Paul J Christos

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

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Publications (189)669.37 Total impact

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    ABSTRACT: 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.
    Ophthalmic plastic and reconstructive surgery. 08/2014;
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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; · 3.15 Impact Factor
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    ABSTRACT: Object Incidental colloid cysts are frequently managed with surveillance imaging rather than surgical excision. This approach is born out of their purported indolent growth pattern and the surgical morbidity associated with microsurgical removal. The advent of endoscopic colloid cyst removal may offer renewed assessment of these patients who carry a risk of acute neurological deterioration. An evidence-based recommendation should weigh the risks of operative treatment. Thus far, there has been no concentrated assessment of cyst removal in patients with incidental colloid cysts. The major objective in this study was to define the risks associated with the endoscopic surgical removal of incidentally diagnosed colloid cysts Methods A retrospective review of the medical records was performed to search for patients evaluated for a colloid cyst between the years 1996 and 2012. Eighty-seven patients underwent colloid cyst resection, and 34 were managed with nonoperative surveillance imaging. Microsurgical resections, endoscopic resections of residual or recurrent colloid cysts, and cases with unknown preoperative symptomatic status were excluded from further analysis. Seventy-seven cases of primary endoscopic resections were identified. Twenty resections were performed in patients with an incidental diagnosis and 57 in symptomatic individuals. Presenting characteristics and surgical outcomes were compared between the incidental and symptomatic groups. Results The mean age at surgery was 39.65 years for the incidental and 43.31 years for the symptomatic group (p = 0.36). The median maximal cyst diameter was 9.7 mm (range 3-31 mm) for the incidental and 12 mm (range 5-34 mm) for the symptomatic group. The mean frontal and occipital horn ratio was 0.3928 for the incidental and 0.4445 for the symptomatic group (p = 0.002). Total resection was achieved in 90% of the incidental and 82.3% of the symptomatic cases (p = 0.49). The median hospital stay was 1 day for incidental and 2 days for symptomatic cases (p = 0.006). There were no deaths. There was one case of aseptic meningitis in the incidental group. In the symptomatic group there were 3 complications: one patient with subjective memory impairment, one with transient short-term memory deterioration, and another with a superficial wound infection treated with operative debridement. Two patients from the symptomatic group needed a CSF diversion procedure, and no shunting was needed in the incidental group. There were two recurrences in the symptomatic group (78 and 133 months postoperatively) and none in the incidental group (p = 1). Conclusions Age and cyst diameter were not correlated with the absence or presence of symptoms in patients with a colloid cyst of the third ventricle. Operative results were highly favorable in both groups and did not reveal a higher risk of morbidity in the patient presenting with an incidental lesion. The results support endoscopic resection as a legitimate therapeutic option for patients with incidental colloid cysts. Generalization of the operative results should be cautiously made, since this is a limited series and the results may depend on the degree of neuroendoscopic experience.
    Journal of Neurosurgery 04/2014; · 3.15 Impact Factor
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    ABSTRACT: ABSTRACT Radioimmunotherapy (RIT) is effective treatment for indolent non-Hodgkin's lymphomas (NHL), but response durations are usually limited, especially in aggressive NHL. We hypothesized that administration of bortezomib as a radiosensitizer with RIT would be tolerable and improve efficacy in NHL. This Phase 1 dose escalation study evaluated escalating doses of bortezomib combined with (131)I-tositumomab in patients with relapsed/refractory NHL. Twenty-five patients were treated. Treatment was well tolerated, with primarily hematologic toxicity. Maximum tolerated dose (MTD) was determined to be 0.9 mg/m(2) bortezomib, in combination with standard dose of 75 cGy (131)I-tositumomab. Sixteen patients responded (64%), including 44% complete responses (CR), with 82% CR in follicular lymphoma (FL) patients. At median follow up of 7 months, median progression-free survival was 7 months, and 7 of 11 FL patients remained in remission at a median of 22 months. In conclusion, bortezomib can be safely administered in combination with (131)I-tositumomab with promising response rates.
    Leukemia & lymphoma 04/2014; · 2.61 Impact Factor
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    ABSTRACT: Background Endoscopic endonasal (EE) transphenoidal surgery is as an important surgical approach to the treatment of sellar pathology, particularly for pituitary adenomas. Risk factors for the radiographic recurrence of pituitary adenomas resected using a purely endoscopic approach have not been established. This study investigates outcomes and identifies risk factors for recurrence following EE transphenoidal surgery for pituitary adenoma.
