tbuckley/cabot-search huggingface dataset:
Cost-utility analysis of lapatinib in treatment of HER2-positive advanced breast cancer
Authors: Q. A. Le, J. Hay
Journal: Journal of Clinical Oncology (2008)

6553 Background: The EGF100151 clinical trial demonstrated that the addition of lapatinib to capecitabine in the treatment of HER2-positive advanced breast cancer increases median time to progression (TTP) by 8.5 weeks (18.6 weeks versus 27.1 weeks, p = 0.00013). A cost-utility analysis (CUA) was conducted to estimate projected lifetime clinical and economic effectiveness of this therapy from the U.S. societal perspective. Methods: We constructed a Markov model comprising of four health-states: metastatic breast-cancer (MBC) treatment with disease-free progression, respond-to-therapy, disease progression, and death. The model used Monte Carlo simulation to imitate the clinical course of a typical patient with MBC and is updated with response rates and major adverse effects. Transition probabilities were estimated based on the results from phase II (EGF20002) and phase III (EGF100151) of lapatinib clinical trials. Each cycle of the model was 6 weeks. The overall survival of the combined treatment was assumed to be approximately 2 months longer because the TTP was roughly 2 months longer when compared with the monotherapy. Direct costs of the therapy, major adverse events, laboratory tests, and disease progression; and indirect costs of patient time/travel were obtained from published sources. Health-state utilities were obtained from CUA study of Elkin et al (JCO, 2004). The model used 3% discount rate and reported in 2007 U.S. dollars. Results: Over a lifetime, the addition of lapatinib to capecitabine in the combination therapy is estimated to cost an additional $21,484, with an expected gain of 0.127 quality-adjusted life year (QALY) or incremental cost-utility ratio (ICUR) is $172,031/QALY. The 95% confidence limits of the base case ICUR ranged from $154,680 to $183,624/QALY. Cost-effectiveness acceptability curve indicated less than 10% probability that the base-case ICUR would be lower than $150,000/QALY. In sensitivity analyses, results ranged from $109,440 to $242,652/QALY; and were most sensitive to the cost of lapatinib. Conclusions: Compared with commonly accepted willingness to pay thresholds in oncology treatment the addition of lapatinib to capecitabine is not clearly cost effective, and is most likely to result in ICURs somewhat higher than threshold limits. No significant financial relationships to disclose.
Gamma knife surgery for non-small cell lung cancer patients with brain metastasis: A community cancer center experience.
Authors: G. Johnson, J. Payne, M. A. Hooks, S. Johnson, H. Vyas, D. Saunders, G. N. Kadis, C. A. Fredericks, R. Sehgal, W. M. McHayleh
Journal: Journal of Clinical Oncology (2011)

e18054 Background: For patients with non-small cell lung cancer (NSCLC) and brain metastasis, the options available for treatment depend on several different factors. For those with brain metastasis who are qualifying candidates, gamma knife surgery (GKS) is an alternative to invasive neurosurgery. At Archbold Lewis Hall Singletary Oncology Center in Thomasville, Georgia, GKS can be provided as an option for treating NSCLC with brain metastasis. Our study performed in a small, community setting has shown results comparable to those found in patients treated in larger university settings. Methods: A retrospective review of 92 patients who had undergone GKS to treat a total of 276 NSCLC metastases was performed. Clinical data encompassing a 7-year treatment interval were collected. The histology of primary NSCLC was classified as adenocarcinoma (n=50), squamous (n=19), or undefined (n=23). Fifty-two patients had no active extra cranial disease at time of treatment with GKS and 24 patients received whole brain radiation therapy (WBRT) prior to GKS. A number of patients received concomitant regimen to primary site with radiation alone (n=10), chemo alone (n=9), radiation and chemo (n=30), surgery (n=31), none (n=9) and unknown (n=3). There were 48 men and 44 women, which were 75% Caucasian, 24% African American, and 1% Hispanic. The average patient age was 64.8. The average Karnofsky Perfomance Scale was 70.3. Results: The overall mean patient survival time was 9.9 months, ranging from 10 days to 78.7 months, from the date of first treatment of GKS. The mean survival time was 8.9 months for those diagnosed with adenocarcinoma, 10.8 months for those diagnosed with squamous cell carcinoma, and 11.6 months for those with undefined pathology. Mean survival time of patients without active extra cranial disease was 10.5 months. The patients that received WBRT prior to GKS averaged a survival of 16.7 months. African American patients had an average survival time of 7.8 months compared to 10.7 months for Caucasian patients. Conclusions: Gamma knife surgery for NSCLC with brain metastasis can serve as a treatment option in a community setting and produce results comparable to those seen in large university settings.
Multidisciplinary management of pancreatic adenocarcinoma with isolated pulmonary metastases.
Authors: Supriya K. Jain, Cheryl Meguid, Stephen Leong, Barish H. Edil, Martin McCarter, Tracey E. Schefter, Richard D. Schulick, Christopher Hanyoung Lieu
Journal: Journal of Clinical Oncology (2016)

