Wilbur D.C.,VisionGate |
Meyer M.G.,VisionGate |
Presley C.,VisionGate |
Aye R.W.,Swedish Hospital |
And 4 more authors.
Cancer Cytopathology | Year: 2015
BACKGROUND The LuCED Lung Test comprises an automated 3-dimensional morphologic analysis of epithelial cells in sputum. For each cell, 594 morphology-based features are measured to drive algorithmic classifiers that quantitatively assess whether neoplastic cells are present. The current interim clinical study involves sputum samples from patients with known benign and malignant outcomes to assess the feasibility of LuCED as an adjunctive test after suspicious low-dose computed tomography (LDCT) results or as an independent screening test for lung cancer. METHODS Sputum samples were fixed, enriched for epithelial cells, and analyzed with a 3-dimensional cell scanner called Cell-CT. Candidate abnormal cells were identified by the classifiers for manual review. The sensitivity, specificity, and negative and positive predictive values were calculated for the detection of neoplastic cases. RESULTS A total of 91 sputum samples from patients with confirmed lung cancer (49 patients) and patients with no known malignancy (42 patients) were evaluated. After cytology review, sensitivity in the positive group was 91.8%, and specificity was 95.2%. Specificity was not 100% because there were 2 cases in which abnormal cells were identified by the Cell-CT that were confirmed as such at the time of manual cytology review. However, at the time of last follow-up, malignancy had not been detected in these 2 cases. Modeling in a population with a 1% prevalence of lung cancer, the positive and negative predictive values would be 95.4% and 99.9%, respectively. CONCLUSIONS LuCED testing is highly sensitive and specific for the detection of lung cancer and has potential value as an adjunctive test after suspicious LDCT findings or as a primary screening test in which LuCED-positive cases would be triaged to diagnostic CT. Further prospective studies currently are underway to evaluate its full usefulness. © 2015 American Cancer Society.
Wolchok J.D.,Sloan Kettering Cancer Center |
Neyns B.,Universitair Ziekenhuis |
Linette G.,University of Washington |
Negrier S.,Center Leon Berard |
And 12 more authors.
The Lancet Oncology | Year: 2010
Background: Ipilimumab is a human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 and has shown promising activity in advanced melanoma. We aimed to ascertain the antitumour efficacy of ipilimumab in patients with advanced melanoma. Methods: We undertook a randomised, double-blind, phase 2 trial in 66 centres from 12 countries. 217 patients with previously treated stage III (unresectable) or stage IV melanoma were randomly assigned a fixed dose of ipilimumab of either 10 mg/kg (n=73), 3 mg/kg (n=72), or 0·3 mg/kg (n=72) every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. Randomisation was done with a permuted block procedure, stratified on the basis of type of previous treatment. The primary endpoint was best overall response rate (the proportion of patients with a complete or partial response, according to modified WHO criteria). Efficacy analyses were done by intention to treat, whereas safety analyses included patients who received at least one dose of ipilimumab. This study is registered with ClinicalTrials.gov, number NCT00289640. Findings: The best overall response rate was 11·1% (95% CI 4·9-20·7) for 10 mg/kg, 4·2% (0·9-11·7) for 3 mg/kg, and 0% (0·0-4·9) for 0·3 mg/kg (p=0·0015; trend test). Immune-related adverse events of any grade arose in 50 of 71, 46 of 71, and 19 of 72 patients at doses of 10 mg/kg, 3 mg/kg, and 0·3 mg/kg, respectively; the most common grade 3-4 adverse events were gastrointestinal immune-related events (11 in the 10 mg/kg group, two in the 3 mg/kg group, none in the 0·3 mg/kg group) and diarrhoea (ten in the 10 mg/kg group, one in the 3 mg/kg group, none in the 0·3 mg/kg group). Interpretation: Ipilimumab elicited a dose-dependent effect on efficacy and safety measures in pretreated patients with advanced melanoma, lending support to further studies at a dose of 10 mg/kg. Funding: Bristol-Myers Squibb. © 2010 Elsevier Ltd. All rights reserved.
PubMed | Eli Lilly and Company, Tennessee Oncology, University of Washington, Rocky Research and 9 more.
