tbuckley/cabot-search huggingface dataset:
Incidence of squamous cell lung cancer.
Authors: Raza Anwar Khan
Journal: Journal of Clinical Oncology (2014)

e19128 Background: Adenocarcinoma is the most common type of non-small cell lung cancer. Squamous cell carcinoma (SCC) was considered to be decreasing since early 1980s. In our practice we have noticed an increase in diagnosis of SCC since the routine use of immunohistochemistry stains to differentiate different types of the non-small cell lung cancers. Methods: Registry search done at Aultman Hospital in Canton, Ohio focused on the number of total diagnosed cases of squamous cell lung cancer vs adenocarcinomas in the years 2006-2012. Registry search was limited to three year before and three years after the introduction of the stains by our pathology lab for definitive diagnosis of adenocarcinoma vs. squamous cell carcinoma. Results: Statistical analysis done on the data showed an increase in number of cases of squamous cell lung cancer since 2009 (year the stain was introduced) in our institution. The 2006-2009 percentages were used with the total number of cases from 2010-2012 to calculate the predicted number of cases for squamous cell lung cancer, adenocarcinomas and NSCLC (uncategorized) for the period of 2010-2012. There were 72 fewer NSCLC cases than predicted. They were equally distributed between adenocarcinoma (57%) and squamous cell cancer(43%) (X2=1.389, p= 0.239). Of the 250 adenocarcinoma cases 41(16.4%) were previously classified as NSCLC. Of the 177 squamous cell cases 31(17.5%) were previously classified as NSCLC. Conclusions: There is a significant decrease in the proportion of individuals diagnosed with NSCLC (uncategorized) between 2006-2009 and 2010-2012 (Z=7.208; p<0.001). During the same time period, there was a significant increase in the proportion of cases diagnosed with adenocarcinoma (z=2.923; p=0.003) and squamous cell carcinoma (z=2.305; p=0.021). This study shows that with the introduction of stains in our institution since July’09 there has been a statistically significant increase in number of diagnosis of squamous cell lung cancer. In addition, a decrease in cases with uncertain NSCLC histology was seen. This will more clearly define the true incidence of squamous cell carcinoma and help in directing research towards developing targeted therapies for squamous cell carcinoma.
Demographic, clinical, and survival features of childhood cancers in Istanbul, Turkey (1990-2012).
Authors: Rejin Kebudi, Dilek Uludag
Journal: Journal of Clinical Oncology (2014)

e21020 Background: The aim of this study is to identify demographic, clinical and survival features of childhood cancers admitted to Istanbul University, Institute of Oncology, Pediatric Hematology-Oncology during 22 years. Methods: Patient charts of all children with cancer <19 years admitted from 1990 to 2012 were evaluated retrospectively for age, gender, birth date, date of diagnosis, place of birth/residence, family history, primary diagnosis, tumor site, stage, presenting symptoms and duration, date of last examination/death. (Istanbul University CMF Clinical Trials; Ethics Committee 83045809-3507). Results: 2413 children diagnosed with cancer were enrolled. Median age of diagnosis was 7 yrs, (3 days-19 yrs), male: female 1,3. Distrubution in age groups were 0-1 yrs 7,9%; 1-4 yrs 31,9 %; 5-9 yrs 24,9%; 10-14 yrs 26,1%; 15-19 yrs 9,2%. Distribution of patients in disease groups were [median age in yrs, 5 yr survival %]: Central nervous system tumors (n=494) 20,5% [6,5; 61]; Malignant bone tumors (n=367) 15,2% [12,6; 61]; Lymphoma (n=360) 14,9% [8,3; 91]; Soft tissue sarcomas (n=317) 13,1% [6,9; 69]; Retinoblastoma (n=207) 8,6% [1,7; 94]; Neuroblastoma (n=164) 6,8% [2,8; 65]; Leukemias (n=133) 5,5% [7,1; 82]; Germ cell tumors (n=130) 5,4% [6,9; 90]; Carcinomas (n=129) 5,3% [12,7; 84]; Renal tumors (n=88) 3,6% 7; 82]; Hepatic tumors (n=24) 1,0% [8,0; 45]. After 2005, the number of patients diagnosed at early stage have significantly increased (p=0,001). 5 yr survival was 74 % for the whole group, 85 % for patients diagnosed at early stage, 57 % for patients with advanced stage (p<0,001). Conclusions: The most common solid tumor in our department, similar to developed countries, was CNS tumors. The frequency of retinoblastoma and bone tumors were high (reference center). Survival in patients diagnosed at an early stage were significantly higher than in patients diagnosed with advanced stage. In recent years, the increase in the ratio of patients diagnosed at early stage is promising. Cancer registry in our country is developing in recent years, registries in major centers help to obtain more detailed data on the epidemiology and clinical characterictics of cancer patients which may help organize health care programs.
Relationship of grade to prognosis in localized primary angiosarcoma of the breast (PAOB).
Authors: Manjari Pandey, Gregory Ryan Sutton, David Craig Portnoy, Kurt W. Tauer, Lee Steven Schwartzberg, Paxton Dickson, Michael Gary Martin
Journal: Journal of Clinical Oncology (2014)

