tbuckley/cabot-search huggingface dataset:
hENT1 gene expression as a predictor of response to gemcitabine and nab-paclitaxel in advanced pancreatic cancer.
Authors: Sheron Perera, Gun Ho Jang, Amy Zhang, Robert Edward Denroche, Anna Dodd, Stephanie Ramotar, Shawn Hutchinson, Yifan Wang, Mustapha Tehfe, Ravi Ramjeesingh, James Joseph Biagi, Bernard Lam, Julie Wilson, Faiyaz Notta, Sandra Fischer, George Zogopoulos, Steven Gallinger, Robert C Grant, Jennifer J. Knox, Grainne M. O'Kane
Journal: Journal of Clinical Oncology (2021)

4011 Background: Human equilibrative nucleoside transporter 1 (hENT1) belongs to a family of nucleoside transporters critical to entry of gemcitabine into cells. The prognostic and predictive characteristics of this biomarker in pancreatic ductal adenocarcinoma (PDAC) have primarily been evaluated by immunohistochemistry, with conflicting results. We explored the impact of hENT1 gene expression in the Comprehensive Molecular Characterization of Advanced Ductal Pancreas Adenocarcinoma for Better Treatment Selection (COMPASS) trial. Methods: Patients were enrolled on COMPASS from December 2015 to June 2020 and underwent a biopsy for whole genome sequencing (WGS) and RNA sequencing prior to first chemotherapy in the advanced setting. Biopsies underwent laser capture microdissection to enrich for tumour epithelium. Chemotherapy regimen was determined based on clinician preference. The cut-off thresholds for hENT1 expression were determined using the maximal chi-squared statistic. Response rates and overall survival (OS) were computed based on hENT1 expression and chemotherapy regimen. Results: 254 patients were included in the analyses with a median follow-up time of 18 months. 146 patients were treated with modified FOLFIRINOX (FFX), 104 with gemcitabine and nab-paclitaxel (GnP), and 16 received no systemic therapy. Based on gene expression levels, 133 patients were classified as hENT1 high and 121 as hENT1 low . hENT1 expression was significantly associated with the modified Moffitt classifier with higher expression seen in classical tumours (p &lt; 0.001). In the entire cohort, median OS was 10.0 months in hENT1 high vs. 8.3 months in hENT1 low (adjusted HR 0.78, 95% confidence interval 0.59 - 1.03, p = 0.08). In patients receiving modified FFX, there was no difference in response rates (32% vs. 31%, p = 1.00) or OS (10.6 vs. 10.6 months, p = 0.94) between the hENT1 high and hENT1 low groups, respectively. However, in patient treated with GnP, response rates were significantly higher in hENT1 high patients compared to those with hENT1 low tumors (45% vs. 21%, p = 0.035). Median OS in this GnP treated cohort was 9.8 months in hENT1 high vs. 6.1 months hENT1 low (p = 0.003). In an interaction analysis, hENT was predictive of treatment response to GnP (p = 0.0002). Conclusions: Biomarkers predictive of response to GnP and FFX are urgently needed. Here we demonstrate that hENT1 gene expression is a predictor of response to GnP in advanced PDAC.
Water and Water Supplies.
Journal: JAMA (1896)

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Final survival results from a multicenter, randomized phase II trial of intravenous paclitaxel plus FOLFOX (ivPOF) and/or intraperitoneal paclitaxel plus FOLFOX (ipPOF) versus mFOLFOX6 as first-line treatment of advanced gastric cancer (AGC): SYLT/FNF 004.
Authors: Shen Zhao, Rongbo Lin, Nan-Feng Fan, Yigui Chen, Xiaofeng Li, Peicheng Lin, Wujin Chen, Wenzheng Fang, Jinfeng Zhu, Hui Li, Jie Liu
Journal: Journal of Clinical Oncology (2021)

