tbuckley/cabot-search huggingface dataset:
Retrospective analysis of chemotherapy for the patients with advanced bladder adenocarcinoma.
Authors: Sung Yong Oh, Young Sam Kim, Ji Hyun Lee, Moonjin Kim, Young Jin Choi, Yong Mi Soel, Min Jae Park, Ki Hyang Kim, Lee Chun Park, Jung Hun Kang, In-Gyu Hwang, Hyo Song Kim, Seung Taek Lim, Sun Young Rha, Soonil Lee
Journal: Journal of Clinical Oncology (2015)

399 Background: By definition, primary adenocarcinoma of the bladder (PAB) is a malignant neoplasm derived from urothelium of the bladder showing histologically pure glandular differentiation. Because of its rarity, role of chemotherapy for metastatic adenocarcinoma of bladder is still questionable. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of metastatic PAB to evaluate the clinical findings at presentation, overall survival (OS) and progression-free survival (PFS) and prognostic factors. Methods: Eligible patients for this retrospective analysis were initially diagnosed with adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. Results: We retrospectively reviewed 29 patients who treated with chemotherapy as metastatic PAB at 10 Korean medical institutions from 2004 to 2014.The median age of patients was 58 years (range, 17 to 78 years) and 51.7% of the patients were female. Fifteen patients were urachal adenocarcinoma. Of 27 symptomatic patients, 22 experienced gross hematuria. Ten patients had two or more metastatic sites of the lungs (51.7%), peritoneum (41.4%), and ovary (20.7%), as the most common sites. Twelve patients were treated with 5-FU based chemotherapy, 5 were gemcitabine based, 3 were taxane and adriamycin based, and others. 13 of them achieved CR (10.3%) or PR (34.5%). Median PFS and OS for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6 months) and 24.5 months (95% CI, 1.2 to 47.8 months), respectively. In the prognostic factor analysis, the cases of urachal adenocarcinoma had worse tendency in PFS and OS (p=0.024 and P=0.046, respectively). Conclusions: Metastatic Despite most of chemotherapy, PFS and OS were short especially in urachal carcinoma, however, there were some long-term survivors, therefore, additional research on the predictive markers of several clinical, pathological differences and their treatments will be needed.
Recurrence score distributions in stage II colon cancers of African American (AA) and Caucasian (CA) patients.
Authors: Rangaswamy Govindarajan, James Posey, Calvin Y. Chao, Ruixiao Lu, Trafina Jadhav, Ahmed Y. Javed, Awais Javed, Fade A. Mahmoud, Raymond U. Osarogiagbon, Upender Manne
Journal: Journal of Clinical Oncology (2015)

613 Background: The 12-gene colon cancer assay (Oncotype DX) can identify groups of stage II colon cancer patients with lower or higher recurrence risk, but distribution of scores based on race/ethnicity has not been assessed. This study compared the distribution of Recurrence Score results and gene expression profiles between African American (AA) and Caucasian (CA) stage II colon cancer patients. Methods: Stage II colon cancer patients were identified from tumor registry data from four institutions: University of Arkansas for Medical Sciences, Little Rock; Veterans Administration Medical Center, Little Rock; Baptist Medical Center, Memphis, and University of Alabama at Birmingham. The 12-gene assay and mismatch repair (MMR) status were performed on formalin-fixed paraffin-embedded tissues by Genomic Health (Redwood City, CA). T-test and Wilcoxon test were used to compare data from the two groups (SAS Enterprise Guide 5.1). Results: Of the 244 subjects, there were 118 women (63 AA, 55 CA) and 126 men (59 AA, 67 CA). Median ages (years) were 66 for AAs and 68 for CAs. Age, gender, surgery year, pathologic T-Stage, tumor location, number of nodes examined, lympho-vascular invasion, and MMR status were not significantly different between groups (p&gt;0.05). Recurrence Score results between AAs (mean 27.9; SD 12.8) and CAs (mean 28.1; SD 11.8) were not statistically different (p&gt;0.05). The proportion of patients with high Recurrence Score values (≥41) was similar between the groups (17/122 AA; 15/122 CA). None of the gene expression variables, either single genes or gene groups, (cell cycle group, stromal group, BGN1, FAP, INHBA1, Ki67, MYBL2, cMYC3 and GADD45B) was significantly different between the racial groups (p&gt;0.05). After controlling for clinical and pathologic covariates, means and distributions of Recurrence Score and gene expression profiles still showed no statistical significance between racial groups (p&gt;0.05). Conclusions: In a cohort of AA and CA stage II colon cancer patients with similar clinical characteristics, the distribution of Recurrence Score results and gene expression data were similar between AA and CA patients.
Adoptive immunotherapy with autologous CD3/CD28-costimulated T cells after fludarabine-based chemotherapy in patients with chronic lymphocytic leukemia.
Authors: S. J. Schuster, C. Hosing, E. J. Shpall, B. Levine, N. Aqui, E. A. Chong, J. Svoboda, A. Gordon, J. D. McMannis, D. Bosque, J. Cotte, A. Brennan, Z. Zheng, L. Leinbach, Y. Xu, E. A. Veloso, W. Decker, C. M. Bollard, M. J. Keating, C. H. June
Journal: Journal of Clinical Oncology (2011)

