tbuckley/cabot-search huggingface dataset:
Do patients with an ECOG of 3 or 4 receive anti-cancer therapy after discharge from subacute rehabilitation?
Authors: Muhammad Azeem Khan, Diana E Stewart, Ami Chitalia, Clint S. Pettit, Hunter Groninger
Journal: Journal of Clinical Oncology (2018)

e18856 Background: Patients with advanced cancer inevitably experience a functional decline diminishing quality of life. Many are admitted to the hospital due to progression of disease and become further deconditioned. Discharge to sub-acute rehabilitation (SAR) to ‘gain strength’ for future anti-cancer therapy is common as participation in more intensive rehab therapy is rarely possible. In this study, we sought to determine if pre-hospitalization ECOG correlated with completing oncology outpatient follow-up and/or receiving anti-cancer therapy after SAR. Methods: At our 926-bed urban academic center, we performed a retrospective chart review from January 2016 to January 2017 of hospitalized patients with solid cancers who were subsequently discharged to SAR. Patients were excluded if they had incomplete follow up, surgery, a cerebrovascular event during their hospitalization or a remote history of cancer. Primary outcomes were achievement of at least one successful visit to outpatient oncology follow-up and receiving at least one anti-cancer treatment. Results: Fifty six patients were identified (median age 69, range 38-91; 86% African American, 68% female. Forty-seven (84%) had metastatic disease. Twenty-nine patients (52%) had a pre-hospitalization ECOG of 1 or 2, of which 16 (55%) successfully completed at least one follow-up oncology visit, 10 (34%) received chemotherapy, and none received radiation (RT). ; Twenty-seven patients (48%) had an ECOG of 3 or 4, of which 11(41%) successfully completed at least one follow-up oncology visit and 5 (19%) received at least one anti-cancer therapy treatment [2 (7%) received RT and 3 (11%) received chemotherapy]. Of 56 total patients, 11 (20%) were readmitted to our institution within 30 days of discharge to SAR. Seven of these 11 (64%) had an ECOG of 3 or 4. Conclusions: Compared to patients with ECOG 1 or 2, patients with ECOG of 3 or 4 were less likely to follow up with their oncologist and receive anti-cancer treatment post SAR. The identification of additional markers of poor prognosis through larger prospective multi-institutional studies will help to delineate which patients are more likely to get anti-cancer therapy after SAR.
Natural history of mucinous ovarian cancer in Ireland.
Authors: Darren Cowzer, Emily O'Donovan, Therese Brown, Noreen Gleeson, David James Gallagher
Journal: Journal of Clinical Oncology (2017)

e17056 Background: Mucinous ovarian neoplasmscan arise as benign, borderline or malignant disease. Primary mucinous epithelial ovarian carcinoma (mEOC) represents 3% of invasive EOC. Differentiating primary from metastatic mucinous ovarian cancer is challenging. Systemic management of mucinous ovarian cancer increasingly follow GI cancer treatment protocols. We examined retrospective data at our institution to investigate incidence, management and site of origin of mEOC. Methods: 1,333 ovarian malignancies either diagnosed at or referred to St James Hospital, Dublin (from 2000 – 2016) were evaluated. The diagnosis was based on reported pathology. Patient demographics and investigations were retrospectively analyzed. Tumours were graded according to FIGO criteria. Results: Between 1/1/2000 and 9/12/2016 1,333 primary ovarian malignancies were diagnosed at our institution. 48 (3.6%) of these were mucinous adenocarcinoma and a further 5 (0.38%) were endometriod carcinoma of the ovary with mucinous differentiation. The average age at diagnosis was 48 (range 19-77 years). The majority of cases (87.5%) were stage I (IA 23, IB 2, IC 17, II 0, IIIA 1, IIIB 1, IIIC 3, IV 1) Staging CT thorax, abdomen and pelvis was completed in 44/48 cases and 24/48 (50%) patients underwent endoscopic evaluation of the uper or lower GI tract: 11 (22.9%) patients had both upper and lower GI endoscopy, 8 (16.7%) underwent OGD only and 5 (10.4%) had colonoscopy only. Gastrointestinal malignancy was not diagnosed in any of the patients. A total of 3 patients had immunohistochemistry for mismatch repair proteins performed, all of which demonstrated normal staining. All patients underwent surgical resection, 14 (29.2%) received adjuvant chemotherapy. 12 (25%) patients have died with a median OS of 11.5 months (range 7-108 months). Median follow up is 20.5 months (range 1-85 months) Conclusions: The incidence of mEOC in our population is 3.6%. The majority of patients diagnosed with mEOC over a 16 year period are still alive without evidence of disease, suggesting the diagnosis were ovarian in origin rather than metastatic. Immunohistochemistry for mismatch repair proteins is ongoing and will be presented at the meeting.
