tbuckley/cabot-search huggingface dataset:
Impact of preoperative neutrophil to lymphocyte ratio on long-term survival in patients with esophageal squamous cell carcinoma.
Authors: Kenichi Kamachi, Soji Ozawa, Akihito Kazuno, Hiroyasu Makuuchi, Junya Oguma, Yasusi Yamasaki, Yamato Ninomiya
Journal: Journal of Clinical Oncology (2015)

33 Background: Elevated neutrophil to lymphocyte ratio (NLR) reflects patients’ inflammation status and closely relates to tumor progression. The aim of this study was to evaluate the clinical significance of the preoperative NLR in patients who undergo an esophagectomy for esophageal squamous cell carcinoma. Methods: A total of 340 patients who underwent an esophagectomy for esophageal squamous cell carcinoma between 2003 and 2008 were retrospectively reviewed. The NLR ≥ 3 was considered to be elevated and the patients were divided into two groups. The overall and disease-free survival curves of the two NLR groups were determined using the Kaplan-Meier method and were compared using a log-rank test. A cox proportional hazards regression analysis was used for the univariate and multivariate analyses. Results: The study included 306 males and 34 females. Seventy-two patients (21%) had an elevated NLR. The 5-year overall survival for patients with high NLR was significantly worse than that for patients with normal NLR (41% vs 69%, p &lt; 0.001). The 5-year disease-free survival for patients with high NLR was significantly worse than that for patients with normal NLR (41% vs 59%, p &lt; 0.001). In multivariate analysis, a high NLR (HR 1.76, 95% CI 1.19-2.60, p = 0.005), an upper tumor location (HR 1.97, 95% CI 1.18-3.30, p = 0.010), an advanced T stage (HR 2.71, 95% CI 1.70-4.31, p &lt; 0.001), and a larger number of metastatic lymph nodes (HR 4.38, 95% CI 1.18-3.30, p &lt; 0.001) were independent predictors of poor overall survival. Conclusions: Our results suggested that the elevated preoperative NLR predicts poor overall and disease-free survival after an esophagectomy for esophageal squamous cell carcinoma.
A phase I dose-finding study of vorinostat (V) combined with capecitabine (X) and cisplatin (P) as first-line therapy in patients with advanced gastric cancer.
Authors: Changhoon Yoo, Min-Hee Ryu, Baek-Yeol Ryoo, Dong Hoe Koo, Inkeun Park, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2013)

73 Background: The purpose of this trial is to determine the recommended dose (RD) of vorinostat (V), a histone deacetylase inhibitor, in combination with capecitabine (X) and cisplatin (P) and to explore feasibility of V-XP at the RD in advanced gastric cancer. Methods: The standard 3+3 method was used to determine the RD of 3-weekly V-XP during the first cycle. The doses of X (days 1-14, p.o.), P (day 1, i.v.), and V (days 1-14, p.o.) were escalated as following scheme; X 1,600 mg/m 2 /day, P 60 mg/m 2 , V 300 mg/day in level 1; X 1,600 mg/m 2 /day, P 60 mg/m 2 , V 400 mg/day in level 2A; X 2,000 mg/m 2 /day, P 60 mg/m 2 , V 300 mg/day in level 2B; X 2,000 mg/m 2 /day, P 60 mg/m 2 , V 400 mg/day in level 3; X 2,000 mg/m 2 /day, P 80 mg/m 2 , V 400 mg/day in level 4. Results: A total of 24 patients were enrolled. Median age was 50 years (range, 25-66), and 11 (46%) were male. Dose limiting toxicity (DLT) was noted in 1 of 6 in level 1 (Grade 4 thrombocytopenia), 0 of 3 in level 2A, 1 of 6 in level 2B (Grade 3 fatigue), 1 of 6 in level 3 (Grade 3 stomatitis) and 2 of 3 in level 4 (Grade 4 thrombocytopenia, and discontinuation of X or V more than 25% of prescribed dosage due to Grade 3 anorexia and Grade 3 fatigue). Level 4 was maximal tolerated dose, and RD was determined as level 3. Six additional patients were enrolled at level 3 to confirm the feasibility, and DLT was not occurred. In 12 patients who received dose level 3, median 6 cycles (range, 3-10) of chemotherapy were given and most frequent Grade 3/4 toxicities were neutropenia (n=5, 42%) and anorexia (n=3, 25%). In overall, the objective responses were confirmed in 9 (47%) out of 19 patients with measurable lesions. With a median follow-up of 9 months, median progression-free survival was 7 months (95% confidence interval, 4 to 10 months), and median overall survival was not reached. Conclusions: Major DLTs of V-XP were thrombocytopenia, fatigue, anorexia and stomatitis. The 3-weekly schedule of X (2,000 mg/m 2 /day on day 1-14), P (60 mg/m 2 on day 1), and V (400 mg/day on day 1-14) is recommended for further development of this regimen in patients with advanced gastric cancer. Clinical trial information: NCT01045538.
Quality appraisal of clinical validation studies for multigene prediction assays of chemotherapy response in early-stage breast cancer.
Authors: N. M. Kuderer, E. Culakova, M. Huang, M. S. Poniewierski, G. S. Ginsburg, W. T. Barry, P. K. Marcom, N. Ready, A. P. Abernethy, G. H. Lyman
Journal: Journal of Clinical Oncology (2011)