2557 Background: Fludarabine-based therapies prolong survival of patients (pts) with chronic lymphocytic leukemia (CLL), but deplete CD4 T-cells causing immunosuppression which increases the risk of infection and may limit control of minimal residual disease by the immune system. Adoptive immunotherapy using autologous CD3/CD28-costimulated T-cells expanded ex vivo (ACTC) enhances immune reconstitution after fludarabine-based therapy of lymphoma (Schuster Blood abstract 2007). Methods: We conducted a multicenter phase I/II trial of ACTC following fludarabine-based therapy of CLL. After leukapheresis, pts received fludarabine-based therapy. 8 - 12 weeks after last chemotherapy, responding pts (CR, nPR, PR) received a single dose of ACTC prepared from autologous T-cells collected before chemotherapy. Results: 34 pts are enrolled (median age 62). To date, 13 pts are evaluable for studies of immune reconstitution at >90 days after ACTC. Prior to ACTC, 8 pts received FCR and 1 pt FR as first therapy, while 3 pts received FCR and 1 pt FCR + bevacizumab for previously treated CLL. Median ACTC dose was 6.81E+09 CD3 cells (range: 4.15E+08 - 1.05E+10). After chemotherapy prior to ACTC (d0), median CD4 count was 116 (range: 12-173); 90 days after ACTC (d90), median CD4 count was 384 (range 62-963) (p = 0.006; median fold CD4 increase 3.2, range 0.5 - 10.5). In contrast, median CD8 count did not change significantly (median: d0 = 79, range: 4-682; d90 = 257, range: 18-514). The increase in CD4 count between day 0 and day 90 was not dependent on ACTC dose. In 5/6 pts studied, significantly enhanced T-cell immunosynapse formation with autologous CLL (assay, Ramsay JCI 2008) was demonstrated by comparing percent synapse formation in post-ACTC product and pre-treatment peripheral blood T-cells (p < 0.005). There were no SAEs; 1 pt developed AIHA after ACTC. For 13 evaluable pts, at a median follow-up of 185 days (range: 92 - 497), PFS from ACTC is 91%. Conclusions: ACTC results in a dose-independent acceleration of CD4+ cell recovery after fludarabine-based chemotherapy compared to historical controls. Further studies of immune reconstitution following ACTC are in progress.
Effect of dosing interval on pharmacokinetics and safety of fentanyl pectin nasal spray.
Authors: Cuiping Chen, Shay Bujanover, Anita Gupta
Journal: Journal of Clinical Oncology (2014)