Analysis of <i>RSPO</i> gene expression in solid tumors.
Authors: Ana Vivancos, Hector G. Palmer, Zighereda Ogbah, Judit Matito, Francesco M Mancuso, Alejandro Navarro, Alex Martinez Marti, Guillem Argiles, Elena Elez, Jordi Rodón, Paolo Nuciforo, Josep Tabernero, Enriqueta Felip
Journal: Journal of Clinical Oncology (2016)

e23235 Background: It is well recognized that mutations in downstream components of the canonical Wnt pathway (e.g. APCand beta-catenin) can contribute to tumorigenesis. Recently, genetic alterations in upstream regulators of the Wnt pathway, such as RNF43 and R-spondins, have also been implicated in tumorigenesis. RNF43 and its homolog ZNRF3 are E3 ubiquitin ligases that promote the degradation of the frizzled family of Wnt receptors. R-spondins, in turn, are secreted proteins that interact with LGR4/5 receptors to promote membrane clearance of RNF43 and ZNRF3. Thereby, R-spondins act as agonists of the pathway. Gene fusions involving R-spondin family members RSPO2 and RSPO3 have been reported to occur in 10% of colon cancer. The gene fusions identified so far promote the acquisition of a strong promoter upstream of the RSPO2 and RSPO3 genes, increasing the levels of transcription. We profiled gene expression of the RSPO1-4 genes in solid tumors and compared to the levels detected in RSPO2/3-fused samples. Methods: We developed a custom codeset with nCounter (Nanostring) technology with probes for the RSPO1-4 genes as well as RSPO2-3 gene fusions. We analyzed FFPE samples from 190 solid tumor of patients that were candidates to clinical trials, as part of our prescreening program. Results: The cohort was composed of colorectal (n = 29), NSCLC (n = 54, adenocarcinoma (ADC) n = 10), breast (n = 21), brain (n = 18), cholangiocarcinoma (n = 17), thyroid (n = 13), bladder (n = 13), urological (n = 5) and a group of rare cancer types. As expected, most samples showed very low expression of any RSPO. However, a subgroup of them presented significantly higher levels of expression. In particular, for RSPO3, 50% of NSCLC ADC (n = 5) and 20% of CRC (n = 6) tumors were particularly positive. Of them, 3 CRC were RSPO3 fused, as confirmed by qRT-PCR. We also detected RSPO4 overexpression only in NSCLC samples (n = 5, 10%). Additional outlier cases of brain, bladder or thyroid tumors show high RSPO expression. Conclusions: These data highlight that a subset of NSCLC shows high expression of different RSPOs, even higher than RSPO3 fusion-positive CRC tumors. Altogether, some lung cancer patients could benefit from targeted anti-WNT treatments, as is the case for CRC.
Identification and characterization of germline pathogenic variants using matched tumor-normal next-generation sequencing in 7363 pan-cancer patients in China.
