tbuckley/cabot-search huggingface dataset:
Comparison of patient-reported symptoms and health behaviors to clinician documentation among patients with breast cancer in follow-up care.
Authors: M. E. Melisko, M. Bock, D. H. Moore, D. Hamolsky, M. Mendelsohn, L. Lawson, H. Orlando, H. S. Rugo, A. J. Chien, J. W. Park, M. M. Moasser, P. N. Munster, A. Goga, L. Esserman
Journal: Journal of Clinical Oncology (2011)

9133 Background: Breast cancer (BC) patients (pts) experience symptoms from disease and treatment. While detection of recurrence is fundamental to follow up care, symptom management is equally important. UCSF has implemented a secure online health questionnaire enabling BC pts to update their health history and symptoms. A report summarizing this information is placed in the chart for clinician review prior to visits. Methods: We randomly selected a sample of stage I-III BC pts (n=41) who completed the questionnaire prior to a medical oncology visit and who consented to have data used for research. We conducted a chart review calculating the number of symptoms reported in the questionnaire, the clinic note only, and both questionnaire and clinic note, excluding chronic symptoms addressed previously. We used a paired t-test to compare the number of symptoms reported in the questionnaire compared to those documented by the clinician. We used a regression plot to determine whether the fraction of symptoms agreed upon by the pt questionnaire and provider clinic note affected symptom management. We also compared self-reported data on exercise and alcohol consumption to documentation of these lifestyle factors in clinic notes. Results: Pts reported significantly more symptoms using the online questionnaire (mean=4, range 0-13) than were documented by the provider in clinic notes (mean=2.8, range 0-9; p=0.028 for the difference). A regression plot comparing the percentage of symptoms agreed upon by the pt and provider and the percentage of symptoms addressed yields a slope of 0.50 (95% CI 0.22 to 0.78, p=0.001). Information on exercise behavior and alcohol consumption was completed in 100% of the online questionnaires, but was documented in only 12/41 (29%) and 27/41 (66%) of charts reviewed. In 6/27 (22%) charts where alcohol consumption was documented, there was discordance between pt and clinician reporting. Conclusions: The integration of the online health questionnaire into clinical practice facilitates symptom and lifestyle factor reporting, may increase the percentage of symptoms addressed, and may identify research targets for improved symptom management.
Will a Peripheral Blood (PB) Sample Yield the Same Diagnostic and Prognostic Cytogenetic Data as the Concomitant Bone Marrow (BM) In Myelodysplasia? An International Study Comparing Cytogenetics and Interphase FISH Using Parallel PB and BM Samples
Authors: Athena M Cherry, Marilyn L. Slovak, Lynda J Campbell, Kathy Chun, Virginie Eclache, Detlef Haase, Claudia Haferlach, Anne Hagemeijer, Barbara Hildebrandt, Anwar M. Iqbal, Suresh C. Jhanwar, Michelle Lebeau, Kazuma Ohyashiki, Francesc Solé, Daniel L. Van Dyke, Gordon Dewald
Journal: Blood (2010)
Early transcriptional and epigenetic regulation of CD8+ T cell differentiation revealed by single-cell RNA sequencing
Authors: Boyko Kakaradov, Janilyn Arsenio, Christella E Widjaja, Zhaoren He, Stefan Aigner, Patrick J Metz, Bingfei Yu, Ellen J Wehrens, Justine Lopez, Stephanie H Kim, Elina I Zuniga, Ananda W Goldrath, John T Chang, Gene W Yeo
Journal: Nature Immunology (2017)
Concurrent chemoradiotherapy with gemcitabine and S-1 for unresectable locally advanced pancreatic adenocarcinoma: A phase I study.
