tbuckley/cabot-search huggingface dataset:
Gemcitabine, paclitaxel plus trastuzumab (GTH) in HER2 ECD-positive metastatic breast cancer
Authors: R. Colomer, J. I. Mayordomo, L. Calvo, J. Hornedo, F. Carabantes, M. Gil, B. Martin, H. Cortes-Funes
Journal: Journal of Clinical Oncology (2004)

740 Background: We have shown that the response of advanced breast cancer to gemcitabine plus paclitaxel in HER2 ECD-positive patients is 42%, while it is 83% in HER2 ECD-negative cases (Ann Onc, 2004). We have now performed a proof-of-concept phase II trial to evaluate whether adding trastuzumab to gemcitabine-paclitaxel is able to reverse the poor response of HER2 ECD-positive metastatic breast cancer, and present here the preliminary results. The objective of the trial was to achieve at least a 66% response rate. Methods: Serum levels of HER2 ECD were screened in 214 cases with histologically confirmed metastatic breast carcinoma, 52 (24%) were positive (>30 ng/ml, Oncogene Science Diagnostics), and 30 patients were enrolled. The GTH regimen was paclitaxel 150 mg/m2 followed by gemcitabine 2500 mg/m2, both on Day 1 of a 14-day cycle, maximum of 10 cycles, and trastuzumab 2 mg/kg weekly, with a loading dose of 4 mg/kg, administered the day before the first chemotherapy dose. Results: Of the 30 cases, 18 are evaluable for toxicity, and 13 for efficacy. Characteristics of non-evaluable cases were: one hypersensitivity reaction to the first trastuzumab dose and two early disease progressions at day 3 and day 8. Median age at diagnosis was 51 years; median performance status was 90; median number of metastatic sites was 2. Most patients (74%) had prior adjuvant chemotherapy, usually involving anthracyclines (68%). Grade 3/4 hematologic toxicities were neutropenia (27%), leukopenia (19%), and thrombocytopenia (1%). No patient had neutropenia and fever. Grade 3/4 nonhematologic toxicities were fatigue (1%), elevation of ALT (6%) or AST (1%), neurosensory (1%), and constipation. Objective response rate was 84% (15% CR; 69% PR); 8% had SD; 8% had PD. Conclusions: The preliminary evaluation of GTH in HER2 ECD-positive metastatic breast carcinoma shows remarkable activity and a favorable toxicity profile. HER2 ECD is a valuable method to select for trastuzumab therapy. Updated results will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb; Eli Lilly Eli Lilly
Characterization of Myelodysplastic Syndromes (MDS) with T-Cell Large Granular Lymphocyte Proliferations (LGL)
Authors: Christa Roe, Najla Alali, Eric Padron, Pearlie K Burnette, Kendra L. Sweet, David Sallman, Lubomir Sokol, Jeffrey E. Lancet, Alan F. List, Rami S Komrokji
Journal: Blood (2016)
The impact of CD34<sup>+</sup> cell dose and comorbidities on engraftment following autologous hematopoietic stem cell transplantation (ASCT).
Authors: Mark A Fiala, Pavan Kumar Bhamidipati, Stephanie Wang, Trisha Sturgill, Feng Gao, Camille N. Abboud, Amanda F. Cashen, Meagan A. Jacoby, Iskra Pusic, Rizwan Romee, Mark A. Schroeder, Geoffrey L. Uy, Ravi Vij, Peter Westervelt, John F. DiPersio, Keith Stockerl-Goldstein
Journal: Journal of Clinical Oncology (2014)