Authors: Yuting Yi, Fei Ma, Michael F Sharpnack, Jun Zhao, Yan-Fang Guan, Pingping Dai, Jiaojiao Huan, Li Liu, Quchang Ouyang, Yidong Zhou, Rongrong Chen, Ling Yang, Xin Yi, David Paul Carbone, Xuefeng Xia, Jinji Yang, Kai He
Journal: Journal of Clinical Oncology (2018)

1545 Background: Comprehensive NGS panel based genetic testing is becoming more common to help clinicians provide personalized cancer care. Matched tumor-normal sequencing is recommended primarily to detect tumor-specific variants. Previously under-explored, it could also detect pathogenic germline alterations in cancer patients. Using targeted matched tumor-normal NGS, we identified and characterized germline variants in a large pan-cancer patient cohort in China. Methods: We surveyed the germline variants in 7363 Chinese patients across more than 18 diverse cancer types. Germline variants in 62 cancer-susceptibility genes were called from a 1021 gene NGS panel analyzing matched normal DNA. Following AMCG guidelines, variants were classified into pathogenic, likely pathogenic, variant of unknown significance, likely benign, or benign. Results: 385 germline pathogenic and likely pathogenic variants (GPVs) were identified in 374/7363 (5.1%) patients. Ovarian cancer (27.6%, 37/134) represented the highest prevalence. Breast cancer (11.3%, 92/813), colorectal cancer (8.3%, 66/791), pancreatic cancer (6.2%, 8/130), renal cell cancer (6%, 5/84), and gastric cancer (5.1%, 14/273) displayed relatively high rates of GPVs in line with expectations. Interestingly, NSCLC (2.5%, 88/3572) and hepatocellular cancer (2.3%, 5/214) also showed such events. In total, only 192/385 (49.9%) participants presented with GPVs in cancer-susceptibility genes in the expected cancer types. BRCA2 and BRCA1 were the top two common genes, which were found in 146 patients across 15 cancer types including 27/3572 (1%) NSCLC and 3/214 (1.4%) hepatocellular cancer patients. 285/385 (74%) of the GPVs were actionable for targeted therapy. Conclusions: Germline variants can be identified on routine targeted matched tumor-normal NGS and commonly exist in patients with cancers of diverse tissue origin. Recognition of germline variants may be valuable in therapeutic interventions and genetic risk analysis. We are currently performing retrospective family history analysis and genetic counseling for those patients with unreported GPVs.
Impact of sorafenib treatment on portal hypertension in hepatocellular carcinoma patients.
Authors: Sahin Lacin, Reham Abdel-Wahab, Mohamed Elbanan, Shady Abdelbaki, Ahmed S Shalaby, Manal Hassan, Wei Wei, Jia Sun, Khaled M. Elsayes, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2016)

e15637 Background: Portal hypertension (PH) is the most common complication in cirrhotic hepatocellular carcinoma (HCC) patients. Although, several preclinical and clinical data have shown decreased portal pressure under sorafenib, clinical significance remains unclear. Our study aimed to evaluating changes in PH in HCC patients under Sorafenib treatment, and correlates these changes with patients’ overall survival (OS). Methods: We reviewed 69 Sorafenib treated patients at MD Anderson Cancer Center who received sorafenib ≥ 1 month. Analysis of radiological, laboratory, and clinical parameters was done pre-sorafenib, and at end of Sorafenib therapy. Mean and standard deviation (SD) was measured for radiological and laboratory PH parameters. Univariate and multivariate logistic regression models were used to detect the ability of these parameters in predicting survival. Results: We found that higher bilirubin and lower albumin are predictors for