Authors: T. Ioka, N. Fukutake, K. Ikezawa, S. Tanaka, S. Nakamura, K. Nishiyama
Journal: Journal of Clinical Oncology (2011)

305 Background: The primary objective of this study is to assess the toxicity of concurrent radiotherapy with a combination of gemcitabine (GEM) and S-1 for unresectable locally advanced pancreatic cancer. Methods: Chemotherapy-naive patients with histologically or cytologically proven unresectable locally advanced pancreatic adenocarcinoma were enrolled to this trial. The patients received gemcitabine intravenously over 30 min on days 1 and 8 and S-1 orally b.i.d. from days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/msq/week) and S-1 (mg/msq/day) at five dose levels: 600/50 (level 1), 600/60 (level 2), 800/60 (level 3), 800/70 (level 4) and 1000/70(level 5). Radiation therapy was delivered through four fields as a total dose of 50.4 Gy in 28 fractions over 5.5 weeks, and no prophylactic nodal irradiation was given. Dose-limiting toxicity (DLT) was defined as grade 4 thrombocytopenia, grade 4 neutropenia, or grade 3 nonhematologic toxicity. All patients were evaluated for response with RECIST criteria by a radiologist. Results: Fifteen patients were enrolled in this study between 05/12 and 07/05. Treatment was well tolerated; 14 patients completed all protocol therapy, but one cannot because of anorexia. The maximum-tolerated dose was level 2, Gem 600mg/ S-1 60mg. Six patients experienced DLT (four patients with anorexia and two patients with Gr4 neutropenia). Response rate (RR) was 33.3% and disease control rate was 87.0%. And 1-year and 2-year survival rate was 86.7% and 44.4% respectively. Conclusions: The chemoradiation therapy a combination of gemcitabine (GEM) and S-1 can be delivered almost safely for unresectable locally advanced pancreatic cancer. No significant financial relationships to disclose.
The role of mTOR and hypoxia pathway activation in promoting tumorigenesis of intrahepatic cholangiocarcinoma.
Authors: A. J. McRee, S. Chen, B. H. O'Neil, K. Rathmell
Journal: Journal of Clinical Oncology (2011)

218 Background: Cholangiocarcinoma (CC) is an aggressive malignancy that often presents in advanced stages with poor response rates to conventional chemotherapy. Recent studies of CC have uncovered several oncogenes and tumor suppressors implicated in the transition from biliary hyperplasia to malignancy. We have developed a mouse model of intrahepatic CC that results from deletion of the phosphatase and tensin homolog (PTEN) gene and the von Hippel Lindau (VHL) gene, a tumor suppressor that regulates hypoxia inducible factor (HIF) expression. Immunohistochemical (IHC) analysis of the liver tumors revealed strong staining of p-AKT and HIF-1α. This study aims to determine the expression of the same downstream targets p-AKT and HIF1α in a dataset of human CC tumors. Methods: Archived samples from 33 CC patients were sectioned and stained via IHC for p-AKT and HIF1α expression. Samples were evaluated using a proportion score (PS) for neoplastic cells on a scale of 0 to 5, and an intensity score (IS) expressed on a scale of 0 to 3. Normal liver samples were used as controls. Results: Using a combined score of at least 5 to determine positive expression, 18% of the 33 evaluated samples displayed positive p-AKT expression and 61% displayed positive HIF1α expression. 15% of cases displayed concomitant expression of both p-AKT and HIF1α, while 39% of evaluated samples had expression of neither protein. Conclusions: Delineating the molecular pathways that lead to CC formation is crucial in developing novel therapeutics for a disease in drastic need of more effective therapies. Our group has developed a mouse model of intrahepatic CC that suggests a synergistic role of PTEN and VHL in the tumorigenesis of CC with upregulation of p-AKT and HIF1α. A modest percentage of a cohort of human samples demonstrates a similar expression pattern, potentially defining a distinct molecular subtype of this cancer with implications for tumor behavior and response to treatment. Future studies will correlate these molecularly-defined subtypes to the clinicopathologic characteristics of the tumors with the ultimate aim of establishing biomarkers of disease prognosis as well as potential predictive indicators of treatment activity. No significant financial relationships to disclose.
Efficacy of belinostat in advanced hepatocellular carcinoma (HCC): Phase I and II multicentered study of the Mayo Phase 2 Consortium (P2C) and the Cancer Therapeutics Research Group (CTRG).