7046 Background: The minimum CD34+ cell dose needed to ensure hematopoietic recovery following ASCT is 2x106cells/kg. Recent studies suggest that 5x106cells/kg or 8x106cells/kg is the optimal dose as it results in more rapid and sustained engraftment. To date, little is known about the impact of comorbidities on engraftment. Methods: We performed retrospective chart review of 639 consecutive patients with a diagnosis of multiple myeloma (MM), non-Hodgkin’s lymphoma (NHL) or Hodgkin’s lymphoma (HL) who underwent mobilization and ASCT at the Siteman Cancer Center/Washington University School of Medicine from 2008 to 2011. Independent variables analyzed were: CD34+cell dose, age, gender, diagnosis, coronary artery disease, diabetes mellitus (DM), hyperlipidemia, and hypertension. Kaplan-Meier curves were performed to compare the median time to neutrophil engraftment (TTNE) and the median time to platelet engraftment (TTPE). Results: The median age was 58 years (range 18-74); 58% were male; 52% had MM, 39% had NHL, and 9% had HL. The median CD34+ cell dose administered was 4.1x106cells/kg (range 1.9-42.5). 8 patients received stem cell doses < 2x106cells/kg and, therefore, were excluded from analysis. Administration of ≥ 5x106cells/kg was associated with improved TTNE and TTPE (10 and 16 days, respectively, compared to 11 and 18 days; p< 0.001) but had no effect on the rates of platelet engraftment failure or 100 day mortality. Cell doses ≥ 8.0 x106cells/kg had no additional impact on engraftment kinetics or 100 day mortality. TTNE for patients with DM (n=84) was 11 days compared 10 days for patients without (p = 0.01). Conclusions: Administration of ≥ 5x106 CD34+cells/kg resulted in only marginal improvement in TTNE and TTPE, and did not improve the platelet engraftment failure or 100 day mortality rates. Therefore, CD34+ cell doses of ≥ 2x106cells/kg should be considered effective, and additional days of cell collection to achieve a cell dose of ≥ 5x106cells/kg may not be warranted. DM has been previously reported to increase the length of hospital stay post-ASCT, but its effect on TTNE observed in our cohort is a novel finding.
Obesity at diagnosis increases relapse rate and shortens time to relapse in breast cancer patients
Authors: S. Hussain, D. Quispe, D. Quispe, C. Herrington, R. Shi, A. Sun
Journal: Journal of Clinical Oncology (2007)

21123 Objective: Breast cancer is the most common cancer in US women. One in eight women will develop breast cancer in their lifetime. Obesity, one of the 10 leading US health indicators, is associated with breast cancer risk and outcome in various studies. Louisiana is one of the three states with obesity prevalence above 30%. Feist-Weiller Cancer Center (FWCC) in Shreveport serves a large area of Louisiana as far as Baton Rouge. There is a large population of African American patients who are followed in FWCC. The objective of this study is to examine the association of obesity with breast cancer in our patient population. Study Design: A retrospective study from single institution. Medical records of the breast cancer patients in FWCC electronic data management system are reviewed. National Institutes of Health criteria are used to stratify patients: normal or underweight (NW, body mass index or BMI &lt; 25kg/m2, overweight (OW, BMI 25–29.9), and obese (OB, BMI &gt; = 30). Relapse and time to relapsed are compared among three groups. Result: In analysis using multivariant Cox proportional regression model, BMI at diagnosis is a statistical significant predictor of time to relapse. In univariant analysis, increased BMI at diagnosis is associated with 3.3% risk of disease relapse per year. The results demonstrates a positive association of obesity and disease course in breast cancer patients treated at FWCC. No significant financial relationships to disclose.
Radiotherapy (RT), temozolomide (TMZ), procarbazine (PCB), and the integrin inhibitor cilengitide in patients (pts) with glioblastoma (GBM) without methylation of the MGMT gene promoter (ExCentric): Results of an Australian phase II clinical trial.
Authors: Mustafa Khasraw, Sally Anne McCowatt, Marc E. Buyse, Zoltan Kerstes, Michael Back, Ganessan Kichenadasse, Helen Wheeler
Journal: Journal of Clinical Oncology (2014)

