in U.S. Adults With Young-Onset Type 2 or Type 1 Diabetes
Authors: Michael Fang, Justin B. Echouffo-Tcheugui, Elizabeth Selvin
Journal: Diabetes Care (2020)

Young-onset type 2 diabetes has a more aggressive clinical course than type 2 diabetes that occurs at an older age (1). Accruing evidence suggests that young adults with type 2 diabetes have complication rates exceeding those of individuals of similar age with type 1 diabetes (1–3). However, prior studies have focused on select populations and the generalizability of their findings is not clear. To address this gap in the literature, we analyzed recent national data to characterize the prevalence of complications among U.S. adults with young-onset type 1 and type 2 diabetes.

We pooled data from the 2016 and 2017 National Health Interview Survey (NHIS). The NHIS is the only representative U.S. study that collects self-reported information on types of diabetes. Participants reported whether they had ever been diagnosed with diabetes other than during pregnancy. Those with diagnosed diabetes reported the type of diabetes (type 1, type 2, other), age of diagnosis, and use of antidiabetes medication.

Following past research, we defined young-onset type 2 diabetes as being diagnosed before age 40 (1). We defined young-onset type 1 diabetes using this same cut point for comparability. We classified …
Disparities in Palliative Care in Patients With Cancer
Authors: Jennifer J. Griggs
Journal: Journal of Clinical Oncology (2020)

In the United States, racial and ethnic minorities and people with lower socioeconomic status (SES) face structural, health system, and interpersonal barriers to optimal health care, including palliative care. Much of the available data on palliative care in racial and ethnic minorities and people with lower SES have identified disparities according to race, ethnicity, and SES. Limitations to understanding disparities in palliative care include the fact that much of the available data are cross-sectional, drawn from administrative or claims data, or based on qualitative work in limited geographic areas. To advance our knowledge and achieve health equity with respect to palliative care in patient groups that have been understudied or that are known to receive disparate care, gaining a deeper understanding of the barriers to palliative care is necessary from patients, families, referring providers, and communities. In addition, cultural competency training for all members of the palliative care team and referring providers needs to be changed from being obligatory to being intentional and assessed continuously. Finally, concerted changes in coordination of care, payment structures, and policy are needed.
A United States Rectal Cancer Consortium study of inferior mesenteric artery versus superior rectal artery ligation: How high do we need to go?
Authors: Michael K. Turgeon, Adriana C. Gamboa, Rachel M. Lee, Jeffrey Maniko, Lillias Maguire, Maryam Mohammed, Jennifer Holder-Murray, Sherif Abdel-Misih, Charles Kimbrough, Jason T. Wiseman, Kamren Edwards-Hollingsworth, Alexander Hawkins, Philip Bauer, Matthew Silviera, Shishir K. Maithel, Glen C. Balch
Journal: Journal of Clinical Oncology (2020)

47 Background: The optimal level of pedicle ligation during proctectomy for rectal cancer, either at the origin of the inferior mesenteric artery (IMA) or the superior rectal artery (SRA), is still debated. Reasons for IMA ligation include facilitating a tension-free anastomosis and improved clearance of regional lymph nodes. Our aim was to determine if SRA ligation portends inferior outcomes. Methods: The US Rectal Cancer Consortium database (2007-2017) was reviewed for pts with primary, non-metastatic rectal adenocarcinoma who underwent treatment with low anterior resection or abdominoperineal resection. Primary outcomes were anastomotic leak rate and lymph node (LN) harvest. Secondary outcomes were locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS). Results: Of 877 pts, median age was 59 years (IQR52-67) and 62% were male (n = 541). 86% received an IMA ligation (n = 755) while 14% SRA (n = 122). 12% were pathologic stage 0 (n = 101), 33% stage I (n = 281), 24% stage II (n = 206), and 31% stage III (n = 269). Median follow-up was 34 mos. SRA ligation was more common in stage III disease (43vs30%, p = 0.005) while IMA ligation was more often performed with a minimally invasive approach (70vs42%, p &lt; 0.001). SRA ligation was associated with a nearly identical anastomotic leak rate compared to IMA (9vs8%, p = 1.0). Similarly, the median number of LNs removed was the same between both ligation groups (15vs15, p = 0.38). On multivariable analysis accounting for an open approach, advanced pathologic stage, and positive resection margin status, SRA ligation was not associated with increased anastomotic leak rate or reduced LRFS, RFS, or OS (all p &gt; 0.1). Conclusions: If a tension-free anastomosis is feasible, SRA ligation is not associated with either a worse technical outcome or inferior lymph node harvest. Furthermore, all cancer survival metrics are similar between SRA and IMA ligation. Given that either approach is safe and feasible from both a technical and oncologic standpoint, this study questions the routine practice of IMA ligation.