tbuckley/cabot-search huggingface dataset:
Cabozantinib (XL184) in metastatic castration-resistant prostate cancer (mCRPC): Results from a phase II randomized discontinuation trial.
Authors: M. Hussain, M. R. Smith, C. Sweeney, P. G. Corn, A. Elfiky, M. S. Gordon, N. B. Haas, A. L. Harzstark, R. Kurzrock, P. Lara, C. Lin, A. Sella, E. J. Small, A. I. Spira, U. N. Vaishampayan, N. J. Vogelzang, C. Scheffold, M. D. Ballinger, F. Schimmoller, D. C. Smith
Journal: Journal of Clinical Oncology (2011)

4516 Background: Cabozantinib (Cabo) is an inhibitor of MET and VEGFR2. MET signaling promotes tumor growth, invasion and metastasis. Methods: mCRPC patients (pts) with progressive measurable disease (mRECIST) received Cabo at 100 mg qd PO over a 12 week (wk) lead-in stage. Response was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label Cabo, pts with SD were randomized to Cabo vs placebo, and pts with PD discontinued. Primary endpoint was objective response rate (ORR) per mRECIST in the lead-in stage. Up to 200 pts could be enrolled to target 70 randomizations. Bone scans (b-scans) were independently reviewed. Results: Accrual was halted at 168 pts based on an observed high rate of clinical activity. 100 pts are currently evaluable for the lead-in stage; median age 68, 47% with visceral disease, 78% with bone metastasis, and 47% docetaxel (D) pretreated. Median f/u was 4 months (range, 1-15); median PFS not yet reached. Most common related Grade 3/4 AEs were fatigue (11%), HTN (7%), and hand-foot syndrome (5%); no related Grade 5 AEs reported. Dose reductions for AEs occurred in 51% of pts, and discontinuations in 10%. Bone effects: 86% (56/65 pts evaluable by b-scan) had complete or partial resolution of lesions on b-scan as early as wk 6. Eight pts (12%) had SD and 1 pt (2%) had PD. In 28 pts receiving narcotics for bone pain, 64% had improved pain and 46% decreased or halted narcotics, per investigator. Median maximum rise in hemoglobin in anemic pts (Hb < 11 g/dL) was 2.2 g/dL (range, 0.6-3.5). Osteoclast and osteoblast effects were observed: 55% had declines of ≥50% in plasma C-Telopeptide; 56% of pts with elevated tALP had declines of ≥50%. Soft tissue effects: Objective tumor shrinkage occurred in 84% of pts. ORR at wk 12 was 5%; 3 additional PRs await confirmation. PSA changes were independent of clinical activity. Overall, wk 12 disease control rate (PR+SD) was 71%. Randomization was halted and pts unblinded due to high rates of b-scan resolution and pain relief. Conclusions: Cabo showed clinical activity regardless of prior D in mCPRC pts, particularly in pts with bone disease, as reflected by high rates of b-scan resolution and pain relief, in addition to improvements in Hb and tumor regression.
Incidence of diabetes among patients with colorectal cancer.
Authors: Simron Singh, Paula Rochon, Geoffrey Anderson, Craig Earle, Hadas Fischer, Peter Austin, Lingsong Yun, Lorraine Lipscombe
Journal: Journal of Clinical Oncology (2014)