3082 Background: Despite enthusiasm concerning the potential for genomic predictors of chemotherapy response, considerable uncertainty about optimal research methodology remain. A comprehensive literature search and quality appraisal of multigene signatures predictive of response to chemotherapy in breast cancer were initiated as part of NIH ARRA grant funding. Methods: Validation studies of multigene signatures for prediction of chemotherapy response in breast cancer were sought. A priori inclusion/exclusion criteria and data extraction were applied in a dual blinded fashion. Conflict resolution was based on consensus among three reviewers. Detailed information on the genomic assay, patient population, specific chemotherapeutic agents, clinical prognostic measures, and study outcomes were extracted. In addition, a formal quality appraisal was conducted, utilizing a modified quality scoring system from EGAPP, REMARK, and the STREGA Statements. Results: A total of 37 fully eligible studies were identified. These papers present results on 68 multigene predictors. The primary outcome is treatment response in 51 (75%) analyses and time to recurrence or survival in 17 (25%). A high percentage of studies fail to report the following quality measures: sample size rationale (95%), patient selection (49%), study protocol (81%), quantity/quality of specimen tumor content (33%), assessment of prognostic subgroups (70%), adjustment for false discovery rate (63%), blinding of assay results to clinical outcome (95%), model ROC (56%), complete model specification (96%) or source code for analysis (96%), and clinical utility assessment in univariate (59%) or multivariate (62%) analysis. On a 3-point scale from poor to good, studies were graded as poor to fair for patient characteristics (41%), study endpoints (30%), tissue handling (65%), statistical methods (76%), and statistical model development (81%). Conclusions: Validation studies of multigene signatures of chemotherapy response in patients with early-stage breast cancer vary substantially in terms of study design, methodology, and most studies exhibit major reporting and quality limitations.
Symptom control in cancer using an integrative treatment approach: The Cancer Treatment Centers of America experience
Authors: C. G. Lis, T. C. Birdsall, J. F. Grutsch, D. Gupta
Journal: Journal of Clinical Oncology (2008)

