tbuckley/cabot-search huggingface dataset:
Screening for hepatitis B virus (HBV) prior to chemotherapy: A cost-effectiveness analysis.
Authors: U. Zurawska, L. K. Hicks, G. Woo, C. M. Bell, M. Krahn, K. K. Chan, J. J. Feld
Journal: Journal of Clinical Oncology (2011)

6059 Background: Hepatitis B virus (HBV) reactivation during chemotherapy may lead to disruption of chemotherapy, hospitalization for hepatitis, or even death. Prophylactic therapy with lamivudine (LAM) has been shown to prevent HBV reactivation. However, screening for HBV is uncommon in practice, and it remains unclear whether its benefits will outweigh its costs and inconvenience. Methods: A decision analytic model was developed for patients with lymphoma to compare the clinical outcomes and costs over a 1-year horizon of 3 strategies for HBV screening prior to R-CHOP chemotherapy: (1) screen all patients for HBsAg (All), (2) screen patients identified as being high risk for HBV infection (HR), and (3) screen no one (None). Patients testing positive were given LAM until 6 months following completion of chemotherapy. Those not screened were initiated on LAM only when HBV hepatitis occurred. Risks for HBV hepatitis, recovery, HBV-related death, and lymphoma outcomes were derived from systematic literature review from 1997-2009. A third-party direct payer perspective in 2010 Canadian dollars was used. Results: See table. Screening all patients was the dominant strategy. It was both least costly and most effective in increasing the 1-year survival rate. This is likely because it reduced both hospitalization and death from HBV-related hepatitis, which are associated with considerable cost. The analysis was sensitive to the cost of HBsAg testing, the prevalence of HBsAg positivity in both the high risk and low risk groups, and the effectiveness of LAM in preventing reactivation. Conclusions: In patients receiving CHOP-R for lymphoma, screening all patients for HBV is more clinically effective and less costly than screening only high-risk patients or screening no patients. Further study is needed to examine the cost-effectiveness of screening of HBV in other settings. Outcome/strategy Screen all Screen HR Screen none Cost ($CDN 2010) $30,367 $30,371 $30,413 1-year survival rate (%) 0.8500 0.8497 0.8489 HBV hepatitis (per 1,000 patients) 0.4 1.8 6 HBV hepatitis requiring hospitalization (per 1,000 patients) 0.1 0.8 2.7 Hepatitis death (per 1,000 patients) 0 0.1 0.4
Hormone therapy versus chemotherapy as first-line treatment for estrogen receptor-positive metastatic breast cancer (MBC) patients.
Authors: T. Y. Chang, C. Lin, Y. Lu, S. H. Kuo, S. Huang, C. Huang, A. Cheng
Journal: Journal of Clinical Oncology (2011)

622 Background: Hormone therapy (H/T) and chemotherapy (C/T) have both improved significantly in the past two decades; however, there were no study addressing head to head comparison between these 2 treatments in estrogen receptor (ER) positive metastatic breast cancer (MBC) patients. Methods: We retrieved the study cohort from the National Taiwan University Hospital cancer registry database, from 2001~2006. All ER(+) and HER2(-) MBC subjects were collected and reviewed. ER(+) was defined as ≥10% positively stained nuclei under immunohistochemical stain. Time to treatment failure (TTF) was defined as the start date of 1st line treatment to disease progression or the start date of 2nd line treatment whichever happened first; or the date of death or last follow-up. Overall survival (OS) was defined as the date of diagnosis of MBC to death or last follow-up date. Statistical analysis was performed by Kaplan-Meier method and log-rank test. Results: Excluding 21 pts for lack of sufficient data, 3 pts for OS<3m, and 14 pts received combination of H/T and C/T, a total of 301 pts were analyzed. The choice of treatment modality was under the discretion of attending physicians. H/T was chosen as 1st treatment in ≥ 60% pts throughout various subgroups. The diseases extent and severity were well balanced between the two groups of patients. We found no significant difference between H/T or C/T in TTF or in OS. Conclusions: There is no significant difference for OS and TTF in ER(+) HER2(-) MBC patients receiving H/T or C/T as their 1st line treatment. Grant support: DOH 99-TD-C-111-001. Whole group Visceral organ metastasis (+) No. of metastatic site ≥ 2 No. visceral organ metastatic site ≥ 2 H/T C/T p-value H/T C/T p H/T C/T p H/T C/T p Pt No. 199 102 105 59 79 39 28 11 TTF (m) 5.03 4.86 0.008 3.17 4.67 0.313 2.93 5.13 0.249 2.57 2.73 0.377 OS (m) 46.80 45.20 0.303 59.53 36.13 0.162 46.07 33.90 0.164 37.73 NA 0.761
Fracture risks of prostate cancer and androgen-deprivation therapy in men: A Canadian provincial population-based analysis
Authors: Y. Lau, C. E. Lee, H. J. Prior, L. Lix, C. J. Metge, W. D. Leslie
Journal: Journal of Clinical Oncology (2008)

