4574 Background: Hepatocellular carcinoma (HCC) is one of the most common cancers globally and its incidence of in USA is increasing. Unfortunately, most patients with HCC are unsuitable for surgical resection or transplantation. Because of the heterogeneity of this disease and poor liver function in many patients, there is no generally accepted standard chemotherapy regimen for HCC. Efforts have been made to investigate effective and tolerable therapy for patients with advanced HCC. We conducted a phase II study to evaluate the efficacy and feasibility of the combination of bevacizumab, oxaliplatin and capecitabine in patients with advanced or metastatic HCC. The primary goal of the study was to evaluate the progression-free survival rate. The secondary endpoints include response, overall survival and toxicity. Methods: Patients with advanced or unresectable untransplantable metastatic HCC who had adequate bone marrow, liver and renal function (ANC ≥ 1,500/mm3, platelets ≥ 75,000/mm3, serum creatinine ≤ 2.0 mg/dl, total bilirubin ≤ 3.0 mg/dl, transaminases ≤ 5 upper limit of normal, and INR ≤ 1.5) were eligible to the study. Bevacizumab (5 mg/kg) and oxaliplatin (130 mg/m2) were administered intravenously day 1 of each 21- day cycle. Capecitabine (825 mg/m2, twice a day) was administered days 1 to 14. Results: Thirty patients (male/female ratio of 23/7) have been enrolled, with a median age of 57 (range 23–85). The average number of treatment cycles was 8 (2–25 cycles). Of evaluable patients, 3 patients (11%) achieved partial response, 21 patients had stable disease (78%) with a disease control rate of 89%. The mean PFS was 5.4 months with 3- and 6- months PFS of 70%, and 40%. There were 33% Gr. 2/3 oxaliplatin-related peripheral neuropathy and 11 % capecitabine-related Gr. 2/3 hand- foot syndrome. One patient had gastrointestinal perforation and sepsis after his first administration of bevacizumab and oxaliplatin. Two patients had esophageal varices-related bleeding, likely disease-related. Conclusions: The results demonstrate that the combination of bevacizumab, oxaliplatin and capecitabine is effective and tolerable in treatment of advanced HCC and should be considered for the further investigation. [Table: see text]
Recent data show that overall survival after endoscopic mucosal resection (EMR) is similar to esophagectomy, however, limited data exists regarding the comparative efficacy of definitive radiotherapy (RT) for the treatment of T1N0 esophageal cancer. We sought to investigate the patterns of practice for the treatment of T1N0 esophageal cancer in the United States as well as to evaluate the comparative efficacy of esophagectomy vs EMR vs RT. Materials/Methods: Patients with clinical T1N0 esophageal carcinoma who underwent esophagectomy, EMR or RT (45 e 70 Gy) were identified from the National Cancer Database (NCDB) from 2004 to 2013. Univariate (UVA) and multivariable (MVA) effects of treatment type on survival were assessed using Cox proportional hazards regression. Overall survival (OS) was compared using Kaplan-Meier analysis and the log-rank test. Variables with p<0.001 were included in the MVA for OS. Results: 6,262 met criteria for inclusion in this study: 2,995 (48%) underwent esophagectomy, 2,130 (34%) underwent EMR and 1,137 (18%) underwent RT. Only 3 patients underwent esophageal brachytherapy. Median age was 68 years, and patients undergoing RT were older (72 y) compared to those undergoing esophagectomy (65 y) or EMR (70 y) (p<0.0001). In the esophagectomy, EMR and RT groups, 70%, 75% and 72% of patients had a Charlson score of 0, respectively. Median follow-up was 34 months. Median RT dose was 50.4 Gy and 78% underwent concurrent chemotherapy. 30 day mortality was 3.1% for esophagectomy and 0.6% for EMR. In recent years, EMR was more frequently utilized, rising from 23% to 43% whereas esophagectomy and RT were less frequently utilized in the same time period (p<0.0001). RT was more frequently utilized at non-academic centers than academic centers, 30.3% vs 9.3%, p<0.0001. Of the patients who underwent esophagectomy, 614 (21%) were upstaged. On MVA, patients with Charlson/Deyo score 1 (HR 1.2, pZ0.0003), older age (HR 1.03, p<0.001), Medicaid or no insurance (HR 1.5, pZ0.003), treatment at non-academic centers (HR 1.1, pZ0.009) and squamous histology (HR 1.3, p<0.001) were predictors of worse OS. There was no difference in OS between patients undergoing esophagectomy or EMR (pZ0.4) and this finding persisted when analysis was limited to T1a patients (pZ0.69). Patients requiring post-operative chemotherapy had a worse OS (HR 1.3, p<0.001). Patients who received definitive RT had a worse OS compared to patients who underwent esophagectomy or EMR (HR 1.8, p<0.001). Conclusion: EMR is increasingly utilized compared to esophagectomy and definitive RT for early esophageal cancer, whereas the utilization of esophageal brachytherapy was rare. Adoption of EMR in lieu of esophagectomy has not compromised survival. Patients undergoing esophagectomy and EMR had a superior OS compared to those who underwent definitive RT. Patients undergoing definitive RT appear to have unfavorable features likely affecting OS.
