Tong C.C.L.,Mount Sinai Medical Center |
Ko E.C.,Mount Sinai Medical Center |
Sung M.W.,Mount Sinai Medical Center |
Cesaretti J.A.,Florida Radiation Oncology Group |
And 10 more authors.
PLoS ONE | Year: 2012
Background: Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. Methods: Twenty five patients with oligometastases, defined as 1-5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1-28) and IGRT 50 Gy (days 8-12 and 15-19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). Results: The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. Conclusions: Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. Trial Registration: ClinicalTrials.gov NCT00463060. © 2012 Tong et al.
Pusic M.V.,Columbia University |
Pusic M.V.,New York University |
Andrews J.S.,University of Minnesota |
Kessler D.O.,Columbia University |
And 6 more authors.
Medical Education | Year: 2012
Objectives Using a large image bank, we systematically examined how the use of different ratios of abnormal to normal cases affects trainee learning. Methods This was a prospective, double-blind, randomised, three-arm education trial conducted in six academic training programmes for emergency medicine and paediatric residents in post-licensure years 2-5. We developed a paediatric ankle trauma radiograph case bank. From this bank, we constructed three different 50-case training sets, which varied in their proportions of abnormal cases (30%, 50%, 70%). Levels of difficulty and diagnoses were similar across sets. We randomly assigned residents to complete one of the training sets. Users classified each case as normal or abnormal, specifying the locations of any abnormalities. They received immediate feedback. All participants completed the same 20-case post-test in which 40% of cases were abnormal. We determined participant sensitivity, specificity, likelihood ratio and signal detection parameters. Results A total of 100 residents completed the study. The groups did not differ in accuracy on the post-test (p=0.20). However, they showed considerable variation in their sensitivity-specificity trade-off. The group that received a training set with a high proportion of abnormal cases achieved the best sensitivity (0.69, standard deviation [SD]=0.24), whereas the groups that received training sets with medium and low proportions of abnormal cases demonstrated sensitivities of 0.63 (SD=0.21) and 0.51 (SD=0.24), respectively (p<0.01). Conversely, the group with a low proportion of abnormal cases demonstrated the best specificity (0.83, SD=0.10) compared with the groups with medium (0.70, SD=0.15) and high (0.66, SD=0.17) proportions of abnormal cases (p<0.001). The group with a low proportion of abnormal cases had the highest false negative rate and missed fractures one-third more often than the groups that trained on higher proportions of abnormal cases. Conclusions Manipulating the ratio of abnormal to normal cases in learning banks can have important educational implications. © Blackwell Publishing Ltd 2012.
Kao J.,Good Samaritan Hospital Medical Center |
Chen C.-T.,New York University |
Tong C.C.L.,Mount Sinai Medical Center |
Packer S.H.,Mount Sinai Medical Center |
And 3 more authors.
Targeted Oncology | Year: 2014
Preliminary results demonstrated that concurrent sunitinib and stereotactic body radiation therapy (SBRT) is an active regimen for metastases limited in number and extent. This analysis was conducted to determine the long-term survival and cancer control outcomes for this novel regimen. Forty-six patients with oligometastases, defined as five or fewer clinical detectable metastases from any primary site, were treated on a phase I/II trial from February 2007 to September 2010. The majority of patients were treated with 37.5 mg sunitinib (days 1-28) and SBRT 50 Gy (days 8-12 and 15-19) and maintenance sunitinib was used in 39 % of patients. Median follow up for surviving patients is 3.6 years. The 4-year estimates for local control, distant control, progression-free and overall survival were 75 %, 40 %, 34 % and 29 %, respectively. At last follow-up, 26 % of patients were alive without evidence of disease, 7 % were alive with distant metastases, 48 % died from distant metastases, 2 % died from local progression, 13 % died from comorbid illness, and 4 % died from treatment-related toxicities. Patients with kidney and prostate primary tumors were associated with a significantly improved overall survival (hazard ratio=0.25, p=0.04). Concurrent sunitinib and SBRT is a promising approach for the treatment of oligometastases and further study of this novel combination is warranted. © 2013 Springer-Verlag.
Jones V.S.,Good Samaritan Hospital Medical Center
Journal of Pediatric Surgery | Year: 2015
Background Though single incision laparoscopic cholecystectomy (SILC) is cosmetically appealing, it is technically a difficult operation. The recent introduction of robotic single-site cholecystectomy (RSSC) has made single incision cholecystectomy easier to perform. While a few papers have reported its application in adults, it has not been documented in children. Methods Data on seventeen consecutive children who underwent RSSC by a single surgeon over a ten-month period were retrospectively reviewed. Patient demographics, total operative time, console time, hospital stay, complications and reasons for procedural delay were recorded. Results Sixteen operations were completed robotically using the single incision robotic platform. No major postoperative complications were noted. Median total operative time was 94 minutes with interquartile range (IQR) being 81.5-119.5 minutes. The median console time was 39 minutes (IQR: 30-72 minutes). The median total operative time for the first eight cases was 118 minutes (IQR: 103-127 minutes) and for the next nine cases 90 minutes (IQR: 76-93 minutes). Common causes for procedural delay were slipped clips, bile spillage, bleeding and leaking Single-Site® port. Conclusions This unique series of RSSC documents its feasibility and safety in children. A short learning curve and operative times comparable to RSSC in adults and SILC in children were observed. Being technically easier, RSSC becomes an attractive alternative to SILC to sustain its cosmetic benefit. © 2015 Elsevier Inc. All rights reserved.
Parikh F.,Mount Sinai School of Medicine |
Duluc D.,Baylor Institute of Immunology |
Imai N.,Mount Sinai School of Medicine |
Clark A.,Mount Sinai School of Medicine |
And 13 more authors.
Cancer Research | Year: 2014
While viral antigens in human papillomavirus (HPV)-related oropharyngeal cancer (HPVOPC) are attractive targets for immunotherapy, the effects of existing standard-of-care therapies on immune responses to HPV are poorly understood. We serially sampled blood from patients with stage III-IV oropharyngeal cancer undergoing concomitant chemoradiotherapy with or without induction chemotherapy. Circulating immunocytes including CD4+ and CD8+ T cells, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) were profiled by flow cytometry. Antigen-speci fi c T-cell responses were measured in response to HPV16 E6 and E7 peptide pools. The role of PD-1 signaling in treatment-related immunosuppression was functionally de fi ned by performing HPV-specific T-cell assays in the presence of blocking antibody. While HPV-specific T-cell responses were present in 13 of 18 patients before treatment, 10 of 13 patients lost these responses within 3 months after chemoradiotherapy. Chemoradiotherapy decreased circulating T cells and markedly elevated MDSCs. PD-1 expression on CD4+ T cells increased by nearly 2.5-fold after chemoradiotherapy, and ex vivo culture with PD-1-blocking antibody enhanced HPV-specific T-cell responses in 8 of 18 samples tested. Chemoradiotherapy suppresses circulating immune responses in patients with HPVOPC by unfavorably altering effector:suppressor immunocyte ratios and upregulating PD-1 expression on CD4+ T cells. These data strongly support testing of PD-1-blocking agents in combination with standard-of-care chemoradiotherapy for HPVOPC. ©2014 AACR.