5174 Introduction: Prostate cancer is the most common lethal malignancy diagnosed in men. The use of androgen-deprivation therapy (ADT) is the mainstay of treatment at the advanced stage of the disease. Prostate cancer in men has been associated with osteoporosis. The use of ADT further increases the risk of osteoporosis in men with prostate cancer, with associated higher risk of fracture than their age-matched control counterparts. We sought to explore the association of fracture risk in men with prostate cancer, and to confirm that in those who were on ADT in the Manitoba population. Methods: We used the Manitoba Health Population Health Research Data Repository to identify all cases of fractures of the hip, vertebra, or wrist in men aged 50 years and older occurring between 1996 and 2004, who were each matched by age, sex, and medical comorbidity. We calculated the odds ratios (OR) for fracture with prostate cancer, and with or without ADT after adjusting for possible confounding variables (sociodemographic variables and diagnoses known to influence risk of fracture). Results: 4,696 cases of fracture were matched with 14,080 controls. There were 276 cases of fracture out of 1, 074 men with prostate cancer. After controlling for confounding variables, there was no significant association between prostate cancer and fracture risk (OR = 0.973, p= 0.75). We detected a significant association between ADT and fracture risk in men. The adjusted OR for current and past ADT usage were 1.689 (95% confidence intervals (CI): 1.118 - 2.550, p= 0.013) and 2.505 (95% CI: 1.471–4.263, p= 0.0007) respectively. Conclusions: Despite the association between prostate cancer and osteoporosis, our findings suggest that the disease itself does not increase the risk of fracture. Nonetheless, our findings of increased fracture risk in men on ADT in our population corroborate published results, demonstrating an association between ADT and fractures. No significant financial relationships to disclose.
Detection of early cardiac effects through strain rate imaging in patients undergoing breast cancer treatment with trastuzumab.
Authors: V. Michalaki, G. Koutroulis, S. Gennatas, C. G. Gennatas
Journal: Journal of Clinical Oncology (2011)

e11093 Background:Trastuzumab prolongs survival in patients with human epidermal growth factor receptor type 2-positive breast cancer. Sequential left ventricular (LV) ejection fraction (EF) assessment has been mandated to detect myocardial dysfunction. Changes in cardiac function induced by this therapy, however, are subtle and difficult to quantitate by conventional imaging methods. Doppler myocardial imaging-based velocity, strain, and strain rate measurements have been shown to sensitively quantify abnormalities in cardiac function in other settings. The aim of this study was to determine if sensitive indices of left ventricular (LV) dysfunction, specifically strain rate imaging, would be useful for addressing the early detection of trastuzumab mediated cardiotoxicity. Methods:In a pilot study, we examined 12 women (age 59.8 +/- 3.6 years) with breast cancer receiving 18 cycles of trastuzumab. Conventional and Doppler myocardial imaging echocardiography were obtained at baseline and every 3 months of treatment. Segmental peak systolic longitudinal and radial velocity, strain, and strain rate (SR) were measured. Results:There was no overall change in Left ventricular dimensions, ejection fraction, and systolic myocardial velocity. In contrast, a significant reduction in longitudinal and radial strain and strain rate was found after 9 cycles (longitudinal strain -12.8% +/- 2.2% vs baseline (P = .001); radial strain 29.3% +/- 7.1% vs 50.3% +/- 10.6%, P < .001 vs baseline). Changes in radial function appeared earlier and were more pronounced than in longitudinal direction. Conclusions:In contrast with conventional echocardiography myocardial velocity measurements allowed detecting subtle changes in longitudinal and radial left ventricular function after 9 cycles of trastuzumab. We suggest that strain rate imaging identifies preclinical myocardial dysfunction earlier than conventional measures in women undergoing treatment with trastuzumab for breast cancer and should be used for cardiac function monitoring.
Impact of dosing schedule of doxorubicin and cyclophosphamide (AC) chemotherapy on rates of hospitalization and resource utilization.
Authors: Helen O Donovan, Kate Murphy, Brian Richard Bird, Conleth G. Murphy
Journal: Journal of Clinical Oncology (2015)