384 Background: Metastatic pancreatic adenocarcinoma (PAC) with isolated pulmonary metastases has recently been associated with prolonged overall survival. The purpose of this study was to review multi-disciplinary management and outcomes of these patients. Methods: Patients with PAC with pulmonary-only metastases were queried between 2012 to 2015 from a prospective single-institutional database. Results: Ten patients (median age: 71 yrs) were identified. Median number of lung metastases at diagnosis was 3 (range: 1 to innumerable). Seven patients had biopsy-proven lung metastases. Five presented with synchronous metastatic disease and five developed metachronous lung metastases as their first site of progression. Median time to progression between diagnosis of primary cancer to diagnosis of pulmonary metastases was 15 months (range: 4 to 31). Seven patients are alive as of this analysis. Median overall survival (OS) of this series (including two patients diagnosed 3 and 6 months ago) is 17 months, with longest overall survival = 40+ months (patient is still alive). All patients received gemcitabine-based chemotherapy; however, systemic regimens differed and included investigational agents. 3 of 5 patients with metachronous metastases underwent pancreaticoduodenectomy and are long-term survivors (34-40+ months). 2 of these 3 patients had diagnostic VATS of lung metastases and are alive with overall survival of 36+ months (resection of 2/3 nodules) and 34+ months (resection of all visible disease). Two patients with metachronous disease underwent neoadjuvant chemotherapy and pancreatic SBRT with progression to lung prior to planned surgery (OS: 30 months (deceased) and 6+ months (recently diagnosed)). 0 of 5 patients with synchronous metastatic disease had surgical resection; 3 of 5 received pancreatic SBRT. 3 of 10 patients are deceased due to visceral disease (14 months), pulmonary failure (18 months), and unknown causes (30 months). Conclusions: We report a recent single-institutional series of PAC with isolated lung metastases. Our data support that metastatic PAC patients with isolated pulmonary metastases have prolonged overall survival and suggest that local intervention may be beneficial.
A single institution’s experience with bevacizumab and cytoxic chemotherapy in progressive malignant glioma
Authors: T. M. Mayer, J. Lacy, J. Baehring
Journal: Journal of Clinical Oncology (2008)