148 Background: Fentanyl pectin nasal spray(FPNS) contains fentanyl citrate and is approved for treatment of breakthrough cancer pain. Nasal delivery allows direct nasal epithelium-to-blood absorption of fentanyl, and thus rapid and effective pain relief. This study evaluated the effect of dosing interval on pharmacokinetics (PK) and safety/tolerability of FPNS. Methods: This was an open-label randomized study in healthy volunteers. Five treatments were administered under naltrexone block to the right nostril, with a ≥3-day washout period: 1 x 100 μg (A); 2 x 100 μg, 4-hr (B), 2-hr (C), and 1-hr apart (D); and 8 x 100 μg consecutively (E). Blood samples were collected and analyzed for plasma fentanyl concentrations. PK data were derived using a non-compartmental model method. Results: 13 subjects were enrolled, 10 (77%) completed the study. For the two-dose regimens, C max was higher after the second dose than the first; the increase was statistically significant for the 1- and 2-hr intervals, but not the 4-hr. There were no significant differences in AUC among them. Eight consecutive 100-µg doses resulted in an ~5-fold in C max and AUC of those of a single 100-µg dose, suggesting a less than dose proportional increase in rate (peak) and extent (AUC). No new adverse events (AEs) were observed. 53% of subjects reported ≥1 AE, with dizziness (11.9%) and somnolence (4.9%) most common. 12.9% of subjects discontinued due to AEs. All AEs rapidly decreased to sustained low levels after 4–5 weeks. Conclusions: FPNS at 100-800 µg was well tolerated. The shorter the dosing interval, the higher the second C max . Dosing interval had no effect on AUC. Exposure plateaued after 8 consecutive 100 µg doses to the same nostril, suggesting an additional safety feature of FPNS. [Table: see text]
Outcomes of critically ill cancer patients aged ≥ 70 years
Authors: M. Soares, C. G. Ferreira, J. I. F. Salluh, R. R. Luiz, J. R. Rocco, N. Spector
Journal: Journal of Clinical Oncology (2005)

6075 Background: Information about outcome predictors for older patients requiring critical care is limited. Our objective was to identify characteristics associated with increased six-month mortality. Methods: From May 2000 and May 2004, every cancer patient aged ≥70 years admitted to our medical-surgical intensive care unit (ICU) because of a severe illness was prospectively evaluated. Patients with acute coronary syndromes and those who had been considered cured from their cancer for > 5 years were excluded. Data were collected at admission and during ICU stay. Patients were categorized according to their age in three groups: 70–74 (n=114), 75–79 (n=60) and ≥ 80 (n=46) years old. Variables selected in the univariate analysis (p<0.25) were entered into a multivariable Cox proportional hazards regression model having as the dependent variable the six-month mortality. Results: A total of 220 patients were included and the mean age was 76±5 (range: 70–98) years. There were 185 (84%) patients with solid tumors and 35 (14%) patients had hematologic malignancies. The main reasons for ICU admission were sepsis (46%) and acute respiratory failure (11%). During ICU stay, 155 (70%) patients received mechanical ventilation and 26 (12%), hemodialysis. The hospital and six-month mortality rates were respectively, 59% and 64%. End-of-life decisions were taken in 37 (17%) patients. Baseline characteristics were similar for the three groups. The following variables were selected in the Cox model: performance status (PS) 3–4 [hazard ratio (HR)=1.67(95% confidence interval (CI)=1.1–2.54)]; uncontrolled newly-diagnosed cancer [HR=1.92(95% CI=1.22–3.02)]; cancer recurrence/progression [HR=1.90(95% CI=1.24–2.90)]; number of organ failures (OF) [HR=2.78(95% CI=1.60–4.82), for patients with 1–2 OF and HR=7.19(4.05–12.78), for patients with >2 OF]; and age ≥ 80 years [HR=1.91(1.25–1.93)]. Conclusions: The severity of acute organ failures, poor PS and uncontrolled cancer were the main determinants of increased six-month mortality. Among older critically ill cancer patients, those aged ≥ 80 years had a worse prognosis. Older patients should not be denied ICU care on the basis of age alone. No significant financial relationships to disclose.
Falls and frailty in prostate cancer survivors on androgen deprivation therapy.
Authors: Esther L Moe, Carolyn Borsch, Bharti Garg, Jessica C Dobek, Rumen Doggett, Julie Nicole Graff, Tomasz M. Beer, Kerri M Winters-Stone
Journal: Journal of Clinical Oncology (2016)