10559 Background: PAOB is rare and institutional series have provided conflicting data on the impact of grade on prognosis. Methods: Using case listing session of SEER 18 (1973-2010) we examined outcomes for patients with PAOB. Analyses were conducted with SEER*Stat 8.1.2, Microsoft Excel 2007 and GraphPad Prism 6. Comparisons were made using the chi-squared test and log-rank test (Mantel-Cox); all p values were 2-sided. Results: 226 women with PAOB were identified; median age 49 (range 15-107); 82% white. 72% had localized disease, 15% regional disease, 7% distant disease; 14% had grade 1, 24% had grade 2 and 30% grade 3 disease. Median OS for patients (pts) with localized, regional, and distant disease was 172, 24 and 16 months, respectively (p<0.001). Median OS for pts with localized grade 1 and 2 disease was not reached versus 36 months for grade 3 disease (p<0.0001); 3-yr OS was 89% v 47%. There was a strong trend for pts with grade 3 disease to undergo mastectomy (44% v 23%) (p=0.0695) and 24% of all pts received radiation. Radiation did not improve survival for localized grade 1 and 2 disease (p=0.6759) or grade 3 disease (p=0.5888); surgery and grade subgroups were too small for meaningful comparisons regarding radiation. Conclusions: Histologic grade is a significant predictor of survival for patients with localized PAOB. Regardless of grade, adjuvant radiation did not confer a survival benefit for pts with localized disease.
Concomitant Targeting of FLT3 and BTK with CG'806 Overcomes FLT3-Inhibitor Resistance through Inhibition of Autophagy
Authors: Weiguo Zhang, Guopan Yu, Hongying Zhang, Charlie Ly, Bin Yuan, Vivian Ruvolo, Sujan Piya, Seemana Bhattacharya, Qi Zhang, Gautam Borthakur, Venkata Lokesh Battula, Marina Y. Konopleva, William G Rice, Michael Andreeff
Journal: Blood (2018)
Increased Temporal Discounting in Social Anxiety Disorder Normalizes after Oxytocin Treatment
Authors: René Hurlemann, Dirk Scheele, Thomas M. Kinfe, Ruben Berger, Alexandra Philipsen, Marisol J. Voncken, Kim P.C. Kuypers, Koen Schruers
Journal: Psychotherapy and Psychosomatics (2019)
Pharmacokinetics of the BCL2-targeted DNA interference (DNAi) nanoparticle PNT2258 in patients with recurrent or refractory non-Hodgkin lymphoma.
Authors: Wael Harb, Nehal J. Lakhani, Ana Logsdon, Mary Steigelman, Heidi Smith-Green, Shari Gaylor, Michael Woolliscroft, Wendi V. Rodrigueza, Mina Patel Sooch, Richard Adam Messmann, Ayad M. Al-Katib
Journal: Journal of Clinical Oncology (2014)