2050^ Background: Building on our preclinical data, we proposed that combination of low dose TMZ and PCB may overcome TMZ chemoresistance in MGMT unmethylated GBM. We proposed adding Cilengitide, a selective αvβ3 and αvβ5 integrin inhibitor, to PCB, TMZ and RT. Methods: Newly diagnosed GBM pts with unmethylated MGMT received cilengitide 2000 mg twice weekly over 18 months. On week 2 of cilengitide, RT (60 Gy, 2 Gy per fraction) was started for 6 weeks with daily TMZ (60 mg/m2) and PCB (50 mg if BSA < 1.7; 100 mg if BSA ≥ 1.7) followed by 6 cycles of adjuvant TMZ (50mg/m2 in first cycle, 60 mg/m2in subsequent cycles) and PCB (50 mg if BSA < 1.7; 100 mg if BSA ≥ 1.7) given D1 to 20 every 28 days. The primary endpoint was 12m Overall Survival (12 mOS). The probability of accepting insufficiently active treatment was set to 10% and the probability of rejecting an active treatment was set to 20%. If 16 of 29 pts (55%) or less were alive at one year, the treatment was to be declared inactive. Secondary endpoints include 6-month progression-free survival (6mPFS) and toxicity. Results: MGMT was tested in 60 pts to enrol 29 evaluable GBM pts with unmethylated MGMT status (median age: 55 y, range 24-74 y; 11 women and 18 men). ECOG status was 0, 1 and 2 in 16, 11 and 2 pts, respectively. The last pt was enrolled in June 2013 and at time of submission of this abstract 18 of 29 included pts (62%) were alive, 11 (38%) who have been followed-up for a year or more and 7 (24%) less than a year. Current median OS and PFS are 58 (95% CI 44-72) and 30 (95% CI 20-39) weeks respectively. Grade (G) 3 and 4 toxicities included thromboembolism (1 G 4 and 2 G3), seizures (1 G4 and 2 G3), neutropenia without fever (5 G3) and asymptomatic elevated transaminases (1 G4 and 6 G3). Conclusions: The safety profile of the combination was confirmed. As of Jan 2014, the 12mOS has not yet been reached. Of the 7 pts still alive, 5 will need to survive 12 months or more after enrolment for the primary endpoint of 12 mOS to be met. Updated endpoints, including 12 mOS, will be available and presented at the ASCO annual meeting. Clinical trial information: NCT01124240.
Risk Factors Affecting Cardiac Left Ventricular Systolic and Diastolic Function and Hypertrophy in the Chronic Phase Post-Allogeneic Hematopietic Cell Transplantation
Authors: Mitsutaka Nishimoto, Hirohisa Nakamae, Takahiko Nakane, Hideo Koh, Yoshiki Hayashi, Mika Nakamae, Masahiro Yoshida, Masato Bingo, Hiroshi Okamura, Mizuki Aimoto, Masahiro Manabe, Takuro Yoshimura, Akiko Inaba, Satoshi Nanno, Asao Hirose, Kiyoyuki Hagihara, Yoshitaka Nakao, Yoshiki Terada, Masayuki Hino
Journal: Blood (2011)
Primary care vs. oncology-driven surveillance following adjuvant chemotherapy in resected pancreas cancer.
Authors: Haider H Samawi, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2017)