Type: Journal Article | Journal: Clinical breast cancer | Year: 2016
Use of antiangiogenic agents in treatment of metastatic breast cancer (MBC) remains controversial. We evaluated the efficacy and safety of ramucirumab and eribulin versus eribulin alone as third- to fifth-line therapy in women with advanced breast cancer.In this randomized (1:1), open-label, phase II study, US women aged 18 years or older with 2 to 4 previous chemotherapy regimens for locally recurrent or MBC, previous anthracycline and taxane treatment, and Eastern Cooperative Oncology Group performance status of 0 or 1 received ramucirumab with eribulin or eribulin alone in 21-day cycles (eribulin 1.4 mg/mOne hundred forty-one women were randomized to ramucirumab with eribulin (n= 71) or eribulin alone (n= 70). Median PFS for ramucirumab with eribulin was 4.4 months (95% confidence interval [CI], 3.1-6.7) compared with 4.1 months (95% CI, 3.2-5.6) for eribulin (hazard ratio [HR], 0.83; 95% CI, 0.56-1.23; P= .35). Median overall survival in patients who received ramucirumab with eribulin was 13.5 months (95% CI, 10.4-17.9) compared with 11.5 months (95% CI, 9.0-17.3) in patients who received eribulin alone (HR, 0.91; 95% CI, 0.59-1.41; P= .68); objective response rate was 21% (13 of 62 patients) for the combination and 28% (17 of 60 patients) for eribulin alone. No unexpected toxicity was identified for the combination.Ramucirumab combined with eribulin did not significantly improve PFS in advanced MBC.
Andtbacka R.H.I.,University of Utah |
Kaufman H.L.,Rutgers Cancer Institute of New Jersey |
Collichio F.,University of North Carolina at Chapel Hill |
Amatruda T.,Minnesota Oncology |
And 26 more authors.
Journal of Clinical Oncology | Year: 2015
Purpose Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial Patients and Methods Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously > 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate Results Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P < .001). Overal response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P = .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in ≥ 2% of T-VEC-treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred Conclusion T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma. © 2015 by American Society of Clinical Oncology.
Ohri N.,Yeshiva University |
Duan F.,Brown University |
MacHtay M.,Case Western Reserve University |
Gorelick J.J.,Brown University |
And 7 more authors.
Journal of the National Cancer Institute | Year: 2015
Background: ACRIN 6668/RTOG 0235 evaluated the prognostic value of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) uptake before and after definitive, concurrent, platinum-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). In this secondary analysis, we evaluate volumetric pretreatment PET measures as predictors of clinical outcomes. Methods: Patients with stage III NSCLC underwent FDG-PET prior to treatment. A commercially available gradient-based segmentation tool was used to contour all visible hypermetabolic lesions on each scan. For each patient, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity (TGA) for all contoured lesions were recorded. Cox proportional hazards regression models were used to evaluate clinical variables and PET metrics as predictors of overall survival (OS) and locoregional control (LRC). Time-dependent covariables were added to the models when necessary to address nonproportional hazards. All statistical tests were two-sided. Results: Complete data were available for 214 patients in the OS analysis and 189 subjects in the LRC analysis. In multivariable analysis incorporating clinical and imaging data available prior to treatment, MTV was an independent predictor of OS (HR = 1.04 per 10cm3 increase, 95% CI = 1.03 to 1.06, P <. 001). High MTV was also associated with increased risk of locoregional failure at baseline (HR = 1.16 per 10cm3 increase, 95% CI = 1.08 to 1.23, P <. 001) and at six months (HR = 1.05 per 10cm3 increase, 95% CI = 1.02 to 1.07, P <. 001) but not at 12 months or later time points. Conclusion: Pretreatment MTV is a predictor of clinical outcomes for NSCLC patients treated with chemoradiotherapy. Quantitative PET measures may serve as stratification factors in clinical trials for this patient population and may help guide novel trial designs. © 2015 The Author. Published by Oxford University Press. All rights reserved.
PubMed | Thomas Jefferson University, University of Washington, Brown University, University of Michigan and 6 more.
Type: Journal Article | Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine | Year: 2016
In a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/RTOG 0235, high pretreatment metabolic tumor volume (MTV) on (18)F-FDG PET was found to be a poor prognostic factor for patients treated with chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). Here we utilize the same dataset to explore whether heterogeneity metrics based on PET textural features can provide additional prognostic information.Patients with locally advanced NSCLC underwent (18)F-FDG PET prior to treatment. A gradient-based segmentation tool was used to contour each patients primary tumor. MTV, maximum SUV, and 43 textural features were extracted for each tumor. To address overfitting and high collinearity among PET features, the least absolute shrinkage and selection operator (LASSO) method was applied to identify features that were independent predictors of overall survival (OS) after adjusting for MTV. Recursive binary partitioning in a conditional inference framework was utilized to identify optimal thresholds. Kaplan-Meier curves and log-rank testing were used to compare outcomes among patient groups.Two hundred one patients met inclusion criteria. The LASSO procedure identified 1 textural feature (SumMean) as an independent predictor of OS. The optimal cutpoint for MTV was 93.3 cm(3), and the optimal SumMean cutpoint for tumors above 93.3 cm(3) was 0.018. This grouped patients into three categories: low tumor MTV (n = 155; median OS, 22.6 mo), high tumor MTV and high SumMean (n = 23; median OS, 20.0 mo), and high tumor MTV and low SumMean (n = 23; median OS, 6.2 mo; log-rank P < 0.001).We have described an appropriate methodology to evaluate the prognostic value of textural PET features in the context of established prognostic factors. We have also identified a promising feature that may have prognostic value in locally advanced NSCLC patients with large tumors who are treated with chemoradiotherapy. Validation studies are warranted.
