tbuckley/cabot-search huggingface dataset:
HPV vaccinations one year post FDA approval
Authors: S. Sheinfeld Gorin, R. Franco, C. Westhoff
Journal: Journal of Clinical Oncology (2008)

1513 Background: High risk types of HPV are necessary though not sufficient causes of the vast majority of cervical cancers. With the approval by FDA of the HPV vaccine among women age 9–26, dissemination is critical. Fewer than one-third of the US population has heard of HPV. Few know about its association with cervical cancer, and how to prevent its spread. Yet, physician recommendation is key to vaccination. Methods: The study examines vaccination intentions and practices among a sample of 235 multi-ethnic/racial, urban primary care physicians who are enrolled in an RCT of an educational intervention. Intention was measured via self-report prior to FDA approval, and vaccination rates were assessed one year later using medical audit. Results: Prior to the approval of the vaccine, findings revealed strong intention to vaccinate among physicians, at 92% extremely or somewhat likely to vaccinate. Multivariate analyses of primary care physicians revealed that those who regularly performed recto-pelvic examinations on asymptomatic women (β=0.21, p=0.03), and those who were more familiar with the ACS screening guidelines held stronger intentions to vaccinate (β=0.24, p=0.01) than did comparable others. Female primary care physicians had stronger intentions to vaccinate for HPV than male providers (β=0.21, p=0.03). One year post-approval, 10% of age-eligible girls and young women have been vaccinated. Major barriers are awareness, cost, and availability of the vaccine. Conclusions: The findings reveal stronger intentions to vaccinate than contemporaneous population-based surveys (80%), but similar predictors in gender and knowledge. The rate of vaccination is comparable to the 14% for the Hepatitis B vaccine among children one year post-approval, but much lower than among pediatricians in a Boston metropolitan hospital (57%) during a similar period of time. This is the first study to observe vaccination intentions among urban physicians working in under-resourced communities, and to systematically report the HPV vaccination practices among primary care physicians who are practicing in these same neighborhoods. Targeted dissemination strategies to urban primary care physicians in under-resourced areas are critical. No significant financial relationships to disclose.
Does visceral fat area (VFA) have predictive value for hypertension (HTN) and progression-free survival (PFS) in patients (pts) with stage IV NSCLC receiving bevacizumab (Beva)?
Authors: O. Mir, R. Coriat, S. Ropert, J. Chapron, P. Boudou-Rouquette, J. Durand, T. Bui, D. Dusser, F. Goldwasser
Journal: Journal of Clinical Oncology (2011)

e18005 Background: Visceral fat releases pro-angiogenic factors that may promote tumour growth. VFA has been suggested as a predictor of outcome in colorectal and renal cancer pts receiving anti-VEGF agents (Guiu, Gut 2010; Ladoire, Oncologist 2011). Moreover, HTN seems to reflect the intensity of VEGF pathway inhibition, and could also predict outcomes in pts receiving Beva. We postulated that VFA could impact both the activity and toxicity of Beva. Methods: An electronical medical record review identified all pts with stage IV non-squamous NSCLC who received a platinum doublet plus Beva as first-line treatment in our outpatient unit. Beva was continued until disease progression or unacceptable toxicity in pts with response or stable disease after 6 cycles. VFA was determined from pre-treatment CT scans. HTN was monitored at home twice daily according to international guidelines, and graded according to the NCI-CTC v4.0 criteria. Pts were dichotomized according to their VFA (above or below the median), and potential associations linking VFA to HTN, PFS and OS were examined. Results: A total of 77 pts (65% males, 64% smokers, 36% with a PS of 2, median age: 57 years, range 38-86) were eligible for this analysis. Eighteen pts (23%) had a past history of HTN, well controlled at initiation of Beva. A total of 730 cycles of bevacizumab (median/pt: 6, range 2-22) were given. Grade ≥ 2 HTN was observed in 26 (34%) pts. At a median follow-up of 10.1 months (range: 1.0-35.3), the median PFS and OS were 6.9 months (95%CI: 5.6-8.6) and 10.6 months (95%CI: 9.8-11.7), respectively. Median VFA was 113.2 cm2 (range: 27.2-265.2). HTN was significantly more frequent in pts with a low VFA (46% vs. 21 %, OR 3.1, p = 0.03). Patients with a low VFA had a significantly longer PFS: 8.5 (95%CI: 6.4-9.4) vs. 5.6 months (95%CI: 4.8-7.5), p = 0.04. No difference was observed regarding OS. Conclusions: In this series of unselected NSCLC pts receiving bevacizumab-based chemotherapy, pts with a low VFA were more likely to experience HTN and a better PFS than pts with a high VFA. Further studies are required to validate this biomarker in different datasets.
The impact of economic recession on the incidence and treatment of cancer.
Authors: K. Y. Ennis, M. Chen, G. C. Smith, A. V. D'Amico, Y. Zhang, L. B. Harrison, R. D. Ennis
Journal: Journal of Clinical Oncology (2011)