421 Background: Major oncology societies outline different recommendations following curative intent treatment for pancreas cancer and this has resulted in wide variations in practice among institutions. We aim to describe patterns of surveillance and evaluate their impact on outcomes. Methods: A total of 147 adult patients who received at least one cycle of adjuvant chemotherapy with gemcitabine or 5-fluorouracil monotherapy at any of the British Columbia Cancer Agency centers between 2004 and 2015 were included in this analysis. Surveillance strategies were divided into two groups: discharged to primary care physicians (PCP) or follow up with oncologists that included regular clinical assessments, laboratory testing and/or diagnostic imaging. Results: Median age at diagnosis was 64 (range 38-85) years and 48% were men. More patients were followed by oncologists than PCP (66% vs. 44%). Among the measured prognostic factors, only patients with advanced tumor stage (T3/4) were more likely to be followed by cancer specialists (78% vs. 62%, P = 0.03), while age, gender, performance status, node status, pathologic grade and surgical margins were balanced between the two groups. In the entire cohort, 100 (68%) patients had a documented recurrence. Patient followed by oncologists were more likely to receive chemotherapy on recurrence than those followed by PCP (58% vs. 34%, respectively, P = 0.03). The median overall survival (OS) was 2.82 (95% CI 2.17-3.32) years in the oncology group and 3.35 (95% CI 2.85-5.06) years in the PCP group while the median relapse free survival (RFS) was 2.4 (95% CI 2.07-4.59) and 1.4 (95%CI 1.37-1.77) years, respectively. On multivariate analysis, there was no significant difference in OS between oncology and PCP-driven surveillance (HR 1.23; 95% CI 0.74-2.04, P = 0.4); however, RFS favored the PCP group (HR 1.62; 95% CI 1.01-2.56, P = 0.04, for oncology). Conclusions: In this population-based analysis, surveillance tests and imaging performed by oncologists detected recurrences earlier when compared to follow up by PCPs, but this did not result in OS differences. PCPs may have a larger role in the follow up care of selected patients with resected pancreas cancer.
Do care pathways help us choose wisely in the setting of neoadjuvant therapy for breast cancer? Results of a pre-post analysis.
Authors: Rachel Adilman, Dimas Yusuf, Zia Poonja, Sheridan Marie Wilson, Stephen K. L. Chia, Robyn Leonard, Yanchini Rajmohan, Christine E. Simmons
Journal: Journal of Clinical Oncology (2015)

e17539 Background: Guidelines suggest that neoadjuvant therapy (NAT) should be an option for any breast cancer patient to whom adjuvant therapy would be offered. Studies show that those with aggressive subtypes (TNBC, Her2+) receive the most benefit from NAT in terms of pCR rate. As coordination of NAT can be complex, many centres have implemented care pathways and databases to track these patients. Still, it is unknown whether a care pathway may improve patient selection for NAT. This study aimed to compare breast cancer patients selected for NAT at BCCA Vancouver both pre- and post-implementation of a care pathway program, and to evaluate wait times and pCR rates. Methods: Breast cancer patients referred for consideration of NAT from May 2012 - May 2013 (retrospective cohort) and May 17, 2013 - September 2014 (prospective cohort) were included in a secure database. Wait times and tumour characteristics were assessed and are reported using descriptive statistics. Results: 155 cases were referred for consideration of NAT post-implementation of the care pathway; 104 received NAT. Prior to implementation, 78 received NAT, indicating a 33% increase in use of NAT. There was a significant increase in use of NAT in more aggressive subtypes post-implementation, and a decrease in use of NAT in less aggressive subtypes (Table 1). Median wait time from a patient’s medical oncology consult to commencing chemotherapy was 13 days in the retrospective cohort and 12 days in the prospective cohort. Rate of pCR rose significantly from 19% pre- to 39% post-implementation (p = 0.00672). Conclusions: Our findings illustrate an improvement in patient selection with a shift toward treating more aggressive and chemo-sensitive breast cancers with NAT since implementation of a care pathway program. Wait times improved modestly. There remains a need to improve and expedite multidisciplinary care for high-risk breast cancer patients; strategies are being piloted in this regard. Patients receiving NAT, by subtype. TNBC % (n) Her2+ % (n) Aggressive Subtypes Pooled % (n) ER+/Her2- % (n) Pre-implementation (n=78) 20% (16) 23% (18) 44% (34) 56% (44) Post-implementation (n=104) 26% (27) 36% (37) 62% (64) 38% (40) p = 0.0164 p = 0.0164
Tailored support to self manage asthma improves control and cuts emergency care, review finds
Authors: Susan Mayor
Journal: BMJ (2017)

Providing tailored support to help patients self manage their asthma, including a personalised action plan, education, and regular review, improves asthma control and quality of life and reduces unscheduled consultations and hospital visits, a large review has found.1