13010 Background: A recent phase II study with bevacizumab/irinotecan indicated that this combination may represent one of the most active treatments in patients with progressive glioma (Vredenburgh JJ, et al. Clin Cancer Res. 2007;13:1253–1259.). However, limited published experience regarding use of bevacizumab for CNS tumors raises concerns regarding toxicity, particularly with respect to hemorrhage and thromboembolism. Methods: We performed a retrospective analysis of 36 patients with progressive malignant glioma after prior resection, chemotherapy and radiation who were treated with bevacizumab at our institution. Patients were evaluated for bevacizumab related adverse events, time to treatment failure (TTF), and overall survival (OS). Two patients who progressed or died prior to completion of 4 cycles of bevacizumab were analyzed for adverse events only. Results: Patient characteristics: median age 50 (range 24–76); 22 glioblastoma multiforme and 14 other progressive gliomas; 18 prior chemotherapy with temozolomide only and 18 temozolomide plus other salvage chemotherapy. Regimens included: 1 bevacizumab alone, 31 bevacizumab + irinotecan, and 4 bevacizumab + carboplatin. Bevacizumab dose ranged from 5–10mg/kg, typically given every 2 weeks. In 34 patients who received ≥4 cycles of bevacizumab (median 8, range of 4–23 cycles), median TTF and OS were 16 and 30 weeks. Six patients are still being actively treated at the time of this analysis. Progression free survival at 6 months was 25%. In the 36 total patients there was 1 arterial thrombotic event, specifically MI (2.8%), 4 venous thrombotic events (11.1%), and 5 intracranial hemorrhages, but only 3 were clinically significant (8.3%). Conclusions: Overall, our results confirm the efficacy and safety of bevacizumab in combination with chemotherapy in patients with progressive malignant glioma. Although the TTF and OS were less than previously reported with bevacizumab/irinotecan, this was an unselected and heavily pretreated patient population with 50% of patients having received >1 prior chemotherapy regimen. No significant financial relationships to disclose.
The effects of metformin on pathologic complete response (pCR) rates in diabetic breast cancer (BC) patients receiving neoadjuvant systemic therapy (NST)
Authors: S. Jiralerspong, S. H. Giordano, F. Meric-Bernstam, C. M. Barnett, S. Kau, M. C. Hung, G. N. Hortobagyi, A. M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2008)

528 Background: Recent epidemiologic studies suggest that metformin use in diabetic patients decreases cancer incidence and cancer-related mortality. Metformin inhibits the growth of breast cancer cell lines by activating AMP kinase and thereby inhibiting the mTOR pathway/protein translation. We hypothesized that the antiproliferative effects of metformin might increase the efficacy of NST in diabetic BC patients. Methods: From the M.D. Anderson Breast Medical Oncology database, we identified 2,529 patients that received NST for early- stage BC. Patients' characteristics were compared by groups: non-diabetic (ND), diabetics taking metformin (DM) during NST, and diabetics not taking metformin (DN) during NST. pCR was defined as no residual disease in breast and nodes. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier product. Results: There were 2,374 (94%) ND, 68 (2.7%) DM, and 87 (3.4%) DN patients. Median age was 49 (range 21–87). 1,513 (60%) were stage I-II; 1,004 (40%) were stage III. 64% of tumors were hormone- receptor (HR) and 25% were HER2-positive. Prognostic factors were balanced overall in the 3 groups, though ND patients were more frequently white and pre-menopausal. pCR was seen in 16% ND, 24% DM, and 8% DN patients (p=0.03). At a median follow-up of 39 months, there have been 622 recurrences and 500 deaths. RFS was not statistically different between the three groups (p=0.84). The 3-year OS was significantly better in the ND (85.9%) group compared to the DM (80.9%) and DN (77.6%) groups (p=0.02). After adjustment for stage, grade, HR and HER2 status, ethnicity, and menopausal status, the odds ratio for achieving pCR was 1.32 (95% CI=0.69, 2.51; p=0.08) for DM and 0.45 (95%CI = 0.20, 1.02; p=0.03) for DN, as compared to ND patients. We are currently expanding our analysis cohorts. Conclusions: Diabetic BC patients receiving NST and metformin have higher pCR rates than those not receiving metformin. As metformin has a novel mechanism of action, further studies to evaluate its potential as an antitumor agent are warranted. No significant financial relationships to disclose.
Evaluation of the adverse event of nimotuzumab combined therapy in patients with advanced carcinoma.
Authors: L. Chen, H. Chen, X. Zhang, B. Liang, G. Zhang, G. MA, J. Zheng
Journal: Journal of Clinical Oncology (2011)