393 Background: Emerging data show an increasingly recognized risk of colorectal cancer (CRC) in patients with type 2 diabetes (DM) likely due to common biologic pathways. Few data are available on DM incidence among patients with CRC. Our objective was to determine whether patients with CRC have a higher incidence of DM compared to those without CRC. Methods: We conducted a population-based retrospective cohort study in Ontario, Canada, using administrative databases comparing the incidence of DM among all CRC patients identified in the Ontario Cancer registry from Jan 1, 2002 to Dec 31, 2011 with an age-matched control population without CRC. We used Cox proportional hazard to study the association. We modeled the effect of CRC on the cause-specific hazard of developing DM and censored subjects at the time of a competing event. Subgroup analysis was performed on patients receiving chemotherapy vs. not, metastatic disease vs. not and colon vs. rectal cancer. Results: We identified 39,707 persons with CRC and 198,535 controls. The mean age was 68 and 48.6% were female. We found an overall DM incidence of 8.7% over a mean follow up time of 4.8 years. On multivariable analysis, the effect of CRC on the instantaneous hazard of the DM incidence varied over time, and thus we estimated instantaneous hazard ratios (IHR) for years 1-5 of follow up. The risk of DM among CRC patients was significantly higher than controls for at least five years post CRC diagnosis. The overall DM incidence was higher in patients with no metastasis (10.6% vs 8.6%, p&lt;0.01), and lower in patients who received chemotherapy (8.0% vs 9.0%, p&lt;0.01). Conclusions: This is among the first study to report an increased DM incidence among CRC survivors. This association may be due to common risk factors rather than a treatment effect, as the risk remains elevated for at least five years post diagnosis. The hazard may be underestimated, as patients with advanced cancer may not be formally diagnosed with DM. These results strengthen our understanding of the common biologic pathway of both diseases and have major implications for survivorship care in patients with CRC. [Table: see text]
Bcr-Abl Mediated-Depletion of Dual-Specificity MAP Kinase Phosphatase, DUSP1, Expression Promotes the Cell Proliferation.
Authors: Yasuyuki Nagata, Satoki Nakamura, Tomonari Takemura, Daisuke Yokota, Isao Hirano, Takaaki Ono, Kazuyuki Shigeno, Shinya Fujisawa, Kazunori Ohnishi
Journal: Blood (2010)
Usefulness of digital breast tomosynthesis (DBT) in evaluation of pathological response after neoadjuvant chemotherapy (NAC) for breast cancer.
Authors: Ayano Arasaki, Nachiko Uchiyama, Takayuki Kinoshita
Journal: Journal of Clinical Oncology (2015)

119 Background: Digital breast tomosynthesis (DBT) has been developed recently and it provides an advantage in detection of breast masses compared to 2D mammography (MMG) since it allows to separate the tissue layers and to noticeably reduce occlusions caused by overlapping anatomical structures. Neoadjuvant chemotherapy (NAC) has been used increasingly for the treatment of breast cancer. The imaging methods that have been used until now to assess tumor response to NAC have serious limitations. Attaining pathological complete response (pCR) is the most important predictor of long-term survival in patients receiving NAC. We assessed the radiological findings and capability of DBT to predict response to NAC in comparison with 2D MMG. Methods: 33 woman (mean age, 47.3 y.o.) having 36 lesions were recruited. Image utilizing adjunction of DBT to 2D MMG were taken for diagnosis from January, 2010 to March, 2015. Pathological subtypes were IDC (n = 34), ILC (n = 1), and IMPC (n = 1). Pathological responses of the lesions to NAC were Grade1 (n = 16), Grade2 (n = 11), and Grade3 (n = 9). The clinical image data sets were acquired with a DBT system (MAMMOMAT Inspiration, Siemens, Germany).For each patient, CC and MLO views were taken for diagnosis. With one-view 2D MMG and DBT, those radiation dose, utilizing the ACR phantom 156, were 1.20mGy and 1.80mGy. Results: The clinical response to NAC was classified into the following categories: 1) Fairly Response (FR): reduction in size of the tumor by more than 70% including Complete Response (CR), 2) Partial Response (PR): reduction in size of the tumor by 30% or more but less than 70%, 3) Stable disease (SD): reduction in size of the tumor by less than 30%. DBT findings of pathological Grade2-3 cases were all suggested FR (28/28, 100.0%) Grade3 cases were all suggested CR (9/9,100.0%). Regarding the Grade1b cases, all lesions were suggested PR (8/8, 100.0%). Regarding the Grade1a cases, 3 out of 8 (36.5%) lesions were suggested CR, and 2 out of 8 (25%) lesions suggested PR, and 3 out of 8 lesions suggested SD. Conclusions: DBT will contribute to improved diagnosis accuracy with regard to NAC response to breast cancer in comparison with 2D MMG.
<sup>68</sup>Ga-PSMA PET/CT imaging predicting intraprostatic tumor extent prior to radical prostatectomy in patients with prostate cancer.
Authors: Christoph A. J. von Klot, Axel S. Merseburger, Markus A. Kuczyk, Sebastian Schmuck, Frank M. Bengel, Thorsten Derlin
Journal: Journal of Clinical Oncology (2016)