4041 Background: Progression-free (PFS) and overall (OS) survival for SYLT/FNF 004 were previously reported in ASCO and ASCO-GI 2019. At that time, PFS was statistically significantly improved with ivPOF or ipPOF compared to mFOLFOX6 as first-line treatment of AGC; however, there were no significant between-treatment differences in OS. Herein, we report final survival results for this trial. Methods: Subjects were randomly assigned to one of three treatments: intravenous paclitaxel 135 mg/m 2 + mFOLFOX6 omitting the 5-FU bolus (ivPOF); intraperitoneal paclitaxel 80 mg/m 2 + mFOLFOX6 omitting the 5-FU bolus (ipPOF); or mFOLFOX6 (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 followed by 5-FU 400 mg/m 2 bolus and 5-FU 2400 mg/m 2 as a 46-hour continuous infusion). Treatment cycles were repeated every 14 days for up to 9 cycles. Thereafter, maintenance treatment with S-1 80 mg/m 2 /day for 14 days every 3 weeks until disease progression, unacceptable toxicity, patient refusal, or physician decision. The original study objective was to compare ivPOF or ipPOF vs. mFOLFOX6 for PFS. Due to slow accrual, the protocol was later amended to compare POF (ivPOF and ipPOF) with mFOLFOX6 for PFS. Results: Between Nov 2015 and May 2018, 89 subjects (30 ivPOF, 29 ipPOF, 30 mFOLFOX6) were enrolled. As of the data cutoff on Dec 31, 2020, median follow-up was 41 (IQR: 37-43) months. The median number of cycles administered was 7 (IQR: 4-9) for POF; 6 (IQR: 4-9) for ivPOF; 9 (IQR: 4-9) for ipPOF; and 4 (IQR: 3-9) for mFOLFOX6. Median PFS and OS, respectively, were 6.23 (95% CI: 4.90 to 9.07) and 10.17 (95% CI: 8.97 to 16.4) months for POF and 4.55 (95% CI: 2.73 to 6.87) and 6.87 (95% CI: 5.83 to 13.6) months for mFOLFOX6. Both PFS and OS were statistically significantly better with POF, ivPOF or ipPOF versus mFOLFOX6 (Table). Safety was consistent with previous reports. Conclusions: POF, ivPOF or ipPOF improved both PFS and OS compared with mFOLFOX6, with similarly manageable adverse effects. Clinical trial information: NCT02845908. [Table: see text]
Soundings: Gangsta rappa
Authors: Liam Farrell
Journal: BMJ (2001)

She was embarrassed. “My boyfriend and I had . . . anal intercourse last night,” she stammered, “and now I'm bleeding from my . . . back passage.”

I urged her not to worry. It was quite a normal practice between consenting adults, I said, but the next time make sure he uses a condom, to prevent infection, and try perfumed body oil as an aid to lubrication, which will protect against anal trauma and also smells nice.

It was the perfect consultation, I thought. I was warm, comforting, and empathic, allaying the patient's fears and lack of knowledge and slipping in some health promotion on the way, leaving her reassured, contented, and looking forward to some safe and uninhibited nookie. And then: “You don't understand, Doctor,” she said. “I was doing it to him.”

Is there a perfect world, where perfect consultations happen? A world where E coli urinary tract infections respond to trimethoprim, where bendrofluazide reduces blood pressure, where hypnotics are used on a short term basis only, where local communities raise vast amounts of money to buy scanning machines that will actually make patients better.

But this is the real imperfect world and I am a real general practitioner. When I hear hoofbeats at the window it ain't a zebra, and it probably ain't a horse either, but something in between, maybe some guy with coconuts making a clippety-clop noise. I'm out there at the coalface, on the streets, with the kids, a kind of gangsta rappa.

The perfect consultation, like the best dream and the most exotic sex, is probably unattainable, but trying your hardest to get it remains a source of personal and professional satisfaction, and there was one time . . . I told her to stand up straight, take off her horn rimmed glasses, and lose the frown. I unpinned her hair, which only took a few short minutes, and it poured down over her shoulders in a cascade of gold, like impetigo streaming down an infected chin.

I spoke in a low thrilling tone: “Go, young woman, spread your wings, you can fly, live free, they'll be slavering over you like a pack of wild Pavlovian dogs. Now, git along, little doggie.”

As she left I heard the first shots, the first sign that the streets would soon be strewn with bodies of men shooting themselves for her sake.