Authors: Stephen Lam Chan, Hyun Cheol Chung, Ling-Zhi Wang, Robert S. C. Lim, Joel Picus, Michael J. Boyer, Charles Erlichman, Anthony T. C. Chan, Boon C. Goh, Winnie Yeo
Journal: Journal of Clinical Oncology (2012)

259 Background: Belinostat is a novel histone deactylase inhibitor which demonstrates preclinical activity in HCC. We report the results of a phase I/II study on belinostat in patients (pts) with unresectable HCC. Methods: Major eligibility criteria included histologically confirmed HCC not amenable to curative treatment; PS ≤ 2; adequate organ function; prior systemic therapy was allowed. In the phase I portion, belinostat was given i.v. on D1-5 every 3 weeks with dose levels of 600, 900, 1200 and 1400 mg/m 2 /day. In the phase II portion, belinostat was tested at the MTD. Primary endpoint was PFS and secondary endpoints were RR according to RECIST and OS. CT assessment was done every 8 weeks. Results: Phase I portion: a total of 18 pts were accrued; no DLTs were observed at 1400mg/m 2 /day for 5 days, and this dose was selected for phase II development. Phase II portion: 42 pts were accrued; Median age = 57.5 years; 41 had Child’s A function, and 24 pt had ECOG 0. Sixteen (38%) had previous systemic therapy, and 21 (50%) had previous transarterial therapy. Median follow-up was 20.0 months. The PR and SD rate was 2.4% (1/42) and 45.2% (19/42). Median PFS was 2.64 months (95%C.I. 1.55-3.17) and OS was 6.60 months (95%C.I. 4.53-11.60). Grade 3 or higher toxicities (&gt;5% rate) were abdominal pain (9.5%), (9.5%) hyperbilirubinemia (9.5%), raised ALT (9.5%); anemia (7.1%) and vomiting (7.1%). Conclusions: Belinostat demonstrates disease stabilization in a predominantly pretreated population of pts with unresectable HCC with an acceptable safety profile. Further randomized studies are warranted.Supported in part by N01-CM-62205.
Bosutinib (BOS) versus imatinib (IM) in patients (pts) with chronic phase chronic myeloid leukemia (CP CML) in the BELA trial: 18-month follow-up.
Authors: C. Gambacorti-Passerini, J. E. Cortes, D. Kim, H. Kantarjian, N. Khattry, J. H. Lipton, C. Powell, P. Harris, A. M. Countouriotis, T. H. Brummendorf
Journal: Journal of Clinical Oncology (2011)

6509 Background: The phase 3 BELA study compared BOS (competitive dual Src/Abl kinase inhibitor) with IM in newly diagnosed CP CML. Methods: 502 pts with CP CML stratified by Sokal score and region were randomized to oral BOS 500 mg/d (n = 250) or IM 400 mg/d (n = 252). Study design and endpoints have been described (Gambacorti, ASH 2010). Efficacy analyses included all randomized pts (ITT); safety analyses included all treated pts. Results: Median treatment duration was 16.6 mo for BOS and 16.8 mo for IM; 69% and 78% of pts, respectively, were still receiving therapy. CCyR rates at 1 y were 70% (BOS) and 68% (IM); cumulative CCyR rates by 1 y were 79% (BOS) and 75% (IM). MMR rates at 1 y were higher for BOS vs IM (39% vs 26%; P = 0.002), as were cumulative MMR rates by 1 y (47% vs 32%; P <0.001). Time to CCyR and MMR were significantly shorter with BOS (P <0.001 for both). Transformation to accelerated/blast phase occurred in 4 (2%) pts on BOS and 10 (4%) pts on IM (P = 0.053). Common treatment-emergent adverse events (TEAEs; ≥20% of pts) observed with BOS and IM, respectively, were diarrhea (68%, 22%), vomiting (31%, 14%), nausea (31%, 35%), rash (21%, 16%) and muscle cramps (4%, 20%). Pleural effusions were seen in 3% of BOS pts (no IM pts). Grade ≥3 TEAEs (≥2% of pts) seen with BOS were diarrhea (10%), vomiting (3%), pneumonia (3%), and dyspnea (2%). Median cumulative duration of diarrhea was 33 d for BOS and 17 d for IM. Grade ≥3 lab abnormalities (≥10% of pts) with BOS and IM, respectively, were elevated alanine aminotransferase (23%, 3%), thrombocytopenia (14%, 14%), elevated aspartate aminotransferase (11%, 3%), neutropenia (9%, 21%) and hypophosphatemia (4%, 17%). 22% of BOS pts and 6% of IM pts discontinued due to AEs, none due to diarrhea. Deaths occurred in 4 (1.6%) BOS pts and 12 (4.8%) IM pts; overall, 81% died from disease progression. Conclusions: Efficacy and safety were consistent with previously reported results. BOS showed a significantly higher MMR rate at 1 y, significantly faster times to CCyR and MMR, and lower transformation rate vs IM. BOS had a distinct and acceptable toxicity profile and may offer a new therapeutic option in newly diagnosed Ph+ CP CML. Data for 18-mo follow-up will be presented.
