tbuckley/cabot-search huggingface dataset:
Long-term survival and performance status of cancer patients after discharge from ICU (intensive care unit).
Authors: Marta Zafra, Andres Carrillo, Maria Angeles Vicente, Manuel Sánchez Cánovas, Alejandra Ivars Rubio, Inmaculada Ballester Navarro, Alberto Carmona, Francisco Ayala
Journal: Journal of Clinical Oncology (2018)

e18744 Background: ICU admission is frequently questioned in cancer patients although its survival benefit has been demonstrated. Most studies focus on short-term outcomes, but scarce data are available regarding long-term outcomes and quality of life. Our aim was to evaluate what overall survival (OS) and functional situation can be expected in cancer patients after ICU discharge. Methods: We retrospectively analyzed all consecutive critically ill patients with solid tumors admitted to the medical ICU of a general hospital during 5 years (2011-2015); post-surgery admissions or programmed procedures were excluded. Follow-up data, ECOG performance status (PS), and prognostic factors related either to the tumor, the treatment or the cause of admission, were obtained from medical records. Kaplan-Meier curves and Cox models were used for prognostic evaluation. Results: 138 patients included, of whom 25% died during ICU admission and 93 (68%) were discharged from hospital. Patients: 65%, male; tumor location: 31.9% lung, 16.7% breast, 12.3% colorectal, 10.1% genitourinary; stage IV: 52.1%; current treatment: 58% chemotherapy, 19.6% radiotherapy, 7.2% biological drugs; treatment intention: 44% curative, 12% palliative, 44% non-curative with potential survival benefit. Median OS after discharge from ICU was 17.3 months (95%CI: 11.7-22.9). Mortality during ICU admission was related to acute complications, with only SAPS II score (a measure of comorbidity and acute severity) as a significant factor (OR: 0.95; p = 0.03), while most of post-discharge mortality was related to tumor progression (52.4%). The only prognostic factor for post-discharge OS in the multivariate analysis was disease status at time of discharge (HR: 1.92; p = 0.047). Among discharged patients, PS at baseline was: ECOG 0-1, 60%; ECOG 2: 31%; ECOG 3-4: 9%. After 12 months, 79% of alive patients kept an ECOG 0-2 (0-1: 52%; 2: 27%). Conclusions: A substantial group of cancer patients obtain a significant survival and maintain an ECOG 0-2 after ICU discharge. Concerns about long-term functional outcomes and survival should not preclude admission of cancer patients to ICUs, but further research on post-ICU quality of life is warranted.
Retrospective analysis of patients (pts) with metastatic melanoma (MM) showing long-term response (LTR) to vemurafenib (Vb).
Authors: Giulia Galli, Lorenza Di Guardo, Carolina Cimminiello, Stefano Cavalieri, Monica Rodolfo, Licia Rivoltini, Barbara Valeri, Aldo Bono, Elena Tolomio, Michele Del Vecchio
Journal: Journal of Clinical Oncology (2017)

e21001 Background: Efficacy of Vb in the treatment of mm has been established. We aimed to analyze characteristics of pts achieving LTR to Vb in order to identify potential predictive factors of prolonged benefit. Methods: We collected information about pts affected by BRAF V600 mutated mm treated with Vb at Medical Oncology Unit of Istituto Nazionale dei Tumori, Milan, Italy, from 09/2010 to 08/2014. LTR was defined as clinical or radiological benefit longer than 14 months (mos). Biological data about circulating lymphocyte subpopulations and CCL2 levels were also determined. Results: 46 pts (26 men, 20 women) were identified. Median age was 58 years. ECOG performance status was 0 in 44 pts. Disease stage was M1a in 14 pts, M1c in 20 pts. 8 pts had high serum LDH levels and 5 brain metastases at baseline. 41 pts harbored BRAF V600E mutation, 5 V600K. Median follow up was 47 mos. 5 pts had received adjuvant interferon; 9 pts had been treated with up to 3 lines for metastatic disease (either chemotx or ipilimumab). According to RECIST 1.1, 22% of pts showed complete response (CR), 50% partial response and 22% stable disease. Notably, all CRs were maintained for more than 2 years. 26 pts progressed, mostly (38%) with brain metastases; 16 of them continued tx beyond progression. Median duration of response was 33 mos, being significantly longer in M1a than in M1c (44 versus 28 mos). Median PFS was 32.5 mos; median OS was not reached. All pts experienced at least 1 adverse event (AE); the AEs were moderate or severe in 22% of cases. 19 pts underwent dose reduction, but no discontinuation due to AEs was observed. After 6 mos of tx, pts with LTRs had less myeloid derived suppressor cells (CD11b+ CD14+) and more memory Th1 cells (CD8+ CXCR3+) if compared with pts not bearing LTRs. The same pts after 1 mo of tx showed lower plasma levels of CCL2, a marker of acquired resistance to Vb. Conclusions: Vb can induce LTRs in a subset of pts with mm also in presence of unfavorable prognostic factors, though M1a pts are more likely to obtain prolonged benefit. Toxicity is frequent, but manageable with limited dose reductions. Exploratory biological analyses suggest an immunomodulatory effect of Vb and the existence of circulating biomarkers of LTR.
Muscleblind-like 1 regulates epithelial to mesenchymal transition markers in triple-negative breast cancer
Authors: A. Adam Artigues, E. Tormo, E. Cerro-Herreros, M. Sabater, I. Garrido-Cano, B. Pineda Merlo, B. Pattanayak, P. Cabello, R. Artero, P. Eroles
Journal: Annals of Oncology (2018)