2586 Background: PNT2258 contains PNT100, a DNA interference (DNAi) oligonucleotide encapsulated in a lipid nanoparticle. PNT2258 targets the BCL2 gene and is undergoing evaluation in patients with r/r NHL (NCT01733238). PNT2258 exhibits single-agent anti-tumor effect (50% ORR) in patients with r/r follicular or diffuse large B-cell lymphoma. The study also evaluated pharmacokinetic (PK) parameters in this target population, as reported here. Methods: Patients received 120 mg/m2of PNT2258 IV on days 1-5 of a 21-day cycle. The concentrations of PNT2258 (measured as total PNT100) were determined pre-infusion and at 30, 60, 90, 120 and 150 minutes and at 24 hours by a validated hybridization-ligation bioanalytical method that measured PNT100 content using a complementary template probe followed by visualization by ELISA. Results: No free PNT100 was found in the plasma samples and detergent solubilization of intact PNT2258 in plasma was required to release encapsulated PNT100, indicating the stability of the PNT2258 liposome in serum. PNT2258 infusion resulted in minimal inter-patient variability when measuring encapsulated PNT100 concentrations on days 1 and 4. Day 4 plasma concentrations were consistently higher than day 1 levels without evidence of cumulative toxicity. Preliminary data indicate a serum half-life (t½) of 9-12 hours. AUC exposure levels on days 1 and 4 were 87300 and 208000 ng.hr/ml, respectively, and additional day 4 values include Tmax = 2.39 hr (SD 0.22 hr), Cmax = 13,800 ng/ml (SD 10,000 ng/ml) and R AUC Days 1-4 = 10.1. Conclusions: Pre-clinically, levels of > 22,377 ng.hr/ml PNT2258 resulted in activity in WSU-DLCL2 xenograft models. Clinical PK data confirm serum levels of the BCL2-targeted oligonucleotide that were 4-9 times greater than what was required to exhibit anti-tumor effect in the preclinical models. The data provided in this abstract indicate that the BCL2-targeted DNAi oligonucleotide PNT2258 is the first of this new class of therapeutic to provide systemic exposure, a manageable clinical safety profile and measureable anti-tumor effect warranting further clinical development. Clinical trial information: NCT01733238.
The efficacy and safety of bevacizumab beyond first progression in patients treated with first-line XELOX followed by second-line XELIRI in advanced colorectal cancer.
Authors: Vasiliki Michalaki, George Fragulidis, Theodosios Theodosopoulos, Ioannis Papaconstantinou, Nikolaos Dafnios, Constantine Gennatas
Journal: Journal of Clinical Oncology (2014)

e14637 Background: Therapies that target angiogenesis and the VEGF pathway are a component of treatment for patients with metastatic colorectal cancer (mCRC). The aim of this study was to evaluate the efficacy and safety of the planned continuation of bevacizumab beyond first progression in patients with mCRC. Methods: Previously untreated patients with assessable disease were treated with XELOX plus bevacizumab until tumor progression, followed by XELIRI plus bevacizumab. The primary endpoint of the study was the second progression-free survival (2nd PFS), defined as duration from enrollment until progression after the second-line therapy. Secondary endpoints of the study were progression-free survival (PFS), response rate (RR), and safety. Results: In the first-line setting, 39 patients treated with XELOX plus bevacizumab achieved RR of 51.7 %, and median PFS of 11.3 months (95 % CI, 7.7-16.1 months). Twenty – eight patients went on to receive a second-line therapy with XELIRI plus bevacizumab and achieved RR of 26.5 %, and median PFS of 6.1months (95 % CI, 4.2-9.3 months). Median 2nd PFS was 15.0 months (95 % CI, 12.2 -19.3 months). Bevacizumab-related significant adverse events included hypertension (2.3 %) and proteinuria (1.3 %). Conclusions: Bevacizumab beyond first progression could be considered a treatment strategy even in patients progressed after first-line bevacizumab plus doublet chemotherapy. The planned continuation of bevacizumab during a second-line treatment is feasible and safe for mCRC patients. However the need to identify surrogate biomarkers towards a more personalized approach is becoming increasingly important.
Clinical efficacy and correlation with tumor PD-L1 expression in patients (pts) with melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475.
Authors: Richard Kefford, Antoni Ribas, Omid Hamid, Caroline Robert, Adil Daud, Jedd D. Wolchok, Anthony M. Joshua, F. Stephen Hodi, Tara C. Gangadhar, Peter Hersey, Jeffrey S. Weber, Roxana Stefania Dronca, Amita Patnaik, Hassane M. Zarour, Marisa Dolled-Filhart, Jared Lunceford, Kenneth Emancipator, Scot Ebbinghaus, Soonmo Peter Kang, Wen-Jen Hwu
Journal: Journal of Clinical Oncology (2014)