Phase Ib study of dulanermin combined with first-line FOLFOX plus bevacizumab (BV) in patients (Pts) with metastatic colorectal cancer (mCRC).
Authors: Mark Kozloff, Wells A. Messersmith, Amy V. Kapp, Avi Ashkenazi, Stephanie Royer-Joo, Chia C. Portera, Zev A. Wainberg
Journal: Journal of Clinical Oncology (2012)

3552 Background: Dulanermin is a recombinant soluble human Apo2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) that activates apoptotic pathways by binding to the pro-apoptotic death receptors DR4 and 5. This study assessed the safety of dulanermin combined with FOLFOX+BV as first-line therapy in mCRC pts. Methods: This was a multicenter, open-label dose-escalation and cohort expansion study with treatment until disease progression or treatment intolerance. Dulanermin was administered intravenously in 14-day cycles on Days 1, 2 and 3 at 4.5 mg/kg or 9 mg/kg, with FOLFOX, and BV 5 mg/kg on Day 1. Dose-limiting toxicity (DLT) was assessed through 2 cycles (Days 1-28). Adverse events (AE) were recorded through all cycles. Response was assessed with RECIST (v1.0). Results: A total of 23 pts received 2-33 cycles (median 15) of dulanermin with FOLFOX+BV. No DLTs were reported. The most frequent AEs reported as dulanermin-related were fatigue (26%), neutropenia and nausea (22% each), and alanine aminotransferase increased and diarrhea (17% each). The most frequent Grade ≥3 AEs reported as dulanermin-related were neutropenia (13%) and infusion-related reaction (9%). Some of these events were reported as related to dulanermin and other study drugs. Three pts (13%) discontinued study treatment due to serious AEs: infusion-related reaction (2 pts, 9%; both reported as dulanermin-related) and pulmonary embolism (1 pt, 4%). Other reasons for discontinuation included disease progression (13 pts, 57%), physician’s decision and pt’s decision (2 pts each, 9%), and non-compliance (1 pt, 4%). Two pts are still receiving treatment. Among the 23 patients, best responses included 13 (57%) partial responses (9 confirmed and 4 unconfirmed), 7 (30%) stable disease and 3 (13%) progressive disease. Conclusions: Addition of dulanermin to first-line FOLFOX+BV was well tolerated overall in these mCRC pts. AEs were similar to those previously reported for FOLFOX+BV alone. Tumor responses suggest no adverse interactions between dulanermin and the standard first-line treatment evaluated in this study.