20656 Background: Patients undergoing cancer treatment suffer from symptoms that are distressing in nature and can interfere with patients’ quality of life (QoL). One of the major goals of palliative medicine in cancer is to control such symptoms. We investigated whether 3 months of therapy at our integrative cancer treatment center could lead to an improvement in patient symptoms. Methods: A case series of 294 cancer patients treated at Cancer Treatment Centers of America (CTCA) at Midwestern Regional Medical Center, Zion, Ill, between 04/01 and 11/04 completed the QoL questionnaire at baseline and 3 months. In addition to receiving aggressive cancer-directed therapy, patients underwent a comprehensive program of nutritional, spiritual, physical, naturopathic, and emotional support. Patient symptoms were evaluated using EORTC QLQ-C30 symptom subscales. The mean symptom scores were compared using paired samples t test across the 2 time periods at baseline and 3 months. Results: Of 294 patients, 106 were males and 188 females. 91 had breast cancer, 52 colorectal, 43 lung, 25 pancreas, 13 prostate, and 70 had other cancers. 112 were newly diagnosed and 182 had received prior treatment elsewhere. Of 112 newly diagnosed patients, 7 had stage I disease at diagnosis, 20 had stage II, 26 had stage III and 59 had stage IV. Fatigue, pain, dyspnea, insomnia, and constipation were statistically significantly improved at 3 months while others were well-maintained (Table 1). Conclusions: In our integrative treatment setting, we observed a statistically significant improvement in several cancer related symptoms among these challenging patients during the 3 months of treatment at our center. We are now more closely examining the impact of specific integrative and supportive care regimens on the QoL outcomes of our patients. Table 1. EORTC Symptoms Baseline 3-month EORTC Symptoms Mean (SD) P-value Fatigue 43.6 (26.6) 37.6 (23.5) < 0.001 Nausea 11.6 (19.9) 14.1 (19.8) 0.06 Pain 34.8 (30.7) 22.9 (26.8) < 0.001 Dyspnea 24.3 (28.9) 20.3 (25.5) 0.01 Insomnia 43.1 (34.2) 29.0 (29.1) < 0.001 Loss of appetite 25.5 (30.4) 24.6 (29.3) 0.65 Constipation 20.6 (29.1) 15.9 (25.3) 0.01 Diarrhea 12.7 (23.9) 13.2 (22.7) 0.78 No significant financial relationships to disclose.
Commercial laboratory testing of ERCC-1 expression in non-small lung cancer: Clinical implications of discordant results.
Authors: J. G. Schneider, N. Farhadfar, A. Sivapiragasam, M. Geller, L. Ogden, E. Selbs
Journal: Journal of Clinical Oncology (2011)

e21176 Background: Excision repair cross-complementation group 1 (ERCC-1) over-expression by non-small cell lung cancer (NSCLC) has been reported to predict for resistance to platinum-based therapies. Several commercial laboratories now offer ERCC-1 testing to facilitate clinical decision making, but test results are not well standardized. After observing substantial differences in the frequency of ERCC-1 over-expression reported by three different commercial laboratories, we chose to evaluate their concordance rates when testing identical patient tumor specimens. Methods: ERCC-1 testing was performed by three different commercial laboratories, herein referred to as labs A, B and C. Labs A and B determined ERCC-1 protein expression by immunohistochemistry (IHC) using the same 8F1 antibody reagent, while lab C determined ERCC-1 mRNA expression levels by RT-PCR. Labs B and C agreed to perform repeat testing of ERCC-1 on tumor specimens previously tested at other labs without charge for the purposes of this comparative study. All specimens were from patients with NSCLC. Results: Independent laboratory ERCC-1 over-expression rates were: 81% at A (n= 32); 44% at B (n=36) and 41% at C (n= 17). Of 20 specimens performed by both lab A and lab B, just 12 were concordant (8 + and 4 - for over-expression). All 8 of the discordant cases were reported as over-expressing by A, but not by B. The results reported by these two labs were shown to correlate poorly (kappa: <0.3; 95% CI: 0.17-0.55) and the difference between ERCC-1 over-expression reported by lab A (80%) and lab B (40%) on identical tumors was highly significant (P=0.008). These discordant results could not be explained by the different IHC threshold criteria used by these two labs to define ERCC-1 over-expression. Although labs B and C had similar independent rates of ERCC-1 over-expression, 4 of 5 specimens tested at both labs so far were discordant. Conclusions: Current rates of discordance in the reporting of ERCC-1 over-expression are unacceptably high. Until lab discrepancies are resolved and ERCC-1 results are standardized to a reliable clinical endpoint, the test should not be used to determine treatment for NSCLC patients.
Preoperative D-dimer measurement for assessment of venous thromboembolism in colorectal cancer cases.
Authors: Kazuha Hatta, Shimpei Ogawa, Yoshiko Bamba, Tomoichiro Hirosawa, Michio Itabashi, Shingo Kameoka
Journal: Journal of Clinical Oncology (2015)