78 Background: 4 cycles ofAC chemotherapy are given as a component of several important and widely used chemotherapy regimens in the adjuvant treatment of breast cancer. We queried whether the use of dose-dense (every 2 week) AC chemotherapy is associated with a lower rate of hospitalization and resource utilization in clinical practice. Methods: We identified patients with early stage breast cancer treated with 3-weekly AC chemotherapy in a single institution. Cases were matched to controls by year of diagnosis and age. Rates of hospitalization during AC chemotherapy as well as duration of hospitalization, associated costs and use of pegfilgrastim were compared between the two groups. Fisher's exact test was used to compare categorical variables, and paired t-test was used to compare continuous variables. Results: 26 patients were included in the analysis. The mean age was 56 in both groups. As expected, rates of growth factor support with pegfilgrastim were higher in the dose dense versus 3-weekly group (52 versus 23 cycles, 2-tailed p = 0.0003). There was no difference in the likelihood of hospitalization among patients treated with dose dense versus 3-weekly AC (Fisher's exact test, p-value = 1.00). There was no difference in the mean duration of hospitalization between groups (mean 2.31 versus 1.23 days, 2-tailed p = 0.3352).Costs pertaining to pegfilgrastim use and hospitalization will be compared. Conclusions: In this clinical setting, dose dense administration of AC was not associated with lower rates or mean duration of hospitalization.
Evaluation of the palliative benefit and toxicity of Ra-223 treatment of men with hormone refractory prostate cancer in a community setting.
Authors: Houman Vaghefi, Bide Xiong, Fang Liu, Elizabeth Garber, James Wheeler
Journal: Journal of Clinical Oncology (2016)

225 Background: The ALSYMCA (Alpharadin in Symptomatic Prostate Cancer) trial was a phase III, placebo controlled, randomized trial in which 921 men with bone metastasis from hormone refractory prostate cancer (HRPC) were randomly assigned to receive radium-223 (Ra-223) or placebo. Ra-223 produced a 30% survival benefit, with a median survival of 14.9 months compared to 11.3 months for patients treated with a placebo, which led to FDA approval in 2013. Methods: We identified through the nuclear medicine records 11 patients who started Ra-223 between March 15, 2013 and December 10, 2015. The Wilcoxon signed rank test was used to compare the published results of the ALSYMPCA patients with those from our institution. Results: The Hodges-Lehman estimate of the median survival of our patients from the date of the first Ra-223 infusion was 7.8 months. The 95% confidence interval (CI) was (2.8, 14.7; p = 0.0122) indicating our patients had a significantly shorter survival. Our patients did not have a statistically significant worse rate of anemia, neutropenia, or thrombocytopenia. Only 27.3% (95% CI: 6.0, 61.0%) of our patients completed all 6 planned infusions significantly less than 63% for the ALSYMPCA patients treated with Ra-223 (p = 0.0239), but not statistically different than the placebo patients (p = 0.236). The median survival from the last Ra-223 was 3.53 months. We used 3 measures of treatment effectiveness: (1) reduction in the pain scores, (2) reduction in the serum PSA, and (3) reduction in the alkaline phosphatase. Compared to the pre-treatment values, numerical reductions were seen at the last follow-up evaluation for both the pain scores and the alkaline phosphatase levels, but the reductions were not statistically significant. Conclusions: Not all patients with castration resistant prostate cancer benefit from Ra-223 to the same extent as the ALSYMPCA patients. It is important to identify patients with a sufficient life expectancy to benefit from this treatment.
Sarcoma gene expression and response to approved and investigational agents: Focus on osteosarcoma.
Authors: Eric Polley, Anne Monks, Joel Morris, Annamaria Rapisarda, Gurmeet Kaur, Susan Mertins, John Connelly, Thomas Silvers, Rene Delosh, Julie Laudeman, Chad Ogle, Russell Reinhart, David Evans, Beverly A. Teicher
Journal: Journal of Clinical Oncology (2014)