Latif N.,University of Florida |
Guthrie T.,Baptist Cancer Institute |
Rana F.,University of Florida
Community Oncology | Year: 2010
Patients affected by myeloproliferative neoplasms have an increased risk of thrombosis, hemorrhage, and occasional leukemic transformation. The recent discovery of the V617F mutation of the janus kinase 2 (JAK2) gene has shed new light on this group of diseases. In this article, we review the updated classification, pathogenesis, and management of myeloproliferative neoplasms. © 2010 Elsevier Inc. All rights reserved.
Latif N.,Florida College |
Rana F.,Florida College |
Guthrie T.,Baptist Cancer Institute
Breast Journal | Year: 2011
The incidence of human immunodeficiency virus (HIV) infection is rising in US women; however its impact on breast cancer incidence, stage at presentation, response and treatment toxicity remains unknown. To address the impact of HIV infection and use of highly active antiretroviral therapy (HAART) on the natural history of breast cancer we present two cases of breast cancer in HIV-infected women and also review the literature. A literature search was done on Medline using the key words HIV/AIDS, breast cancer, and HAART therapy, restricted to English language. There were mostly case reports and one large series of 20 cases reported by Hurley et al. Data concerning the impact of HIV infection and HAART therapy regarding pathogenesis, stage at presentation, tumor type, response, and toxicity associated with treatment were reviewed. The literature review shows that the breast cancer incidence is either same or less in HIV-infected patients compared to the general population. However, the patients with HIV infection present with more advanced stage and aggressive disease, and they also have poor chemotherapy tolerance. The impact of HAART on breast cancer incidence in HIV-infected patients is still unclear. © 2010 Wiley Periodicals, Inc.
Park C.H.,Mount Sinai School of Medicine |
Bonomi M.,Mount Sinai School of Medicine |
Cesaretti J.,Baptist Cancer Institute |
Neugut A.I.,Columbia University |
Wisnivesky J.P.,Mount Sinai School of Medicine
International Journal of Radiation Oncology Biology Physics | Year: 2011
Purpose: To evaluate whether complex radiotherapy (RT) planning was associated with improved outcomes in a cohort of elderly patients with unresected Stage I-II non-small-cell lung cancer (NSCLC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 1998 patients aged >65 years with histologically confirmed, unresected stage I-II NSCLC. Patients were classified into an intermediate or complex RT planning group using Medicare physician codes. To address potential selection bias, we used propensity score modeling. Survival of patients who received intermediate and complex simulation was compared using Cox regression models adjusting for propensity scores and in a stratified and matched analysis according to propensity scores. Results: Overall, 25% of patients received complex RT planning. Complex RT planning was associated with better overall (hazard ratio 0.84; 95% confidence interval, 0.75-0.95) and lung cancer-specific (hazard ratio 0.81; 95% confidence interval, 0.71-0.93) survival after controlling for propensity scores. Similarly, stratified and matched analyses showed better overall and lung cancer-specific survival of patients treated with complex RT planning. Conclusions: The use of complex RT planning is associated with improved survival among elderly patients with unresected Stage I-II NSCLC. These findings should be validated in prospective randomized controlled trials. © 2011 Elsevier Inc.
Gupta E.,Mayo Medical School |
Guthrie T.,Baptist Cancer Institute |
Tan W.,Mayo Medical School
BMC Urology | Year: 2014
Recently, the standard of care for metastatic Castration Resistant Prostate Cancer (mCRPC) has changed considerably. Persistent androgen receptor (AR) signaling has been identified as a target for novel therapies and reengages the fact that AR continues to be the primary target responsible for metastatic prostate cancer. Androgen receptor gene amplification and over expression have been found to result in a higher concentration of androgen receptors on tumor cells, making them extremely sensitive to low levels of circulating androgens. Additionally, prostate cancer cells are able to maintain dihydrotestosterone (DHT) concentration in excess of serum concentrations to support tumor growth. For many years ketoconazole was the only CYP17 inhibitor that was used to treat mCRPC. However, significant toxicities limit its use. Newly approved chemotherapeutic agents such as Abiraterone (an oral selective inhibitor of CYP17A), which blocks androgen biosynthesis both within and outside the prostate cancer cells), and enzalutamide (blocks AR signaling) have improved overall survival. There are also ongoing phase III trials for Orteronel (TAK- 700), ARN- 509 and Galeterone (TOK-001), which targets androgen signaling. In this review, we will present the rationale for the newly approved hormonal treatments, their indications and complications, and we will discuss ongoing trials that are being done to improve the efficacy of the approved agents. Finally, we will talk about the potential upcoming hormonal treatments for mCRPC. © 2014Gupta et al.; licensee BioMed Central Ltd.