e632 Background: The performance of gallium Ga 68 ( 68 Ga)-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) shows promising results with regard to lymph node detection even at low prostate specific antigen (PSA) levels in patients with biochemical recurrence after curative therapy for prostate cancer. In this study we evaluate the usefulness of PSMA-PET/CT for the evaluation of intraprostatic tumor extent prior to radical prostatectomy. Methods: In total 15 patients with prostate cancer underwent a 68 Ga-PSMA-PET/CT before surgical treatment. All patients received either open or laparoscopic radical prostatectomy. Intraprostatic tumor extent was assessed on PET/CT. The peak standardized uptake value (SUV) was correlated with final whole gland histopathology including Gleason grade, lobe infiltration, TNM stage and seminal vesicle invasion. Results: Mean SUV over all patients was 10.64 ±9.19. Median Gleason score was 7. The distribution of TNM stage 2a, 2b, 2c, 3a, 3b, 4 was 0, 2, 6, 5, 2 and 0 patients. Mean intraprostatic SUV for patients with organ confined vs. extraprostatic tumor on histopathology was 6.3 and 15 respectively (p = 0.043). Mean SUV for patients with a Gleason score of ≤ 7a and &gt; 7a was 6.2 and 13.5 (p = 0.046). Sensitivity and specificity for identifying tumor invasion of a prostate lobe was 84.6% and 75% (Positive and negative predictive value (PPV, NPV) for prostate lobe invasion were 95.7% and 42.9%). Sensitivity and specificity for seminal vesicle invasion were 50% and 100% (PPV 100%, NPV 96.6%). Conclusions: These early results need to be further validated in a larger cohort.
Comprehensive genomic profiling of 443 cases of renal cell carcinoma to reveal frequent clinically relevant genomic alterations.
Authors: Sumanta Kumar Pal, Siraj M. Ali, Zachary Chalmers, Jose A. Karam, Julia Andrea Elvin, Juliann Chmielecki, Roman Yelensky, Eliezer Mendel Van Allen, Doron Lipson, Kai Wang, Andre Poisl Fay, Toni K. Choueiri, Vincent A. Miller, Phil Stephens, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2015)

433 Background: Despite the availability of targeted therapy, effective management of advanced RCC is an unmet medical need as treatment is not personalized and is not guided by patient-specific genomic alterations (GAs). To assess the spectrum of clinically relevant GAs (CRGAs) in advanced RCC, comprehensive genomic profiling (CGP) of clinical RCC samples was performed with the goal of informing use of existing and novel targeted therapies. Methods: DNA was extracted from 40 microns of FFPE sections from 443 consecutive patients with relapsed/metastatic RCC. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 646X for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. The CGP assay included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. CRGA were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: There were 73% male and 27% female patients with a mean age of 56 years, and the majority of cases were advanced stage with 198/443 specimens (44.6%) from metastatic sites. 400/443 patients (89%) had at least 1 GA on CGP with a mean 3.1 GA/case. 396/400 RCC harboring GA had at least 1 CRGA involving 111 individual genes with a mean of 1.32 CRGA/UC. The most common novel CRGA in order of frequency were: CDKN2A (21%), BAP1 (12%), ATM (11%), PTEN(8.5%), TSC1(8.3%), mTOR (7%), MET (6.5%), AR (5.3%), DNMT3A (5%) and TSC2 (5%). Moreover, VHL harbored a diversity of GA’s in in 49% of cases. Collecting duct carcinomas harbored an enrichment of NF2 truncating alterations (&gt;40%), distinct from renal medullary carcinoma which did not harbor such GA. Multiple clinical antitumor responses to targeted therapies will be presented. Conclusions: Using a CGP assay capable of detecting all classes of GA simultaneously, a high frequency of CRGA was identified in a large series of patients with advanced RCC. The diversity of CRGA suggests opportunities for the rational application of existing and investigational targeted therapies, and for possible deeper characterization of histological types of RCC.
MK886 Induced Apoptosis in HL-60 Cells Via Inhibition mPGES-1 Expression and Down-Regulation Prostaglandin E2 Synthesize.
Authors: Yiqing Li, Songmei Yin, Shuangfeng Xie, Danian Nie, Liping Ma, Xiuju Wang, Yudan Wu
Journal: Blood (2009)
Integrated care pathways (ICPs) for non-small cell lung cancer (NSCLC) patients (Pts): A multidisciplinary quality improvement project.
Authors: S. Rizzato, V. Merlo, M. Aita, A. Sibau, J. Menis, L. Gurrieri, E. Lugatti, M. Gaiardo, S. Meduri, F. Giacomuzzi, V. Tozzi, G. Fasola
Journal: Journal of Clinical Oncology (2011)

