Paul J Christos

Weill Cornell Medical College, New York, New York, United States

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Publications (220)865.23 Total impact

  • European Urology Supplements 04/2015; DOI:10.1016/S1569-9056(15)60024-0 · 3.37 Impact Factor
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    ABSTRACT: Background Variations in single nucleotide polymorphisms (SNPs) have been associated with enhanced drug efficacy and toxicity in cancer therapy. SNP variations in the ErbB2 gene have been identified that alter the protein sequence of the HER2-neu protein, but how these polymorphisms affect prognosis and response to HER2 targeted therapy is unknown. We examined eleven ErbB2 SNPs that alter the HER2-neu amino acid sequence to determine whether any of these particular polymorphisms were associated with increased trastuzumab cardiotoxicity in a case–control study. Methods 140 subjects were enrolled from a single institution under Weill Cornell Medical College IRB protocol #0804009734. Patients were eligible if they had histologically or cytologically proven HER2-neu positive breast cancer and more than 3 months of trastuzumab therapy. Cases had either symptomatic CHF or a decline in LVEF of 15% (or if the LVEF <55%, a decline in LVEF of 10%) that resulted in at least temporary discontinuation of trastuzumab, whereas controls had no decline in their LVEF. Eleven ErbB2 single gene SNPs that resulted in an alteration in the HER2-neu protein amino acid sequence were studied. Single gene SNP analysis was carried out using SNP genotyping assays from genomic DNA obtained from peripheral blood or buccal swab. Results Only two of the ErbB2 SNPs (Ile 655 Val and Pro 1170 Ala) were found to have variation. There was no association between codon 665 and cardiotoxicity; however the proline variant of amino acid 1170 was more likely than the alanine variant to be found in cases with trastuzumab cardiotoxicity (35% of case patients as compared to 17% of controls, p = 0.04). This association remained significant in multivariable analysis taking into account age, race, and history of hypertension (adjusted OR = 2.60, 95% CI = 1.02, 6.62, p = 0.046). Conclusions The Her2/neu Pro 1170 Ala polymorphism can be used to identify a subset of patients who are at increased risk of cardiotoxicity from trastuzumab therapy. Her2/neu single nucleotide polymorphisms may be useful in conjunction with other biomarkers to risk stratify patients in order to optimize clinical management.
    BMC Cancer 04/2015; 15. DOI:10.1186/s12885-015-1298-6 · 3.32 Impact Factor
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    European Urology Supplements 04/2015; 14(2):e744. DOI:10.1016/S1569-9056(15)60736-9 · 3.37 Impact Factor
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    ABSTRACT: Concerns remain whether robot-assisted radical cystectomy (RARC) compromises survival because of inadequate oncologic resection or alteration of recurrence patterns. To describe recurrence patterns following open radical cystectomy (ORC) and RARC. Retrospective review of 383 consecutive patients who underwent ORC (n=120) or RARC (n=263) at an academic institution from July 2001 to February 2014. ORC and RARC. Recurrence-free survival estimates were illustrated using the Kaplan-Meier method. Recurrence patterns (local vs distant and anatomic locations) within 2 yr of surgery were tabulated. Cox regression models were built to evaluate the effect of surgical technique on the risk of recurrence. The median follow-up time for patients without recurrence was 30 mo (interquartile range [IQR] 5-72) for ORC and 23 mo (IQR 9-48) for RARC (p=0.6). Within 2 yr of surgery, there was no large difference in the number of local recurrences between ORC and RARC patients (15/65 [23%] vs 24/136 [18%]), and the distribution of local recurrences was similar between the two groups. Similarly, the number of distant recurrences did not differ between the groups (26/73 [36%] vs 43/147 [29%]). However, there were distinct patterns of distant recurrence. Extrapelvic lymph node locations were more frequent for RARC than ORC (10/43 [23%] vs 4/26 [15%]). Furthermore, peritoneal carcinomatosis was found in 9/43 (21%) RARC patients compared to 2/26 (8%) ORC patients. In multivariable analyses, RARC was not a predictor of recurrence. Limitations of the study include selection bias and a limited sample size. Within limitations, we found that RARC is not an independent predictor of recurrence after surgery. Interestingly, extrapelvic lymph node locations and peritoneal carcinomatosis were more frequent in RARC than in ORC patients. Further validation is warranted to better understand the oncologic implications of RARC. In this study, the locations of bladder cancer recurrences following conventional and robotic techniques for removal of the bladder are described. Although the numbers are small, the results show that the distribution of distant recurrences differs between the two techniques. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 02/2015; DOI:10.1016/j.eururo.2015.02.003 · 12.48 Impact Factor
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    ABSTRACT: Background Matrix metalloproteinase-23 (MMP-23) can block the voltage-gated potassium channel Kv1.3, whose function is important for sustained Ca2+ signaling during T cell activation. MMP-23 may also alter T cell activity and phenotype through cleavage of proteins affecting cytokine and chemokine signaling. We therefore tested the hypothesis that MMP-23 can negatively regulate the anti-tumor T cell response in human melanoma.Methods We characterized MMP-23 expression in primary melanoma patients who received adjuvant immunotherapy. We examined the association of MMP-23 with the anti-tumor immune response - as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3+ regulatory T cells. Further, we examined the association between MMP-23 expression and response to immunotherapy. Considering also an in trans mechanism, we examined the association of melanoma MMP-23 and melanoma Kv1.3 expression.ResultsOur data revealed an inverse association between primary melanoma MMP-23 expression and the anti-tumor T cell response, as demonstrated by decreased tumor-infiltrating lymphocytes (TIL) (P¿=¿0.05), in particular brisk TILs (P¿=¿0.04), and a trend towards an increased proportion of immunosuppressive Foxp3+ regulatory T cells (P¿=¿0.07). High melanoma MMP-23 expression is also associated with recurrence in patients treated with immune biologics (P¿=¿0.037) but not in those treated with vaccines (P¿=¿0.64). Further, high melanoma MMP-23 expression is associated with shorter periods of progression-free survival for patients receiving immune biologics (P¿=¿0.025). On the other hand, there is no relationship between melanoma MMP-23 and melanoma Kv1.3 expression (P¿=¿0.27).Conclusions Our data support a role for MMP-23 as a potential immunosuppressive target in melanoma, as well as a possible biomarker for informing melanoma immunotherapies.
    Journal of Translational Medicine 12/2014; 12(1):342. DOI:10.1186/s12967-014-0342-7 · 3.99 Impact Factor
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    ABSTRACT: Background Single nucleotide polymorphisms (SNPs) in platelet-associated genes partly explain inherent variability in platelet counts. Patients with monoallelic Bernard Soulier syndrome due to the Bolzano mutation (GPIBA A156V) have variable platelet counts despite a common mutation for unknown reasons.Objectives We investigated the effect of the most common SNP (R307H) in the hematopoietic-specific tubulin isotype β-1 in these Bernard Soulier patients and potential microtubule-based mechanisms of worsened thrombocytopenia.Patients/Methods Ninety-four monoallelic Bolzano mutation patients were evaluated for the R307H β-1 SNP and had platelet counts measured by three methods; the Q43P SNP was also evaluated. To investigate possible mechanisms underlying this association, we used molecular modeling of β-1 tubulin with and without the R307H SNP. We transfected SNP or non-SNP β-1 tubulin into MCF-7 and CMK cell lines and measured microtubule regrowth after nocodazole-induced depolymerization.ResultsWe found that patients with at least one R307H SNP allele had significantly worse thrombocytopenia; manual platelet counting revealed a median platelet count of 124 in non-SNP and 76 in SNP patients (both x 109/L; p<0.01). The Q43P SNP had no significant association with platelet count. Molecular modeling suggested a structural relationship between the R307H SNP and microtubule stability via alterations in the M-loop of β tubulin; in vitro microtubule recovery assays revealed cells transfected with R307H SNP β-1 had significantly impaired microtubule recovery.Conclusions Our data show that the R307H SNP is significantly associated with the degree of thrombocytopenia in congenital and acquired platelet disorders, and may affect platelets by altering microtubule behavior.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 12/2014; 13(4). DOI:10.1111/jth.12824 · 5.55 Impact Factor
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    ABSTRACT: Type II diabetes mellitus (DM) is one of the leading chronic diseases in Qatar as well as worldwide. However, the risk factors for DM in Qatar and their prevalence are not well understood. We conducted a case-control study with the specific aim of estimating, based on data from outpatients with DM in Qatar (cases) and outpatient/inpatient controls, the association between demographic/lifestyle factors and DM. A total of 459 patients with DM from Hamad General Hospital (HGH) outpatient adult diabetes clinics, and 342 control patients from various outpatient clinics and inpatient departments within Hamad Medical Corporation (HMC) (years 2006-2008), were recruited. The association between risk factors and DM was evaluated using bivariate and multivariable logistic regression analyses. In addition to odds ratios (OR) and 95% confidence intervals (95% CI), we estimated the population attributable risk fractions for the DM demographic/lifestyle risk factors. Qatari nationality was the strongest risk factor for DM (adjusted OR = 5.5; 95% CI = 3.5-8.6; p < 0.0001), followed by higher monthly income (defined as ≥ 3000 Qatari Riyals, adjusted OR = 5.1; 95% CI = 3.0-8.7; p < 0.0001), age >65 years (adjusted OR = 3.3; 95% CI = 0.9-11.4; p = 0.06), male gender (adjusted OR = 2.9; 95% CI = 1.8-4.8; p < 0.0001), obesity (BMI ≥ 30, adjusted OR = 2.2; 95% CI = 1.5-3.2; p < 0.0001), no college education (adjusted OR = 1.7; 95% CI = 1.2-2.6; p = 0.009), and no daily vigorous/moderate activity (adjusted OR = 1.5; 95% CI = 0.9-2.3; p = 0.12). Among Qatari nationals, obesity was found to be the main risk factor for DM (unadjusted OR = 3.0; 95% CI = 1.6-5.6; p < 0.0001), followed by no college education (unadjusted OR = 2.7; 95% CI = 1.5-5.1; p = 0.001), while consanguinity did not appear to play a major role in predicting DM (unadjusted OR = 1.5; 95% CI = 0.8-2.8; p = 0.21). Our findings further suggested that eliminating obesity and improving access to education may reduce DM cases by up to one third for the population at large (31.7% and 26.8%, respectively) and up to half (46.9% and 49.3%, respectively) for Qatari nationals. Promoting physical activity may reduce the burden of DM by up to 9.4% for the population at large and up to 17.3% for Qatari nationals. Demographic/lifestyle factors appear to be the main risk factors for the high DM levels observed in Qatar, with a contribution that outweighs that of genetic risk factors. While further evaluation of DM risk factors among the Qatari population (as opposed to the resident population) is important and of interest, these findings highlight the need to focus short-term DM interventions on addressing demographic/lifestyle risk factors to achieve substantial and timely declines in DM levels.
    12/2014; 2014(2):13. DOI:10.5339/qmj.2014.13
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    ABSTRACT: Author Summary BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been used to curtail tumor vasculature and delay tumor progression in hepatocellular carcinoma (HCC). We conducted a phase I trial to evaluate the efficacy and toxicity of thalidomide when combined with TACE in patients with advanced HCC.
    The Oncologist 10/2014; DOI:10.1634/theoncologist.2014-0283 · 4.54 Impact Factor
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    ABSTRACT: Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death.
    American Journal of Clinical Oncology 10/2014; DOI:10.1097/COC.0000000000000144 · 2.61 Impact Factor
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    ABSTRACT: Background Adult respiratory distress syndrome (ARDS) has a high mortality rate and consumes considerable health care resources. It is not clear whether specimens obtained from open lung biopsy (OLB) in ARDS provide a specific diagnosis, alter therapy, or affect outcome. This meta-analysis attempts to determine whether OLB is safe, provides a specific diagnosis, changes therapy, or affects survival. Methods A computerized search was performed of Medline and PubMed from January 1988 to December 2012 of English language studies of acute respiratory failure and diffuse pulmonary infiltrates that evaluated OLB in primarily adult mechanically ventilated patients. Of 194 abstracts retrieved, 64 articles were reviewed; 130 articles were excluded because they did not evaluate OLB. After applying the selection criteria, 24 articles were included. Results OLB in ARDS provided a specific diagnosis in 84% of patients and altered management in 73%. Hospital mortality was 43%. The complication rate for OLB in ARDS was 22%, but death from OLB was rare. Conclusions OLB in ARDS is a potentially productive procedure that provides a specific diagnosis and leads to a change in management in high proportions of patients. ARDS has a high mortality rate, which OLB does not appear to increase. Owing to a lack of randomized controlled trials, a survival advantage of OLB in ARDS could not be demonstrated.
    The Annals of Thoracic Surgery 10/2014; 98(4). DOI:10.1016/j.athoracsur.2014.05.029 · 3.63 Impact Factor
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    ABSTRACT: To evaluate whether non-gated CT can assess left ventricular (LV) function, 101 patients with both CT and echocardiography were selected, with EF < 50% on echocardiography used as a reference standard. CTs were blindly reevaluated, and qualitative assessment of LV dysfunction on CT correlated with echocardiographic dysfunction, odds ratio of 21.0 (95%CI = 6.55-71.0), specificity of 86% (56/65). Systolic and diastolic images were identified on CT, and the ratio of systolic to diastolic LV internal diameters, and ratio of LV to RV internal diameter, were performed, both showing correlation with LV dysfunction on echocardiography (p < 0.0001). Non-gated CT can be used to predict LV dysfunction.
    Clinical imaging 09/2014; DOI:10.1016/j.clinimag.2014.03.015 · 0.60 Impact Factor
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    ABSTRACT: Background: In severe obesity, impairments in health-related quality of life (HRQoL) and dysphoric mood are reported. This is a post-surgery analysis of the relationship between HRQoL and depressive symptoms, and weight change after four different types of bariatric procedures. Methods: A total of 105 consented patients completed the Short-Form-36 Health Survey (SF-36), the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) and the Beck Depression Inventory (BDI) before and 25 months after surgery. Analysis of variance or Kruskal–Wallis test evaluated changes. Results: Patients with Roux-en Y gastric bypass (46 patients), decreased body mass indexes (BMIs; kg m–2) 47–31 kg m–2 (P<0.0001); biliopancreatic diversion with duodenal switch (18 patients), decreased BMIs 57–30 kg m–2 (P<0.0001); adjustable gastric banding (18 patients), decreased BMIs 45–38 kg m–2 (P<0.0001); and sleeve gastrectomies (23 patients), decreased BMIs 58 42 kg m–2 (P<0.0001). The excess percentage BMI loss was 69, 89, 36 and 53 kg m–2, respectively (P<0.0001). Before surgery, the SF-36 differences were significant regarding bodily pain (P=0.008) and social functioning (P=0.01). After surgery, physical function (P=0.03), general health (P=0.05) and physical component (P=0.03) were different. IWQOL-Lite recorded no differences until after surgery: physical function (P=0.003), sexual life (P=0.04) and public distress (P=0.003). BDI scores were not different for the four groups at baseline. All improved with surgery, 10.6–4.4 (P=0.0001). Conclusions: HRQoL and depressive symptoms significantly improvement after surgery. These improvements do not have a differential effect over the wide range of weight change.
    Nutrition & Diabetes 09/2014; 4(9):e132. DOI:10.1038/nutd.2014.29 · 1.52 Impact Factor
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    ABSTRACT: Purpose: The purpose of this study was to determine if a significant difference exists in the nasolacrimal duct volume of subjects with primary nasolacrimal duct obstruction compared with that of controls. Methods: This was a retrospective, case-control study of 70 subjects with prior maxillofacial CT scans, including 35 subjects with obstruction and 35 controls. Volume measurements of the nasolacrimal duct were made on a GE Advantage Workstation using volume viewer software, and measurements were compared using an unpaired Student t test. Interrater and intrarater reliabilities were calculated. Results: There was no significant difference in the nasolacrimal duct volume of patients (0.411 +/- 0.18 cm3) compared with that of controls (0.380 +/- 0.13 cm3) (p = 0.23). Women had smaller volume ducts (0.356 +/- 0.11 cm3) than that of men (0.482 +/- 0.19 cm3) (p < 0.001). Male patients had smaller volume ducts (0.470 +/- 0.23 cm3) than that of male controls (0.493 +/- 0.14 cm3) (p = 0.70), while female patients (0.384 +/- 0.13 cm3) had significantly larger volume ducts than that of female controls (0.328 +/- 0.08 cm3) (p = 0.01). There was excellent interrater and intrarater reliabilities. Conclusions: CT 3-dimensional volumetric software can be used to accurately measure the nasolacrimal duct volume in patients with obstruction. Both the absence of a significant difference in patient's and control's nasolacrimal duct volumes and the overlap in range between the 2 groups imply that the volume of the tear duct is likely not related to the etiology of obstruction. The increase in volume seen in females with obstruction may be due to expansion of the bony canal during the postmenopausal years. The exact etiology of primary nasolacrimal duct obstruction requires further investigation.
    Ophthalmic Plastic and Reconstructive Surgery 08/2014; DOI:10.1097/IOP.0000000000000259 · 0.91 Impact Factor
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    ABSTRACT: Introduction /Background: With improved breast cancer (BC) screening and treatment, the risk for long term toxicities of treatments must be considered, especially in good prognosis patients. This study examined the outcome, risks of second cancers, and cardiac mortality with radiation therapy (RT) for early stage BC from recent years. Materials and Methods Analysis of Surveillance, Epidemiology, and End Results (SEER) database was conducted for women who had Stage T1aN0 BC as their first primary malignancy between 1990-1997 treated with partial or complete mastectomy ± external beam radiation. The overall survival (OS), breast cancer specific survival (BCSS), cardiac cause specific survival (CCS) and deaths from second cancers in the chest area were compared between the RT and no-RT groups. Results Of the 6515 women identified, 2796 received RT and 3719 did not. The median age group (60-64 years) and follow up lengths (∼15 years) were similar. Compared to the RT group, the no-RT group was associated with lower 10-year OS (85.5% vs. 79.3%, p<0.0001), BCSS (97.3% vs. 96.4%, p=0.04), and CCS (97.0% vs. 93.8%, p<0.0001). In the RT group, left sided BC was not associated with higher cardiac mortality. There were no statistically significant incidences in mortality due to subsequent cancers. The most common second cancer mortality included 114 (2%) lung, 25 (0.4%) lymphoma, 19 (0.3%) leukemia, 3 (0.05%) soft tissue, and 2 (0.03%) esophagus. Conclusions This review of SEER data suggests that secondary malignancy in the chest area and cardiac mortality are rare after RT in the 1990’s for T1aN0 BC.
    Clinical Breast Cancer 08/2014; 15(1). DOI:10.1016/j.clbc.2014.07.003 · 2.63 Impact Factor
  • Ye JC, Yan W, Christos P, Nori D, C chao, Ravi A
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    ABSTRACT: Abstract INTRODUCTION/BACKGROUND: With improved BC screening and treatment, the risk for long-term toxicities of treatments must be considered, especially in good prognosis patients. In this study we examined the outcome, risks of second cancers, and cardiac mortality with RT for early-stage BC from recent years. MATERIALS AND METHODS: Analysis of the SEER database was conducted for women who had stage T1aN0 BC as their first primary malignancy between 1990 and 1997 and were treated with partial or complete mastectomy with or without external beam RT. The overall survival (OS), BC-specific survival (BCSS), cardiac cause-specific survival (CCS), and deaths from second cancers in the chest area were compared between the RT and no-RT groups. RESULTS: Of the 6515 women identified, 2796 received RT and 3719 did not. The median age group (60-64 years) and follow-up lengths (approximately 15 years) were similar. Compared with the RT group, the no-RT group was associated with lower 10-year OS (85.5% vs. 79.3%; P < .0001), BCSS (97.3% vs. 96.4%; P = .04), and CCS (97.0% vs. 93.8%; P < .0001). In the RT group, left-sided BC was not associated with higher cardiac mortality. There were no statistically significant incidences in mortality due to subsequent cancers. The most common second cancer mortality included 114 (2%) lung, 25 (0.4%) lymphoma, 19 (0.3%) leukemia, 3 (0.05%) soft tissue, and 2 (0.03%) esophagus. CONCLUSION: This review of SEER data suggests that secondary malignancy in the chest area and cardiac mortality are rare after RT in the 1990s for T1aN0 BC. Copyright © 2014 Elsevier Inc. All rights reserved. KEYWORDS: Breast-conserving therapy; Early stage breast cancer; Late toxicity; Second cancer mortality; Surveillance, Epidemiology, and End Results (SEER)
    Clinical Breast Cancer 08/2014; · 2.63 Impact Factor
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    ABSTRACT: Background An optic disc haemorrhage (DH) has been associated with subsequent structural glaucoma progression, but it is unknown if there is structural progression prior to a DH. We evaluated a cohort of patients to determine whether structural progression occurs before a DH, after a DH or is simply associated with a DH. Methods Eyes meeting inclusion criteria were placed into two groups. Group 1 included eyes that each had a baseline photograph of the optic nerve and a photograph with a DH at follow-up. Group 2 included eyes that each had a photograph of the optic nerve with a DH at baseline and a photograph at follow-up. Flicker images were created and graded by two ophthalmologists for structural glaucomatous change. We compared the proportion of structural progressors between Groups 1 and 2. Patient characteristics were also compared between the two groups. Results 49 patients and 51 unique eyes were included. Groups 1 and 2 had 28 and 38 sets of photographs, respectively. The proportion of global progression in Groups 1 and 2 were 21.4% and 39.5%, respectively (p=0.12). No significant differences in any structural progression feature and patient characteristics (besides age at time of DH (p=0.04) between the two groups were found. Conclusions Patients show structural glaucomatous progression before and after the event of a disc haemorrhage without significant differences. This suggests that a DH is an ongoing structural progression in glaucoma and may not be a discrete event that leads to subsequent progression.
    British Journal of Ophthalmology 07/2014; 99(1). DOI:10.1136/bjophthalmol-2014-305349 · 2.81 Impact Factor
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    ABSTRACT: Purpose: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are considered the most aggressive cancers of the head and neck. The aim of the study was to evaluate and compare survival outcomes in PDTC and ATC in a large population-based cohort. Materials and Methods: Patients with PDTC and ATC diagnosed from 1973 to 2008 were obtained from Surveillance, Epidemiology, and End Results database. Kaplan-Meier survival analysis and log-rank analyses were performed to evaluate (1) The effect of histology on cause-specific survival (CSS) and (2) the influence of factors such as treatment, treatment sequence, race, sex, and age on CSS. Multivariate analysis was performed to assess the independent effect of these factors on CSS. Results: A total of 1352 patients with PDTC and ATC were identified. PDTC constituted 52.4% of patients versus 47.6% for ATC. Median CSS was similar in the two histology groups (P = 0.14). Both PDTC and ATC patients receiving radioisotopes showed a significantly better CSS compared to external beam radiation (P < 0.0001). PDTC and ATC Patients receiving radiation prior to surgery demonstrated a significantly lower CSS compared to patients receiving radiation postoperatively (P < 0.0001). Female gender and black/nonwhite race tended to improve CSS in PDTC and ATC patients (P = 0.29 and P = 0.03, for gender and race, respectively). However, multivariate analysis revealed only type of radiation treatment and age to be independently associated with CSS. Conclusion: This is the first large population-based study evaluating PDTC and ATC outcomes in patients who received radiation treatment. Radioisotope use and timing of radiotherapy (postoperative vs. preoperative) were associated with improved CSS in both histologies.
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    ABSTRACT: Recent reports highlight the potential for integrase-defective lentiviral vectors (IDLV) to be developed as vaccines due to their ability to elicit cell-mediated and humoral immune responses after intramuscular administration. Differently from their integrase-competent counterpart, whose utility for vaccine development is limited by the potential for insertional mutagenesis, IDLV possess a mutation in their integrase gene that prevents genomic integration. Instead, they are maintained as episomal DNA circles that retain the ability to stably express functional proteins. Despite their favorable profile, it is unknown whether IDLV elicit immune responses after intranasal administration, a route that could be advantageous in the case of infection with a respiratory agent. Using influenza as a model, we constructed IDLV expressing the influenza virus nucleoprotein (IDLV-NP), and tested their ability to generate NP-specific immune responses and protect from challenge in vivo. We found that administration of IDLV-NP elicited NP-specific T cell and antibody responses in BALB/c mice. Importantly, IDLV-NP was protective against homologous and heterosubtypic influenza virus challenge only when given by the intranasal route. This is the first report demonstrating that IDLV can induce protective immunity after intranasal administration, and suggests that IDLV may represent a promising vaccine platform against infectious agents.
    PLoS ONE 05/2014; 9(5):e97270. DOI:10.1371/journal.pone.0097270 · 3.53 Impact Factor
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    ABSTRACT: Object Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate > 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. Methods After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded (131)Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. Results The median follow-up was 19.3 months (range 12.89-29.57 months). The median age was 65 years (range 45-84 years). The median size of resected tumor was 2.7 cm (range 1.5-5.5 cm), and the median volume of resected tumor was 10.31 cm(3) (range 1.77-87.11 cm(3)). The median number of seeds used was 12 (range 4-35), with a median activity of 3.82 mCi per seed (range 3.31-4.83 mCi) and total activity of 46.91 mCi (range 15.31-130.70 mCi). Local FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI 63.2%-99.1%). One-year distant FFP was 48.4% (95% CI 26.3%-67.4%). Median OS was 9.9 months (95% CI 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI 29.1%-67.8%). Complications included CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. Conclusions The use of postresection permanent (131)Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.
    Journal of Neurosurgery 05/2014; 121(2). DOI:10.3171/2014.3.JNS131140 · 3.15 Impact Factor
  • American Radium Society (ARS); 04/2014

Publication Stats

4k Citations
865.23 Total Impact Points

Institutions

  • 2001–2015
    • Weill Cornell Medical College
      • • Division of Biostatistics and Epidemiology
      • • Department of Neurological Surgery
      • • Department of Public Health
      New York, New York, United States
  • 2014
    • Albert Einstein College of Medicine
      • Department of Radiology
      New York, New York, United States
  • 2000–2014
    • New York Presbyterian Hospital
      • Department of Public Health
      New York City, New York, United States
  • 2004–2013
    • Cornell University
      • Department of Public Health
      Итак, New York, United States
  • 2012
    • CUNY Graduate Center
      New York City, New York, United States
  • 2001–2004
    • Memorial Sloan-Kettering Cancer Center
      • Department of Medicine
      New York City, NY, United States
  • 2003
    • Temple University
      • Department of Medicine
      Filadelfia, Pennsylvania, United States