TPS799 Pre-operative D-dimer Measurement for Assessment of Venous Thromboembolism in Colorectal Cancer Cases Background: In Japan, the incidence of venous thromboembolism (VTE) has recently been increasing and gaining attention. Operation or Malignancy is one of the major factors leading to VTE. Thus, there is an urgent need for appropriate pre-operative risk assessment and thorough preventive measures. Caprini score has proven effective and is widely used, however, since the point system is a little cumbersome, there is a strong demand for a risk assessment system that can be more easily used extensively. Methods: This study involving general surgery cases was performed in our department a period of one-half of a year. In order to screen for pre-operative VTE, D-dimer level was measured in 471 general surgical cases (143 colorectal cancer cases, and 99 the other cancer cases, 229 non-cancer cases), and the cases with high D-dimer levels (&gt;1 μg/mL) underwent venous duplex scanning and enhanced computed tomography. Caprini score was measured in all cases for individual VTE risk assessment. By comparing D-dimer levels and Caprini score, the significance of D-dimer testing for VTE screening and risk assessment was reviewed. Results: D-dimer levels were measured in 471 general surgical cases. The 157 cases with high D-dimer levels (&gt;1 μg/mL) underwent venous duplex scanning and enhanced computed tomography. Pre-operative VTE was detected in 16 cases, and the overall prevalence of VTE was 3.4%. For individual VTE risk assessment, Caprini score was derived for all 471cases. Average Caprini score was 5.54 (±1.78) in the high D-dimer group and 4.67 (±1.76) in the low D-dimer group. Using the t-test, Caprini score increased with increasing D-dimer level (P=&lt;0.001). Focused on 143 colorectal cancer cases, 55 with high D-dimer levels and pre-operative VTE detected in 5 cases (3.5%), and Caprini score was 6.51(±1.46) in the high and 5.91(±1.28) in the low (P=0.0141). Conclusion: This observational study suggested that simple D-dimer testing might be worth discussing and considering not only to screen for pre-operative VTE, but also to assess the perioperative VTE risk levels.
A Single-Centre Experience of Clinico-Pathological Features, Risk Factors and Treatment Outcome of Posttransplant Lymphoproliferative Disorders (PTLD) after Renal Transplantation.
Authors: Esben Sondergaard, Charlotte Strandhave, Robert S. Pedersen, Kaj A. Jorgensen, Knud Bendix, Francesco d’Amore
Journal: Blood (2007)
Administration of Tumor-Specific Cytotoxic T Lymphocytes Engineered to Resist TGF-ß to Patients with EBV-Associated Lymphomas
Authors: Catherine M Bollard, Gianpietro Dotti, Stephen Gottschalk, Enli Liu, Andrea Sheehan, Martha Mims, Hao Liu, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop, Cliona M Rooney
Journal: Blood (2010)
The acute effects of palonosetron on ECG parameters in patients with cancer.
Authors: C. Akosman, C. Ordu, B. Oyan
Journal: Journal of Clinical Oncology (2011)

e19693 Background: Serotonin receptor (5HT3) antagonists like dolasetron, ondansetron, granisetron and tropisetron have shown to cause QT prolongation. However, there is few data about palonosetron-related cardiac side effects. In this study, we aimed to determine the acute effects of palonosetron on QT interval, heart rate and arterial blood pressure. Methods: 101 cancer patients (51 female, 50 male) were enrolled to the study. Pts with acute ischemic heart disease and arrhythmia were excluded. Pts received 0.25 mg of palonosetron for prevention of chemotherapy-induced emesis. Standard 12-lead ECG recordings, heart rate (HR) and blood pressure (BP) measurements were performed at baseline, 30 minutes and 60 minutes after the palonosetron administration. By using Bazzet Formula, corrected QT interval (QTc) and QT dispersion (QTd) were calculated. Results: The mean age of pts was 54 ±13 years. In whole patient group, there were no differences in QTc, QTd measurements at 30 and 60 minutes after palonosetron injection when compared to baseline measurements. However, HR significantly decreased at 30 and 60 minutes after palonosetron injection. Compared with the baseline, systolic BP decreased nonsignificantly at 30 minute and then returned to baseline levels at 60 minute after palonosetron administration. When body surface area was taken into consideration, patients who received palonosetron over a dose of 0.13 mg/m2 had a decrease of QTc, HR and systolic BP at 30 minute and increase of these parameters at 60 minute. Conclusions: Palonosetron does not cause QT prolongation in standard doses, but causes a decrease in heart rate. Although there is no significant risk of QT prolongation with palonosetron, caution should be taken when QT prolonging drugs are used concomitantly and in patients with long QT syndrome. The routine administration of the drug at a fixed dose without any adjustment for body weight and body surface area can increase the risk of cardiac side effects in lean patients.
Palliative Care Always as a massive open online course (MOOC) to build primary palliative care in a global audience.
Authors: Erika Lauren Tribett, Kavitha Ramchandran, Joshua Fronk, Judy Passaglia, Kelly Bugos, Manuela Kogon, Lori Klein, Ellen Brown, Sandy Chan, Lynn Hutton, Grace Lyo, Kimberly Frost Sickler
Journal: Journal of Clinical Oncology (2016)