6005 Background: Normal fluctuations of the economy result in periods of recession. This study investigated the relationship between these periods and the incidence and treatment of cancer. We assessed if this relationship differs based on type of cancer, and racial/socioeconomic groups. We hypothesized that this effect would be greatest for cancers for which screening is common or often present with easily minimized symptoms. Methods: Data on incidence and treatment (radiation therapy [RT], surgery) for all cancers, and breast and pancreatic specifically, were collected using the Surveillance Epidemiology and End Results (SEER) database for 1973-2007. The data was subsequently divided by race (AA, White, other) and into quartiles for socioeconomic sub-groups: household income, percent with high school education. Unemployment rate by month was found on the Bureau of Labor Statistics website and used as the measure of economic recession. Data was log transformed; and multivariate linear regression was used to analyze the data. Results: Adjusting for race and socioeconomic factors, the rates of cancer incidence, treatment with RT and treatment with surgery for all cancers revealed a significant inverse correlation with unemployment (p<0.0001). Every 1% increase in unemployment is associated with a 3% (95% CI: 2.1-3.3%) decline in cancer incidence, 9% (7-10.4%) decrease in RT, and 12% (9.7-14.6%) decline in surgery. Breast cancer incidence and treatment had a dramatic relationship (p<.0001, 7 [5.7-9.1]%, 17 [15.4-18.2]%, 24 [22.2-25.5]%, respectively). For pancreatic cancer, there was less of a relationship for incidence (p=0.059, 1 [-0.1-2.7]% for every 1% change in unemployment), RT (p<0.001, 1 [0.8-2.1]%) and surgery (p<0.0001, 9 [7.6-9.4]%). Models testing for a disparity in the effects of the economy due to race or socioeconomic groups yielded no discernable trends. Conclusions: Independent of socioeconomic status, increasing unemployment rates during times of economic recession are associated with a decline in the incidence and treatment of all cancers. This effect is more pronounced for cancers that often have lesser symptoms (e.g. breast cancer) and is less evident for cancers that present with severe symptoms (e.g. pancreas).
Development of an assay to predict oxaliplatin sensitivity from formalin-fixed, paraffin-embedded (FFPE) colorectal cancer tissues.
Authors: J. A. Freedman, T. Osada, K. A. Tsamis, M. Morse, B. M. Clary, H. K. Lyerly, J. R. Nevins, T. M. Clay, S. D. Hsu
Journal: Journal of Clinical Oncology (2011)

429 Background: Genomic profiling has improved our understanding of the underlying biology of tumors, accuracy of diagnosing disease, predictions of the courses of disease, and ability to determine the therapeutic agents that will be most effective in the treatment of particular tumors. However, in order for assays involving microarray data to be useful in the clinical setting, the ability to generate reliable and consistent data from FFPE tissues is essential. Methods: Cancer cell lines from the NCI-60 collection exhibiting greatest sensitivity or resistance to oxaliplatin were identified. These cells were grown in culture, fixed for 24 hours in formalin, and paraffin-embedded. RNA from the FFPE cells was isolated, amplified, and hybridized to Affymetrix arrays. A Bayesian binary regression analysis was used to generate a predictor of oxaliplatin sensitivity from the gene expression data. Metastatic derived xenografts (MDXs) from resected colorectal tumors were established and treated with oxaliplatin. Samples from tumors prior to treatment were paraffin-embedded and used for RNA extraction, amplification, and hybridization to Affymetrix arrays. The gene expression signature predicting sensitivity to oxaliplatin was then validated with response data from MDXs treated with oxaliplatin. Results: A predictor consisting of 300 genes that could predict sensitivity to oxaliplatin was generated using FFPE samples. Significant correlation was observed between the predicted probability of oxaliplatin sensitivity and the tumor growth inhibition measurement for a given MDX (p=0.0012). Conclusions: Reliable and consistent predictions of oxaliplatin sensitivity can be obtained from gene expression data from FFPE tissues. This method has potential utility in the clinical setting. The ability to predict response to a therapeutic in a FFPE sample has the potential to guide the choice of therapeutics, resulting in an option that could be most effective in treating an individual with metastatic colorectal cancer. No significant financial relationships to disclose.
Prognostic role of derived neutrophil to lymphocyte ratio (dNLR) in men with metastatic castration resistant prostate cancer (mCRPC) treated in a phase 3 trial (VENICE).
Authors: Arnoud J. Templeton, Francisco Emilio Vera-Badillo, Florence Mercier, Guru Sonpavde, Eitan Amir, Bertrand F. Tombal, Mark Rosenthal, Ian Tannock
Journal: Journal of Clinical Oncology (2014)