e13081 Background: To evaluate the adverse events of Nimotuzumab combined with chemotherapy, radiotherapy or chemo-radiotherapy in treatment of advanced carcinomas. Methods: From January 2010 until October 2010, 835 patients with pathologically diagnosed malignant tumor, staged between II to ‡W with practical metastasis treated by Nimotuzumab combined with radiotherapy, chemotherapy or chemo-radiotherapy (NCT00983047GNCT074021GNCT985998GNCT01232374GNCT980417GNCT910117GNCT972465GNCT01180166, etc.). Generally, patients were receiving a dose of 45Gy-72Gy radiotherapy. The patients who were mainly receiving combination of chemotherapy program of the platinum’s. All patients were receiving 100-200mg of Nimotuzumab once a week at the same time of the other therapies. Results: There were 792 cases' medical records can be analyzed, of which 241 patients have diagnosed as Nasopharyngeal cancer (28.86%), followed by: 153 cases of head and neck cancer (18.32%), etc. Patients aged 37-75 years-old with median age of 63. Male and female ratio was 5:2. Pathology diagnosed of more than 90% was squamous cell carcinoma. Adenosquamous carcinoma and adenocarcinoma were less than 10%. Cancer staged as ‡W, III and II were 38.2%, 53.7% and 10.1%, and with 23.6% of them with metastasis. 22 patients (2.63%) had adverse reactions which doubt as due to Nimotuzumab, including chills and fever in 8 cases (0.96%), rash in 5 cases (0.6%), oral mucositis in 3 cases (0.36%), gastrointestinal symptoms (vomiting or diarrhea) in 2 cases (0.24%), and dizziness in 1 case (0.12%). Patients with significant fatigue, thrombocytopenia, and decreased white blood cell count of the total number of cases of 0.12% (1 case), 0.6% (5 cases) and 0.6% (5 cases). Nimotuzumab caused allergy accounted for only 0.12% (1 case). Conclusions: Nimotuzumab combined with chemotherapy, radiotherapy or chemo-radiotherapy for patients with advanced carcinoma is well tolerated and safe, it will not increase the radiotherapy, chemotherapy radiotherapy induced adverse reaction rate and its' degree.
Impact of a clinical care online intake form in a breast care clinic.
Authors: Tracy M. Layton, Karen Messer, John P. Pierce, Lisa Madlensky, Lisa Cadmus, Ruth E. Patterson, Peter W. Chase, Susan Faerber, Richard B. Schwab, Sarah Blair, Anne M. Wallace, Barbara A. Parker
Journal: Journal of Clinical Oncology (2013)

137 Background: An online self-reported clinical care intake form was provided to new surgery patients of the Moores UCSD Breast Care Clinic, as part of a pilot project in collaboration with the University of California Athena Breast Health Network. Clinical care goals were 1) to reduce clinic time by pre-visit collection of patient histories, co-morbidities, and medications and 2) provide patient reported data to clinicians and the electronic medical record (EMR). Clinical research goals were to 1) identify individuals diagnosed with breast cancer, 2) collect baseline measures related to co-morbidities, psychosocial parameters, and lifestyle factors and 3) increase research opportunities and enrollment. Methods: We developed an online intake form for patients to complete at home prior to their appointment. Patients were informed to complete the intake form before their appointment and were sent instructions via email. Patients without an email address had the opportunity to complete their intake form on an iPad in clinic. A summary of intake form answers was uploaded into the EMR for all patients. Patients could consent to future contact, to have their intake data kept in a research registry and/or to provide a blood or tissue sample. Results: From March 2010 to May 2013, 1,224 sequential new breast surgery clinic patients were contacted to complete the online intake form as part of their clinical care. 890 patients completed the intake form prior to their visit (73%). 802 of the 890 patients consented to contact for future research opportunities (90%) and 624 of the 802 consented to share data and EMR access for research (78%). We have coordinated enrollment with our ongoing UCSD biorepository study and have collected 210 blood and 51 tissue samples. Additionally, using future contact consent, we recruited more than 100 participants to multiple lifestyle and survey-based clinical studies. Conclusions: The use of an online intake form is well accepted by patients and provides patient reported data to all clinicians involved in patient care. In conjunction with consented EMR access, these data can be evaluated routinely for quality and efficiency purposes. Initial consent for future contact greatly facilitates participant recruitment to research studies.
Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology
Authors: Antonia R. Sepulveda, Stanley R. Hamilton, Carmen J. Allegra, Wayne Grody, Allison M. Cushman-Vokoun, William K. Funkhouser, Scott E. Kopetz, Christopher Lieu, Noralane M. Lindor, Bruce D. Minsky, Federico A. Monzon, Daniel J. Sargent, Veena M. Singh, Joseph Willis, Jennifer Clark, Carol Colasacco, R. Bryan Rumble, Robyn Temple-Smolkin, Christina B. Ventura, Jan A. Nowak
Journal: Journal of Clinical Oncology (2017)