134 Background: Androgen deprivation therapy (ADT) treatment for prostate cancer is associated with muscle loss, weakness and weight gain that could lead to falls and frailty, but the prevalence of these conditions in prostate cancer survivors (PCS) is poorly understood. The aim of this study is to describe the prevalence of falls and frailty in PCS on ADT and their associations with modifying factors, such as age and timing of ADT. Methods: Health history, cancer treatment and falls were self-reported by 146 PCS on ADT (mean age: 74+8 years). ADT usage and current versus past usage was confirmed against electronic medical records. Frailty was determined by self-report to 5 questions asking about presence or absence of fatigue, weakness, mobility difficulty, comorbidities, and weight loss, which could represent sarcopenia. Presence of each condition was summed to categorize men into one of three frailty phenotypes: frail (3-5), pre-frail (1-2) or not frail (0) groups. Since fat gain, rather than weight loss, is common with ADT and can impact function we also recalculated frailty as an “obese frailty” phenotype substituting obesity (BMI &gt; 30 kg/m 2 ) for weight loss. Comparisons were performed using chi-square. Results: 38% of PCS on ADT experienced a fall in the past year and among fallers, 61% experienced a fall that resulted in an injury. Using the frailty phenotype, 29% of PCS were pre-frail and 10% were frail; however, using the obese frailty phenotype, 47% of PCS were pre-frail and 15% were frail. The absence of frailty was significantly less in older men than younger men using the frail (p = 0.013), but not obese frail phenotype (p = 0.54). Fall and frailty rates did not significantly differ between PCS who were current versus past users of ADT (p = 0.65 and 0.26 for falls and frailty, respectively). Conclusions: Regardless of the frailty phenotype used, the rate of falls and prevalence of frailty among PCS on ADT was greater than fall rate (25%) and the frailty prevalence (4%) reported in large community-based samples of similarly aged men. These data also suggest that falls and frailty may continue after men stop ADT use. Research to identify risk factors for falls and frailty in PCS on ADT is warranted so that effective interventions can be developed and tested.
The final results of the SWOG S9304 phase III intergroup trial’s pharmacogenetic analysis: Association of polymorphisms with survival and toxicity in stage II/III rectal cancer patients treated with 5-fluorouracil (5-FU) and pelvic radiation (RT).
Authors: P. M. Wilson, P. O. Bohanes, C. J. Rankin, J. K. Benedetti, C. M. Ulrich, S. R. Smalley, K. W. Makar, W. Zhang, T. Winder, Y. Ning, A. Gerger, L. Benhaim, R. El-Khoueiry, M. J. Labonte, C. D. Blanke, H. Lenz
Journal: Journal of Clinical Oncology (2011)

3542 Background: Postoperative chemoradiation (CRT) for locally advanced rectal cancers has improved overall survival (OS) and pelvic control. The SWOG S9304 (INT 0144) trial was designed to investigate the benefit of protracted venous infusion (PVI) versus bolus 5-FU before, during and after postoperative RT. All arms provided similar disease-free survival (DFS) and OS. We tested whether 16 functional polymorphisms in 12 genes (GSTP1, TS, ERCC1, VEGF, VEGFR, IL8, CXCR2, COX2, CCND1, EGF, EGFR, ICAM1) predicted survival and toxicity. Methods: Tissue samples from 746 stage II/III rectal patients enrolled in the S9304 phase III trial were analysed. Genomic DNA was extracted from FFPE tumor tissue. The polymorphisms were analysed using direct DNA-sequencing or PCR-RFLP. 383 out of 746 patients were still alive at the time of data analysis with a median follow-up of 123 months. The median age of our cohort is 61 years old (range 16-86). Most patients are males (64%) and Caucasian (93%). 30% have N0 tumor, 42% have N1 tumor and 27% have N2-3 tumor. Results: In univariate analyses, GSTP1-Ile105Val (rs1695) appeared to be associated with DFS and OS (p=0.02 for each, no adjustment for multiple comparisons). The 3-year DFS was 60% for the low activity genotype (Val/Val), 72% for Val/Ile and 65% for Ile/Ile patients (and 78%, 83% and 79% for OS respectively). In patients treated with PVI 5-FU combined with RT, the homozygous IL8-251A/A genotype (rs4073) was associated with a lower risk of any grade 3-5 toxicities compared to A/T or T/T genotypes (41%, 62% and 62%; p=0.04). Also, the homozygous VEGFR2 exon 11 A/A genotype (rs1870377) was associated with a higher risk of grade 3-5 esophagitis/stomatitis compared to A/T or T/T genotypes (17%, 5% and 8%; p=0.037) in the PVI arm only. However, exon 11 A/A was associated with lower risk in the bolus 5-FU arm (p=0.004). Conclusions: Our data suggest that GSTP1-Ile105Val is associated with DFS and OS and IL8-251A/T and VEGFR exon 11 with toxicity in rectal cancer patients treated with adjuvant CRT. Validation would be required to confirm these relationships.
Factors associated with use of chemoradiation for rectal cancer.
Authors: Mary E. Charlton, Chi Lin, Jane F Pendergast, Elizabeth A. Chrischilles, Robert B Wallace
Journal: Journal of Clinical Oncology (2012)

