tbuckley/cabot-search huggingface dataset:
Accidental intrathoracic disseminated pM1a: Distinguished lung cancer with favorable prognosis.
Authors: Wenzhao Zhong, Wei Li, Xue-Ning Yang, Riqiang Liao, Qiang Nie, Song Dong, Xuchao Zhang, Yi-Long Wu
Journal: Journal of Clinical Oncology (2014)

e18522 Background: In the 7thedition of lung cancer TNM stage, the prognosis of the pM1aIV is better than pIIIB. Subgroups of lung cancer patients who underwent incomplete resection (R1/R2) gain favorable prognosis. This study compares the prognosis between accidental local residue and intrathoracic disseminated pM1a after incomplete resection. Methods: Patient characteristics, histological and molecular profiles of lung cancer patients who receiving accidental incomplete resection were retrospectively collected. All patients were divided into local residual Group and intrathoracic disseminated pM1a Group. Progression-free survival (PFS) and overall survival(OS) were evaluated by Kaplan–Meier and Cox regression. Results: From 2008 to 2013, 1483 lung cancer patients received thoractomy in Guangdong Lung Cancer Institute. 58 patients receiving incomplete resection(R1/R2) were enrolled, including 38 patients of local residue (2.6%) and 20 patients of disseminated pM1a (1.3%). Patient characteristics, histological and molecular profiles of the 2 group were different. Compared to local residual Group, disseminated pM1a Group harboring more female(P=0.002), more patients younger than 60 years old (P=0.01), more non-smokers (P=0.037), higher R2/R1 resection ratio (P=0.013), less patients with lymph nodes metastasis (P=0.013), higher stage IV/IIIB ratio P<0.001), more adenocarcinomas (P<0.001), more adenocarcinomas with lepidic pattern (P<0.001), higher CEA level (P=0.06), higher EGFR mutation rates (P<0.001), lower EGFR expression (P=0.022). Median PFS of local residue and disseminated pM1a were 8.7 and 18.8 months (P=0.120), and median OS were 11.9 and 36.0 months (P=0.002), respectively. Cox regression analysis revealed that Groups (local residue vs. disseminated pM1a) was the only independent prognostic factor (P=0.005) for OS. Conclusions: Accidental intrathoracic disseminated pM1a is a distinguished lung cancer subtype with favorable prognosis comparing to patients of local residue. The prolong PFS and OS might contribute to the natural history of the distinguished subtype and the favorable response to EGFR-TKI.
Pattern of glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80) expression in peripheral blood as a marker for myeloid-derived suppressor cells (MDSCs) in metastatic renal cell cancer (mRCC) patients.
Authors: Tomoyuki Kato, Yuji Takeda, Yuta Kurota, Hiromi Ito, Akemi Araki, Hidetoshi Nara, Hironobu Asao, Norihiko Tsuchiya
Journal: Journal of Clinical Oncology (2017)

504 Background: Metastatic renal cell cancer (mRCC) patients are afflicted with the immunosuppressed condition, and myeloid-derived suppressor cells (MDSCs) are considered to be associated with this condition. MDSCs are difficult to detect in peripheral blood as their cell structures are not uniform, resembling both neutrophils and monocytes. GPI-80 is known as a regulator of Mac-1 (CD11b/CD18) and closely related with neutrophilic maturation. In this study, we investigated whether the pattern of GPI-80 expression could serve as a useful marker for the detection of MDSCs in peripheral blood among mRCC patients. Methods: This study was approved by the Ethics Committee of Yamagata University’s Faculty of Medicine. Peripheral blood samples, collected from 12 mRCC patients before treatment and 12 healthy volunteers, were stained with several differentiation markers such as CD11b, CD16, CD15, CD33, and GPI-80. The samples were examined using flow cytometry to detect unusual differentiation of myeloid cells. To investigate the immunosuppressive function of GPI-80 positive cells, reactive oxygen species (ROS) was measured, and T cell proliferation assay was performed. Results: The coefficient of variation (CV) of GPI-80 was significantly augmented in the CD16 hi neutrophil cell population (p = 0.0001). The mean fluorescence intensity (MFI) of GPI-80 was significantly increased in the CD33 hi monocyte cell population (p = 0.0074) in the peripheral blood cells of mRCC patients. Furthermore, the GPI-80 CV in the CD16 hi population was inversely correlated with the proliferative ability of T cells (p = 0.0214), and the GPI-80 MFI of the CD33 hi population was correlated with ROS production (p = 0.0497). Conclusions: These results showed that the pattern of GPI-80 expression in peripheral blood cells is a simple and useful marker for unusual differentiation, which is linked to MDSC functions among mRCC patients. Further studies are, however, required to identify the role of GPI-80 as a prognostic or predictive marker in such patients.
A phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of the selective aurora kinase inhibitor GSK1070916A.
Authors: Iain McNeish, Alan Anthoney, Paul Loadman, Dan Berney, Simon Joel, Sarah E. R. Halford, Emily Buxton, Amanda Race, Mohammed Ikram, Andrew Scarsbrook, Angela Patikis, Andrea Rockall, Nicola A Dobbs, Christopher Twelves
Journal: Journal of Clinical Oncology (2013)