Or maybe it was just a car backfiring.
Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial.
Authors: Thomas Powles, Daniel P. Petrylak, Se Hoon Park, Srikala S. Sridhar, Claudia Caserta, Antoine Thiery Vuillemin, Hyo Jin Lee, Joaquim Bellmunt, Yoshiaki Yamamoto, Jeanny B. Aragon-Ching, Bo Huang, Keith A. Ching, Craig B. Davis, Alessandra Di Pietro, Yohann Loriot, Petros Grivas
Journal: Journal of Clinical Oncology (2021)

4520 Background: In the phase 3 JAVELIN Bladder 100 trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) vs BSC alone in patients (pts) with advanced UC that had not progressed on 1L platinum-based chemotherapy (HR, 0.69 [95% CI: 0.56, 0.86; 1-sided P= 0.0005]). We report post hoc analyses in previously unreported clinical and genomic subgroups. Methods: In JAVELIN Bladder 100 (NCT02603432), eligible pts had unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L gemcitabine + cisplatin or carboplatin, and were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350). The primary endpoint was OS, in all randomized pts and pts with PD-L1+ tumors (Ventana SP263 assay). In this exploratory analysis, we analyzed OS in disease stage and site subgroups, in pts with PD-L1+ tumors who received 1L gemcitabine + carboplatin, and in genomic subtypes (RNAseq whole-transcriptome profiling of tumor tissue) defined using data from The Cancer Genome Atlas (TCGA 2017). Interaction tests were not performed. Results: Prolonged OS was observed in the avelumab + BSC arm vs the BSC alone arm in pts with upper or lower tract tumors, metastatic or locally advanced (LA) and unresectable disease (prior to chemotherapy), and lymph node-only disease post-chemotherapy (Table). OS was also prolonged with avelumab + BSC in pts in PD-L1+ tumors who had received 1L gemcitabine + carboplatin, consistent with findings in the overall population. In genomic subtypes, the OS benefit for avelumab + BSC was apparent across TCGA subtypes except luminal. Conclusions: An OS benefit was seen for avelumab 1L maintenance + BSC vs BSC alone across subgroups of interest. Results are consistent with previously reported findings, further supporting avelumab 1L maintenance as a standard of care for pts with advanced UC that has not progressed with 1L platinum-containing chemotherapy. Clinical trial information: NCT02603432. [Table: see text]
Impact of hospital type and surgical volume on outcomes of biliary cancer resection.
Authors: Jasmeet Kaur, Waqas Qureshi, Vaibhav Sahai
Journal: Journal of Clinical Oncology (2021)

e16168 Background: The mainstay of treatment for patients with early-stage biliary cancer (gallbladder or cholangiocarcinoma) is surgical resection. Herein, we evaluated the predictors for biliary cancer resection outcome and association with hospital volume and teaching status. Methods: A national representative cohort of 18485 biliary cancer patients was included for the years 2016 – 2018 from the national inpatient sample database. The study population included patients ≥ 18 years diagnosed with biliary cancer who underwent elective surgical resection (ICD 10). Hospitals were categorized based on teaching status (yes, if ACGME approved residency program, member of the council of teaching hospitals, or with residents to beds ratio of .25 or higher, versus non-teaching); and hospital volume (high if ≥ 20 biliary cancer surgeries performed per year, otherwise low). The primary outcome was biliary resection and the secondary outcomes included post-operative complications, in-hospital mortality, length of stay (&lt; or ≥ 7 days), and health care cost (&lt; or ≥ median) based on hospital teaching status and biliary cancer surgical volume. Association with outcomes was assessed using multivariable logistic regression models adjusted for age, sex, race, household income, service payer, Elixhauser co-morbidity score, hospital volume, teaching status, bed size, location, and region. Results: Out of 18,485 patients hospitalized with biliary cancer, 7,030 patients underwent elective biliary cancer resection during the study period. Patients undergoing resection were likely to have higher than national household median income with Medicare as primary insurance payor. In multivariate adjusted logistic regression models, high volume centers showed significantly lower length of stay (adjusted odds ratio (aOR) 0.73; 95% CI 0.54 - 0.97; p=0.03), and lower in-hospital mortality (aOR 0.28; 95% CI 0.15 - 0.80; p=0.01), but no significant difference in post-operative complications or healthcare cost compared to low volume centers. Surgeries performed in a teaching hospital were associated with decreased risk of post-operative complications (aOR 0.74; 95% CI 0.55 - 1.0; p=0.05), significant decrease in in-hospital mortality (aOR 0.44; 95% CI 0.27 - 0.69; p=0.001), but higher inflation-adjusted healthcare cost (aOR 1.77; 95% CI 1.37-2.26; p&lt;0.001) with no difference in length of stay. Conclusions: Patients who underwent elective biliary cancer surgery at a teaching or high-volume hospital had a significant decrease in their risk of in-hospital mortality. Additionally, surgeries at teaching hospitals were associated with a significantly lower post-operative complication rate compared to similar procedures at a non-teaching hospital, although teaching hospitals did have a significantly higher healthcare cost when adjusted for length of stay.
Impact of race and socioeconomic status on breast cancer outcomes within the AJCC staging system.
Authors: Olga Kantor, Monica L. Wang, Kimberly Bertrand, Mariana Chavez-MacGregor, Rachel A. Freedman, Lori J. Pierce, Tari A. King, Elizabeth A. Mittendorf
Journal: Journal of Clinical Oncology (2021)