e16573 Background: ICPs are structured multidisciplinary care plans for a specific clinical condition; they describe the tasks to be carried out together with their timing and sequence and the discipline involved in completing the task. They have been proposed as quality improvement strategies of both clinical and organizational aspects of patient-oriented care. Nowadays few data are available to detail existing ICPs for NSCLC pts and the methodology for designing an optimal care plan. Aim of this project was to review current clinical pathways in the care of NSCLC pts who were referred to the University Hospital of Udine, Italy. Methods: A multidisciplinary focus group was established to: 1) map existing local care pathways for NSCLC pts; 2) review the literature and available guidelines to identify quality benchmarks and corresponding, specific indicators; 3) apply these indicators to assess the quality of existing ICPs; 4) recognize key areas for process improvement. Results: Eleven quality indicators were identified. They consist in intermediate outputs of the care process and may assess both clinical, organizational and economical aspects of pts care. Indicators were used to survey the ICPs of 175 NSCLC pts who were referred to our Hospital in 2008; data for 6 representative indicators are shown below (Table). Conclusions: By means of a limited set of quality indicators, we were able to verify the adherence of routine clinical practice to clinical guidelines and to elicit some critical issues in the care of NSCLC pts. Results need to be shared and discussed with Hospital Managers, with the aim of guiding the redesign of ICPs and improving the clinical, organizational and economic efficiency of the care process. Indicator Median Benchmark Days from first evaluation in a lung unit to histological diagnosis 15 15-20* Surgical pts undergoing a CT-PET followed by a mediastinoscopy (%) 2 80-100* Pts multidisciplinary evaluation (%) 50 55* Days from histological diagnosis to surgery 49 28-35** Poor (>1) ECOG PS pts receiving a two-drug regimen (%) 1 0* >3 lines of cytotoxic treatment (%) 0 0* According to * evidence-based guidelines or ** expert consensus.
Prognostic factors of adjuvant chemotherapy with taxane, cisplatin, and 5FU combination (TPF) in patients (pts) with nodal metastases of penile squamous cell carcinoma (PSCC).
Authors: Andrea Necchi, Salvatore Lo Vullo, Nicola Nicolai, Daniele Raggi, Patrizia Giannatempo, Maurizio Colecchia, Mario Catanzaro, Tullio Torelli, Luigi Piva, Davide Biasoni, Silvia Stagni, Luigi Mariani, Roberto Salvioni
Journal: Journal of Clinical Oncology (2016)

479 Background: Little is known about the outcomes and prognostic factors of adjuvant chemotherapy for locally advanced PSCC after regional lymphadenectomy (LAD). Perioperative TPF combination regimen showed activity in PSCC in our series (Nicolai N et al, Clin Genitourin Cancer 2015). Methods: We retrospectively reviewed the clinical and histological data of 21 pts who had received 3-4 cycles TPF (q3wks) in the adjuvant setting at our center. Univariable and multivariable Cox regression analyses were done evaluating potential prognostic factors of disease-free (DFS) and overall survival (OS) of TPF: number of prior LAD, time from diagnosis of nodal disease to start TPF, time from LAD to start TPF, pN3, pelvic, and bilateral nodal disease, and p53 immunohistochemical (IHC) expression in nodal metastases. Results: Pts had received TPF from 07/04 to 07/12, after inguinal (n = 6) or inguinal + pelvic LAD (n = 15) and the median follow up was 52 months. LAD was radical in all cases and none had received radiotherapy. After surgery, 13 (61.9%) had pelvic and 5 (23.8%) bilateral inguinal nodal metastases. Median time from LAD to TPF was 5.4 wks (IQR: 4.1-7.3) and median time from diagnosis of N disease to TPF was 8.3 wks (IQR: 4.1-15.4). 11 of 19 available pts (57.9%) had p53+ve IHC. Univariably, only p53+ve IHC trended to poorer DFS (HR: 4.14, 95%CI: 0.87-19.68, p = 0.074) and OS (HR: 4.54, 95%CI: 0.95-21.56, p = 0.056). The same results were obtained multivariably for DFS (HR: 3.76, 95%CI: 0.78-17.96, p = 0.096) and OS (HR: 4.29, 95%CI: 0.89-20.57, p = 0.067). The bias-corrected c-indexes of the models were 0.64 and 0.62, respectively. Median DFS was 8.9 months (IQR: 5.9-22.7) for p53+ve pts vs not estimable (NE) for p53-ve pts (p = 0.051) and median OS was 17.2 months (IQR: 12.8-22.7) and NE, respectively (p = 0.037). Conclusions: In pts who had received adjuvant TPF for node-positive PSCC, p53 IHC positivity seemed to be associated with poorer outcome, and further study is warranted in larger datasets to confirm these findings. This information might be useful to select the optimal candidates to multimodal therapy for advanced PSCC.
Abstract P038: US Consumer Attitudes Toward Sodium in Baby and Toddler Foods
Authors: Katherine A John, Mary E Cogswell, Lixia Zhao, Joyce Maalouf, Janelle P Gunn, Robert Merritt
Journal: Circulation (2016)