2525 Background: GSK1070916A is a potent and selective inhibitor of Aurora B and C. This phase I study in collaboration with GlaxoSmithKline was part of the Cancer Research UK Clinical Development Programme. Methods: Patients (pts) with advanced/metastatic solid cancers for whom there was no standard therapy, with adequate performance status and organ function were eligible for GSK1070916A (1 hour i.v. infusion days 1 – 5, every 21 days). The primary objectives were to determine the safety profile, dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of GSK1070916A. The starting dose was 5mg/m 2 /day, with initial single pt cohorts, followed by “3 + 3” cohorts and expansion at the MTD. DLTs included prolonged (&gt; 5 days) or complicated grade 4 neutropenia; the MTD was the highest dose at which &lt; 1 of 3 - 6 pts experienced DLT. Cycle 1 blood and healthy skin biopsies were obtained for PK and PD assays. The expanded cohort included 6 pts having pre- and post-treatment functional imaging studies (FDG PET-CT and MRI), and a further 6 having paired tumour biopsies for PD studies. Results: Nine single pt cohorts received up to 73mg/m 2 /day of GSK1070916A with no grade 3 or 4 related adverse events. At 102.2mg/m 2 /day, 1 pt had a DLT (febrile neutropenia) and 2 pts non-DLT grade 4 neutropenia; this dose was considered unacceptably toxic and 23 pts received a lower dose of 85mg/m 2 /day; 7/23 pts had prolonged/complicated grade 4 neutropenia, 5 of whom continued GSK1070916A with dose reduction +/- delay. There were no treatment related deaths. A pt with ovarian cancer (102.2mg/m 2 /day) had a RECIST PR; 19 pts had stable disease for &lt; 223 days. GSK1070916A PK were linear with a strong correlation between exposure (AUC) and reduction in neutrophils (r 2 0.91). At the 85 mg/m 2 dose, mean day 1 t 1/2 was 8.98 hours and Cl 9.2 l/h; AUC inf was 10% higher on day 5 than day 1. PD results in healthy skin (phosphoHistone-H3, Ki 67 and cleaved caspase-3) were inconsistent. Conclusions: The MTD of GSK1070916A as a 1 hour i.v. infusion on days 1 – 5, every 21 days is 85mg/m 2 /day, with predictable and manageable neutropenia as the DLT and evidence of clinical activity. Serum levels of cytokeratin-18, tumour PD and functional imaging data will be presented. Clinical trial information: NCT01118611.
ACE inhibitors and angiotensin receptor blockers use and breast cancer outcomes in patients treated with neoadjuvant systemic chemotherapy.
Authors: Young Kwang Chae, Erika N. Brown, Xiudong Lei, Amal Melhem-Bertrandt, Sharon Hermes Giordano, Jennifer Keating Litton, Gabriel N. Hortobagyi, Ana M. Gonzalez-Angulo, Mariana Chavez-Mac Gregor
Journal: Journal of Clinical Oncology (2012)