Clinical pharmacokinetics (PK) of two oral dosing schedules of gimatecan in a phase I study: Implications for safety and efficacy
Authors: M. M. Woo, J. Zhang, F. Rocha, A. Fandi, H. F. Schran
Journal: Journal of Clinical Oncology (2008)

2512 Background: Gimatecan (Gim), a novel oral topoisomerase I inhibitor is a lipophilic 7-oxyiminomethyl derivative of camptothecin. Its in vitro cytoxicity is more sustained than irinotecan and topotecan, it has potent antitumor properties in mouse xenografts, and shows promising activity in ongoing Ph II trials. This study compares two oral dosing schedules in advanced cancer patients (pts): daily x 5 of a 28-day cycle representing early dose intensity versus continuous Monday/Thursday (M/Th) regimen providing consistent exposure to exploit Gim’s S-phase specific cytotoxicity. Methods: Cohorts of 6 pts with advanced cancer were randomized to receive Gim at escalating doses of 0.25, 0.5, 1, 1.25, and 1.5 mg/day either as dx5 q 28 days or every M/Th continuously. Serial plasma samples were obtained for gim PK evaluation (total and lactone only using specific LC/MS/MS methods) in 79 patients (n=36 dx5; n= 43 M/Th) after the 1st and 5th and 9th (M/Th only) dose. Results: Lactone represented >87.5% of total gim in plasma (n=5 last cohort). Gim disposition was best described by a two-compartment model with first-order absorption (median (range) Tmax 1 h (0.5 to 3 h)) and elimination (t1/2 ∼80 h). Dose had no influence on Gim apparent oral clearance (CL/f) (0.5 ± 0.4 L/h, mean ±SD) suggesting linear kinetics, and CL/f was not correlated with age, body weight or gender. Both schedules showed similar interpatient variability in CL/f (70% M/Th, 88% dx5) and similar 1st cycle AUC0–28days, whereas Cmax of 5th dose dx5 was 2-fold higher than Cmax M/Th. Dose-limiting toxicities (mainly myelosuppression) were reported in 4/15 pts (27%) at 1 mg dx5 and 6/8 pts (75%) at 1.25 mg dx5 compared to no DLTs at 1 mg M/Th and 5/13 pts (38%) at 1.25 mg M/Th. Preliminary response data show PRs only at Gim doses of ≥1.25 mg. Conclusions: The lower Cmax and consistent drug exposure with the M/Th schedule may provide a wider therapeutic window. The PK model allows exploration of additional Gim-dosing schedules. No significant financial relationships to disclose.
Robotic-assisted Ivor-Lewis esophagectomy in the elderly patient.
Authors: Andrea M. Abbott, Tobin Joel Crill Strom, Nadia Saeed, Ravi Shridhar, Sarah E. Hoffe, Khaldoun Almhanna, Kenneth L. Meredith
Journal: Journal of Clinical Oncology (2014)

93 Background: Esophageal cancer continues to increase in incidence worldwide with the age of diagnosis continuing to move towards an older onset. Robotic assisted approaches to esophagectomy have demonstrated decreased complications and length of hospitalization (LOH). We sought to examine the impact of age on outcomes in patients undergoing robotic assisted esophagectomy (RAIL). Methods: From 2009-2013, we identified patients undergoing robotic assisted Ivor Lewis esophagectomy. Patients were then stratified according to 3 age groups. Cohort 1, age less then 50, cohort 2, age 50-70, and cohort 3 &gt;70. Statistical comparisons between LOH, operative time (OT), estimated blood loss (EBL), adverse events (AE) and mortality were made with Kruskal-Wallis and Chi-square tests. Results: We identified 134 patients who underwent RAIL and found no statistically significant difference between the three cohorts for OT, LOH, days spent in intensive care, AE or mortality. There was a difference in EBL with higher median blood loss (150 cc) seen in cohort 1 (50-600cc) and 3 (50-400cc) compared to cohort 2 (100 cc, (25-400cc)), p &lt; 0.01. The most common AE were arrhythmia and pneumonia but this was not significantly different between the cohorts. The overall AE rate was 10% (cohort 1), 21% (cohort 2), 34% (cohort 3), p=0.14. There were 4 leaks (p =0.38) and 2 deaths (p=0.90) in the entire cohort. A separate analysis was done to compare elderly (&gt;70) to the non-elderly (&lt;70). Median EBL was higher in the elderly cohort (100cc (25-600) vs 150cc (50-400), p &lt;0.01). There was a trend towards longer LOH in the elderly (9 (4-35) vs 11 (6-38) days, p =0.06). AE and mortality were not significantly different, although there was a trend toward increased AE (19.8% vs 34%, p=0.07) in the elderly, with arrhythmia being the most common AE. Conclusions: RAIL is a safe surgical technique for use in an aging patient population. We demonstrated there was no increased risk of LOH, AE or death in the elderly patients compared to their younger cohort.