e22067 Background: Sarcomas are rare heterogeneous cancers with significant unmet medical need. Identification of gene expression associated with response to potential novel clinical agents is important. Methods: Response of 62 adult and pediatric human sarcoma cell lines was evaluated against approved (93 drugs) and investigational (350 compounds) anticancer agents. Lines were exposed to 9 concentrations (10uM-1.5nM) for 96h (384-well format); cell viability was determined using Alamar Blue. Gene expression was generated using the Affymetrix Human Exon 1.0 ST arrays according to manufacturer’s instructions. Results: The RTK ErbB family had variable gene expression across the lines. High ERBB4 expression was evident in 50% of Ewing sarcoma lines, and was highly expressed in 2/10 osteosarcoma lines. Of 18 approved and investigational broad spectrum kinase inhibitors and selective FGFR, KIT and MET inhibitors, the most sensitive osteosarcoma lines included CHA59, HOS, and Hu09 while SA-OS-2 was less sensitive. SA-OS-2 expresses high KIT and FGFR2 which may drive resistance. The sensitive lines had lower expression of FGF receptors, MET, KIT and KDR. OHS, CHA59, HOS and Hu09 cells were sensitive to 2 bromodomain inhibitors, JQ1 and GSK-1210151A. These agents target MYC transcription, and OHS, CHA59 and SAOS2 express high MYC, although other sensitive lines did not. Aberrant hedgehog and WNT signaling in osteosarcoma are documented. Only Hu09 cells respond to inhibitors of these pathways at concentrations up to 10uM. However, the Hu09 line does not differentially express the putative targets of these pathways; unlike the SJSA-1 line which expresses high GLI1, PTCH1 and PTCH2, but is insensitive to the inhibitors tested. Conclusions: Evaluation of targeted, investigational agents in a sarcoma line panel with parallel molecular characterization may help identify new drugs and sarcoma patients most likely to benefit.
Assessment of adrenal function and health-related quality of life in patients with advanced gastric cancer who received first-line chemotherapy.
Authors: H. Lee, H. R. Kim, S. Song, C. Kim, S. S. Lee, S. K. Song, S. Lim, G. M. Kim, S. H. Noh, S. Y. Rha
Journal: Journal of Clinical Oncology (2011)

e14609 Background: General weakness, fatigue, and anorexia are troublesome adverse effects that hinder quality of life, while the patients receive chemotherapy. The precise cause of these non-specific symptoms was overlooked and did not receive attention. We performed this prospective study to identify both the incidence of adrenal insufficiency and health-related quality of life (HRQOL) in advanced gastric cancer patients who received the S-1 plus cisplatin (SP) regimen as first-line palliative chemotherapy. Methods: In this pilot study, fifty-two patients with advanced gastric cancer were enrolled between January 2009 and June 2010, and received the SP regimen as first-line palliative chemotherapy. Adrenal function was assessed at baseline and 12-weeks after systemic chemotherapy using the low dose ACTH stimulation test. HRQOL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 (EORTC-QLQ C30). Results: Among total 52 patients, the incidence of adrenal insufficiency was 30.8% (16 patients) after 12 weeks of follow-up. Among the 23 asymptomatic patients, six patients (26.1%) were diagnosed with adrenal insufficiency. The adrenal insufficiency group showed a trend of deterioration in terms of global health quality of life, compared with non-adrenal insufficiency group. Conclusions: This is the first comprehensive prospective study assessing adrenal function in advanced gastric cancer patients who received chemotherapy. The incidence of secondary adrenal insufficiency in advanced gastric cancer patients is not rare and was not significantly correlated with the presence of symptom. Asymptomatic patients with adrenal insufficiency have risk with potentially life threatening consequence. Thus, the evaluation of adrenal insufficiency could be suggested in these patients.
Nomogram predicting treatment-related urinary incontinence for men with localized prostate cancer treated by radical prostatectomy (RP), external-beam radiotherapy (EBRT), or brachytherapy (PI).
Authors: Joseph C. Klink, Martin G. Sanda, Mark S. Litwin, Montserrat Ferrer, Meredith M. Regan, Christopher Saigal, Lorna Kwan, Tianming Gao, Eric A. Klein, Michael W. Kattan, Andrew J. Stephenson
Journal: Journal of Clinical Oncology (2012)