537 Background: There is a growing body of evidence to suggest that ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) might have anti-tumor properties. We investigated whether the use of ACEI/ARBs during chemotherapy affects the clinical outcomes of breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy. Methods: We included in this analysis 1449 patients with diagnosis of invasive primary breast cancer diagnosed at the MD Anderson Cancer Center between 1995 and 2007 who underwent neoadjuvant chemotherapy. Of them, 160 (11%) patients were identified by review of their medical record, as ACEI/ARBs users. We compared pathologic complete response (pCR) rates, relapse-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) between ACEI/ARB users and non-users. pCR was defined as no evidence of invasive carcinoma in the breast and axillary lymph nodes at the time of surgery. Descriptive statistics and Cox proportional hazards model were used in the analyses. Results: There was no difference in the pCR rates between ACEI/ARB users (16%) versus non-users (18.1%) (p=0.50). After adjustment for important demographic and clinical characteristics, no significant differences between ACEI/ARB users and nonusers were observed in RFS (HR=0.81; 95% CI=0.54-1.21; P=0.30), DSS (HR=0.83; 95% CI=0.52-1.31; P=0.42), or OS (HR=0.91; 95% CI =0.61-1.37; P=0.66). In a subgroup analysis among ARB users, the 5-year RFS was 82% vs 71% in ACEI/ARB non-users (P=0.03). In the multivariable analysis, ARB use was also associated with a decreased risk of recurrence (HR=0.35; 95% CI=0.14-0.86; P=0.02). However, no statistically significant differences in DSS or OS were seen. Conclusions: No differences in pCR and survival outcomes were seen between ACEI/ARB users and non-users among breast cancer patients receiving neoadjuvant chemotherapy. ARB use may be associated with improved RFS. Further research is needed to validate this finding.
New aspects regarding the induction chemotherapy with TPF and radio chemotherapy in head and neck cancer.
Authors: Edwin Boelke, Christiane Matuschek, Stephan Gripp, Kai Kammers, Wilfried Budach
Journal: Journal of Clinical Oncology (2015)

6025 Background: Induction chemotherapy with docetaxel, cisplatin, and 5 FU (TPF) before radiotherapy (RT) or radio-chemotherapy (RT-CHX) improves the overall survival rate compared to induction chemotherapy with cisplatin and 5 FU in locally advanced squamous cell carcinoma of the head and neck (SCCHN). If TPF induction before RT-CHX improves clinical outcome in comparison to RT-CHX alone is still uncertain. Recently, the results of 5 randomized trials addressing this question have become available. Methods: 1060 patients with locally advanced SCCHN were randomly assigned to receive either TPF induction CHX followed by concurrent RT-CHX or concurrent RT-CHX alone. Platin or taxane based CHX was used during RT. 53,4% of patients had oropharyngeal, 17,3% hyopharyngeal, 6,4% laryngeal, 18,5% oral cavity and 4,4% other SCCHN. Published hazard ratios and hazard ratios extracted from available survival curves for overall survival (OS) and progression free survival (PFS) were basis of the meta-analysis. Meta-analysis of the effect sizes on OS and PFS was performed using a random effects model based on parameter estimates of log hazard ratios in Cox models and their standard errors. Results: Additional induction CHXwith TPF before RT-CHX did not result in a significant improvement of overall survival (Hazard Ratio: 0.950, 95% confidence limits (CL) 0.791-1.140 p = 0.579). Conclusions: Additional induction CHX with TPF before RT-CHX does not improve overall survival in SCCHN.
Phase 1 study of CP-868,596 an oral, highly specific PDGFR inhibitor
Authors: N. Lewis, J. P. Eder, F. Guo, K. J. Pierce, A. J. Olszanski
Journal: Journal of Clinical Oncology (2007)