#6043 Background: ACRIN 6657, the imaging component of the I-SPY trial (CALGB 150007/150012), is a multi-center study testing the ability of MRI to provide in-vivo quantification of breast tumor response to neoadjuvant chemotherapy, for early prediction of response and stratification of risk-of-recurrence following treatment. We report results from preliminary analysis comparing MRI variables for correlation with pathologic response and disease progression. Methods: Women with ≥3 cm invasive breast cancer receiving an anthracycline-cyclophosphamide (AC) neoadjuvant chemotherapy regimen followed by a taxane (T) were enrolled between May 2002 and March 2006. Contrast-enhanced MRI was performed prior to start of treatment (baseline), following 1 cycle of AC chemotherapy (t2), between AC and T regimens (t3), and after all chemotherapy but prior to surgery (t4). MRI assessments included tumor longest diameter (MRLD), tumor volume (MRVol), and signal enhancement ratio (SER), a measure of contrast enhancement kinetics. Clinical size (cSize) and mammographic longest diameter (MGLD) were also recorded. Linear dimension was measured by the radiologist for MGLD and MRLD; MRVol was calculated by computer using SER thresholds. Pathologic residual disease size (pSize) and residual cancer burden (RCB) index were evaluated following surgery. Results: 237 patients were enrolled at 9 institutions. 216 patients with complete imaging formed the preliminary analysis set. At time of analysis 42 patients had progressed or died with mean time-to-progression of 21 months; 174 patients were progression-free with mean follow-up time of 42 months. At t4, MRVol was more strongly correlated with pSize than MRLD, SER or cSize (r=.61 vs .28, .24 and .43), while SER showed a stronger correlation with RCB than MRLD, MRVol or cSize (r = .45 vs .30, .31 and .37). MGLD at t4 did not show a significant correlation with either pSize or RCB. Early measurements of tumor size change from baseline by MRVol at t2, and MRVol, MRLD and SER at t3, all showed significant correlation with RCB. In univariate logistic regressions, all t4 measurements were found to be predictive of disease progression. Conclusion: Among clinical and imaging measurements of residual breast tumor size, MRI appears to most accurately reflect pathologic extent of disease following neoadjuvant treatment. Preliminary findings also suggest that tumor size and contrast kinetics measured by MRI may be useful early predictors of treatment response. ACRIN 6657 is continuing to collect follow-up data toward the primary aim testing MRI for stratification of post-treatment risk groups according to 3-year disease-free survival. This work is funded by NIH/ACRIN Grant U01 CA79778S2, CALGB Grants CA31946 and CA33601, and NCI SPORE Grant CA58207. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6043.