607 Background: Adjuvant or neoadjuvant chemotherapy (chemo) and radiation therapy (RT) have been the standard of care for virtually all patients with stages II/III rectal cancer for 20 years. However, recent analyses of the SEER database have demonstrated variation in treatment. Leveraging the clinical characteristics and patient beliefs available in the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) cohort, we determined the proportion and associated characteristics of those who received chemo and RT. Methods: We identified CanCORS patients with stage II/III rectal cancer with primary site resection, and used data from patient surveys and abstracted medical records to construct variables (age, gender, marital status, race, education, income, insurance status, stage, comorbidity, patient treatment beliefs, staging procedures, tumor location/size, types of providers seen). Results: Of the 310 eligible patients, 14% received neither chemo nor RT, 13% received chemo or RT, and 73% received both. Receipt of chemo and RT was associated with younger age, stage III, rectosigmoid junction (vs. rectum NOS) tumor, receipt of staging PET, and patient beliefs that chemo/RT would help them live longer, cure their cancer and help with symptoms. In a logistic model, age (&lt;55 vs &gt;65; OR=2.2, 95% CI: 1.31, 3.46), stage (III vs. II; OR=1.52, 95% CI: 1.06, 2.17), PET (OR=2.41, 95% CI: 1.15, 5.03) and rectosigmoid junction tumor (OR=1.59, 95% CI: 1.10, 2.29) were associated with receipt of chemo; similarly, age and rectosigmoid junction tumor were associated with RT. Of those who did not receive chemo or RT, 35% reported they did not think chemo/RT would help, 65% reported their doctor said chemo/RT would not help and 18% were worried about side effects; 65% reported they never saw a medical or radiation oncologist and 26% reported that no doctor ever discussed the possibility of chemo or RT. Conclusions: A significant proportion of patients with stage II/III rectal cancer did not receive chemo and RT, and a number of those reported that no doctor ever discussed the possibility of chemo or RT with them. While deviation from guidelines may be warranted and/or patient driven, further analyses should determine reasons for lack of recommended treatments.
Toll-like receptor (TLR) 7 and TLR8 expression in CD133+ cells in colorectal cancer and role for inflammation-induced TLRs in tumorigenesis and tumor progression.
Authors: M. Gasser, M. Grimm, M. Kim, A. Rosenwald, C. T. Germer, A. Waaga-Gasser
Journal: Journal of Clinical Oncology (2010)

10626 Background: Nuclear factor-kappaB (NF-κB) was identified as a key modulator in driving inflammation to cancer. Toll like receptor (TLR) stimulation results in activation of NF-κB and mitogen-activated protein kinases (MAPKs) that have been shown to recruit mitotic and cyclooxygenase-2 (COX-2) induced pathways in carcinogenesis. Here we asked whether different TLR, COX-2 and stem cell marker expression profiles in colorectal cancer (CRC) provide further evidence for this hypothesis from a clinical perspective. Methods: We analysed gene and protein expression of TLR7-10, COX-2, and CD133 in CRC patients (n=65). FACS and immunofluorescence staining of TLR7 and TLR8 were specifically used to detect expression in CD133+ colon cancer initiating cells. Results: Gene analysis demonstrated significantly upregulated TLR7, TLR8, TLR9, TLR10, and COX-2 expression in CRC tumor tissues. Immunofluorescence double staining and FACS analysis of isolated tumor cells from primary tumors and from a tumor cell line showed co-expression of TLR7 and TLR8 with CD133 and gave evidence for a subpopulation of colon cancer-initiating cells. In multivariate analyses TLR8 expression was found to be an independent prognostic factor. We found significantly increased TLR7 and TLR8 expression in CD133+ colon cancer cells. Conclusions: Persistent TLR-specific activation of NF- κB in CRC and particularly in tumor initiating cells may thus sustain further tumor growth and progression through perpetuated signalling known from inflammatory and tissue repair mechanisms with consecutive self-renewal in pluripotent tumor cells. Activation through self-ligands or viral RNA fragments may putatively maintain this inflammatory process, suggesting a key role in cancer progression. No significant financial relationships to disclose.