5047 Background: We evaluated retrospectively the prognostic impact of derived neutrophil to lymphocyte ratio (dNLR), a marker of host inflammation, in men with progressive metastatic castration-resistant prostate cancer (mCRPC) treated in VENICE, a phase 3, multicenter, trial of aflibercept versus placebo in combination with docetaxel and prednisone funded by Sanofi and Regeneron (Tannock et al. Lancet Oncology 2013). Methods: The arms were combined for analysis, since no difference was observed in the primary endpoint of overall survival (OS). dNLR was calculated as the absolute count of neutrophils divided by the absolute white cell count minus the absolute count of neutrophils. A logarithmic transformation was applied to non-normal factors. The Kaplan-Meier method was used for OS estimation. To adjust for baseline patient and tumor characteristics we used Cox proportional hazards regression with backward stepwise selection, stratifying for ECOG PS (0 vs. 1-2) and treatment group. Results: Complete data for construction of a prognostic model were available in 876 men. Patients with a dNLR greater than the median (2.0) had significantly worse survival (2y OS: 38% vs. 54%, log-rank P<0.001; HR (univariate) 1.48 [95% CI 1.29 - 1.69], Pfor stratified Cox model <0.001). The factors that remained individually significant for OS in multivariable analysis are shown in the Table. Conclusions: High dNLR was associated with worse survival in men with mCRPC treated with docetaxel. These data warrant external validation. HR 95% CI P value Age ≥ 68 years (median) 1.24 1.06-1.44 0.01 Alkaline phosphatase ≥ 142 U/L (median) 1.58 1.35-1.86 <0.001 Duration of first ADT < 15 months (median) 1.39 1.20-1.62 <0.001 Hemoglobin < 127 g/L (median) 1.40 1.20-1.63 <0.001 Pain (PPI) ≥ 2 1.47 1.25-1.72 <0.001 Number of metastatic organs involved ≥ 2 1.20 1.03-1.40 0.02 dNLR ≥ 2.0 (median) 1.31 1.13-1.52 <0.001 Abbreviations: ADT, androgen deprivation therapy; CI, confidence interval; HR, hazard ratio; PPI, Present Pain Intensity scale from the McGill–Melzack questionnaire, which uses verbal descriptors; scores can range from 0 to 5, with higher scores indicating greater pain.
Relationship of novel genetically engineered mouse and the epithelial-mesenchymal transition in the metastastic progression of gastric cancers.
Authors: Hark K. Kim, Jun Won Park, Jeffrey E. Green
Journal: Journal of Clinical Oncology (2014)