    Clinical neurology and neurosurgery 04/2014; 119:75-79. · 1.30 Impact Factor
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    ABSTRACT: Object Surgical interventions for medically refractory epilepsy are effective in selected patients, but they are underutilized. There remains a lack of pooled data on complication rates and their changes over a period of multiple decades. The authors performed a systematic review and meta-analysis of reported complications from intracranial epilepsy surgery from 1980 to 2012. Methods A literature search was performed to find articles published between 1980 and 2012 that contained at least 2 patients. Patients were divided into 3 groups depending on the procedure they underwent: A) temporal lobectomy with or without amygdalohippocampectomy, B) extratemporal lobar or multilobar resections, or C) invasive electrode placement. Articles were divided into 2 time periods, 1980-1995 and 1996-2012. Results Sixty-one articles with a total of 5623 patients met the study's eligibility criteria. Based on the 2 time periods, neurological deficits decreased dramatically from 41.8% to 5.2% in Group A and from 30.2% to 19.5% in Group B. Persistent neurological deficits in these 2 groups decreased from 9.7% to 0.8% and from 9.0% to 3.2%, respectively. Wound infections/meningitis decreased from 2.5% to 1.1% in Group A and from 5.3% to 1.9% in Group B. Persistent neurological deficits were uncommon in Group C, although wound infections/meningitis and hemorrhage/hematoma increased over time from 2.3% to 4.3% and from 1.9% to 4.2%, respectively. These complication rates are additive in patients undergoing implantation followed by resection. Conclusions Complication rates have decreased dramatically over the last 30 years, particularly for temporal lobectomy, but they remain an unavoidable consequence of epilepsy surgery. Permanent neurological deficits are rare following epilepsy surgery compared with the long-term risks of intractable epilepsy.
    Journal of Neurosurgery 02/2014; · 3.15 Impact Factor
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    ABSTRACT: Purpose To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo. Methods Forty-one patients with advanced GEJ (89 %) or gastric (11 %) adenocarcinoma received bortezomib (1.3 mg/m(2) days 1, 4, 8, 11) plus irinotecan (125 mg/m(2) days 1, 8) every 21 days as first line therapy (N = 29), or bortezomib alone as second line therapy (N = 12). The trial was designed to detect a 40 % response rate for the combination, and 20 % response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies. Results Objective response occurred in 3 of 29 patients (10 %, 95 % confidence intervals [CI] 2 %, 27 %) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8 %, 95 % CI 0 %, 39 %) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 h after therapy with bortezomib alone (N = 2) or the combination (N = 10). Conclusions We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population.
    Investigational New Drugs 02/2014; · 3.50 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 01/2014; · 2.42 Impact Factor
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    ABSTRACT: Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) cause significant visual impairment. The role of thrombophilia and cardiovascular testing is uncertain, and optimal treatment strategies have not been determined. We reviewed medical records of 39 patients with RVO and RAO (23 women and 16 men). Thrombophilia and cardiovascular evaluations were performed and outcomes were reviewed. In all, 24 (61.5%) patients had at least 1 thrombophilia. Elevated factor VIII levels were found in RVO (n = 5) but not in RAO. There are no other significant differences in thrombophilias in RVO compared to those in RAO. Most patients had hypertension(41.2% RAO and 55% RVO) and hyperlipidemia (35.5% RAO and 81.8% RVO). In all, 4 women were using oral contraceptives, 2 were pregnant or postpartum. Follow-up data was available for 28 patients (13 RAO, 15 RVO). Nineteen were treated with aspirin, four with warfarin, and one with low molecular weight heparin. Eight patients reported improvement in vision at time of follow-up (5 RAO, 3 RVO). Multiple risk factors are associated with RVO and RAO, and a complete assessment should include thrombophilia and cardiovascular studies.
    Clinical and Applied Thrombosis/Hemostasis 12/2013; · 1.02 Impact Factor
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    ABSTRACT: Prostate-specific membrane antigen (PSMA) has been found to be expressed in the tumor-associated neovasculature of multiple solid tumor types including breast cancers. However, thus far, the number of cases studied from some tumor types has been limited. In this study, we set out to assess PSMA expression in the tumor-associated vasculature associated with invasive breast carcinomas in a sizable cohort of patients. One hundred and six patients with AJCC stage 0-IV breast cancer were identified. Ninety-two of these patients had primary breast cancer [invasive breast carcinoma with or without co-existing ductal carcinoma in situ (DCIS) (74) or DCIS alone (18)]. In addition, 14 patients with breast cancer metastases to the brain were identified. Immunohistochemical staining for PSMA and CD31 was performed on parallel representative tumor sections in each case. Tumor-associated vascular endothelial cell PSMA immunoreactivity was semi-quantitatively assessed based on two parameters: overall percent of endothelial positivity and staining intensity. PSMA expression for tumor-associated vascular endothelial cells was scored 0 if there was no detectable PSMA expression, 1 if PSMA staining was detectable in 5-50%, and 2 if PSMA expression was positive in >50% of microvessels. CD 31 staining was concurrently reviewed to confirm the presence of vasculature in each case. Tumor-associated vasculature was PSMA-positive in 68/92 (74%) of primary breast cancers and in 14/14 (100%) of breast cancers metastatic to brain. PSMA was not detected in normal breast tissue or carcinoma cells. All but 2 cases (98%) showed absence of PSMA expression in normal breast tissue-associated vasculature. The 10-year overall survival was 88.7% (95% CI = 80.0%, 93.8%) in patients without brain metastases. When overall survival (OS) was stratified based on PSMA score group, patients with PSMA scores of 0, 1, and 2 had 10-year OS of 95.8%, 96.0%, and 79.7%, respectively (p = 0.12). When PSMA scores of 0 and 1 were compared with 2, there was a statistically significant difference in OS (96.0% vs 79.7%, respectively, p = 0.05). Patients with a PSMA score of 2 had a significantly higher median tumor size compared with patients in the lower PSMA score groups (p = 0.04). Patients with higher nuclear grade were more likely to have a PSMA score of 2 compared with patients with lower nuclear grade (p < 0.0001). Patients with a PSMA score of 2 had a significantly higher median Ki-67 proliferation index compared with patients in the lower PSMA score groups (p < 0.0001). Patients with estrogen receptor (ER)-negative tumors were more likely to have a PSMA score of 2 compared with patients with ER-positive tumors (p < 0.0001). Patients with progesterone receptor (PR)-negative tumors were more likely to have a PSMA score of 2 compared with patients with PR-positive tumors (p = 0.03). No significant association was observed between PSMA score group status and lymph node involvement (p = 0.95). Too little variability was present in Human epidermal growth factor receptor-2 (Her2/neu) amplified tumors to correlate with PSMA score group status. To date, this is the first detailed assessment of PSMA expression in the tumor-associated vasculature of primary and metastatic breast carcinomas. Further studies are needed to evaluate whether PSMA has diagnostic and/or potential therapeutic value.
    Apmis 12/2013; · 2.07 Impact Factor
  • Samuel J Mann, Paul J Christos
    Journal of Clinical Hypertension 11/2013; · 2.36 Impact Factor
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    ABSTRACT: To examine a relationship between serum transforming growth factor β -1 (TGF-β1) values and radiation-induced fibrosis (RIF). We conducted a prospective analysis of the development of RIF in 39 women with American Joint Committee on Cancer stage 0-I breast cancer treated with lumpectomy and accelerated partial breast irradiation via intracavitary brachytherapy (IBAPBI). An enzyme-linked immunoassay (Quantikine, R&D, Minneapolis, MN) was used to measure serum TGF-β1 before surgery, before IBAPBI, and during IBAPBI. Blood samples for TGF-β1 were also collected from 15 healthy, nontreated women (controls). The previously validated tissue compliance meter (TCM) was used to objectively assess RIF. The median time to follow-up for 39 patients was 44 months (range, 5-59 months). RIF was graded by the TCM scale as 0, 1, 2, and 3 in 5 of 20 patients (25%), 6 of 20 patients (30%), 5 of 20 patients (25%), and 4 of 20 patients (20%), respectively. The mean serum TGF-β1 values were significantly higher in patients before surgery than in disease-free controls, as follows: all cancer patients (30,201 ± 5889 pg/mL, P=.02); patients with any type of RIF (32,273 ± 5016 pg/mL, P<.0001); and women with moderate to severe RIF (34,462 ± 4713 pg/mL, P<0.0001). Patients with moderate to severe RIF had significantly elevated TGF-β1 levels when compared with those with none to mild RIF before surgery (P=.0014) during IBAPBI (P≤0001), and the elevation persisted at 6 months (P≤.001), 12 months (P≤.001), 18 months (P≤.001), and 24 months (P=.12). A receiver operating characteristic (ROC) curve of TGF-β1 values predicting moderate to severe RIF was generated with an area under the curve (AUC)ROC of 0.867 (95% confidence interval 0.700-1.000). The TGF-β1 threshold cutoff was determined to be 31,000 pg/mL, with associated sensitivity and specificity of 77.8% and 90.0%, respectively. TGF-β1 levels correlate with the development of moderate to severe RIF. The pre-IBAPBI mean TGF-β1 levels can serve as an early biomarker for the development of moderate to severe RIF after IBAPBI.
    International journal of radiation oncology, biology, physics 10/2013; · 4.59 Impact Factor
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    ABSTRACT: The goal of this pilot study was to explore the feasibility of (89)Zr-labeled J591 monoclonal antibody positron-emission tomography (PET) of localized prostate cancer (PCa). Prior to scheduled radical prostatectomy, eleven patients were injected intravenously with (89)Zr-J591 followed 6 days later by whole-body PET. Patients underwent surgery the day after imaging and the specimens were imaged by ex vivo micro-PET and custom 3 Tesla magnetic resonance scanner coil. PET imaging studies and histopathology were correlated. Median age was 61 years (range, 47-68 years), median PSA was 5.2 ng/mL (3.5-12.0 ng/mL), and median biopsy Gleason score of the 11 index lesions was 7 (range, 7-9). On histopathology, a total of 22 lesions were identified. Median lesion size was 5.5 mm (range, 2-21 mm) and median post-RP Gleason score was 7 (range, 6-9). On in vivo PET, 8 of 11 index lesions were identified (72.7%). Lesion identification improved with increasing lesion size for in vivo (p<0.0001) and ex vivo PET imaging (p<0.0001), and increasing Gleason score (ex vivo PET imaging, p=0.01; in vivo, p=0.14). SUV appeared to correlate with increased Gleason score but was not significant (p=0.19). This is the first report describing (89)Zr-J591/PSMA PET imaging in localized PCa. In this setting, (89)Zr-J591-PET binds to tumor foci in situ and identifies primarily Gleason ≥7 and larger sized tumors, likely corresponding to clinically significant disease warranting definitive therapy. Future work is planned in a larger clinical validation trial to better define the utility of (89)Zr-J591-PET in localized PCa.
    The Journal of urology 10/2013; · 4.02 Impact Factor
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    ABSTRACT: To assess pain rates and relationship to radiation-induced fibrosis (RIF) in patients treated with intracavitary brachytherapy accelerated partial breast irradiation (IBAPBI). Thirty-nine patients treated with IBAPBI were assessed prospectively for development of pain pretreatment, 1 month post-IBAPBI, and every 6 months thereafter. A qualitative subjective Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) questionnaire assessed pain. Use of pain medications was assessed as "no", "sometimes", or "regularly". A quantitative objective validated pressure threshold (PTH) measured pain in the site of IBAPBI breast (index) and its mirror-image in the nonirradiated breast (control). A validated tissue compliance meter (TCM) quantitatively assessed RIF in the index and control breasts at all time points. Mean ΔPTH(kg) and ΔTCM(mm) values reflected mean difference between the index and control breasts. Median follow-up is 44 months (range 5-59 months). According to LENT-SOMA, pain occurred in 89% at 1 and 24 months, 67% at 30 months, 30% at 36 months, 29% at 40 months, and 20% at 48 months. No patient used pain medication "regularly" but the use "sometimes" decreased over time: 61% at 1 month, 42% at 18 and 24 months, 13% at 36 months, and 10% at 40 months. Mean ΔPTH values, compared to Δ0 kg at baseline, peaked in absolute value by 1 month to -1.36 kg (p < 0.0001), persisted after 18 months at -0.99 kg (p < 0.0001) and 24 months at -0.73 kg (p < 0.0001), and returned to nearly baseline by 40 months at -0.11 kg (p < 0.57). Mean ΔPTH and ΔTCM correlated significantly with subjective patient reports of pain at each time point (p < 0.0001). To date, this is the first report to prospectively assess pain employing quantitative and qualitative inventories in patients treated with IBAPBI. Pain is experienced in the majority of patients experienced pain within the first 2 years, sometimes requiring a medication, and though subsides, it may persist 4 years after IBAPBI.
    The Breast Journal 09/2013; · 1.83 Impact Factor
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    ABSTRACT: Human papillomavirus (HPV) is a pathogenic factor of squamous cell carcinoma in various mucosal locations, including anal carcinoma (ACA). It is also known that patients positive for HIV are at high risk of ACA. The goal of this study was to examine clinical outcome in ACA in relation to HPV/p16 positivity, histologic tumor differentiation, and HIV status. Patients with oropharyngeal cancers that are positive for HPV and show overexpression of p16 as well as having non-keratinizing/basaloid histology have been reported to have better outcomes following chemoradiation (CRT). However, such relationships in ACA remain unknown. Forty-two patients with SCC of the anus treated with CRT between 1997 and 2009 were identified. The tumors were subclassified as either non-keratinizing (including basaloid) or keratinizing categories. HPV testing was performed using SPF10-PCR, and all cases were immunostained for p16. There were 23 men and 19 women; 43 % of men and 11 % of women were HIV-positive (p = 0.04). Fifty-five percent of patients had local disease (stages I and II) and 41 % were stages III and IV, with 4 % stage unknown. All tumors were positive for high-oncogenic risk HPVs, and all were positive with p16 immunostain. Sixty-four percent of tumors were non-keratinizing/basaloid and 36 % were keratinizing. The keratinizing tumors were more common in HIV-positive patients (67 %), whereas non-keratinizing/basaloid tumors were more common in HIV-negative patients (77 %) (p = 0.008). Thirty-one percent of patients had recurrence of disease, including 50 % HIV-positive patients and 23 % HIV-negative patients (p = 0.09). There was no difference in the recurrence rate between non-keratinizing and keratinizing tumor subtypes (p = 0.80). The 24-month recurrence-free survival for the cohort was 66 % (95 % CI = 46 %, 81 %), with HIV-positive patients having worse recurrence-free survival compared to HIV-negative patients (HR = 2.85, 95 % CI = 0.95, 8.53; p = 0.06). The regional and distant failure rate was not related to HPV/p16 positivity or histologic differentiation of ACA; however, HIV positivity appeared to be associated with a higher recurrence rate and worse recurrence-free survival.
    Journal of Gastrointestinal Cancer 09/2013;
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    ABSTRACT: PURPOSE: To assess the efficacy of a single infusion of radiolabeled anti-prostate specific membrane antigen monoclonal antibody J591 (177Lu-J591) by PSA decline, measurable disease response, and survival EXPERIMENTAL DESIGN: In this dual-center phase II study, 2 cohorts with progressive metastatic castration-resistant prostate cancer received one dose of 177Lu-J591 (15 patients at 65 mCi/m2, 17 at 70 mCi/m2) with radionuclide imaging. Expansion cohort (n=15) received 70 mCi/m2 to verify response rate and examine biomarkers RESULTS: 47 patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received 177Lu-J591. 10.6% experienced > 50% decline in PSA, 36.2% experienced > 30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. 25.5% experienced grade 4 neutropenia with 1 episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m2) resulted in more 30% PSA declines (46.9% vs 13.3%, p=0.048) and longer survival (21.8 vs 11.9 months, p=0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious non-hematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond CONCLUSIONS: A single dose of 177Lu-J591 was well-tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose-response. Imaging biomarkers appear promising.
    Clinical Cancer Research 05/2013; · 7.84 Impact Factor
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    ABSTRACT: This is a phase I study to determine the maximal tolerated dose (MTD) of CPX-351 when administered sequentially with allogeneic hematopoietic stem cell transplantation (HSCT) in patients with refractory acute leukemia. CPX-351 is a novel liposomal formulation, which combines cytosine arabinoside (ara-c) and daunorubicin in a fixed, molar ratio of 5:1. Patients in cohorts of 3 were treated with CPX-351 followed by fludarabine and busulfan (Bu/Flu) conditioning at 4 (schedule A) or 3 weeks (Schedule B) intervals. CPX-351 doses were escalated in 20 units/m(2) increments starting at 60 units/m(2) x 3 doses. Thirty-six patients were enrolled, 29 patients were able to undergo HSCT and 7 patients did not proceed to transplantation, primarily on schedule A, due to rapid disease progression. The MTD of CPX-351 was not reached at the 120 units/m(2) x 3 dose level. All 29 patients who proceeded to transplant had adequate neutrophil and platelet engraftment. The median follow-up time on the study for all 36 patients was 205 days (range: 20-996 days). The 1-year cumulative incidence of relapse and non-relapse mortality (NRM) for the 36 patients, were 60.1% (95% CI = 43.4%, 77.3%) and 23.8% (95% CI = 10.9%, 47.4%) respectively. The 1-year overall survival (OS) and leukemia free survival (LFS) were 37% (95% CI = 21%-53%) and 27% (95% CI = 13%-43%) respectively. A phase II trial should incorporate CPX-351 120 units/m(2) x 3 on schedule B. Patients with good performance status and those who achieve effective cytoreduction from CPX-351 derived the most benefit.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2013; · 3.15 Impact Factor
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    ABSTRACT: Identification of radiation-induced fibrosis (RIF) remains a challenge with Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA). Tissue compliance meter (TCM), a non-invasive applicator, may render a more reproducible tool for measuring RIF. In this study, we prospectively quantify RIF after intracavitary brachytherapy (IB) accelerated partial breast irradiation (APBI) with TCM and compare it with LENT-SOMA. Thirty-nine women with American Joint Committee on Cancer Stages 0-I breast cancer, treated with lumpectomy and intracavitary brachytherapy delivered by accelerated partial breast irradiation (IBAPBI), were evaluated by two raters in a prospective manner pre-IBAPBI and every 6 months post-IBAPBI for development of RIF, using TCM and LENT-SOMA. TCM classification scale grades RIF as 0 = none, 1 = mild, 2 = moderate, and 3 = severe, corresponding to a change in TCM (ΔTCM) between the IBAPBI and nonirradiated breasts of ≤2.9, 3.0-5.9, 6.0-8.9, ≥9.0 mm, respectively. LENT-SOMA scale employs clinical palpation to grade RIF as 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Correlation coefficients-Intraclass (ICC), Pearson (r), and Cohen's kappa (κ)-were employed to assess reliability of TCM and LENT-SOMA. Multivariate and univariate linear models explored the relationship between RIF and anatomical parameters [bra cup size], antihormonal therapy, and dosimetric factors [balloon diameter, skin-to-balloon distance (SBD), V150, and V200]. Median time to follow-up from completion of IBAPBI is 3.6 years (range, 0.8-4.9 years). Median age is 69 years (range, 47-82 years). Median breast cup size is 39D (range, 34B-44DDD). Median balloon size is 41.2 cc (range, 37.6-50.0 cc), and median SBD is 1.4 cm (range, 0.2-5.5 cm). At pre-IBAPBI, TCM measurements demonstrate high interobserver agreement between two raters in all four quadrants of both breasts ICC ≥ 0.997 (95% CI 0.994-1.000). After 36 months, RIF is graded by TCM scale as 0, 1, 2, and 3 in 10/39 (26%), 17/39 (43%), 9/39 (23%), and 3/39 (8%) of patients, respectively. ΔTCM ≥6 mm (moderate-severe RIF) is statistically different from ΔTCM ≤3 mm (none-mild RIF) (p < 0.05). At 36 months post-IBAPBI, TCM measurements for two raters render ICC = 0.992 (95% CI 0.987-0.995) and r = 0.983 (p < 0.0001), whereas LENT-SOMA demonstrates κ = 0.45 (95% CI 0.18-0.80). SBD and V150 are the only factors closest to 0.05 significance of contributing to RIF. This prospective study indicates that TCM is a more reproducible method than LENT-SOMA in measuring RIF in patients treated with IBAPBI. This tool renders a promising future application in assessing RIF.
    The Breast Journal 05/2013; 19(3):250-8. · 1.83 Impact Factor
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    ABSTRACT: Objective: To further examine the psychometric properties of a 9-item version of the Arm Motor Ability Test (AMAT-9) in persons with stroke. Subjects: Thirty-two community-dwelling persons > 6 months post-stroke undergoing robotics treatment (mean age = 56.0 years, time post-stroke = 4.1 years, National Institutes of Health Stroke Scale score = 4.1, and AMAT-9 score = 1.22). Methods: Construct validity (including Rasch analyses) used baseline data prior to treatment (n = 32). Standardized response mean was calculated for subjects completing the protocol (n = 29). The Wolf Motor Function Test (WMFT), Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), and Stroke Impact Scale (SIS) were also administered. Results: Spearman-rank correlation coefficients between AMAT-9 and the WMFT, FMA, and ARAT were strong (0.78-0.79, all p < 0.001). The correlation between the AMAT-9 and SIS Hand Function sub-score was stronger than that between the AMAT-9 and the Communication sub-score (0.40, p = 0.025 and -0.16, p = 0.39, respectively). Rasch analyses provided evidence for an appropriate hierarchical structure of item difficulties, unidimensionality, and good reliability. The AMAT demonstrated a comparable standardized response mean of 0.98. Conclusions: The AMAT-9 is valid and responsive among subjects scoring in the lower range of the scale. It has the advantage of assessing function and by eliminating the standing item from the previous iteration, it may be more easily used with severely impaired patients.
    Journal of rehabilitation medicine: official journal of the UEMS European Board of Physical and Rehabilitation Medicine 03/2013; · 1.88 Impact Factor
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    ABSTRACT: OBJECTIVE: To compare the admission Berg Balance Scale (BBS) and Postural Assessment Scale for Stroke (PASS) in predicting outcomes at discharge from an inpatient rehabilitation unit (IRU). We hypothesized that discharge outcomes would be better predicted by (1) the PASS compared with the BBS, and (2) by the PASS changing position subscore compared with the PASS maintain posture subscore. DESIGN: A retrospective study analysis of admission BBS and admission PASS scores, and gait velocity (GV) at discharge, as well as selected functional independence measures (FIM) items assessed at discharge. GV was analyzed as both a continuous variable and a categorical variable (GV-A ≤ 0.4 m/s, GV-B = 0.4-0.8 m/s, and GV-C ≥ 0.8 m/s). SETTING: An IRU in an academic medical center. PARTICIPANTS: Fifty-five subjects with stroke and mean (standard deviation [SD]) age of 71.5 ± 13.8 years, admission FIM of 57.2 ± 17.2 points, and IRU length of stay of 17.3 ± 9.7 days. METHODOLOGY/MAIN OUTCOME MEASUREMENTS: Admission and discharge BBS and PASS scores, GV at discharge, and selected FIM items at discharge were measured. GV was analyzed both as continuous and categorical variables (GV-A ≤ 0.4 m/s, GV-B = 0.4-0.8 m/s, and GV-C ≥ 0.8 m/s). RESULTS: The Spearman rank correlation coefficient (r) was strong between admission BBS and PASS (r = 0.90, P < .0001). Correlations between admission BBS and PASS and discharge GV were 0.32 (P = .03) and 0.28 (P = .06), respectively. Analysis of variance was significant for both balance measures when grouped by the discharge gait speed category (P < .0001). Pairwise comparisons were significant between GV-A and the other 2 categories but not between GV-B and GV-C. The magnitude of the observed correlation with discharge GV was greater for PASS maintain posture subscore (r = 0.35, P = .02) than for PASS changing position subscore (r = 0.23, P = .13). Both subscores were significantly associated with both toileting and transfers (r = 0.43-0.56, all at least P ≤ .001). CONCLUSIONS: Contrary to our hypotheses, the BBS and PASS performed equally well in our study sample and were best at predicting patients discharged in the slowest GV category. There were few differences between the PASS subscores. Further research should compare how well admission BBS and PASS predict gait speed, falls, and other functional parameters in the community after IRU discharge.
    PM&R 02/2013; · 1.37 Impact Factor

Publication Stats

3k Citations
669.37 Total Impact Points

Institutions

  • 2001–2014
    • Weill Cornell Medical College
      • • Division of Biostatistics and Epidemiology
      • • Department of Neurological Surgery
      • • Division of Hospital Medicine
      • • Neonatal Intensive Care Unit (NICU)
      • • Breast Center
      • • Department of Public Health
      New York City, New York, United States
  • 2000–2013
    • New York Presbyterian Hospital
      • Department of Thoracic Surgery
      New York City, New York, United States
  • 2012
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 2008–2011
    • New York University
      • Department of Dermatology
      New York City, NY, United States
  • 2007
    • Partners HealthCare
      Boston, Massachusetts, United States
    • Mount Sinai School of Medicine
      • Department of Radiology
      Manhattan, NY, United States
  • 1997–2005
    • Cornell University
      • • Cardiothoracic Surgery
      • • Department of Surgery
      Ithaca, NY, United States
  • 1999–2004
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Medicine
      • • Hematology Service
      New York City, NY, United States
  • 2003
    • Temple University
      Philadelphia, Pennsylvania, United States