Background: Muscleblind-like 1 (MBNL1) has been deeply investigated because its implication in myotonic dystrophy. However, the role of RNA-binding proteins in breast cancer remains unknown. Recent findings suggest the role of MBNL1 as a suppressor of metastasis by stabilization of other genes in triple-negative breast cancer cell lines. Methods: MDA-MB-231 (triple-negative) and MCF10a (non-tumoral negative control) breast cancer cell lines were selected. Silencing of MBNL1 was performed by siRNA (Termofischer) at 100nM and using Lipofectamine 2000 (Invitrogen). Effect of MBNL1 depletion on EMT markers was analized by RT-PCR and Western blot. 72 hours after MBNL1 siRNA transfection functional assays were performed. Effect on proliferation was measured by MTT and viability was measured by flow cytometry. Death cells were stained by propidium iodide and florescence was analized by FACS Fortessa. Changes of invasion and migration capacity were studied by transwell assays after 24h. Relation between MBNL1 expression and patients' survival was studied by KM-Plotter software. Results: MBNL1 silencing upregulated gene and protein expression of epithelial-to-mesenchymal transition (EMT) markers in MDA-MB-231 cell line. Cell proliferation and viability decreased in MDA-MB-231 after siRNA transfection. Downregulation of this gene increased invasion but not migration capacity in triple-negative cell line by upregulation of pro-metastatic genes. In non-tumoral control cell line MBNL1 silencing had no effect on functional assays nor on EMT genes expression. Expression of MBNL1 in patients' public databases showed that a higher expression significantly correlates with longer distant metastasis free survival and relapse free survival, as expected. Conclusions: MBNL1 is involved on triple-negative breast cancer progression and metastasis through regulation of EMT markers. Regulation of MBNL1 could be a new strategy to control disease progression and avoid metastasis in breast cancer patients. Legal entity responsible for the study: INCLIVA Reserach Institute. Funding: INCLIVA Research Institute. Disclosure: All authors have declared no conflicts of interest.
Importance of genetic counseling referrals for high-risk women with endometrial cancer despite intact mismatch repair immunohistochemistry.
Authors: Jessica Lee, Allison L Brodsky, Deanna Gerber, Julia Fehniger, Shabnam Asgari, Anna Cantor, Jessica Martineau, Julia Anne Smith, Ophira M. Ginsburg, Bhavana Pothuri
Journal: Journal of Clinical Oncology (2018)