Guidelines published over the past 25 years have unequivocally recommended that people with asthma should be given self management education and plans. But research has shown that only a minority of asthma patients …
Regulatory B cell-myeloma cell interaction confers immunosuppression and promotes their survival in the bone marrow milieu
Authors: L Zhang, Y-T Tai, M Ho, L Xing, D Chauhan, A Gang, L Qiu, K C Anderson
Journal: Blood Cancer Journal (2017)

Regulatory B cell-myeloma cell interaction confers immunosuppression and promotes their survival in the bone marrow milieu
Comparison of early tumor shrinkage between oxaliplatin plus S-1 and cisplatin plus S-1 in first-line chemotherapy with advanced gastric cancer.
Authors: Hiroki Osumi, Daisuke Takahari, Eiji Shinozaki, Keisho Chin, Mariko Ogura, Izuma Nakayama, Tomohiro Matsushima, Takeru Wakatsuki, Takashi Ichimura, Mitsukuni Suenaga, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2017)

75 Background: Early tumor shrinkage (ETS) is regarded as predictive marker in metastatic colorectal cancer. In the phase III study comparing oxaliplatin plus S-1 (SOX) to cisplatin plus S-1 (SP) in patients with advanced gastric cancer (AGC), although response rates were almost same between two groups, ETS wasn’t evaluated. Therefore, in AGC, it is controversial whether ETS is predictive or not and which is more suitable regimen, especially as neo adjuvant chemotherapy (NAC). The aim of this study is to compare ETS in SOX with SP and to evaluate the relationship between ETS and clinical outcomes in AGC. Methods: We retrospectively enrolled consecutive 469 patients (SOX 128, SP 341) with histopathologically confirmed HER2 negative AGC treated as 1st-line chemotherapy or NAC in our institution between January 2010 and June 2016. ETS was defined relative change in the sum of the longest diameters of target regions at week 8 (±4) compared to baseline. (Cut-off: 20%). Tumor response was assessed computed tomography using the RECIST 1.1. Patients with peritoneal metastasis and/or bone metastasis without target region were excluded in this study. Results: 192 patients (SOX 60, SP 132) were included in this study. Median tumor shrinkage between SOX and SP were 30% (min-35%, max77%) and 21% (min-89%, max73%), respectively ( p= .16). The ratio of ETS between SOX and SP was 53.3% and 50.7%, respectively ( p= .75). ETS &gt; 20% was associated with longer OS and PFS when compared with ETS≦20% in SOX group. (ETS &gt; 20% vs≦20%: OS 15.3 vs 10.1 months, HR 0.47 p= .03 PFS 7.6 vs 4.2 months, HR 0.58 p= .09) On the other hand, ETS &gt; 20% was associated with significantly longer PFS only when compared with ETS≦20% in SP group and significant independent predictive factor. (ETS &gt; 20% vs≦20%: OS 15.7 vs 10.9 months, HR 0.79 p= .29 PFS 7.7 vs 4.0 months, HR 0.57 p= .01) In multivariate analysis, ETS remained significant independent predictive factor for PFS in SP group (HR 0.53, p= .006). Conclusions: The ratio of ETS was similar between SOX and SP. ETS may be an early-on-treatment predictor in AGC.
Development and pilot test of a dyadic psychosocial intervention for couples coping with head and neck cancer.
Authors: Hoda Badr
Journal: Journal of Clinical Oncology (2017)