3524 Background: CP-868,596 is an orally available, highly specific inhibitor of platelet-derived growth factor receptors (PDGFR). PDGF and its receptor play an important role in angiogenesis, modulation of tumor interstitial fluid pressure (IFP), and influence cell growth, migration, and survival through signal-transduction pathways. Methods: The safety, tolerability and pharmacokinetics (PK) of daily oral CP-868,596 administered in 4-week cycles were assessed in patients with advanced solid malignancies. Original dose escalation cohorts were 100, 200, 280 and 340 mg QD administered on an empty stomach. Prevalence of persistent Grade 1 nausea and vomiting led to amendments that include “with food” cohorts. Safety assessments included adverse events (AEs), clinical laboratories, and ECG monitoring. PK blood samples were collected after a single dose and at steady state. PK parameters were estimated by non compartmental techniques. Results: Data is available for all 59 patients enrolled in the trial [(29 M/30F); mean age (range): 58.6 (18–80)]. The most common treatment related AEs were nausea (67.8%), vomiting (55.9%) and diarrhea (25.4%). The MTD with coadministration of anti-emetics on an empty stomach was 200 mg/day. Coadministration of CP-868,596 with food resulted in a decrease of nausea and vomiting. The recommended phase 2 dose is 100 mg BID given with food. CP-868,596 was rapidly absorbed after oral administration. Median Tmax ranged from 1 to 4 hours. Cmax and AUC of CP-868,596 increased with dose more-than proportionally. Moderate accumulation occurred with a mean AUC accumulation ratio of 1.4–4.0. The mean terminal t1/2 ranged from 11.6 to 16.8 hours and was similar across all dose levels. The effect of food on PK appeared to be dose-dependent in this parallel cohort design with a limited number of patients (n=3–8). Analysis of safety data showed increasing liver enzymes with increasing PK exposures. No objective responses were seen. Conclusion: Daily administration of CP-868,596 appears to be safe and well tolerated. DLTs were: N/V (2), elevated ALT/GGT (2/2), increased Mg (1), Hematuria (1), and Insomnia (1). Mean steady state serum concentrations in all dose cohorts exceeded the preclinically predicted minimal efficacious exposure (16 ng/mL). No significant financial relationships to disclose.
Association of CYP19A1 gene variants with differences in disease progression in breast cancer patients from different racial/ethnic backgrounds.
Authors: Reina Villareal, Angela W. Meisner, Lina Aguirre, Vibhati Kulkarny, Vallabh Shah, Clifford Qualls, Zoneddy Ruiz Dayao, Melanie Royce
Journal: Journal of Clinical Oncology (2012)

1558 Background: Polymorphisms in the aromatase (CYP19A1) gene result in differences in the risk for breast cancer and response to treatment. We hypothesize that allele frequencies in the CYP19A1 gene vary according to race and may result in differences in progression of breast cancer among women from different racial backgrounds. The objectives of this study are: 1) to determine the allele/genotype frequencies in the CYP19A1 gene among women with breast cancer from different racial backgrounds, and, 2) to determine the association between disease progression and CYP19A1 gene variants. Methods: Clinical data and stored DNA from 327 patients participating in the Expanded Breast Cancer Registry (EBCR) program at the University of New Mexico were analyzed. These patients were followed-up for a period of 1 to 6 years. Comprehensive genotyping for CYP19A1 gene single nucleotide polymorphisms (SNPs) was performed using microarray (Illumina). Results: Data from 164 non-Hispanic white and 119 Hispanic women were analyzed. Four SNPs (rs1259269, rs17703883, rs16964211, rs28757101) were associated with differences in genotype/allele frequencies between the 2 racial groups. Furthermore, 3 SNPs (rs4646, rs17647478, and rs6493486) were associated with differences in disease progression. The rare allele (G) for the rs17647478 (G/T) is associated with poor progression compared those without the allele (41.7% vs. 17.1%, p=0.04). Similarly the minor (A) allele for the rs4646 (A/C) and the rs6493486 (A/G) is also associated with a greater chance of worsening disease (23.2% vs. 12.4%, p=0.02 and 23.4% vs. 12.4%, p=0.02, respectively). A significant percentage of women carrying the A allele for both rs4646 and rs6493486 and the T allele for the rs17647478 have more advanced disease at the time of presentation. None of the SNPs analyzed result in racial differences in breast cancer progression. Conclusions: Polymorphisms in the CYP19A1 gene influence overall disease progression in breast cancer patients but have no impact on the racial differences of disease behavior. Women carrying the risk alleles present at a more advanced stage and are also at greater risk of progression.
異時性対同時性転移性結腸直腸癌(CRC)における臨床像と病理像
Authors: Mekenkamp L.J.M., M Koopman, S Teerenstra, Van Krieken J.H.J.M., L Mol, I D Nagtegaal, Punt C.J.A.
Journal: Annals of Oncology (2010)
Management approaches and outcomes of lung cancer patients hospitalized for malignant pleural effusions.
Authors: Madhusmita Behera, Conor Ernst Steuer, Sungjin Kim, Rathi Narayana Pillai, Zhengjia Chen, Taofeek Kunle Owonikoko, Chandra Prakash Belani, Fadlo Raja Khuri, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2014)