1537 Background: Lynch syndrome (LS) accounts for most inherited endometrial cancers (EC). The identification of probands presents a chance to prevent other cancers and enable cascade testing. Professional organizations have released guidelines for genetic counseling referrals (GCR) based on high-risk (HR) criteria including loss of mismatch repair (MMR) protein expression on tumor immunohistochemistry (IHC). Methods: All women diagnosed with EC from 2012 to 2017 were retrospectively identified and evaluated. Comparative analyses were performed with appropriate two-sided statistical tests. HR criteria were defined as age ≥50 at diagnosis, significant family or personal histories of LS-related cancers or positive MMR IHC. Results: A total of 716 women were diagnosed with EC and of these, 230 (32%) had at least one HR criteria. Of the HR women, 51% were given GCR and 13 (19%) were found to have LS. Mid-2015, we implemented universal MMR IHC. GCR rates among HR women were higher after January 2016 (72% vs 52%, p = 0.01). Among women with positive MMR IHC, there were higher rates of GCR after January 2016 that trended towards significance (94% vs 67%, p = 0.08). Table 1 lists GCR and LS rates. Of the 13 women with LS, 11 underwent MMR IHC. Of the 11 women, six (55%) had loss of MMR expression and one (9%) had intermediate MSH6 expression. Three (27%) had retained expression and one (9%) had loss of MLH1 and PMS2 expression but positive MLH1 promoter methylation; these four women all had significant family histories. All LS women had ≥ one HR criteria to warrant GCR Table 1. Conclusions: The initiation of universal MMR IHC correlates with a time of increased awareness for GCR among HR women, resulting in higher GCR rates. Although retained MMR expression is regarded as an indication to forgo GCR, almost 40% of LS women had MMR IHC findings which were not suggestive of LS. It is important to consider all HR characteristics even with intact MMR IHC to capture all LS cases. Cohort GCR / Cohort LS / GCR women All HR women 118 / 230 (51%) 13 / 118 (11%) Before 2016 69 / 133 (52%) 8 / 69 (12%) After 2016 49 / 68 (72%) 5 / 49 (10%) + MMR IHC women 39 / 52 (75%) 8 / 39 (21%) Before 2016 24 / 36 (67%) 5 / 24 (21%) After 2016 15 / 16 (94%) 3 / 15 (20%)
Scientific rationale for revisiting targeting mTOR pathway in gastric cancer.
Authors: Purnima Sravanti Teegavarapu, Bhuvanesh Dave, Alexandria T. Phan
Journal: Journal of Clinical Oncology (2016)

e15558 Background: Gastric cancer is the third leading worldwide cause of cancer deaths typically presenting at an advanced stage with a median survival of < 11 months. Conventional chemotherapy results in short lasting tumor control with dismal overall prognosis with an imperative need to identify new therapeutic target by exploring novel molecular pathways. PI3k/Akt/mTOR is known to play a major role in proliferation, survival and maintenance of therapy resistant cancer cells. Methods: We evaluated mTOR pathway using gene signatures S6k and 4EBP-1 in 1,065 gastric cancer patients with a mean follow up of 33 months across all TNM stages in the Kaplan-meier plotter to determine correlation of mTOR gene signatures to overall survival (OS). Targeting mTOR pathway using ATP-site inhibitors (1-10 mm) in therapy resistant gastric cancer cell lines, KATOIII and NCI-N87, both alone and in combination with docetaxel (10nm), assessment for proliferation (WST-1) and apoptosis (Annexin V) were performed. Results: Kaplan-meier estimation demonstrated that mTOR pathway with 4EBP-1 signature significantly associated with prolonged OS for gastric cancers [HR1.37 (1.15-1.62), p = 0.0003], while the mTOR with S6K signature does not [HR = 0.86 (0.72-1.02), p = 0.0739]. Our in-vitro experiments showed significant dose dependent decrease in proliferation with concomitant increase in apoptosis (p < 0.05, One way ANOVA) with ATP-site competitive inhibitor of mTOR in 2 gastric cell lines (KATOIII and NCI-N87) with even further reduction when combined with docetaxel. Autophagy is upregulated upon mTOR inhibition. Our data analysis of autophagy markers p62 [HR = 0.68 (0.55-0.83), p = 0.0002] and Beclin 1 [HR = 0.68 (0.57-0.81), p = 1.5e-05] demonstrated a significant prognostic value for these biomarkers using the Kaplan-meier estimation of OS. Conclusions: Integrated gene-clinical data and in-vitro studies of 2 therapy resistant gastric cancer cell lines (KATOIII and NCI-N87) suggests anti-proliferative activity with mTOR ATP site inhibitors for gastric cancer with downstream upregulation of autophagy. Results of our analyses advocates that combination inhibition of mTOR and autophagy can be a novel treatment strategy for gastric cancer.
Potential underuse of repeat resection among patients with high-grade non-muscle invasive bladder cancer.
Authors: Devon Check, David S. Aaronson, Valerie S. Lee, Matthew Nielsen, Li Tang, Lawrence H. Kushi, Marilyn L. Kwan
Journal: Journal of Clinical Oncology (2017)