e18565 Background: The persistent racial and socioeconomic status (SES) disparities in breast cancer outcomes are partially attributed to propensity towards more aggressive cancers or presentation at higher stages among these groups. Chronic stressors related to race and SES are another major mechanism underlying these inequities. This study aims to examine the effect of race and SES within the AJCC 8th-edition staging system, which incorporates anatomic extent of disease and tumor biology. Methods: The SEER breast cancer database linked with county-level census data was used to identify patients with invasive breast cancer from 2010-2015. The database includes a composite SES-index which was analyzed in quintiles. Cox proportional-hazards regression was used to estimate disease-specific survival (DSS). Results: 259,852 patients were included: 176,369 (67.9%) non-Hispanic white, 28,510 (11.0%) Black, 29,737 (11.4%) Hispanic, and 22,887 (8.8%) Asian. Black race, lower SES, public insurance, lower education, and increased poverty were associated with decreased DSS. Adjusted survival analysis for patient, SES, tumor, and treatment characteristics demonstrated that patients of black race had inferior DSS within each stage. Fully adjusted models also showed patients residing in lower SES counties had inferior DSS [Table]. Conclusions: Racial and SES disparities in breast cancer-specific mortality were evident across all stages of disease. Future efforts to improve breast cancer outcomes should systematically assess and address racial and socioeconomic factors as fundamental drivers of inequitable outcomes. Adjusted 5-year DSS Estimates, Stratified by Race and SES.[Table: see text]
Pooled analysis of clinical activity of immune checkpoint immunotherapy in relapsing/refractory ES-SCLC.
Authors: Venkata Vosuri, Joseph McGreevy, Ghulam Ghous, Donald C. Doll, Tolga Tuncer
Journal: Journal of Clinical Oncology (2021)

e20572 Background: ES-SCLC is an aggressive lung cancer with high rates of relapse following induction regimens. Immune checkpoint immunotherapy (ICI) seems promising in the refractory/relapsing setting based on a smaller number of studies with smaller sample sizes. Here we report a pooled estimate of clinical activity of ICI in above patients based on published phase II/III trials so far. Methods: PubMed, EMBASE, Cochrane review, and clinicaltrials.gov databases were searched for phase II/III randomized controlled trials studying immune checkpoint immunotherapy in second or third line setting for ES-SCLC treatment. Data were extracted based on Reviews and Meta- Analysis guidelines. DerSimonian-Laird (DL) random effects model was used to estimate the pooled proportion of patients achieving objective response rate (ORR), pooled proportion of patients experiencing therapy related adverse events (TRAEs grade ≥ 1), pooled median progression free survival (PFS) and pooled median overall survival (OS), and weights were estimated using inverse variance method. Statistical heterogeneity was calculated using the I 2 and chi-squared test. Outcomes were calculated by using ‘Metafor’ and ‘Meta’ packages by R-Studio and “CRAN” project. Results: Five studies with a total of 698 patients who received immune checkpoint immunotherapy were analyzed. Median age of patients who received treatment was 63 yrs. The pooled proportion of patients who achieved ORR was 15% (95% CI 0.11 to 0.20). Pooled Median PFS was about 1.54 (95% CI, 1.34- 1.74) months and median OS was 6.46 (95% CI, 5.13- 7.73) months. The pooled proportion of patients who experienced adverse events during the treatment was 49% (95% CI 0.38 to 0.60). Conclusions: ICI as second or third line treatment choice offers modest improvement in progression free survival and overall survival in ES-SCLC patients who have not received ICI as first line in combination with etoposide and platinum based therapies.
Клінічний перебіг і морфологічні особливості хронічного гастриту в пацієнтів із найбільш поширеною гастроентерологічною патологією
Authors: A.S. Svintsytskyi, H.A. Soloviova, O.H. Kuryk, N.Ye. Dolhaia, I.V. Korendovych
Journal: GASTROENTEROLOGY (2014)