Introduction: Average US sodium intake is 9 times higher among toddlers 12-24 months of age than among infants 0-6 months of age. About 80% of US toddlers aged 1-3 years consume excessive dietary sodium and research indicates that what children eat in the first 2 years of life may influence subsequent preference for salty-tasting foods. Information on consumer attitudes can influence strategies to reduce sodium in commercially packaged baby and toddler foods. Hypothesis: The objective of the study was to describe the prevalence of adult consumer attitudes and related sociodemographics on the importance of baby and toddler foods being low in sodium. We hypothesized that parents of children younger than 2 years, individuals with or at higher risk of cardiovascular disease, and those who agree that too much sodium intake is harmful or who are trying to reduce sodium intake would be more likely to agree that toddler foods should be low in sodium. Methods: Data was obtained from Porter Novelli’s 2012 ConsumerStyles online survey sent to a random sample of 11636 US adults aged ≥ 18 years enrolled in their national probability-based consumer panel. Of those who completed the survey (N=6728), 6378 responded to the statement, “It is important for baby and toddler foods to be low in sodium.” The data from the respondents were weighted to match 2011 US Current Population Survey Proportions. Compared with non-respondents (N=350), a higher proportion of respondents were male (49% v 34%), but respondents did not differ by race, age, education, income, or region of residence. Potential determinants of agreement included demographic, health, and sodium-related attitudes and behaviors. We used logistic regression to describe the association of adult consumer attitudes and related sociodemographic characteristics with the importance of baby and toddler foods being low in sodium. Results: About 7 in 10 (68%, 95% CI: 66%-70%) participants agreed it was important for baby or toddler foods to be low in sodium. More than 6 of 10 in most subgroups agreed, with the highest agreement among parents of children aged 65 years compared with adults aged 18-34 years, those of other non-Hispanic races compared with non-Hispanic whites, participants who reported having high cholesterol, and those currently watching or reducing their own sodium intake. Conclusions: The majority of respondents agree it is important for baby and toddler foods to be low in sodium, particularly among parents with children younger than 2 years of age, persons trying to reduce sodium, and those who agree sodium is harmful to their health. In conclusion, these data suggest broad support for strategies to lower sodium in these foods.
Washington University experience with FOLFIRINOX in pancreatic cancer.
Authors: Parvin F. Peddi, Benjamin R. Tan, Joel Picus, Steven Sorscher, Rama Suresh, Albert C. Lockhart, Christine Menias, David Linehan, Andrea Wang-Gillam
Journal: Journal of Clinical Oncology (2012)

354 Background: The FOLFIRINOX (5-FU, leucovorin, irinotecan, oxaliplatin) regimen has recently been shown to be an effective treatment with a significant survival benefit in patients with metastatic pancreatic cancer. Concern for treatment-related toxicity, however, has hampered the adoption of this regimen in clinical practice. A FOLFIRINOX registry was created at our institution to document FOLFIRINOX tolerability and efficacy. Methods: Patients with pancreatic cancer who had received at least one dose of FOLFIRINOX were enrolled in the registry. Demographic information, treatment dosage, adverse events, and efficacy data were obtained. Radiographic response was independently verified by a radiologist. Results: Between January 2010 and August 2011, 29 patients were identified with a median age of 57 (range 37-71). 26 (92.8%) had ECOG performance status of 0-1. FOFIRINOX was given to 16 patients with metastatic disease, 12 with locally advanced disease, and one with borderline resectable disease. 17 (61%) received the first cycle with a dose reduction in either irinotecan and/or 5-FU dosage. UGT1A1*28/*28 homozygous genotype was found in 4 patients who all received dose reduced irinotecan. 13 patients (46%) were started on G-CSF prophylactically with the first cycle while 5 additional patients (18%) had G-CSF support added in later cycles. Main adverse events were neutropenia (grade 3-4 in 14.2%), and abdominal pain and diarrhea (grade 3-4 in 7% and 4% respectively). One incidence of neutropenic fever was observed. Four patients were hospitalized for treatment-related toxicity while three had therapy discontinued due to intolerance. At present, 19 patients have imaging available to determine efficacy: 5 (26%) had partial response, 12 (63%) stable disease, and 2 (11%) had progression of disease as their best response. For patients with locally advanced disease, 11 out of 12 had clinical benefit on FOLFIRINOX. Conclusions: In our practice, FOLFIRINOX was well tolerated and was efficacious, consistent with previously published data. It was frequently used in the setting of locally advanced disease and had similar benefit and tolerability in this setting.