e16028 Background: For patients diagnosed with non-muscle invasive bladder cancer (NMIBC), guidelines recommend that those with high-grade (HG) T1 disease and potentially those with lower risk HG Ta disease receive a repeat resection within six weeks of initial resection. For these patients, repeat resection has diagnostic, prognostic, and therapeutic value and is critical for informing treatment decision-making, and ultimately optimizing outcomes. Current rates of repeat resection in practice are unknown. Methods: We conducted a retrospective analysis of patients diagnosed with HG T1 and HG Ta NMIBC between 1/1/2015 and 3/1/2016 using cancer registry-linked electronic medical record data. Our analysis included 118 patients with HG T1 disease and 114 patients with HG Ta disease who did not undergo a cystectomy. We used modified Poisson regression with clustered standard errors to assess the associations of patients’ clinical and socio-demographic characteristics and providers’ characteristics with patients’ receipt of repeat resection. We present adjusted risk ratios (aRR) and 95% confidence intervals (CI). Results: 40% of HG patients (55% of T1 patients; 24% of Ta patients) underwent repeat resection, with no differences in receipt by patient age, gender, race, or comorbidity burden. In addition to HG T1 (vs. HG Ta) disease (aRR: 2.20, 95% CI: 1.53-3.22), higher census-tract median household income was associated with increased likelihood of repeat resection (aRR highest vs. lowest income quartile: 1.42, 95% CI: 1.08-2.23). At the treating urologist level, more time in practice was negatively associated with likelihood of repeat resection receipt (aRR highest vs. lowest quartile of number of years in practice: 0.56, 95% CI: 0.41-0.77). Conclusions: Our data suggest that a large proportion of potentially eligible HG patients did not undergo a repeat resection, and that variation in practice is driven by patients’ social characteristics and treating urologist characteristics. Further research is needed to understand whether the variation observed reflects a quality improvement need versus patient-centered decision-making that accounts for preferences and treatment eligibility.
After a near decade’s wait, patient appeals for a heart donor
Authors: Alison Shepherd
Journal: BMJ (2018)

Danny Lawson/PA

Gareth Evans, 45, from Stockport, with his wife, Danielle, at Wythenshawe Hospital in Manchester, have launched an appeal that they hope will help patients like Evans who have waited for years for an organ transplant.

Evans last week broke an unenviable record, having been on the heart transplant waiting list since February 2009, longer than anyone else in the …
The expression of programmed death ligand-1 (PD-L1) and use of PD-1 inhibitor-directed therapy with nivolomab in oral cavity cancer arising from recreational use of areca nut.
Authors: Michael Castro
Journal: Journal of Clinical Oncology (2016)

e17504 Background: Oral cavity cancer (OCC) caused by the carcinogen arecoline from recreational use of areca nut (AN), i.e. betel nut chewing is one of the most prevalent cancers in SE Asia and India where it accounts for up to 30% of all cancer. In contrast, OCC in the West due to tobacco and alcohol accounts for 90% of cases, and HPV the rest. In the US, immunotherapy utilizing anti-PD-1 therapy yielded a 24.8% response rate (RR) against head & neck cancer (HNC) with 50% RR for high PD-L1 expression, while HPV+ disease has even odds of responding to this approach. Thus far, no studies have focused on whether anti-PD-1 immunotherapy is effective in AN-derived OCC or if PD-L1 expression occurs in these cancers. The, the use of nivolomab in a patient with PD-L1 positive (+) OCC caused by AN is presented. Methods: A 45-yo, Chuukese man non-smoker and user of AN presented with massive, locally recurrent cancer originating from P16 negative, squamous cell carcinoma of the gum. The disease was treated with radical surgery, chemoradiotherapy, cetuximab-chemotherapy, and salvage chemotherapy. After 2 years, progressive disease replaced the floor of the mouth and a majority of the left face and neck. A tracheostomy was needed due to airway obstruction. His cancer tested PD-L1 3+ 80% + (Cell Signaling Co., E1L3N) and PD-1 negative (CellMarque Co., MRQ-22). Nivolomab 3 mg/kg q2w was obtained through a patient access program at BMS. Results: The patient achieved a 90% regression of cancer. The disappearance of cancer was interpreted by a radiologist, “the facial tumor seen on the previous CT scan appears to have been surgically removed.” A portion of the facial tumor sloughed and was evaluated histologically showing a necroinflammatory infiltrate with abundant residual keratin and no cancer. The response lasted 3 months before a mixed response ensued. No autoimmune toxicities were encountered. Conclusions: OCC caused by AN appears similar to other HNC in the expression PD-L1 and response to anti-PD-1 directed immunotherapy. The high prevalence of OCC in India and SE Asia provides a unique opportunity for investigating the optimal use of this immune strategy.
Expression and prognostic significance of PDGF ligands (A, B, C, and D) and PDGFR (A, B, and L) in soft-tissue sarcomas and GIST.
Authors: Tom Lesluyes, Jean-Yves Blay, Patrick Schoffski, Antoine Italiano, Axel Le Cesne, Maria Debiec-Rychter, Olivier Mir, Raf Sciot, Maud Toulmonde, Isabelle Laure Ray-Coquard, Maria Rios, Mehdi Brahmi, Christine Chevreau, Nicolas Isambert, Sylvie Bonvalot, Sophie Piperno-Neumann, Jean-Michel Coindre, Frederic Chibon
Journal: Journal of Clinical Oncology (2017)