Purpose Molecular testing of colorectal cancers (CRCs) to improve patient care and outcomes of targeted and conventional therapies has been the center of many recent studies, including clinical trials. Evidence-based recommendations for the molecular testing of CRC tissues to guide epidermal growth factor receptor (EGFR) -targeted therapies and conventional chemotherapy regimens are warranted in clinical practice. The purpose of this guideline is to develop evidence-based recommendations to help establish standard molecular biomarker testing for CRC through a systematic review of the literature. Methods The American Society for Clinical Pathology (ASCP), College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) convened an Expert Panel to develop an evidence-based guideline to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for patients with CRC. A comprehensive literature search that included over 4,000 articles was conducted to gather data to inform this guideline. Results Twenty-one guideline statements (eight recommendations, 10 expert consensus opinions and three no recommendations) were established. Recommendations Evidence supports mutational testing for genes in the EGFR signaling pathway, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize molecular testing for predictive and prognostic molecular biomarkers involve selection of assays, type of specimens to be tested, timing of ordering of tests and turnaround time for testing results. Additional information is available at: www.asco.org/CRC-markers-guideline and www.asco.org/guidelineswiki.
Spatiotemporal progression of ubiquitin-proteasome system inhibition after status epilepticus suggests protective adaptation against hippocampal injury
Authors: Tobias Engel, Jaime Martinez-Villarreal, Christine Henke, Eva M. Jimenez-Mateos, Amaya Sanz-Rodriguez, Mariana Alves, Yasmina Hernandez-Santana, Gary P. Brennan, Aidan Kenny, Aoife Campbell, Jose J. Lucas, David C. Henshall
Journal: Molecular Neurodegeneration (2017)

The ubiquitin-proteasome-system (UPS) is the major intracellular pathway leading to the degradation of unwanted and/or misfolded soluble proteins. This includes proteins regulating cellular survival, synaptic plasticity and neurotransmitter signaling; processes controlling excitability thresholds that are altered by epileptogenic insults. Dysfunction of the UPS has been reported to occur in a brain region- and cell-specific manner and contribute to disease progression in acute and chronic brain diseases. Prolonged seizures, status epilepticus, may alter UPS function but there has been no systematic attempt to map when and where this occurs in vivo or to determine the consequences of proteasome inhibition on seizure-induced brain injury.To determine whether seizures lead to an impairment of the UPS, we used a mouse model of status epilepticus whereby seizures are triggered by an intra-amygdala injection of kainic acid. Status epilepticus in this model causes cell death in selected brain areas, in particular the ipsilateral CA3 subfield of the hippocampus, and the development of epilepsy after a short latent period. To monitor seizure-induced dysfunction of the UPS we used a UPS inhibition reporter mouse expressing the ubiquitin fusion degradation substrate ubiquitinG76V-green fluorescent protein. Treatment with the specific proteasome inhibitor epoxomicin was used to establish the impact of proteasome inhibition on seizure-induced pathology.Our studies show that status epilepticus induced by intra-amygdala kainic acid causes select spatio-temporal UPS inhibition which is most evident in damage-resistant regions of the hippocampus, including CA1 pyramidal and dentate granule neurons then appears later in astrocytes. In support of this exerting a beneficial effect, injection of mice with the proteasome inhibitor epoxomicin protected the normally vulnerable hippocampal CA3 subfield from seizure-induced neuronal death in the model. These studies reveal brain region- and cell-specific UPS impairment occurs after seizures and suggest UPS inhibition can protect against seizure-induced brain damage. Identifying networks or pathways regulated through the proteasome after seizures may yield novel target genes for the treatment of seizure-induced cell death and possibly epilepsy.