OS. Notably, radiological parameters showed a strong and consistent trend of improved PH findings based on imaging parameters, although they weren’t statistically significant (Table 1). OS of patients with cirrhosis was 8.1 (95%Cl; 3.7-12.6) and the average OS after sorafenib discontinuation was 3.6 (95%Cl; 2.1-5.1) Conclusions: Our study revealed evidence of decreased PH parameters measured by radiological criteria and decreased survival after sorafenib discontinuation. Future prospective studies on a larger sample size are warranted. Sorafenib start N (Mean ± SD) Sorafenib end N (Mean ± SD) Baseline - Treatment end OR (95%CI) [P-value] Splenic Vein diameter 68 (10 ± 2.3) 67 (9.3 ± 2.5) 1.02 (0.99 - 1.06) [0.24] Superior Mesenteric Vein diameter 68 (12.5 ± 2.1) 67 (12.2 ± 2.5) 0.99 (0.95 - 1.03) [0.64] Main Portal Vein diameter 68 (15.4 ± 2.6) 67 (14.6 ± 2.7) 0.99 (0.93 - 1.04) [0.58] Spleen Volume 68 (442.3 ± 300.5) 67 (401.3 ± 234.5) 1.005 (0.98 - 1.03) [0.64] AST 64 (91.4 ± 65.8) 64 (127.1 ± 116.3) 1.003 (0.999 - 1.008) [0.17] ALT 68 (67.7 ± 104.5) 68 (81.6 ± 126.3) 1.001 (0.998 - 1.004) [0.53] Bilirubin 68 (1 ± 1.2) 68 (1.6 ± 1.7) 1.009 (1.003 - 1.02) [0.0001] Albumin 68 (4 ± 0.5) 68 (3.7 ± 0.6) 0.93 (0.89 - 0.97) [0.0007] PLT 68 ( 194.3 ± 108.3) 69 (187.7 ± 110.4) 1.008 (0.994 – 1.022) [0.26]
Trends and determinants of antimicrobial susceptibility of Neisseria gonorrhoeae in the Netherlands, 2007 to 2015
Authors: Sanne HI Hofstraat, Hannelore M Götz, Alje P van Dam, Marianne AB van der Sande, Birgit HB van Benthem
Journal: Eurosurveillance (2018)

Background Neisseria gonorrhoeae antibiotic resistance surveillance is important to maintain adequate treatment. We analysed 2007–15 data from the Gonococcal Resistance to Antimicrobials Surveillance (GRAS), which currently includes 19 of 25 sexually transmitted infection (STI) centres in the Netherlands. Methods : From each patient with a gonorrhoea culture, the minimum inhibitory concentration (MIC) for several antibiotics was determined. Time trends were assessed by geometric means and linear regression of logarithmic MIC. Determinants for decreased susceptibility to ceftriaxone (MIC &gt; 0.032 mg/L) and resistance to cefotaxime (MIC &gt; 0.125 mg/L) and azithromycin (MIC &gt; 0.5 mg/L) were assessed using stratified logistic regression. Results : 11,768 isolates were analysed. No ceftriaxone resistance was found. In 2015, 27 of 1,425 isolates (1.9%) were resistant to cefotaxime and 176 of 1,623 (10.9%) to azithromycin. Ceftriaxone susceptibility showed no trend (p = 0.96) during the study period, but cefotaxime MIC decreased (p &lt; 0.0001) and azithromycin MIC increased (p &lt; 0.0001) significantly. Concerning ceftriaxone, isolates of men who have sex with men (MSM) from 2013 (p = 0.0005) and 2014 (p = 0.0004) were significantly associated with decreased susceptibility. Significant determinants for cefotaxime resistance were having ≥ 6 partners for women (p = 0.0006). For azithromycin, isolates from MSM collected in 2012 (p = 0.0035), 2013 (p = 0.012), and 2014 (p = 0.013), or from non-Dutch (p &lt; 0.0001) or older (≥ 35 years; p = 0.01) MSM were significantly associated with susceptibility. Resistance in heterosexual men was significantly associated with being ≥ 25 years-old (p = 0.0049) or having 3–5 partners (p = 0.01). Conclusions : No ceftriaxone resistance was found, but azithromycin MIC increased in 2007–15. Resistance determinants could help with focused intervention strategies.
Association of genomic alterations (GAs) in circulating tumor DNA (ctDNA) with progression on abiraterone acetate (AA) or enzalutamide (enza) in advanced prostate cancer.