123 Background: Primary palliative care (PC) is critical to improve access to PC from the point of diagnosis. Still, barriers exist to providing primary PC worldwide, including a lack of awareness, time, and training. Interactive online learning experiences can help overcome these. This project describes a massive open online course (MOOC)--Palliative Care Always--designed to build primary PC skills in a global audience. Methods: A team of PC providers and online instructional experts developed 12 modules that included: patient scenes, brief lectures, empathy exercises, and Google Hangout discussions. Course objectives included awareness of PC, practicing effective communication skills, basic symptom assessment and management. The target audience included oncology clinicians; secondary audience included patients and families. The MOOC launched January-April 2016. Participant engagement, satisfaction and self-reported knowledge were assessed through pre- and post-surveys. Multiple choice assessments captured knowledge gain. Follow-up assessments will be distributed three months post-MOOC. Results: By April 2016, the course reached 1,300 participants from 91 countries. 54% were from the US, followed by India, Brazil, and Canada. 76% were healthcare professionals, the majority being nurses (40%), physicians (19%) and social workers (13%). The remaining 24% included patient, caregivers, and others interested in PC. Top reasons for enrolling were interest in PC, personal growth and job relevance. On average, 27% of enrollees actively engaged week-over-week. Eighty-six percent of respondents were “very satisfied” with the amount learned, and over 50% cited learning “a great deal” in: communicating difficult news, goals of care, psychosocial and hospice care. 93% cited being “very likely” to recommend the course. Conclusions: Interactive MOOC experiences have the potential to build PC awareness, primary skills and global PC networks. Upcoming iterations will incorporate: accommodations for varying levels of PC knowledge; additional opportunities for interaction between participants, including social networks; blended learning; and evaluation of impact on practice and healthcare outcomes.
The role of FGF signaling in VEGF-pathway targeted therapy resistance: Data from patients and model systems.
Authors: Thai Huu Ho, Carla L. Warneke, Anh Hoang, Pheroze Tamboli, Fen Wang, Eric Jonasch
Journal: Journal of Clinical Oncology (2013)

386 Background: Angiogenesis plays a role in tumor growth and is partly mediated by factors in both the fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) pathways. Brivanib inhibits both VEGF receptor 2 and FGF receptors (FGFR)-1/2. Methods: Nephrectomy material from 40 patients with metastatic renal cell carcinoma (RCC) receiving sorafenib ± interferon was assessed by immunohistochemical (IHC) staining. The Ariol imaging platform was used to stratify the specimens based on intensity of staining for FGF biomarkers: FGFR-1 and fibroblast growth factor receptor substrate 2 (pFRS2). The relationship between fibroblast growth factor pathway marker levels and progression-free survival (PFS) was analyzed using Kaplan-Meier and Cox proportional hazards regression methods. To assess the efficacy of dual targeting of VEGF and FGF receptor signaling by brivanib, we treated a xenograft RCC mouse model with sunitinib, brivanib, or sunitinib followed by brivanib. Results: Our analysis indicated that more intense FGFR-1 staining was associated with shorter PFS (p = 0.0452), and that pFRS2 staining were not significantly associated with PFS (p = 0.2610). FGF pathway activation was associated with decreased PFS in patients with metastatic RCC treated with sorafenib. Xenograft mice were treated with 20 mg/kg sunitinib and after an initial stabilization phase, resistance developed by day 20. A switch to 30 mg/kg brivanib prolonged the stabilization phase after progression on sunitinib (p = 0.0033). Conclusions: The PFS of patients treated with sorafenib is associated with FGF pathway activation. In a xenograft RCC mouse model, brivanib overcame the tumor escape after initial treatment with sunitinib. Switching from sunitinib to brivanib at the time of tumor escape prolonged the stabilization phase and overcame a sunitinib-induced resistance phenotype. The results suggest that FGF pathway activation mediates both innate and acquired tumor resistance to VEGF receptor inhibition. The efficacy of dual inhibition of FGF and VEGF in the subset of patients with increased FGF activation prior to treatment requires further study.