3005^ Background: MK-3475 demonstrated antitumor activity and acceptable safety in a phase I MEL cohort. We provide updated efficacy data and correlation with tumor PD-L1 expression. Methods: 135 pts received MK-3475 10 mg/kg Q2W (n = 57), 10 mg/kg Q3W (n = 56), or 2 mg/kg Q3W (n = 22). Response was assessed every 12 wk by RECIST 1.1 by independent central review and by immune-related response criteria (irRC) by investigator. Biopsy was required in the 60 d before MK-3475. Tumor PD-L1 expression was assessed by IHC. A preliminary cutoff of 1% of stained tumor cells defined PD-L1 positivity. Results: As of 10/18/2013, all pts had ≥13 mo follow-up. Median time on treatment was 23 wk (range, 1 dose to 97 wk). In pts with measurable disease, ORR was 41% by RECIST (Table). Objective responses were observed as late as 64 wk, with some conversions to CR seen as late as 72 wk. Median response duration was not reached; responses were ongoing for 87% of responders. Median PFS was 31 wk. Median OS was not reached, and OS rate at 1 y was 81%. Tumor PD-L1 expression was evaluable in 71 pts with measurable disease and ≥1 tumor evaluation (77% PD-L1+). Of these pts, PD-L1 expression was associated with improved ORR by RECIST (51% vs 6%, P = .0012 [Fisher's exact]) and PFS (median 12 vs 3 mo, HR 0.31, 95% CI 0.16-0.61, P = .0004 [log-rank]). 1-y OS rate was 84% in PD-L1+ and 69% in PD-L1– pts (P = .2146 [log-rank]). There were no treatment-related deaths; 14% of pts experienced drug-related grade 3/4 AEs. Conclusions: MK-3475 induces durable responses and favorable 1-y OS with acceptable safety in MEL. Although tumor PD-L1 positivity was associated with improved ORR and PFS, antitumor activity was also observed in pts with low baseline PD-L1 expression. These preliminary data require confirmation. Clinical trial information: NCT01295827. RECIST 1.1 irRC 2 Q3W 10 Q3W 10 Q2W Total 2 Q3W 10 Q3W 10 Q2W Total ORR, % (95% CI) 45 (23-69) 31 (18-47) 49 (35-63) 41 (32-51) 32 (14-55) 32 (20-46) 58 (44-71) 43 (35-52) Median response duration, wk (range) NR (9+ – 60+) NR (11 – 72+) NR (8+ – 76+) NR (8+ – 76+) NR (9 – 60+) NR (11 – 65+) NR (12 – 93+) NR (9 – 93+) Median PFS, wk (95% CI) 72 (12-NR) 24 (12-36) 50 (24-NR) 31 (19-50) 72 (12-NR) 30 (15-NR) 84 (24-NR) 54 (24-NR) 24-wk PFS, % 56 44 60 53 51 54 64 58
A randomized, controlled study comparing NCI’s original and revised informed consent templates.
Authors: Holly A Massett, Nancy Atkinson, Christine Brittle, Jeanne Adler, Nancy Roach, Robert Bailey, Marjorie J. Good, Danielle Burgess, Margaret M. Mooney, Jeffrey S. Abrams
Journal: Journal of Clinical Oncology (2014)

6523 Background: In 1997, the National Cancer Institute (NCI) began using a standardized template to develop Informed Consent Documents (ICD) for its clinical trials. NCI recently revised the template based on expert input from five working groups to reduce its complexity and length. We report findings from a study comparing the application of the original and the revised, concise template to a Phase 3 colon cancer treatment trial. Methods: Two ICDs for the same trial were compared using a randomized, controlled design. Participants were randomly assigned to Group 1 (the control) which reviewed the original ICD (O-ICD) or Group 2, which reviewed the concise ICD (C-ICD). We hypothesized that viewing the C-ICD would result in higher knowledge and satisfaction scores than viewing the O-ICD. Participants’ likelihood to consider a clinical trial (CT) after seeing the ICD was assessed. Participants were adult colorectal cancer survivors who completed treatment in the past 10 years and had never taken part in a CT. Pre- and post-test responses were collected via an online survey. Results: The groups (O-ICD, N=72; C-ICD, N=81) did not differ on age, gender, education, income or prior CT knowledge. No group differences were found on number of knowledge items correct (O-ICD: avg=20.3/24 total; C-ICD: avg=21/24; p=.20) or satisfaction (O-ICD: avg=4.23/5.0; C-ICD: avg=4.16/5; p=.23 [1 low; 5 high]). Higher education predicted greater number correct (p=.04). Less education and more prior CT knowledge predicted higher satisfaction with the ICDs (p=.01). All respondents reported lower intentions to participate in a CT after viewing the ICDs. Conclusions: The C-ICD’s format applied plain language principles and was shorter by two pages (11 vs. 13 pgs for O-ICD). Although the C-ICD did not prove superior, it maintained high knowledge and satisfaction scores similar to the O-ICD. This study allowed unlimited time to read the ICDs and did not carry the same emotional implication as an actual CT situation where brevity may have greater impact. Finally, education about CTs appears beneficial as those reporting prior CT knowledge had significantly increased satisfaction scores and were more likely to consider a clinical trial in the future.
Effective use of electronic medical record (EMR) data in analysis of association between KRAS mutations and depression in colorectal cancer patients.
Authors: Jenny Jing Li, Jessica Harper, Hong Zhu, Nizar Bhulani, Chad Michael Guenther, Alejandra Madrigales, Samantha Gates, Syed Mohammad Ali Kazmi, Udit Verma, Marisa Toups, Muhammad Shaalan Beg
Journal: Journal of Clinical Oncology (2018)