Authors: Andrew W Hahn, Elisa Ledet, David D. Stenehjem, Roberto Nussenzveig, Matthew Braithwaite, Benjamin Louis Maughan, Michael B. Lilly, A. Oliver Sartor, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2018)

5048 Background: Two androgen axis inhibitors, enza and AA plus prednisone, are approved for the treatment of advanced prostate cancer (aPC). Although initial responses are common with these agents, almost all men experience disease progression. Due to advances in next-generation sequencing (NGS) of ctDNA, it is feasible to assess the tumor genomic landscape in these men at different time points in their treatment. Here, we aim to identify GAs in ctDNA that contribute to resistance to AA and/or enza, which may guide development of novel therapies targeting these GAs. Methods: Men with aPC who underwent NGS of ctDNA using G360 (Guardant Health, Inc., Redwood City, CA) from the Huntsman Cancer Institute, University of Utah, and Tulane University were included. Non-matched men were classified as pre-AA/enza, post-AA/enza, and others were excluded. Post-AA/enza was defined as disease progression on AA or enza as one’s most recent treatment at the time of testing. G360 is a 73 gene panel that provides complete sequencing of selected exons in order to maximize detection of known somatic mutations, as well as, copy number amplifications across 18 genes and selected fusions in 6 genes. Two-sided Fisher exact tests and t-tests were used to assess the frequency and number of alterations pre- or post-AA/enza, respectively. P values of less than .05 were considered statistically significant. Results: Of 354 men with advanced prostate cancer and ctDNA NGS available, 128 were pre AA/enza and 84 were post AA/enza. Compared with pre-AA/enza profiles, post-AA/enza studies showed higher mean number of GAs (5.01 vs. 3.03, p=0.02). GAs were significantly higher in AR (54.8% vs. 25.8%, p<0.0001), TP53 (51.2% vs. 32.0%, p=0.006), PIK3CA (20.2% vs. 9.4%, p=0.04), and CCNE1 (10.7% vs. 3.1%, p=0.04). Patients with liver metastases had significantly more GAs than those without (11.7 vs. 3.5, p<0.0001). Conclusions: In these hypothesis-generating data, men who progress on AA or enza have more alterations in AR, TP53, PIK3CA, and CCNE1 and increased number of GAs. These alterations may contribute to treatment resistance and be targets of interest for further drug development.
Is antibiotic prophylaxis mandatory in laparoscopic incisional hernia repair? Data from the herniamed registry
Authors: Philipp Kirchhoff, Henry Hoffmann, Ferdinand Köckerling, Daniela Adolf, Reinhard Bittner, Ralph F. Staerkle
Journal: International Journal of Surgery (2018)

Several meta-analyses showed that laparoscopic incisional hernia repair is associated with lower surgical site infection (SSI) rates compared to open repair. However, the efficiency of antibiotic prophylaxis (AP) in laparoscopic incisional hernia repair alone is unknown and needs evaluation. Due to increasing antimicrobial resistance, a major global health care problem, AP needs to be critically evaluated. The aim of this study was to investigate the impact of AP on the rate of SSI and complication-related reoperations in patients undergoing laparoscopic incisional hernia repair.Prospectively documented data from the Herniamed Hernia Registry from 2009 to 2017 were retrospectively analysed. Multivariable analyses were used to study the influence of AP as well as further patient and surgery-related risk factors on SSI and complication-related reoperation rates. This was verified in a sensitivity analysis using propensity-score matching.In the analysed time period 13'513 patients undergoing elective laparoscopic incisional hernia repair were recorded, of which 14.4% (n = 1949) did not receive AP. The overall SSI rate showed no significant difference when directly comparing patients with (0.74%) and without AP (0.97%; p = 0.262). In the multivariable analysis the presence of patient related risk factors (p = 0.015) and defect size >10 cm (p = 0.035) significantly increased the rates of SSI and complication-related reoperations. The propensity-score matching analysis verified that SSI rates are not significantly different between the two groups (p = 0.265).In cases of laparoscopic incisional hernia repair in patients without risk factors and moderate hernia diameter (<10 cm), routine administration of AP in laparoscopic incisional hernia repair does not seem to be justified.
The effect of Newcastle disease virus on tumor proliferation and cellular immunity.