9646 Background: Malignant pleural effusion (MPE) in lung cancer is associated with significant morbidity and poor prognosis. There has been a significant lack of progress regarding the current and recommended management of MPE. We studied MPE management in a large cohort of hospitalized lung cancer patients (pts). Methods: We utilized nationwide inpatient data from 2008-2010 from the Agency for Healthcare Research and Quality- Healthcare Cost and Utilization Project. All lung cancer pts with MPE among top 3 discharge diagnoses were selected. Therapeutic procedures used were identified using ICD 9-CM procedure codes. All analyses were performed using SPSS 20.0. Results: A total of 8570 pts, accounting for 2.5% of all lung cancer-related hospitalizations, had MPE (median age- 71 years, whites-66%, females- 48%, teaching hospitals-46%, urban locations- 88%, elective admissions- 16%, median costs- $29,967). Median length of stay (LOS) was 5 days; mortality rate was 10.5% and 70% had major or extreme loss of function at discharge. Rural hospitals had a higher mortality compared to urban (14% vs. 10%, p=0.002). Thoracentesis(T), thoracostomy tubes(TT) and pleurodesis(P) were the top three procedures, with 48% having a T. Overall pneumothorax rate was 7.4%. There were significant differences in LOS and severity measures in pts sub-groups based on type of intervention (p<0.001). The TT group had higher mortality (Table). Univariate analyses showed significant difference in outcomes between elective and non-elective admissions in P group (p<0.001). Conclusions: Elective admissions for the management of MPE are associated with lower mortality and reduced loss of functional capacity over emergency hospitalizations. Pleurodesis is associated with longer length of stay, but lower mortality and better functional status at discharge. Outcomes T (N=2860) TT (N=1382) P Total (N=1616) P Elective (N=492) P Nonelective (N=1120) Mortality 223(8) 177(13) 128(8) 20 (4) 108 (10) Extreme/major loss of function 2021 (71) 992 (72) 1044(64.6) 238(48%) 803(72%) Cost ($10,000) 3.8 (± 4) 5.4 (± 5.4) 6.2(± 5.6) 4.6 (± 4) 6.9 (± 6) LOS (days) 5.8 (± 4.8) 8.5(± 6.2) 9.7(± 6.4) 7 (± 5) 10.9 (± 6.5) Data are presented as N (%) or mean(± SD).
Access to cancer chemotherapy and predictors of early mortality for childhood cancers in Uganda.
Authors: Innocent Mutyaba, Jackson Orem, Henry Wabinga, Warren Phipps, Corey Casper
Journal: Journal of Clinical Oncology (2013)

10070 Background: Although many childhood cancers respond well to chemotherapy, survival among children with cancer in sub-Saharan Africa is poor. Little is known about children’s access to specialized cancer care in SSA or factors contributing to poor early outcomes. We aimed: 1) To estimate the proportion of childhood cancer patients without access to chemotherapy in Uganda; 2) To describe 30-day survival rates and predictors of mortality post diagnosis among children with lymphoma or Kaposi sarcoma (KS), the two most common pediatric cancers in Uganda. Methods: A retrospective study of incident childhood (age&lt; 20 years) cancers diagnosed in Kyandondo County, Uganda from 2006-2009. We compared records of the population-based Kampala Cancer Registry (KCR) and patient records at the Uganda Cancer Institute (UCI), Uganda’s sole dedicated cancer treatment center. Patient characteristics were compared using Mann-Whitney and Pearson’s chi-square tests. Kaplan-Meier method and Cox regression models were used to describe mortality. Results: Of the 658 pediatric cases recorded in the KCR, only 238 (36%) presented to UCI. Patients identified in the KCR who did not present for care were more likely to be female, diagnosed in earlier years of the study, and to have a cancer other than KS or lymphoma. Of the 177 lymphoma and KS cases at UCI, 43.7% were Burkitt lymphoma (BL), 32.5% KS, and 23.8% other lymphomas. The post diagnosis 30-day overall survival rate was 77%. In multivariate analysis, age, gender, HIV status, platelets, and stage of cancer did not impact mortality. An increased risk of death at 30 days was predicted by presence of B-symptoms (HR=10.3, p=0.05), a diagnosis of BL compared to other lymphomas (HR=14.8, p=0.007), poor performance status (Karnofsky score &lt;70, HR=14.7, p&lt;0.001), and anemia (HR 1.5-fold per 1g/dL decrease in hemoglobin, p=0.002). Conclusions: Childhood cancer patients in Uganda have limited access to comprehensive care. Among those presenting to the UCI, a significant proportion die before they can benefit from chemotherapy. BL diagnosis, B-symptoms, performance status and hemoglobin level may be important predictors of early mortality among childhood cancer patients in sub-Saharan Africa.