tbuckley/cabot-search huggingface dataset:
Predictors of survival after resections of synchronous lung cancers located in mutiple lobes: A multi-institutional pooled analysis.
Authors: Tawee Tanvetyanon, David J. Finley, Thomas Fabian, Marc Riquet, Luca Voltolini, William J Fulp, Celalettin Kocaturk, Bernard J. Park, Lary Robinson
Journal: Journal of Clinical Oncology (2012)

7024 Background: Surgical resection is a treatment option for patients with multiple primary lung cancers. However, for synchronous disease, it is often difficult to differentiate this condition from metastatic disease, especially when cancers are distributed in multiple lobes or in both lungs. Some people believe that surgery should be avoided when patients have bilateral cancers or when all cancers have the same histology. To date, however, available evidences are limited by small sample size. Methods: Studies (published 2008-2011) of curative resection for patients with synchronous (&lt; 2-year interval) multiple lung cancers located in ≥ 2 lobes, but without radiographic evidence of distant metastasis, were identified from literature. Corresponding authors were contacted and individual patient data were obtained. Patients with multiple cancers, but localized only to one lobe, were not included. Databases were pooled and multi-variable Cox Proportional Hazard models were fit to adjust for confounders. Results: There were 467 patients included from 6 studies. Median overall survival was 52.0 months (95% CI: 45.6-63.7). Postoperative (30-day) mortality rate was 1.9%. In a multivariable model, study site or having pneumonectomy did not independently impact on survival. However, age, gender, nodal stage, tumor location, and histological similarity were independent predictors of survival. Advanced age increased mortality (p=0.012). Male sex increased mortality compared with female: HR 1.64 (95% CI: 1.23-2.19, p=0.0008). N2 or N1 increased mortality over N0: HR 1.85 (95% CI 1.29-2.66, p=0.0008) and 1.97 (1.43-2.73, p=0.0001), respectively. Unilateral location increased mortality over bilateral location: HR 1.62 (95% CI 1.23-2.13, p=0.0002). Different histology increased mortality over similar histology: HR 1.45 (95% CI 1.11-1.90, p=0.0069). Conclusions: In this largest multi-institutional database of resected multiple lung cancers of multiple lobes to date, we found no evidence of inferior survival among patients having bilateral cancers or having all cancers with the same histology. In fact, the survival among such patients appears superior to their counterparts.
Molecular subtyping of breast cancer using dedicated breast PET-CT.
Authors: Katja Pinker-Domenig, Heinrich Magometschnigg, Marius Mayerhoefer, Peter Christian Dubsky, Rupert Bartsch, Zsuzsanna Bago-Horvath, Georgios Karanikas, Michael Weber, Thomas Helbich
Journal: Journal of Clinical Oncology (2013)

e22090 Background: Recently dedicated breast 18 FDG breast PET-CT has emerged as an additional imaging tool for assessment and staging of primary breast cancer. Expression of specific molecular markers such as estrogen receptor (ER), progesterone receptor (PR), and HER2 status, has direct prognostic and therapeutic implications in patient management. This study aimed to determine whether correlations exist between 18 FDG up-take of the primary breast cancer lesions and these predictive and prognostic factors. Methods: Before undergoing surgery 114 patients with primary breast cancer underwent 18 FDG breast PET-CT. The maximum standardized uptake value (SUVmax) of the primary breast cancer was measured in each patient and standard immunohistochemistry was performed on a surgical specimen to characterize the receptor state of tumor cells. Appropriate statistical tests were used to test for any association that may exist among ER, PR, and HER2. Results: A significant association was found between a triple negative status and the SUVmax (p &lt; 0.001) of breast tumors. ER-negative tumors (mean SUVmax, 10.4) demonstrated a significantly higher SUVmax than did ER-positive tumors (median SUV, 5.1) (p= 0.045). No statistical significant difference was found for SUVmax of PR-negative vs. PR-positive lesions with a mean SUVmax of 8.6 and 4.9 (p=0.15) respectively. No statistical significant difference was found for SUVmax of HER2-negative vs. HER2-positive lesions with mean SUVmax of 6.4 and 5.3 respectively (p=0.55). If either ER or PR was positive, then the other tended to be positive as well (chi2 = 84%, P &lt; 0.01). No such significant relationship was detected between PR or ER and HER2 (P &gt; 0.05). Conclusions: ER-negative breast cancer tumors display higher 18 FDG uptake than ER-positive tumors. Triple-negative breast tumors are associated with increased 18 FDG uptake commensurate with their aggressive biology. The data suggest that SUVmax measurements of 18 FDG breast PET-CT can provide valuable information about the state of ER, PR, and HER2 and the associated glucose metabolism of the primary breast cancer lesions. Such an association may be of importance to treatment planning and outcome in these patients.
Italian multicentric trial comparing chemotherapy with or without low-dose interleukin-2 (IL-2) in advanced non-small cell lung cancer: Results from a phase III randomized study
Authors: M. Ballardini, L. Ridolfi, O. Bertetto, A. Santo, E. Naglieri, M. Lopez, F. Recchia, P. Lissoni, L. Fumagalli, R. Ridolfi
Journal: Journal of Clinical Oncology (2009)