Стаття присвячена особливостям клінічного перебігу та морфологічного стану слизової оболонки шлунка в пацієнтів із найбільш поширеною гастроентерологічною патологією, а саме: захворюваннями жовчного міхура та жовчовивідних шляхів, неалкогольною жировою хворобою печінки, функціональною диспепсією та виразковою хворобою дванадцятипалої кишки. Встановлено, що біль в епігастрії частіше турбує пацієнтів із захворюваннями жовчного міхура, жовчовивідних шляхів і функціональною диспепсією; біль у правому та лівому підребер’ї частіше відмічався в пацієнтів із неалкогольним стеатогепатитом. Наявність запалення та активності антрального гастриту вірогідно частіше зустрічається в пацієнтів із виразковою хворобою дванадцятипалої кишки. Атрофічні, метапластичні та диспластичні зміни слизової оболонки тіла шлунка були найбільш вираженими в пацієнтів із неалкогольною жировою хворобою печінки.
Venetoclax for the treatment of multiple myeloma: Outcomes outside of clinical trials
Authors: M. Hasib Sidiqi, Abdullah S. Al Saleh, Shaji K. Kumar, Nelson Leung, Dragan Jevremovic, Eli Muchtar, Wilson I. Gonsalves, Taxiarchis V. Kourelis, Rahma Warsame, Francis K. Buadi, Martha Q. Lacy, Robert A. Kyle, Ronald Go, Miriam Hobbs, Angela Dispenzieri, David Dingli, Suzanne R. Hayman, Morie A. Gertz, S. Vincent Rajkumar, Prashant Kapoor
Journal: American Journal of Hematology (2021)

Multiple myeloma (MM) remains an incurable disease despite incorporation of novel agents. Venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor is approved for some hematologic malignancies but not yet for MM, although clinical trials have shown efficacy in patients with MM, particularly those harboring t(11;14). We reviewed the medical records of relapsed and/or refractory MM patients to study the efficacy and safety of venetoclax used outside of clinical trials at Mayo Clinic between December, 2016 and March, 2019. The data cut-off date was August 06, 2020. We identified 56 patients of whom 42 (75%) harbored t(11;14). The median number of prior therapies was six (range 1-15) and 14% of patients had received ≥10 prior lines of therapy. Fifty-three (95%) patients were refractory to an immunomodulatory drug and proteasome inhibitor. Venetoclax was used as monotherapy or doublet, in combination with dexamethasone in 55% (n = 31) and a triplet or quadruplet in 45% of patients. No patient experienced tumor lysis syndrome. Overall response rate in 52 evaluable patients was 44%. The median time to best response was 2 months and median duration of response was 13.6 months. The median PFS for the entire cohort was 5.8 (95% CI 4.9-10.3) months and median OS was 28.4 (95% CI 14.6-not reached) months. The presence of t(11;14) was associated with improved PFS (median 9.7 months vs. 4.2 months, p = 0.019) and OS (median not reached vs. 10.8 9 months, p = 0.015). Venetoclax demonstrates encouraging activity in heavily-treated patients with relapsed/refractory MM, particularly the t(11;14) patient-population.