187 Background: Patients receiving radiotherapy for head and neck cancers (HNCs) experience significant persistent side effects such as abnormally reduced salivation, difficulty swallowing, and taste changes. To control these side effects and minimize discomfort, intensive self-care protocols are prescribed, but adherence is poor. Spouses/partners play a critical role in supporting adherence, but often lack knowledge, experience high rates of distress, and display poor communication that can interfere with patient self-management and self-care. Methods: We developed and pilot-tested a skills-training intervention comprised of tailored manuals and 6 counseling sessions delivered over the telephone to HNC patients and their partners. The goal is to reduce healthcare utilization and improve patient and partner quality of life (QOL). To guide the development and content of the intervention, qualitative interviews with 6 HNC patients (83% male) and 6 spouses were analyzed using a grounded theory approach. For the pilot test, couples completed surveys prior to initiating radiotherapy and were randomized to the intervention or usual medical care. Eight weeks later, they completed follow-up surveys. Results: Based on the qualitative findings, we developed the intervention to teach: 1) self-management skills; 2) communication skills; and 3) strategies to improve communal coping and confidence in the ability to work as a team. To date, 20 couples (Mean Age = 57 years; SD = 8) have participated. Solid recruitment (83%) and low attrition rates demonstrate feasibility. Strong program evaluations (Mean = 8.7 out of 10) and homework completion rates (85%) support acceptability. Conclusions: This is the first program in HNC that actively involves both members of the couple to address barriers in the home environment in which self-management occurs. By empowering couples with the skills to coordinate care and support, the program holds great promise for improving self-management behaviors, reducing costly hospitalizations and treatment interruptions, and improving patient and partner QOL.
Clinical trials outcomes of combined BKM120 and cetuximab compared to BKM120 in recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M-SCCHN).
Authors: Hye Ryun Kim, Han Na Kang, Mi Ran Yun, Sun Min Lim, Chang Gon Kim, Myung-Ju Ahn, Jong-Mu Sun, Joo-Hang Kim, Soonmyung Paik, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2015)

6049 Background: To investigate clinical activity, safety and biomarkers of a pan-PI3K inhibitor BKM120 in R/M-SCCHN and identify optimal combinations by conducting co-clinical trials. Methods: Patients with R/M-SCCHN who had progressed on platinum chemotherapy were eligible and treated with BKM120 100mg/day. The primary endpoint was DCR at 8 weeks. Secondary endpoints were RR, PFS, OS and safety. Patient-derived xenografts (PDXs) and cell lines (H01, H02) with genomic annotations were established from study patients to evaluate novel drug combinations. Results: A total of 37 patients were enrolled and evaluable for efficacy and toxicity. Patient characteristics included median age (55years); male (84%); ECOG 0/1 (19%/76%); locoregional/metastatic (30%/38%); oral cavity/oropharynx (38%/27%); prior chemotherapy regimens 1/ ≥ 2 (40%/60%). DCR at 8 weeks was 64.8% and RR was 2.7%. A responder harboring PIK3CAE542Kmutation had response duration of 53 weeks. Common toxicities were anorexia (62%) and hyperglycemia (59%). Median PFS and OS were 7.4 weeks and 19.2 weeks. In 3 PDXs established from patients showing progression, BKM120 was tested alone or in combination with cetuximab, afatinib, paclitaxel. All PDXs showed resistance to single-agent BKM120, resembling the responses of corresponding human cancers. Combined treatment of BKM120 and cetuximab showed strong synergistic inhibition of tumor growth, compared with either agent alone. Cell viability assay showed synergistic growth inhibition with combined BKM120 and cetuximab, compared with either agent alone. BKM120-induced AKT suppression did not attenuate FoxO phosphorylation, suggesting FoxO-mediated transcriptional upregulation of EGFR may not be responsible for synergy of combined PI3K and EGFR inhibition. Based on the integrated clinical and preclinical data, study protocol had been revised to combine BKM120 and cetuximab to explore whether cetuximab increases the efficacy of BKM120 in R/M-SCCHN. Conclusions: BKM120 showed modest efficacy in R/M SCCHN.A co-clinical trial provided a rationale to combine BKM120 and cetuximab for the treatment of R/M-SCCHN. Clinical trial information: NCT01527877.
Interaction of High Molecular Weight Kininogen with Endothelial Cell Receptors suPAR, gC1qR and Cytokeratin 1 by Surface Plasmon Resonance (BiaCore).
Authors: Ricardo G. Espinola, Robin A. Pixley, Berhane Ghebrehiwet, Kusumam Joseph, Alice Kuo, Douglas B. Cines, Robert W. Colman
Journal: Blood (2005)