8019 Background: Non small cell lung cancer (NSCLC) is associated with an IL-2-dependent cell-mediated immunodeficiency, and lymphocyte count is considered an independent prognostic factor as it seems to correlate with overall survival. A phase III randomized Italian multicentric trial was conducted to evaluate the efficacy of subcutaneous low-dose IL-2 added to standard CT on overall survival (OS) in advanced NSCLC patients. Methods: Histologically/cytologically confirmed stage IIIb or IV non operable NSCLC patients with measurable disease, ECOG PS 0–2, age 18–70 years and adequate bone marrow, renal and liver function were eligible for the study. Randomization was stratified by center, ECOG PS, stage of disease and percentage of weight loss. All patients received gemcitabine (1000mg/m 2 ) on days 1 and 8 + cisplatin (100mg/m 2 ) on day 2 every 21 days for a maximum of 6 cycles (CT arm). In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3–5; 9–11; 15–17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 120 patients per arm. Results: From June 2000 to October 2004, 241 patients were randomized (arm A/B: 127/114). At a median follow up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 logrank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, logrank). Conclusions: The study did not show any relevant difference in clinical outcome by the addition of IL-2 to CT. Safety and subgroup analyses are ongoing to verify the efficacy of IL-2 as a function of clinical and biological characteristics of patients and tumors. Future studies to investigate the role of T-regulators in chemoimmunotherapy strategies, unknown when the study was originally planned, could be conducted. No significant financial relationships to disclose.
Trends and outcomes of severe sepsis in hematopoietic stem cell transplant recipients.
Authors: Achuta Kumar Guddati, Gagan Kumar
Journal: Journal of Clinical Oncology (2013)

7127 Background: Sepsis is common in hematopoietic stem cell transplant (HSCT) patients due to deficient immune system in the early part of the transplant and in patients with graft versus host disease (GVHD). There is very limited data on outcomes and trends of severe sepsis (SS) in these groups of patients. Methods: Using the Nationwide Inpatient Sample 2000-2008, patients older than 18 years, discharged with SS were identified using ICD-9-CM codes. Status of HSCT was identified using ICD-9-CM codes 41.0x. We also identified subsequent hospital admissions using ICD-9-CM codes V42.81-82 and 996.85 and GVHD using 279.5x. Hospital mortality was the primary outcome studied. Chi square test was used for comparison. Logistic regression model was constructed to examine the independent effect of HSCT on mortality in patients with SS. We adjusted for age, gender, race, insurance, hospital characteristics, Charlson's co-morbidity index and severity of sepsis using number of organ failures. Results: Of the 291,182 admissions with HSCT from 2000 to 2008, 7.5% had SS. The rate of SS was 5 times higher in HSCT when compared to non transplant group. In engraftment period, allogenic transplant had higher rates of SS when compared to autologous (13.2% vs. 5.2%, p&lt;0.001). During engraftment, in-hospital mortality with SS was higher in allogenic transplant (55.1%) compared to autologous group (30.1%) (mortality in non-transplant was 32.9%). On adjusted analysis, compared to non transplant group, the odds of mortality was 4.69 times (95%CI 2.85-7.69) higher in allogenic transplants while it was similar in autologous group. In subsequent admissions, the odds of mortality were 2.38 times (95%CI 2.10-2.69) higher in GVHD and 1.45 times higher (95%CI 1.28-1.65) in non-GVHD patients when compared to the non-transplant group. The in-hospital mortality in HSCT decreased from the year 2000 to 2004 but has not changed ever since, while in the non-transplant group the mortality has continued to decrease. Conclusions: Higher mortality is observed in allogenic transplant patients and in those developing GVHD when compared to non-transplant patients. The mortality due to SS in HSCT patients has not changed since 2004 and may warrant more aggressive interventions.
Efficient detection of <i>EGFR</i>, <i>KRAS</i>, and <i>BRAF</i> mutations in cell-free DNA from pleural effusions.
Authors: Christine Sagan, Audrey Vallee, Marc G. Denis
Journal: Journal of Clinical Oncology (2013)

e19151 Background: Detection of EGFR gene alterations is critical for predicting the response to tyrosine kinase inhibitors in patients with non-small-cell lung cancer. Analysis of other biomarkers might also be mandatory in the future, requiring more biological material. In routine practice, molecular testing is usually performed on tissues such as bronchial or transthoracic biopsies and surgical resections. We investigated the feasibility of using both cytology cell blocks and cell-free DNA from pleural effusions. Methods: Pleural effusion samples were centrifuged to form a pellet, fixed in formaldehyde, and processed as a cell block. DNA was extracted from 10-µm sections after paraffin removal using the Forensic kit and an iPrep system (Invitrogen). Cell-free DNA was extracted from the centrifugation supernatants using the QIAamp Circulating Nucleic Acid kit (Qiagen). Detection of molecular alterations were performed by allele-specific PCR (EGFR p.L858R mutation, BRAF p.V600E mutation), fragment size analysis (EGFR exon 19 deletions), and Sanger sequencing (KRAS mutations, codons 12 and 13). Results: Between January 2010 and December 2012, we tested 65 cell pellets (32 women and 33 men) and collected 34 paired supernatants. With the cell pellets, all the EGFR status were successfully determined (13 mutations; 20%), 9 mutations of KRAS on the 42 cases sequenced (17.6%), and 2 BRAF mutations on the 50 samples tested (4%) were found. We next investigated the potential use of the cell-free DNA from supernatants. Quantification by real-time PCR revealed significant amounts of DNA (mean = 306 ng extracted from 2 ml). EGFR, KRAS and BRAF tests were contributive for all these samples: 2 EGFR p.L858R mutations, 6 KRAS mutation (p.G12C, n=2; p.G12D, n=2; p.G13C, n=1 and p.G12F, n=1) and 1 BRAF p.V600E mutation were found. Most interestingly, the molecular status of the cell-free DNAs perfectly matched those obtained with the corresponding cell pellets. Conclusions: Pleural effusions provide high quality material for molecular testing and are suitable samples for routine practice. Cell-free DNA can also be successfully tested thus saving material for morphological / immunohistochemical / FISH analysis.
SNAI1 Promotes the Cholangiocellular Phenotype, but not Epithelial–Mesenchymal Transition, in a Murine Hepatocellular Carcinoma Model
Authors: Meng Xu, Jingxiao Wang, Zhong Xu, Rong Li, Pan Wang, Runze Shang, Antonio Cigliano, Silvia Ribback, Antonio Solinas, Giovanni Mario Pes, Katja Evert, Haichuan Wang, Xinhua Song, Shu Zhang, Li Che, Rosa Maria Pascale, Diego Francesco Calvisi, Qingguang Liu, Xin Chen
Journal: Cancer Research (2019)

Abstract Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has limited treatment options. Snail family transcriptional repressor 1 (SNAI1) is a master regulator of epithelial–mesenchymal transition (EMT) and has been implicated in HCC initiation and progression. However, the precise role of SNAI1 and the way it contributes to hepatocarcinogenesis have not been investigated in depth, especially in vivo. Here, we analyzed the functional relevance of SNAI1 in promoting hepatocarcinogenesis in the context of the AKT/c-Met–driven mouse liver tumor model (AKT/c-Met/SNAI1). Overexpression of SNAI1 did not accelerate AKT/c-Met–induced HCC development or induce metastasis in mice. Elevated SNAI1 expression rather led to the formation of cholangiocellular (CCA) lesions in the mouse liver, a phenotype that was paralleled by increased activation of Yap and Notch. Ablation of Yap strongly inhibited AKT/c-Met/SNAI-induced HCC and CCA development, whereas inhibition of the Notch pathway specifically blocked the CCA-like phenotype in mice. Intriguingly, overexpression of SNAI1 failed to induce EMT, indicated by strong E-cadherin expression and lack of vimentin expression by AKT/c-Met/SNAI tumor cells. SNAI1 mRNA levels strongly correlated with the expression of CCA markers, including SOX9, CK19, and EPCAM, but not with EMT markers such as E-CADHERIN and ZO-1, in human HCC samples. Overall, our findings suggest SNAI1 regulates the CCA-like phenotype in hepatocarcinogenesis via regulation of Yap and Notch. Significance: These findings report a new function of SNAI1 to promote cholangiocellular transdifferentiation instead of epithelial–mesenchymal transition in hepatocellular carcinoma.
Abstract P063: The Association Between Physical Activity and Fasting and 2-Hour Glucose in US Adults: NHANES 2013-2014
Authors: Joshua R Sparks, Xuewen F Wang
Journal: Circulation (2018)

Background: Glucose concentrations in a fasted and during a glucose challenged state rely on different mechanisms for regulation. In a fasted state, hepatic regulation of glucose is important; while in a glucose challenged state, muscle glucose disposal becomes more important. Evidence suggests that physical activity of moderate or higher intensities can increase muscle glucose disposal during an insulin-stimulated state, but has less effect on hepatic insulin sensitivity. The purpose of this study was to examine the associations between glucose concentrations (fasting and after an oral glucose ingestion) and minutes of physical activity at moderate- and vigorous-intensity in a large population. Methods: The sample included 2,807 adults (47.4% male and 52.6% female) aged 18-80 years who participated in the National Health and Nutritional Examination Surveys (NHANES) from 2013-2014 and who did not take any diabetic medications. Minutes being physically active at moderate- and vigorous-intensities during work, and recreationally, were collected using the Physical Activity Questionnaire, which was based on the Global Physical Activity Questionnaire. Moderate-intensity physical activity was defined as any activity that caused a small increase in breathing or heart rate, while vigorous-intensity physical activity was defined as large increases in breathing or heart rate. Both intensities had to be performed for a minimum of 10 continuous minutes. Plasma glucose concentrations at fasting and 2 hours after consumption of a drink containing 75g glucose (2-hour glucose) were determined. Pearson product correlations were performed for analysis. Results: The population had 141±133 (mean±SD) minutes of moderate-intensity physical activity during work and 63±56 minutes recreationally, as well as 174±156 minutes of vigorous-intensity physical activity during work and 77±56 minutes recreationally. Minutes of vigorous-intensity physical activity performed during work was associated with 2-hour plasma glucose concentrations (r=0.15; p=0.045); this association was not affected after adjusting for age, race, and sex (p=0.049), but was no longer significant after BMI was also adjusted (p=0.059). Recreational or total minutes of vigorous-intensity physical activity, and moderate-intensity physical activity was not associated with 2-hour glucose (p&gt;0.20). Additionally, none of the physical activity minutes was associated with fasting glucose (p&gt;0.27). Conclusion: Self-reported vigorous-intensity physical activity during work was positively associated with 2-hour glucose, but not fasting glucose. The results are surprising. Further studies with objective physical activity measures are needed to examine the associations with fasting and 2-hour glucose.
The attack and defense mechanisms: Perspectives from behavioral economics and game theory
Authors: Subhasish M. Chowdhury
Journal: Behavioral and Brain Sciences (2019)

Abstract This commentary complements the article by De Dreu and Gross (2019) from the perspectives of behavioral economics and game theory. It aims to provide a bridge between psychology/neuroscience research and economics research in attack-and-defense by stipulating relevant literature, clarifying theoretical structures, and suggesting improvements in experimental designs and possible further investigations.
Recovery of complete antiemetic response with APF530 during treatment with moderately (MEC) and highly (HEC) emetogenic chemotherapy regimens in patients who failed palonosetron.
Authors: Roberto Arevalo-Araujo, Erin O'Boyle, William Cooper, Paul Alexander Robertson
Journal: Journal of Clinical Oncology (2013)

e20569 Background: Several 5-HT 3 antagonists are available to prevent chemotherapy-induced nausea and vomiting (CINV); when control is inadequate with one agent, another may be used. Using data from a randomized phase III trial (Grous et al. ASCO 2009, #9627), we examined the efficacy of APF530, a sustained delivery formulation of the 5-HT 3 antagonist granisetron, in patients (pts) who failed to achieve a complete response (CR; no emesis or rescue medication) with palonosetron (PALO) in preventing acute (0-24 h) and delayed (24-120 h) CINV in pts receiving MEC or HEC. Methods: 1,428 pts receiving single doses of MEC or HEC were randomized to APF530 250 mg (5 mg granisetron) subcutaneously (SC), APF530 500 mg (10 mg granisetron) SC, or PALO 0.25 mg intravenously (IV) in cycle 1 (C1). Prior to C2, pts who received PALO in C1 and remained on study were re-randomized to APF530 250 mg or 500 mg SC. CR rates in C2 were assessed for pts receiving APF530 500 mg who did not achieve CR in C1 with PALO. Results: 446 pts received PALO in C1 (208 MEC; 238 HEC). Of these, 194 (43.5%) were overall (0-120 h) failures (100/208 [48.1%] MEC; 94/238 [39.5%] HEC). Of 194 C1 PALO failures, 72 were re-randomized prior to C2 to APF530 500 mg (38 MEC; 34 HEC). Of 38 MEC PALO failures who received APF530 in C2, overall CR was 39.5% (57.9% acute; 38.2% delayed). Of 34 HEC PALO failures who received APF530 in C2, overall CR was 41.2% (58.3% acute; 45.5% delayed). In the acute phase, &gt; 50% of MEC and HEC pts who failed PALO in C1 achieved CR to APF530 500 mg in C2. CR rate for pts receiving MEC or HEC was slightly less in the delayed vs acute setting. Conclusions: APF530 500 mg demonstrated substantial activity (ie, CR) in pts receiving MEC or HEC who had failed PALO in C1. Failure to achieve an initial CR to PALO 0.25 mg IV does not predict failure of APF530 500 mg SC in subsequent MEC or HEC cycles. Further studies are needed to confirm these observations. Clinical trial information: NCT00343460. [Table: see text]
Elderly and younger patients with non-small cell lung cancer (NSCLC) derive similar benefit from second-line chemotherapy: A retrospective subset analysis of second-line chemotherapy trials conducted from the Hellenic Cooperative Research Group (HORG).
Authors: Sofia Agelaki, Dora Hatzidaki, Lampros Vamvakas, Athanasios G. Pallis, Athanasios Karampeazis, Athina Agelidou, Maria Agelidou, Vassilis Chandrinos, Aristidis Polyzos, Vassilis Georgoulias
Journal: Journal of Clinical Oncology (2012)

7564 Background: Elderly patients (pts) achieve a similar survival benefit, with acceptable toxicity, from first-line chemotherapy for the treatment of advanced NSCLC compared with their younger counterparts. There have been no second-line trials specifically designed for elderly pts and few data exist on the efficacy and tolerability of second-line therapy in this population. Moreover, little if any information exists on the frequency of administration of second-line chemotherapy in these pts. Methods: The files of 2004 pts with advanced NSCLC enrolled into first-line chemotherapy trials performed by HORG from 1995 to 2007 were reviewed. A total of 600 pts who received second-line chemotherapy within the context of clinical trials were identified. Patients’ data were analysed for efficacy and toxicity according to age. Results: Second-line chemotherapy was administered in 24% and 34% of pts ≥65 and &lt;65 years old after failure of prior therapy (p=0.0001). A total of 219 (24.8%) of 600 pts who received second-line treatment were ≥65 years old (median age 70 yrs, range 65-82). Response rates to second-line therapy were 11.9% for older pts compared to 12.3% for younger pts (p=ns). TTP was 2.8 and 3.1 months for older and younger pts, respectively (p=ns). Elderly pts receiving second-line chemotherapy had a median survival of 7.7 months compared with 8.2 months for younger pts (p=ns). Similar rates of haematological and non-haematological toxicities were encountered between the two groups. Conclusions: The participation of elderly pts to second-line chemotherapy trials was lower compared to younger patients. There was no significant difference in outcome or toxicity between elderly and younger pts. For elderly pts with advanced NSCLC and good performance status, second-line chemotherapy is appropriate. However, specific second-line trials in older pts are required since those included in the current analysis were probably highly selected to fit the inclusion criteria.