3 Background: By creating mice deficient in E-cadherin, Smad4, and p53, we evaluated whether and how Cdh1 heterozygosity may accelerate the development and progression of gastric cancer, in combination with loss of Smad4 and p53. Methods: Compound conditional knockout mice of Smad4, p53, and E-cadherin were mated with Pdx-1-Cre transgenic mice. Offsprings were monitored for the development of gastric adenocarcinomas. Results: Gastric adenocarcinomas spontaneously arose in Pdx-1-Cre;Smad4 F/F ;Trp53 F/F ;Cdh1 F/+ mice and recapitulated human diffuse type gastric cancers in histopathology. Gastric adenocarcinoma was more frequent in Pdx-1-Cre;Smad4 F/F ;Trp53 F/F ;Cdh1 F/+ mice than in Pdx-1-Cre;Smad4 F/F ;Trp53 F/F mice. When compared to Pdx-1-Cre;Trp53 F/F ;Cdh1 F/F mice, Pdx-1-Cre;Smad4 F/F ;Trp53 F/F ;Cdh1 F/+ mice developed gastric adenocarcinomas more rapidly, suggesting that Smad4 and E-cadherin cooperate to constrain the development of gastric adenocarcinomas. Lung metastases were identified in three Pdx-1-Cre;Smad4 F/F ;Trp53 F/F ;Cdh1 F/+ mice, but not in the other genotypes. The epithelial-to-mesenchymal transition (EMT), characterized by increased vimentin expression, was identified at the invasive tumor front of gastric adenocarcinomas arising in Pdx-1-Cre;Smad4 F/F ;Trp53 F/F ;Cdh1 F/+ mice. This phenotype was less prominent in mice with intact E-cadherin or Smad4, indicating that the suppression of EMT by E-cadherin or Smad4 may reduce metastatic signaling pathways in Pdx-1-Cre;Smad4 F/F ;Trp53 F/F ;Cdh1 F/+ mice. Conclusions: Loss of E-cadherin and Smad4 cooperate with p53 loss to promote the development and metastatic progression of gastric adenocarcinomas, with similarities to human diffuse type gastric cancer. Thus, our novel genetically-engineered mouse models reveal the importance of EMT in the metastatic progression of gastric cancers, providing a unique model to test agents targeting the metastatic progression in gastric cancers.
Contemporary utilization trends and survival outcomes in patients undergoing radical cystectomy and bladder preservation therapy for muscle invasive bladder cancer.
Authors: David Cahn, Elizabeth Handorf, Michael Nordsiek, Thomas M. Churilla, Eric M. Horwitz, Benjamin T. Ristau, David Y. T. Chen, Rosalia Viterbo, Richard Evan Greenberg, Alexander Kutikov, Robert G. Uzzo, Marc C. Smaldone
Journal: Journal of Clinical Oncology (2016)

387 Background: To compare overall survival (OS) in patients undergoing radical cystectomy (RC) and bladder preservation therapy (BPT) for muscle invasive urothelial carcinoma of the bladder. Methods: We conducted a retrospective, observational cohort study in which we reviewed the National Cancer Database (NCDB) to identify patients with analytic stage II-III (N0M0) urothelial carcinoma of the bladder from 2003-2011. BPT patients were stratified as any external beam radiotherapy (EBRT), definitive radiotherapy (RT) [50-80Gy], and definitive RT + chemotherapy. Treatment trends were evaluated using Pearson Chi-square tests. OS was compared between RC and BPT using unadjusted Kaplan Meier curves and Cox regression models adjusted for year of treatment, hospital volume, and patient/tumor characteristics using increasingly stringent selection criteria to identify those undergoing BPT. Results: Of the 603,298 patients with bladder cancer captured in the NCDB from 2003-2011, 9% (n = 54,518) had analytic stage II-III with urothelial histology. 51.1% (n = 27,843) of these patients were treated with RC (70.9%, n = 19,745) or BPT (29.1%, n = 8,098). Of the patients undergoing BPT, stratified by selection criteria, 26.9% (n = 2,176) and 15.0% (n = 1,215) were treated with definitive RT and definitive RT + chemotherapy, respectively. Following adjustment, improved survival in patients undergoing RC was noted regardless of BPT definition employed in multivariate analysis. However, we noted attenuated differences in OS using increasingly stringent definitions for BPT (EBRT: HR 2.2 [CI 2.15-2.29]; definitive RT: HR 1.94 [CI 1.74-2.14]; definitive RT + chemotherapy: HR 1.56 [CI 1.45-1.68]). Conclusions: In the NCDB, receipt of BPT was associated with decreased OS compared to RC in all patients with stage II-III urothelial carcinoma, in part due to selection biases. However, the use of increasingly stringent definitions of BPT attenuated the observed survival differences. Further randomized prospective controlled trials are needed to compare trimodal BPT to RC to identify optimal candidates for bladder preservation.
Early data on the efficacy and safety of the novel multi-ligand somatostatin analog, SOM230, in patients with metastatic carcinoid tumors refractory or resistant to octreotide LAR
Authors: L. Kvols, K. Oberg, W. de Herder, L. Anthony, J. Glusman, L.-L. Tran, B. Wiedenmann
Journal: Journal of Clinical Oncology (2005)