Concurrent chemoradiotherapy using high-dose rate intracavitary brachytherapy for uterine cervical cancer
Authors: E. Song, N. Lee, J. Kwak, J. Kim, H. K. Lee, C. Yim
Journal: Journal of Clinical Oncology (2008)

16568 Background: We retrospectively reviewed our experience with concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) to assess its feasibility and efficacy in the treatment of patients with uterine cervical cancer. Methods: A total of 88 patients with stage IB2-IVa cervical cancer treated with CCRT using HDR-ICBT were analyzed. External beam radiotherapy (EBRT) with 45 Gy/25 fractions followed by HDR-ICBT with 28 Gy/8 fractions to point A was performed. Chemotherapy consisted of weekly cisplatin at a dose of 40 mg/m2/day for a median of 5.5 courses (range: 1–6 courses) was concurrently administered with radiotherapy. The median follow-up period for all patients was 44 months (range: 3–101 months). Results: The actuarial 3-year overall survival rate was 69.5% and 3-year disease-free survival rate was 67.2%. In the 19.3% of recurred patients, local and systemic failure rate was 11.4% and 17.0%, respectively. The incidence of any grade 3 acute adverse event was 23.9%, but grade 4 adverse event was not detected. Grade 3 neutropenia was the most common acute adverse event (13.6%). The cumulative incidence of late complication rate (all grades) was 11.4%, which were four gastrointestinal complications, three radiation cystitis, two lymphedema and one chronic renal failure. Conclusions: Weekly cisplatin 40 mg/m2 concurrent with EBRT followed by HDR-ICBT is feasible and efficacious for patients with locoregional uterine cervical cancer. No significant financial relationships to disclose.
Exploring racial differences in outcome for metastatic colorectal cancer: Results from a large prospective observational cohort study (BRiTE).
Authors: J. E. Ward, A. Sing, M. Ashby, M. Kozloff, S. Feng, B. N. Polite
Journal: Journal of Clinical Oncology (2010)

e14039 Background: African-Americans are more likely to be diagnosed with metastatic colorectal cancer at the time of presentation than whites, and have shorter survival once diagnosed. This study examines racial differences in clinical outcomes in the setting of a large observational cohort study. Methods: The study cohort consisted of 1,589 white (81.4%) and 227 African-American (11.6%) patients with metastatic colorectal cancer receiving front line bevacizumab therapy enrolled in a large prospective observational cohort study. Differences in time to event endpoints and response incidence were examined by race. Differences in the incidence of baseline and treatment related toxicities associated with bevacizumab were also examined. Finally, differences in patterns of care by race were explored. Results: Median OS was 22.6 months for African Americans and 22.9 months for whites. Median PFS was 9.5 months for African Americans and 9.8 months for whites. Response rates (CR+PR) were 37.5% for African Americans and 46.3% for whites (Adjusted OR 0.66; 95%CI: 0.49-0.89). African Americans had higher rates of baseline diabetes (18.9% vs. 11%; p = 0.002) and hypertension (52.9% vs. 41.4%; p = 0.001), and worsening hypertension while on therapy (13.7% vs. 8.9%; p = 0.02) but no differences in on-treatment Arterial Thromboembolic Events were seen. Conclusions: This large observational cohort study of patients with metastatic colorectal cancer demonstrates that when treated in a similar fashion with modern chemotherapy, African Americans and whites have equivalent cancer outcomes. Encouragingly, no significant differences in bevacizumab related toxicity or patterns of care were seen between African Americans and whites. The lower response rate among African Americans deserves further study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech