tbuckley/cabot-search huggingface dataset:
The prognostic value of signet ring cell histology in resected gastric cancer.
Authors: Lauren McLendon Postlewait, Malcolm Hart Squires, David A. Kooby, George A. Poultsides, Sharon M. Weber, Mark Bloomston, Ryan C. Fields, Timothy M. Pawlik, Konstantinos Ioannis Votanopoulos, Carl Richard Schmidt, Aslam Ejaz, Alexandra W. Acher, David J. Worhunsky, Neil Saunders, Doug S. Swords, Linda X. Jin, Clifford Suhyun Cho, Kenneth Cardona, Charles A. Staley, Shishir Kumar Maithel
Journal: Journal of Clinical Oncology (2015)

128 Background: Conflicting data exist on the prognostic implication of signet ring cell (SRC) histology in gastric adenocarcinoma (GAC). Our aim was to assess the association of SRC with recurrence and survival in patients undergoing resection of GAC. Methods: All pts who underwent curative intent resection for GAC from 2000 to 2012 at 7 academic institutions comprising the US Gastric Cancer Collaborative were included. 30-day mortalities were excluded. Survival analyses included Kaplan Meier log rank and multivariate Cox regression. Primary endpoints were recurrence-free survival (RFS) and overall survival (OS). Stage-specific analysis was performed. Results: Of 965 pts, 768 met inclusion criteria. SRC was present in 39.5% and was associated with female gender (52.9% vs 38.6%; p&lt;0.001), younger age (61 vs 67 yrs; p&lt;0.001), poor differentiation (94.8% vs 50.3%; p&lt;0.001), perineural invasion (PNI: 41.4% vs 23%; p&lt;0.001), distal location (82.2% vs 70.1%; p&lt;0.001), receipt of adjuvant therapy (63% vs 51.2%; p=0.002), and more advanced stage (Stage 3: 55.2% vs 36.5%; p&lt;0.001). SRC was associated with earlier recurrence (56.7mo vs median not reached (MNR); p=0.009) and decreased OS (33.7mo vs 46.6mo; p=0.011). When accounting for other adverse pathologic features, PNI (HR 1.57; p=0.016) and higher TNM stage (HR 2.63; p&lt;0.001) were associated with decreased RFS, but SRC was not. PNI (HR 1.53; p=0.006), higher TNM Stage (HR 2.10; p&lt;0.001), greater size (HR 1.05; p=0.014), and adjuvant therapy (HR 0.50; p&lt;0.001) were associated with OS. SRC was not an independent predictor of OS. Stage-specific analysis showed no association between SRC and RFS or OS in Stage 1 or 3. In Stage 2, SRC was associated with earlier recurrence (38.1mo vs MNR; p=0.005) but not OS. The negative association of SRC with decreased RFS persisted in multivariate analysis (HR 3.11; p=0.015). Conclusions: Signet ring histology is associated with other adverse pathologic features including higher grade and higher TNM stage but is not independently associated with reduced RFS or OS. Identification of signet ring histology during preoperative evaluation should not, in isolation, dictate treatment strategy.
New analysis of the hypertension mechanism in bevacizumab-treated patients using 3-tesla dynamic contrast-enhanced magnetic resonance imaging.
Authors: Y. Hirashima, Y. Yamada, U. Tateishi, K. Kato, M. Miyake, K. Akiyoshi, Y. Horita, K. Nagashima, K. Shirao
Journal: Journal of Clinical Oncology (2011)

450 Background: Vascular endothelial growth factor (VEGF) signaling inhibitors, such as bevacizumab (BV), leads to endothelial dysfunction and microvascular rarefaction in noncancer tissue. Angiotensin II has been reported to induce VEGF production by inhibiting VEGF, but the reasons for activation of angiotensin II are unclear. We conducted a study to examine the relationship between renin-angiotensin axis and renal blood perfusion using dynamic contrast magnetic resonance imaging (DCE-MRI) in colorectal cancer patients. Methods: Sixteen patients with colorectal cancer were enrolled. They received BV+FOLFIRI regimen as second line. DCE-MRI was performed before the treatment and after 12th courses. Renin, angiotensin I, angiotensin II and aldosterone were examined before treatment and at 3, 5, 8, 12th courses. DCE-MRI parameters, Area under the time-intensity curve over the first 90 seconds after injection of contrast material (AUC90) and volume transfer constant of contrast material (Ktrans, Kep) were calculated in the normal kidney and examine the correlation with renin-angiotensin axis. Results: All DCE-MRI parameters decreased significantly after 12th courses compared with before treatment (Variables median: Ktrans -1.51, Kep -2.30, AUC90 -26.0, P &lt; 0.001, all). A decrease in Kep correlated with higher renin, angiotensin I and angiotensin II (renin: P =0.001, angiotensin I: P =0.003, angiotensin II: P =0.002, respectively). A decrease in AUC90 correlated with higher aldosterone (P =0.005). Blood pressure did not correlate with each DCE-MRI parameters. Conclusions: VEGF inhibition decreases vessel permeability and raises interstitial pressure in normal kidney. Our data suggest that renin-angiotensin axis is also one mechanism of hypertension caused by BV. No significant financial relationships to disclose.
Improving the efficiency of a block schedule for treatment planning simulation in a radiation oncology department.
Authors: Neil E. Martin, Spyros Potiris, Robert Mersereau, Mark J. Mackin, Barbara A. Jaehn, Kristopher Nissen, Paul Linh Nguyen
Journal: Journal of Clinical Oncology (2014)

158 Background: The use of a weekly assigned block time schedule to allocate appointment slots to providers for treatment planning simulations caused appointment delays, provider frustration, and a perceived lack of capacity at the Dana-Farber/Brigham and Women's Cancer Center Department of Radiation Oncology. While providing predictability for physician schedules, the slots assigned to individual providers often could not accommodate their patient volume or patient availability. Consequently, providers in need of additional slots had to ‘borrow’ them from other providers. To increase schedule flexibility and reduce the need to ‘borrow’ slots, we proposed opening part of the weekly appointment slots for use by any provider. Methods: Historical data from the scheduling system were obtained to identify the weekly volume of appointment slots used by each provider within and outside their assigned time. Using these data we developed a mathematical model that allowed clinicians to convert a desired number of weekly assigned slots to slots open for use by any provider and examine the resulting effect on the number of ‘borrowed’ slots. The model illustrated the availability and usage of weekly assigned and open slots, as well as the number of ‘borrowed’ slots. Results: In the original schedule, 40% of the weekly appointment slots are ‘borrowed’. The mathematical model revealed that converting 38% of the weekly assigned slots to open slots would completely eliminate the need to ‘borrow’ slots. Conclusions: Data-driven, simple models can address complex problems in clinic operations. A mathematical model that illustrates the effect of opening slots in a block time schedule can help end-users increase efficiency in clinic, as well as eliminate provider and staff frustration, patient dissatisfaction, and delays. [Table: see text]
The Diffuse Large B-Cell Lymphoma Infiltrating Macrophage Transcriptome Signature Is Enriched for Both M1 and M2 Genes and Provides an Excellent Platform for Functional Validation of Macrophage Biology in DLBCL
Authors: Rita Coutinho, Aaron M. Newman, Guglielmo Rossignoli, William Day, Faridah Miraki-Moud, Tracy Chaplin, Jacek Marzec, Robert D. Petty, Sameena Iqbal, Janet Matthews, Ash A. Alizadeh, John G Gribben
Journal: Blood (2012)
Evaluation of PTEN, EGFR, and Ki67 expression as predictors of response to a trastuzumab-containing neoadjuvant chemotherapy regimen in a HER2 overexpressing locally advanced breast cancer (LABC) trial.
Authors: J. Ho, G. Turashvili, M. Hayes, K. A. Gelmon, S. Ellard, N. Macpherson, G. K. Pansegrau, S. K. L. Chia
Journal: Journal of Clinical Oncology (2011)

e11029 Background: In patients with HER-2 over-expressing breast cancer, predictors of trastuzumab response and resistance remain unclear and unvalidated. In an exploratory analysis within a phase II trial, we evaluated various biologic markers as predictors of response or resistance to a trastuzumab containing neoadjuvant chemotherapy regimen. Methods: A tissue microarray (TMA) was constructed from formalin-fixed paraffin-embedded tumor tissue samples obtained prior to neoadjuvant chemotherapy in 21 (from a total of 30) HER-2 positive stage II-III patients. Protocol treatment consisted of 4 cycles of 5-Fluorouracil, Epirubicin and Cyclophosphamide (FEC100) followed by 4 cycles of Docetaxel, Carboplatin (AUC 6) and Trastuzumab (TCH). Immunohistochemical (IHC) analyses of estrogen receptor (ER), progesterone receptor (PR), HER-2, Ki67, EGFR and PTEN were performed utilizing previously published protocols and cut-offs. HER-2 equivocal (2+) by IHC cases was confirmed by prior FISH analysis. Fisher’s exact test was used for statistical analysis. Results: 21 patients had sufficient tumour for analysis. Median age at diagnosis was 49 years old, 67% were pre-menopausal, and biomarker expression was as follows: 43% ER positive, 29% PR positive, and 100% HER-2 positive. 14 patients (67%) had pathologic complete response (pCR) following the completion of neoadjuvant chemotherapy and trastuzumab. In general, tumour samples showed high Ki67 (>14%) staining (62%), low EGFR positivity (14%), and high PTEN expression (71%). Neither high Ki67 expression (p=0.65), any EGFR expression (p=0.26), nor PTEN loss (p=0.60) was associated with higher rates of pCR. Conclusions: In our small cohort of locally advanced HER-2 over-expressing tumours, baseline expression of Ki67, EGFR and PTEN were not associated with pCR to a neoadjuvant sequential anthracycline and taxane/trastuzumab combination regimen. Additional biomarkers for an activated PI3K pathway and for p95 will be attempted.
Effectiveness of gemcitabine and capecitabine in advanced colorectal cancer patients: A retrospective analysis.
Authors: Mercedes Salgado, Margarita Reboredo, Ana Medina, Guillermo Quintero, Maria Luz Pellon, Carlos Romero Reinoso, Mónica Jorge, Ana Fernandez-Montes
Journal: Journal of Clinical Oncology (2012)

649 Background: In ASCO2004, Y. Fernandez et al. showed their experience in gemcitabine/capecitabine use in patients with metastatic advanced colorectal cancer (ACRC), with previous progression or contraindicated standar treatment, with encouraging results. This study was design to evaluate the efficacy and safety of this combination in these patients, in our area. Methods: This is an observational, multicentric and retrospective study performed in metastatic colorectal cancer patients refractory to treatment. The study treatment was to evaluate the gemcitabine/capecitabine (gemcitabine 1000 mg/m 2 , day 1+ capecitabine 1250 mg/m 2 /12hours, days 1-7, every 15 days) until progression or unacceptable toxicity. The principal endpoint was the best overall response rate achieved during the study period. Secondary endpoints were Progresión Free Survival (PFS), Overall Survival (OS) and safety profile. Results: Of 45 patients recruited a total of 39 patients were evaluated. Median age was 66(37-78) and 69.2 were male. 86.8% of the patients were ECOG PS 1. Mean time from diagnostic was 2.7±2.4 years. Primary tumor was: colon 73.7%, rectum 23.7% and both 2.6%. Adjuvant therapy was received in 34.3% of the patients. Metastatic locations were: liver 82.1%, lung 64.1% and lymph nodes 25.6%. Previous treatment lines received: two 48.7%, three 23.1%, four 17.9%, five 7.7% and six 2.6%. The mean of cycles were 6.4±6 and mean time of treatment was 3.3±2.8 months. Best response during treatment period was partial response 2.9%, stable disease 17.6% and progression 79.4%. OS was 7.32 months and median PFS was 3.02 months. Most frequent toxicities grade 3 experienced: Palmar plantar erythrodysesthesia 5.1%, neutropenia 5.1%, asthenia 2.6%, dyspnea 2.6% and hiperbilirrubinemia 2.6%. No grade 4 toxicities were reported. Conclusions: Despite of the adequate safety profile of the gemcitabine/capecitabine combination, our study does not confirm the efficacy figures reported by others authors. New agents or combinations should be investigated in the treatment of this patient subgroup.
Thromboembolic events associated with cisplatin chemotherapy in patients with gastric and esophageal cancer: A single-institution experience.
Authors: Aine O'Reilly, Mark Doherty, William Grogan, Oscar S. Breathnach
Journal: Journal of Clinical Oncology (2014)

146 Background: Upper gastrointestinal tract malignancy, specifically gastric cancer (GC) , is associated with an increased risk of thromboembolic events (TEs). Cisplatin is important in the treatment of GC and oesophageal cancer (OC) but is associated with an increased risk of TEs. We aimed to characterise our experience of thromboembolism in patients (pts) with GC and OC receiving cisplatin. Methods: Patients with GC or OC who received cisplatin based chemotherapy from January 2011 to August 2013 were included in analysis. Retrospective review of patient’s clinical, laboratory and radiological data was pursued. Results: Seventy-four pts, 27 patients with GC and 47 pts with OC, received cisplatin based chemotherapy between January 2011 and August 2013. The median age at the start of chemotherapy was 67 (range 43-86), 48 patients (66%) were male. Nine pts experienced a TE. Seven pts experienced a venous TE (5 deep vein thrombosis (DVT), 1 pulmonary embolism (PE)), 1 pt experienced a middle cerebral artery occlusion and subsequently developed a PE while on therapeutic anticoagulation and 1 pt experienced 2 DVTs, the second occurred while therapeutically anticoagulated. Six pts received cisplatin in the context of metastatic GC, 3 (50%) pts experienced at least one TE. Haemoglobin level, leukocyte count, platelet count and body mass index (BMI) were not associated with TE risk. Twenty-one pts received cisplatin neoadjuvantly for locally advanced GC. Four pts (19%) in this subgroup experienced a least one TE. Haemoglobin level, leukocyte count and BMI were not associated with an increased risk of TE. Patients with a platelet count &gt; 350,000/mm 3 experienced more TEs (p&lt;0.05). Forty seven pts were treated for OC, 7 pts with metastatic disease and 40 pts with locally advanced disease. Two pts experienced a single VTE (DVTs), both had locally advanced disease. Conclusions: Thromboembolic events are common in pts with metastatic and locally advanced GC, receiving cisplatin based chemotherapy. Future studies should focus on characterising the role of prophylactic anticoagulation in this subgroup and identifying biomarkers associated with increased risk of TE.
Racial comparison of outcomes and costs of inpatient neutropenic patients: A multicenter evaluation
Authors: S. E. Motl, K. J. Suda, J. C. Kuth, A. H. Manguso, A. B. Weir, T. J. Gladney
Journal: Journal of Clinical Oncology (2005)

6042 Background: Racial disparities have been reported in the care and outcome of cancer patients. Many reports state that minority patients receive worse care and have poorer outcomes compared to Caucasians. Neutropenia is a common complication of cancer treatment leading to dose reductions, infectious complications, and potential hospitalization. We evaluated whether race would influence the costs and outcomes of inpatient neutropenic cancer patients in a multicenter study. Methods: Patient data from a large health care system in the Midsouth were analyzed between 10/01/02 to 09/30/03. Demographic data, health, and economic outcomes were extracted from a health claims database. Patients with a diagnosis code for neutropenia (Medicode, DRG Expert) were selected. A Student’s t-test and Chi Squared were used for statistical analyses; p-value < 0.05 was considered significant. Results: 360 patients (0.37% of all admits) had a diagnosis of neutropenia in the 16 hospital system. 244 patients (67.8%) were Caucasian and the remaining 116 were minorities (94.8% were African Americans). Minority patients were more likely to be younger (53.68 vs. 61.16 years; p=0.0002) and have no insurance, receive Medicaid assistance, or have a commercial HMO or PPO. Caucasian patients were more likely to be on Medicare (p=0.00004 for all payer analyses). Despite these age and insurance differences, both groups had similar case mix indices (1.56 vs. 1.65), total hospital costs ($12,988 vs. $12,540), medication costs ($2,821 vs. $2,541), laboratory costs ($1,199 vs. $1,204), and length of stay (9.85 vs. 9.99 days); Caucasian vs. minority patients, respectively (P=NS). Discharge status was also not significantly different, with similar proportions of patients discharged home, to hospice, expiring, or receiving additional care. Conclusions: Costs and outcomes did not differ between Caucasians and minority neutropenic cancer patients in this large, multicenter hospital system. Due to the escalating reports of racial disparities in cancer care, these results are encouraging. No significant financial relationships to disclose.
Early outcome of a phase I study of interrupted pulse-dosed axitinib combined with FOLFOX or FOLFIRI in refractory metastatic colorectal cancer.
Authors: Eric Roeland, Kelly Anne Shimabukuro, Paul Timothy Fanta, Bethany H. Parker, Michael Hwang, Tony R. Reid
Journal: Journal of Clinical Oncology (2012)

e14078 Background: Therapeutic inhibition of angiogenesis pathways may improve response of chemotherapy refractory malignancies. We evaluated the combination of axitinib, a multi-target VEGF receptor inhibitor, used intermittently with 5-FU based chemotherapy for refractory mCRC. We hypothesized that intermittent pulse dosed axitinib may improve response by delivering chemotherapy during tumor reperfusion after release from angiogenesis inhibition. We present preliminary data of the Phase I portion evaluating the safety and efficacy of interrupted pulse dosed axitinib + FOLFIRI. Methods: Initially, Pfizer A4061020 was a phase IB study of axitinib + bevacizumab + FOLFOX vs. FOLFIRI to evaluate potential overlapping toxicities. A4061020 was expanded to determine the MTD of 7 days of intermittent pulse dosed axitinib + FOLFIRI or FOLFOX; while secondary outcomes include TTP and OS. Enrollment was open to mCRC with progression on both oxaliplatin and irinotecan-based regimens. Results: Preliminary data of 10 mCRC subjects show intermittent pulse dosed axitinib at 14mg and 20mg in combination chemotherapy treatment is safe and tolerable (few grade 3 and one grade 4 AE). The MTD is 20mg daily. We observed a median clinical TTP of 10.1 mos (0.8 to 21.5 mos) vs. a median TTP of 5 mos on last line of chemotherapy (1 to 13 mos). Subjects treated with pulse dose axitinib appear to demonstrate a favorable OS, however these data are still immature. Conclusions: In 10 heavily pre-treated mCRC subjects, intermittent pulse dosed axitinib demonstrates safety, tolerability, and improved TTP. Subjects treated with this approach demonstrated a favorable TTP compared to the prior line of therapy and OS. Intermittent, pulse dosed axitinib warrants further study in a larger population. [Table: see text]
“I wish I’d had this before”: Meeting the communication needs of patients with breast cancer and their primary care physicians using a multifaceted survivorship care plan.