49 Background: RP, EBRT, and PI for the treatment of clinically localized prostate cancer may negatively impact urinary continence. Predictions of treatment-related urinary problems from patient-reported, prospective data may be useful in treatment decision-making. Methods: Patient-reported data on treatment-related urinary incontinence was obtained from four prospective, longitudinal, health-related quality-of-life (HRQOL) protocols comprising 2,668 patients treated between 1999 and 2011 by RP (n = 1,294), EBRT (n = 630), and PI (n = 744). A single HRQOL instrument was not uniformly used for each study, although questions pertaining to the quantity (pad use) and frequency of urinary incontinence (“never” to “more than once per day”) were identical among the studies. Patient responses were obtained at baseline and at two years after treatment. The endpoint of the model was urinary continence defined as no pad use and leakage of urine less than once per day. Cox proportional hazards regression analysis was used to model the clinical information and follow-up data. Internal validation was performed using bootstrapping. Results: Overall, 1,937 (92%) of patients with complete data available were considered to be continent at baseline. Significant differences in baseline characteristics such as patient age, ethnicity, and disease severity existed between the treatment groups. The overall continence rate at two years was 66%, 88%, and 87% for patients treated by RP, EBRT, and PI, respectively (p &lt; 0.001). In multivariable analysis, age (p = 0.001), baseline frequency of incontinence (p &lt; 0.001), EBRT (p &lt; 0.001), PI (p &lt; 0.001), and ethnicity (p &lt; 0.001) were associated with urinary continence. A nomogram based on the predictive parameters had a concordance index of 0.74 and predictions were well-calibrated with observed outcome. Conclusions: An externally-validated nomogram that predicts two-year urinary continence after treatment for localized prostate cancer has been developed and will be useful for patient counseling regarding treatment options.
Immunoglobulin Heavy Chain (IgH) Gene Rearrangement in Egyptian Precursor B-Acute Lymphoplastic Leukemia - Implication for Assessment of Minimal Residual Disease.
Authors: Dalia A. El-Beshir, Sameh S. Shammaa, Paul P. Evans, Nader G. Abraham, Hasan A. Abd-Elghaffar
Journal: Blood (2007)
Molecular profiles of appendiceal adenocarcinoma: The UCSD experience.
Authors: John P. Shen, Devon Marcus McGee, Andrew M. Lowy, Paul Timothy Fanta
Journal: Journal of Clinical Oncology (2013)

397 Background: Appendix cancer is rare, which precludes its study in randomized trials. As such, no evidence-based guidelines currently exist regarding the optimum systemic therapy for this disease entity. Typically, these patients are treated with regimens for colorectal carcinoma. Previous studies have shown high intra-tumoral mRNA levels of EGFR were significantly associated with response to irinotecan based chemotherapy, and that mucinous colorectal cancer overexpresses markers of resistance to 5-FU and oxaliplatin. We examined pharmacogenomics markers for appendiceal cancer and colon cancer to understand underlying similarities and differences between these tumor types. Methods: Intratumoral gene expression levels were assessed from paraffin-embedded tissue samples, using laser capture microdissection and quantitative real-time PCR from 69 colorectal and 34 appendiceal adenocarcinomas. A retrospective chart review was performed to correlate gene expression with overall survival. KRAS and BRAF mutational analyses and gene expression levels of ERCC1, TS, and EGFR were correlated with overall survival. Results: Appendiceal tumors had significantly higher expression of EGFR, (2.66 vs 1.4, p&lt;.0001). No BRAF V600E mutations were found in the appendiceal tumors, incidence was 8.97% of the colon patients. UPDATE: In appendix cancer, KRAS mutations were noted in 65.5% of patients, there were no BRAF mutations. Median ERCC1, TS, EGFR, and VEGFR2A expression was 1.4, 1.21, 1.57, 2.19 respectively. Patients with metastatic appendiceal cancer had a significantly longer median OS than metastatic colon patients, (113 mo vs 43.9 mo, p = .0154). For appendiceal cancer patients, there was no significant correlation between any of the biomarkers and OS, although the sample size was underpowered for such an analysis. Conclusions: Metastatic appendiceal cancer patients have significantly better outcomes than metastatic colon cancer patients. Molecular analyses reveal significant differences between these tumor types. Further molecular study of appendiceal cancer is needed, as this study and others suggest fundamental differences in biology from colon cancer.