8024 Background: SOM230 is a novel multi-ligand somatostatin analog that exhibits high binding affinity to four somatostatin receptor subtypes: sst1,2,3 and sst5. Compared with octreotide, SOM230 has 30, 5 and 40 times greater affinity for sst1,3 and sst5 receptors, respectively, and a comparable affinity for sst2 receptors. Methods: This was a Phase II open-label, multicenter study in patients with metastatic carcinoid tumors whose symptoms (diarrhea and flushing) were refractory/resistant to octreotide LAR. Enrolled patients had histopathologically confirmed disease, elevated 5-HIAA and/or CgA levels and at least one measurable lesion (excluding bone). Symptom control with subcutaneous SOM230 was evaluated daily using patient diaries. Patients initially received SOM230 300 μg bid. Dose escalation of 150 μg bid, up to a maximum of 1200 μg bid, was allowed every 3 days until adequate symptom control was achieved. Adequate control or partial response (PR) was defined as a mean of <4 bowel movements (BM)/day with no more than 6 BM on any given day, and an average of <2 flushing episodes/day for 15 consecutive days on a fixed dose of SOM230. Complete response was defined as a mean of ≤3 BM/day with no more than 3 BM on any given day, and no flushing episodes. Results: In this interim analysis conducted in September 2004, 21 patients (M and F, aged 40–76 years) qualified for efficacy assessment. PR was indicated in seven patients at doses 450-1200 μg bid. Adverse events (AEs) were assessed in 23 patients, and were primarily gastrointestinal (GI) in nature - abdominal pain (35%) and nausea (26%). Weight loss (26%) and fatigue (13%) were also reported. Most discontinuations were due to GI AEs (n=5); four patients discontinued after they reached maximum dose without a therapeutic response. Conclusions: SOM230 450-1200 μg bid was effective for controlling diarrhea and flushing and was generally well tolerated in these patients. This study is ongoing to better define the potential of SOM230 as a treatment option for metastatic carcinoid tumors refractory/resistant to octreotide LAR. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Novartis
Phase II trial of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma (HCC).
Authors: Aiwu Ruth He, Anteneh Tesfaye, Daniel Smith, John Marshall, Michael J. Pishvaian, Brandon George Smaglo, Louis M. Weiner, Karen Dorsch-Vogel, Hongkun Wang
Journal: Journal of Clinical Oncology (2014)

240 Background: The combination of the imidazotetrazine derivative temozolomide (TMZ) and poly(ADP-ribose) polymerase inhibitor veliparib (ABT-888) has shown in vivo activity against a variety of tumor types through the alkylating effects of TMZ and DNA repair inhibition by ABT-888. To date, no studies have examined the combination of TMZ and ABT-888 in treating advanced HCC refractory to sorafenib. Methods: This is a single arm Phase II trial. Eligible HCC patients have Child Pugh A/B cirrhosis and have failed prior treatment with sorafenib either through intolerance or disease progression. All patients have received ABT-888 40 mg daily on days 1-7 and Temozolomide 150 mg/m2 daily on days 1-5 in 28 day cycles for a maximum of 6 cycles. Tumor response is analyzed every 2 cycles using RECIST criteria. The primary endpoint is time to disease progression. The trial is being conducted using a modified Simon’s two-stage design optimal design as implemented by Hanfelt, et al. Results: The trial is currently in Simon Stage 1 with 16 patients recruited: 9 patients have stopped the study due to disease progression, 3 patients are still on protocol, and 4 patients stopped the study for reasons other than disease progression. 7 patients had disease progression at two months, 1 patient had cancer progression at 4 months, and 1 patient had disease progression at 16 months. Median time to progression in these 9 patients was 56 days (range 42-486 days). The four patients that stopped the study prematurely were for the following reasons: hiccups/dehydration, Mallory-Weiss tear secondary to refractory nausea, intraperitoneal bleeding from exophytic HCC lesion, and development of hepatorenal syndrome in a paracentesis-dependent patient. The most common grade 3 toxicities in this cohort so far have been nausea/vomiting (in 2 subjects), and anemia/thrombocytopenia (in 2 subjects). Defects in DNA repair pathways are being tested from the liver biopsy in the patient who had response to TMZ and ABT-888 for 16 months. Conclusions: The combination of TMZ and ABT-888 is fairly tolerated in patients with advanced HCC. So far, the treatment did not show activities in majority of patients with advanced HCC. Clinical trial information: NCT01205828.