Background Functional MRI techniques may be utilized for characterizing breast tumors and measuring response to neoadjuvant chemotherapy (NAC). Dynamic contrast enhanced (DCE) MRI is the most common functional breast MRI technique. Fitting DCE MRI data to an appropriate pharmacokinetic model allows noninvasive, in vivo measurement of physiological parameters related to tissue perfusion, microvascular permeability, and extracellular/extravascular volume fraction. Diffusion weighted imaging (DWI) MRI is an alternative technique that measures the mobility of water molecules in vivo and is sensitive to tissue characteristics such as cell density, membrane permeability, and microstructure. DWI provides complementary information to DCE MRI about tumor biology and has shown promise for early prediction of response. The master ISPY2 multi-center study is a process targeting the rapid, focused clinical development of paired oncologic therapies and biomarkers. Its framework is an adaptive phase II clinical trial design in the neoadjuvant setting for women with locally advanced breast cancer. As a sub-study, ACRIN 6698 will combine both DCE and DWI MRI data to generate novel imaging biomarkers that correlate with treatment response. The two studies will provide a rich data set that can be used to elucidate molecular pathways and tumor responses to novel investigational drugs with standard chemotherapy. Trial design: ACRIN 6698 will perform advanced DCE and DWI MR imaging as part of the I-SPY TRIAL. The ISPY 2 adaptive therapy design will use different tumor biomarker assays to identify patients with high risk of recurrence. Patients will receive NAC doublet chemotherapy and trastuzumab (if Her2+). Patients will be randomized and stratified into different arms receiving investigational agents of different drug classes. ACRIN 6698 patients will receive four advanced MRI exams (both DCE and DWI) at baseline, early therapy, mid therapy and prior to surgery. Specific aims: The primary aim will determine if the % change in tumor apparent diffusion coefficient (ADC) measured on DWI from baseline to early treatment timepoint is predictive of pathologic complete response (pCR). The secondary aim will determine if the combined measurement of percentage change in tumor ADC on DWI, and percentage change in tumor volume and peak signal enhancement ratio (SER) on DCE MRI is predictive of pCR. Statistical methods: Receiver operating characteristic (ROC) curve and corresponding area under the ROC curves (AUC) for the individual marker, % change in tumor ADC, and % change in tumor volume and peak SER, will be estimated. Linear score of the 3 markers will be derived by fitting the multivariate logistic regression model, where the outcome is a binary variable for pCR and the predictors are the 3 measurements. The ROC curve for the derived linear score will be constructed and its AUC value will be estimated. Target accrual: ACRIN 6698 is open to ISPY 2 sites. The target accrual is 200 of ISPY 2's planned enrollment of 800 participants. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-03-06.
#805 Background: Diffuse optical tomography (DOT) uses near-infrared light to non-invasively image total hemoglobin concentration and blood oxygen saturation in the human breast. Given its low cost, ease of use, and possibility of repeated measured over time, DOT is a promising adjunctive imaging modality for screening, diagnosis and monitoring of neoadjuvant therapy. In this study we explored the performance of DOT to differentiate benign and malignant breast lesions.
 Method and Materials: Forty-seven women with clinical or mammographic abnormalities were prospectively recruited for DOT. Most patients underwent gadolinium-enhanced MRI examination. Three-dimensional oxy-, deoxy-hemoglobin, total hemoglobin concentration, blood oxygen saturation and scattering coefficient images of each breast were reconstructed. Tumor-to-normal (T/N) ratios of these parameters were computed by defining tumor regions with guidance from MRI and radiology reports. In addition, optical index was constructed based on these parameters to maximize the T/N contrast. Only the biopsy-proven lesions were selected (51 breast lesions) and classified into three groups: benign lesions (N=10), malignant lesions where DOT preceded core biopsy (N=20) and malignant lesions where DOT was performed after core-biopsy (N=21). We fit a mixed effects model that estimated the mean optical T/N ratios and optical index for each group, and using the resulting standard errors developed 95% confidence intervals and tested the hypothesis that each optical contrast parameter was unity.
 Results: Malignant cancers showed statistically significant higher total hemoglobin concentration, scattering, oxy-hemoglobin concentration and optical index (P=0.01-0.04) compared to normal tissue. Furthermore, malignant lesions exhibited a two-fold average increase in an optical index derived from the endogenous optical parameters (95% CI: 1.4 - 2.4). To test whether bleeding due to core biopsy influence DOT results, we compared if there was statistically significant differences between two groups measured before or after core-biopsy. There were no statistically significant differences in these groups, suggesting that post biopsy hemorrhage did not alter the DOT results. Benign tumors did not show statistical significance in all of the T/N ratios. AUC of total hemoglobin concentration, scattering, oxy-hemoglobin and optical index suggested good discriminatory power with values between 0.90 and 0.99.
 Discussion: The data demonstrates the feasibility of differentiating benign and malignant lesions by quantitative three-dimensional DOT when the tumor location information is provided by other imaging modality. The main drawback of this study is the small number of benign lesions, which warrants further study. DOT technology is still at its developing stage and needs more investigation to find its niche in breast imaging. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 805.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.