Authors: R. Haq, F. H. Leung, D. Dastur, L. Heus, N. A. Baker, B. Li, J. A. Parsons
Journal: Journal of Clinical Oncology (2011)

e19616 Background: Following treatment, breast cancer patients (BCPs) often report feeling “lost in transition” (IOM, 2005). Family practitioners (FP) also report feeling ill-equipped to provide care to BCPs. In this qualitative pilot study, we designed, implemented and evaluated a multi-faceted survivorship care plan in a shared care model to improve communication between oncologists, BCPs and their FPs. Methods: During pre-implementation, we conducted focus groups and interviews with 35 participants from three stakeholder groups (BCPs, FPs and oncologists), to identify specific communication needs. Based on these findings, a multi-faceted care plan was designed and implemented. Post-implementation, focus groups and interviews were conducted with 22 participants to obtain feedback about the care plan. Results: Pre-implementation, representatives of all three stakeholder groups identified communication needs pertinent to BCP and FPs. BCPs commented that web-based, paper-based and human resources components are essential to any care plan, and identified existing human resources helpful during their recovery. FPs indicated that tools to support them must distil information in a readily accessible and easy-to-use format. Based on these findings, a multi-faceted survivorship care plan was designed and implemented for BCPs and a website was designed to address the needs of FPs. Post-implementation, positive feedback was received from BCPs, indicating that the care plan was effective at addressing many of their needs and commented “I wish I’d had this before”; BCPs did not differentiate the follow-up period, but rather spoke of evolving needs throughout their cancer journey. Suggestions for future improvements to the tool included emphasizing a health-and-wellness framework, rather than one of illness, and eschewing the terms “survivor” and “survivorship” in materials, as many patients do not self-identify with such terms. Conclusions: The multi-faceted care plan we have developed shows promise in addressing the communication and needs of BCPs and their FPs. Next steps should include tool refinement and a broader implementation plan.
Cyclophosphamide Related Cardiac Complication in Hematopoietic Transplantation: Analysis of 1091 Cases in Fukuoka Blood and Marrow Transplantation Group
Authors: Kentaro Kohno, Ken Takase, Masanori Kadowaki, Satoshi Yamasaki, Tomohiko Kamimura, Yuju Ohno, Tetsuya Eto, Toshihiro Miyamoto, Seiichi Okamura, Koichi Akashi
Journal: Blood (2014)
PSA-detected prostate cancer in the United States: A population-based study of 70,345 men with AJCC stage T1cN0M0 disease.
Authors: Hong Zhang, Lois B. Travis, Edward M. Messing, Ollivier Hyrien, Rui Chen, Michael T. Milano, Ralph Anthony Brasacchio, Yuhchyau Chen
Journal: Journal of Clinical Oncology (2013)

50 Background: The U.S. Preventive Services Task Force (USPSTF) recently recommended against prostate-specific antigen (PSA)-based screening for prostate cancer. This recommendation has heightened the debate about risks and benefits of prostate cancer screening, and underscored our limited understanding of PSA-detected prostate cancer. The purpose of this study was to determine the frequency of various risks of prostate cancer based on patient characteristics and PSA levels. Methods: This population-based study used the Surveillance, Epidemiology, and End Results (SEER) program to identify men with AJCC stage T1cN0M0 disease diagnosed between 1/2004 and 12/2008. Multivariate logistic regression was conducted to model the probability of developing low (PSA &lt;10 mg/L and Gleason score ≤6), intermediate (PSA between 10 mg/L to 20 mg/L and/or Gleason score 7), and high risk diseases (PSA ≥20 mg/L, and/or Gleason score ≥8). Results: A total of 70,345 men with PSA-detected T1cN0M0 prostate cancer were evaluated. Among them, 47.6%, 35.9% and16.5% had low, intermediate, or high risk disease, respectively. Odds ratios (OR) of having intermediate or high risk disease in patients ≥75 years old were 4.47 (95% confidence interval (CI) 3.81 to 5.26, p&lt;0.01) and 9.39 (95% CI 7.25 to 12.16, p&lt;0.01), respectively, when compared with patients aged &lt;50. Also, black men had increased ORs for intermediate and high risk disease compared with white men (OR 1.50, 95% CI 1.42 to 1.58, p&lt;0.01 for intermediate risk disease; OR 1.84, 95% CI 1.72 to 19.97, p&lt;0.01 for high risk disease). While men aged &gt;75 accounted for 11.8% of the population at risk, they accounted for 24.3% of intermediate and 26.1% of high risk disease. Conclusions: A substantial number of PSA-detected prostate cancer patients have either intermediate or high risk disease at diagnosis. Men age &gt;75 or of black race have the highest risk of presenting with intermediate or high risk disease.