861 Background: Previous studies have demonstrated that KRAS mutations were associated with higher rates of depression in patients with metastatic colorectal cancer (CRC). The objective of this study was to evaluate the feasibility of extracting EMR data to examine the association between KRAS mutations and positive screening test for depression in CRC patients. Methods: Retrospective review of stage I to IV CRC patients seen between 2011 and 2015 at an academic, NCI-Designated Comprehensive Cancer Center was performed. At each clinic visit, depression was assessed using the Patient Health Questionnaire-2 (PHQ-2), which is part of the institution’s universal Distress Screening tool. PHQ-2 score of 2 and above was considered positive screening test for depression. PHQ-2 and KRAS mutation data were extracted from the EMR via the Clinical Data Exchange Network bioinformatics tool and confirmed by retrospective chart review. Chi-square test was used to assess the association between KRAS mutation and depression. Multiple imputation was used to impute the missing values. Results: Of the 484 CRC patients, KRAS status was known in 45 cases: 22 (49%) were KRAS mutated and 23 (51%) were KRAS wild type. PHQ-2 score was 0 in 42 cases (93.3%), 1 in 2 cases (4.4%), and ≥2 in 1 case (2.3%). The rate of positive PHQ-2 for KRAS mutated vs wild type was 4% vs 0% (p = 0.36). The result based on 50 imputed datasets suggests a trend towards an association between KRAS mutation and depression (p = 0.09). Conclusions: This study did not demonstrate an association between KRAS mutation and depression in patients with colorectal cancer, probably due to a high proportion of missing data. Bioinformatics studies that extract and analyze EMR data are a feasible and effective platform to assess the association of genomic data with clinical outcomes. Additional validated algorithms and data are needed to further optimize such studies.
Impact of tyrosine kinase inhibitor on renal function in patients with advanced renal cell cancer.
Authors: Fumiya Hongo, Masakatsu Oishi, Takashi Ueda, Terukazu Nakamura, Hiroyuki Nakanishi, Yoshio Naya, Kazumi Kamoi, Koji Okihara, Tsuneharu Miki
Journal: Journal of Clinical Oncology (2014)

e15561 Background: Specific adverse events are known in the patients with tyrosine kinase inhibitor (TKI) therapy for advanced renal cell cancer (RCC). Proteinuria is known as one of the adverse events during treatment with axitinib for advanced RCC. However, there are few studies about renal function after TKI therapy. The aim of this study was to assess the change of renal function after TKI therapy for advanced RCC. Methods: We retrospectively assessed the change of serum creatinine and eGFR levels in RCC patients before and after treatment with TKIs. Change of serum creatinine and eGFR were compared to the base line. Median follow up time was 5 months (1 to 39 months) Results: Between April 2008 to August 2013, 56 cases were treated with sunitinib, 42 cases with sorafenib and 26 cases with axitinib, Change of serum creatinine is 12.4±27.8% increasing in sunitnib group, -1.1±26.7% increasing in sorafenib group and 8.3±33.7 % increasing in axitinib group. Serum creatinine is significantly increasing in sunitinib group compared to sorafenib group (p<0.05). Meanwhile, Change of eGFR is 6.5±24.3 % decreasing in sunitnib group, -7.8±26.0 % decreasing in sorafenib group and 2.5±22.0 % decreasing in axitinib group. eGFR is significantly decreasing in sunitinib group and in axitinib group compared to sorafenib group (sunitinib vs. sorafenib: p<0.01, axitinb vs. sorafenib: p<0.05). Conclusions: TKI therapy has a certain impact on renal function in patients with advanced RCC. Sorafenib might have less impact on renal function compared to sunitinib and axitinib. Further studies are required to clarify this consideration.
Bcor Mutations Cooperate with Tet2 Deficiency to Promote RAS Transformation of Mouse Hematopoietic Progenitors
Authors: Iman Fares, Rahul S. Vedula, Shabbir M. Vahanvaty, Christopher S Waters, Marlise R. Luskin, Priti Kumari, Marie McConkey, Anne Charles, Kevin Copson, Gregory A. Abel, Richard M. Stone, Benjamin L. Ebert, R. Coleman Lindsley
Journal: Blood (2018)