11067 Background: Sarcomas are a variety of rare connective tissue cancers. Doxorubicin and olaratumab (Ab against PDGFRA) improved survival in a recent Phase 1/2 study. Besides PDGFRA mutated gastrointestinal stroma tumor (GIST) and dermatofibrosarcoma protuberans, the role of PDGFR and the according ligands in the biology of sarcoma remain unclear. Methods: The expression levels of PDGF (A,B,C,D) and PDGFRs (A,B,L) were studied in a series of 255 sarcoma pts in localized phase using the Agilent 014850 platform. Data are available online (http://atg-sarc.sarcomabcb.org). Histologies were GIST (n = 60), myxoid liposarcoma (MLPS, n = 50), synovial sarcoma (SyS, n = 58), and sarcoma with complex genomics (SCG, n = 87). Expression levels were analyzed and tested for prognostic values for metastasis free survival (MFS) in uni- and multivariate analysis using SPSS 19.0. Results: Expression levels (ELs) of PDGFs and PDGFRs varied across histotypes: PDGFA levels were highest in SyS and lowest in MLPS (p &lt; 0.0001). PDGFB and C levels were lower in GIST (p &lt; 0.0001), while PDGFD ELs were similar across histological subtypes. PDGFRA ELs were highest in MLPS, while PDGFRB &amp; L ELs were lowest in GIST and SyS (p &lt; 0.0001 all). Complex patterns of correlation of expression between ligands and receptors were observed in each individual subtypes. PDGFA ELs above median were associated with a marginally higher risk of metastasis . Conversely, PDGFD ELs above median was associated with a reduced risk of metastasis in the whole cohort (p = 0.02). The ELs of the 3 receptors were not correlated to MFS. In multivariate analysis using Cox model on the non-GIST sarcoma cohort (histology, grade, depth, with size, PDGFA, PDGFD as continuous variables): histology, size, grade and PDGFA ELs were independent adverse prognostic factors (PF), while PDGFD ELs was a favorable PF for MFS. In the GIST cohort, testing AFIP score, PDGFA &amp; D ELs as continuous variable, PDGFD ELs was also an independent favorable PF for MFS, in addition to AFIP score. Conclusions: The expression of PDGFs and the according receptors varies across sarcoma histological subtypes. PDGFA and D expression levels correlate independently to the risk of metastatic relapse.
Abstract 15163: Recent Trends in Atrial Fibrillation and Short Term Outcomes Following Acute Myocardial Infarction : A Population Based Perspective
Authors: Amartya Kundu, Amir Shaikh, Darleen Lessard, Jane Saczynski, Jorge Yarzebski, Chad Darling, Ramses Thabet, Robert Goldberg, David McManus
Journal: Circulation (2015)

Introduction: Atrial Fibrillation (AF) is a common complication during hospitalization for acute myocardial infarction (AMI) and is associated with increased morbidity and mortality in patients with AMI.However, there is limited information on contemporary trends in the incidence of AF in patients admitted with AMI and its impact on clinically relevant in-hospital and post-discharge outcomes. Methods: We examined trends in AF complicating AMI using data from the Worcester Heart Attack Study. The study population consisted of 6384 residents of Worcester, Massachusetts hospitalized with AMI for 7 biennial years from 1999 to 2011. Data was abstracted through the review of hospital medical records. Multivariate logistic regression analysis was used to examine the association between occurrence of AF and various in-hospital complications. Results: Overall incidence of AF complicating AMI was 10.8 %. The rate increased in the first half of the study period from 1999 to 2003 and declined thereafter .In models adjusting for other factors associated with adverse outcomes following AMI, we noted that compared to patients who did not develop AF, those who developed AF following AMI were at a higher risk of developing stroke [OR 2.53, 95 % CI 1.56 to 4.13], heart failure [OR 1.56, 95 % CI 1.31 to 1.87], and cardiogenic shock [OR 3.72, 95 % CI 2.82 to 4.90]. All-cause mortality during hospitalization was higher in those who developed AF[ OR 2.34, 95 % CI 1.87 to 2.94 ]; as was 30 day post discharge mortality [OR 1.29, 95 % CI 0.90 to 1.86] and 30 day post discharge readmission rate [OR 1.37, 95 % CI 1.09 to 1.72]. Conclusion: Our findings show that despite advancements in the treatment of AMI and reduced in-hospital mortality over the last 2 decades, new-onset AF remains common and related to multiple in-hospital and post-discharge adverse outcomes. Increased in-hospital monitoring and short-term post-discharge surveillance appears warranted for patients who develop AF in the context of AMI.