Authors: Anastasia O. Sitkovskaya, Oleg Ivanovich Kit, Elena Yurievna Zlatnik, Oksana G. Shulgina, Elena S. Bondarenko, Ekaterina I. Zolotareva, Elena Petrovna Ulianova, Andrey Dashkov, Vladimir E. Kolesnikov, Fedor N. Grechkin, Georgiy Yu. Egorov
Journal: Journal of Clinical Oncology (2018)

e15174 Background: A combination of strategies aimed both at destroying tumor cells and at inducing an immune response against them by the activation of the innate and adaptive immunity, in particular oncolytic virotherapy, is considered promising for cancer biotherapy. Oncolytic viruses of the Paramyxoviridae family, particularly Newcastle disease virus (NDV), are powerful oncolytic and immunostimulating agents non-pathogenic in humans. Methods: The study included 19 white outbred male rats receiving NDV vaccine (a single dose of 5000 vaccine doses (1 bottle) paratumorally, twice a week, a total of 4 injections): group 1 – injections were started 1 day after subcutaneous Guerin carcinoma transplantation, group 2 – a week before tumor transplantation. All procedures followed the guidelines of the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes. Subpopulations of lymphocytes were determined in the peripheral blood collected from the femoral vein of animals. Relative numbers of CD3+, CD4+, CD8+, CD25+ and CD45RA+ cells were determined by flow cytometry using monoclonal antibodies BD Pharmingen Rat T/B/NK Cell Cocktail, BD Pharmingen Rat Activated T Lymphocyte, BD Pharmingen Rat T Lymphocyte Cocktail. Results: Early after its injections, NDV caused a significant increase in the levels of T lymphocytes with the early activation marker, with a decrease in CD3+CD8+ cells. The stimulation of CD3+CD4+ and CD3+CD25+ lymphocytes was registered in animals with the subsequent tumor transplantation, compared to controls. Conclusions: The results suggested that stimulation of the T-cell component of the immune system of rats by prior NDV injections induced antitumor effect in some animals.
Abstract 17143: Shorter Length of Stay is Associated With Significantly Lower 30-day All-cause Readmission and 30-day All-cause Mortality in Older Medicare Beneficiaries Hospitalized for Heart Failure
Authors: Cherinne Arundel, Ali Ahmed, Rahul Khosla, Charles Faselis, Charity Morgan, Sijian Zhang, Marc Blackman, Ross D Fletcher, Wen-Chih Wu, Gregg C Fonarow, Prakash Deedwania, Javed Butler, Spyridon Deftereos, Wilbert S Aronow, Stefan D Anker, Richard M Allman
Journal: Circulation (2015)

Background: A shorter hospital length of stay, encouraged by Prospective Payment System Act, may result in suboptimal care and early discharge. Heart failure (HF) is the leading cause for 30-day all-cause readmission. However, it is unknown whether hospitalized HF patients with a shorter length of stay may have higher 30-day all-cause readmission, the reduction of which is a goal of the Affordable Care Act. Methods: The 8049 Medicare beneficiaries hospitalized for HF and discharged alive from 106 U.S. hospitals (1998-2001) had a median length of stay of 5 days (interquartile, 4-8 days), of which 4272 (53%) had length of stay ≤ 5 days. Using propensity scores for length of stay 1-5 days, we assembled a matched cohort of 2788 pairs of patients with length of stay 1-5 and ≥6 days, balanced on 32 baseline characteristics. Results: 30-day all-cause readmission occurred in 19% and 23% of matched patients with length of stay 1-5 and ≥6 days, respectively (HR, 0.79; 95% CI, 0.70-0.89; Figure, left panel). When the length of stay of the 8049 pre-match patients was used as a continuous variable and adjusted for the same 32 variables, each day longer hospital stay was associated with a 2% higher risk of 30-day all-cause readmission (HR, 1.02; 95% CI, 1.01-1.03; p&lt;0.001). Among matched patients, HR for 30-day HF readmission associated with length of stay 1-5 days was 0.84 (95% CI, 0.69-1.01; p=0.063). 30-day all-cause mortality occurred in 4.6% and 6.2% of matched patients with length of stay 1-5 and ≥6 days, respectively (HR, 0.73; 95% CI, 0.58-0.91; Figure, right panel). These associations persisted throughout 12 months post-discharge. Conclusions: Among hospitalized patients with HF, length of stay 1-5 days (vs. longer) was associated with significantly lower 30-day all-cause readmissions and all-cause mortality that persisted throughout first year post-discharge.