209 results on '"Christos PJ"'
Search Results
2. Abstract P6-08-01: Analysis of patient-reported outcomes following nipple-sparing mastectomy and implant reconstruction
- Author
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Pharmer, LA, primary, Koslow, SB, additional, Martins, D, additional, Theodore, R, additional, Christos, PJ, additional, Talmor, M, additional, Simmons, RM, additional, Tousimis, E, additional, and Swistel, AJ, additional
- Published
- 2013
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3. A Phase II Trial of Sorafenib in Metastatic Melanoma with Tissue Correlates
- Author
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Chammas, R, Ott, PA, Hamilton, A, Min, C, Safarzadeh-Amiri, S, Goldberg, L, Yoon, J, Yee, H, Buckley, M, Christos, PJ, Wright, JJ, Polsky, D, Osman, I, Liebes, L, Pavlick, AC, Chammas, R, Ott, PA, Hamilton, A, Min, C, Safarzadeh-Amiri, S, Goldberg, L, Yoon, J, Yee, H, Buckley, M, Christos, PJ, Wright, JJ, Polsky, D, Osman, I, Liebes, L, and Pavlick, AC
- Abstract
BACKGROUND: Sorafenib monotherapy in patients with metastatic melanoma was explored in this multi-institutional phase II study. In correlative studies the impact of sorafenib on cyclin D1 and Ki67 was assessed. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-six patients treatment-naïve advanced melanoma patients received sorafenib 400 mg p.o. twice daily continuously. Tumor BRAF(V600E) mutational status was determined by routine DNA sequencing and mutation-specific PCR (MSPCR). Immunohistochemistry (IHC) staining for cyclin D1 and Ki67 was performed on available pre- and post treatment tumor samples. The main toxicities included diarrhea, alopecia, rash, mucositis, nausea, hand-foot syndrome, and intestinal perforation. One patient had a RECIST partial response (PR) lasting 175 days. Three patients experienced stable disease (SD) with a mean duration of 37 weeks. Routine BRAF(V600E) sequencing yielded 27 wild-type (wt) and 6 mutant tumors, whereas MSPCR identified 12 wt and 18 mutant tumors. No correlation was seen between BRAF(V600E) mutational status and clinical activity. No significant changes in expression of cyclin D1 or Ki67 with sorafenib treatment were demonstrable in the 15 patients with pre-and post-treatment tumor samples. CONCLUSIONS/SIGNIFICANCE: Sorafenib monotherapy has limited activity in advanced melanoma patients. BRAF(V600E) mutational status of the tumor was not associated with clinical activity and no significant effect of sorafenib on cyclin D1 or Ki67 was seen, suggesting that sorafenib is not an effective BRAF inhibitor or that additional signaling pathways are equally important in the patients who benefit from sorafenib. TRIAL REGISTRATION: Clinical Trials.gov NCT00119249.
- Published
- 2010
4. DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia
- Author
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Figueroa, ME, Lugthart, Sanne, Li, YS, Erpelinck - Verschueren, Claudia, Deng, XT, Christos, PJ, Schifano, E, Booth, J, Putten, Wim, Skrabanek, L, Campagne, F, Mazumdar, M, Greally, JM, Valk, Peter, Löwenberg, Bob, Delwel, Ruud, Melnick, A, Figueroa, ME, Lugthart, Sanne, Li, YS, Erpelinck - Verschueren, Claudia, Deng, XT, Christos, PJ, Schifano, E, Booth, J, Putten, Wim, Skrabanek, L, Campagne, F, Mazumdar, M, Greally, JM, Valk, Peter, Löwenberg, Bob, Delwel, Ruud, and Melnick, A
- Abstract
We hypothesized that DNA methylation distributes into specific patterns in cancer cells, which reflect critical biological differences. We therefore examined the methylation profiles of 344 patients with acute myeloid leukemia (AML). Clustering of these patients by methylation data segregated patients into 16 groups. Five of these groups defined new AML subtypes that shared no other known feature. In addition, DNA methylation profiles segregated patients with CEBPA aberrations from other subtypes of leukemia, defined four epigenetically distinct forms of AML with NPM1 mutations, and showed that established AML1-ETO, CBFb-MYH11, and PML-RARA leukemia entities are associated with specific methylation profiles. We report a 15 gene methylation classifier predictive of overall survival in an independent patient cohort (p < 0.001, adjusted for known covariates).
- Published
- 2010
5. Abstract P2-16-14: The Effect of Tetrathiomolybdate (TM) on Circulating Endothelial Progenitor Cells in Women at Moderate to High Risk of BC Recurrence
- Author
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Jain, S, primary, Ward, MM, additional, O'Laughlin, J, additional, Chuang, E, additional, Cigler, T, additional, Moore, A, additional, Donovan, D, additional, Schneider, S, additional, Cobham, M, additional, Wiener, N, additional, Lam, C, additional, Christos, PJ, additional, Lane, ME, additional, Rafii, S, additional, and Vahdat, LT., additional
- Published
- 2010
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6. The effect of tetrathiomolybdate on circulating endothelial progenitor cells in patients with breast cancer at high risk of recurrence.
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Blinder, VS, primary, Lane, ME, additional, Ward, MM, additional, Chuang, E, additional, Cigler, T, additional, Moore, AL, additional, Scheff, RJ, additional, Cobham, ME, additional, Donovan, D, additional, Rice, D, additional, Christos, PJ, additional, and Vahdat, LT, additional
- Published
- 2009
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7. Profile of 513 patients with alopecia areata: associations of disease subtypes with atopy, autoimmune disease and positive family history
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Goh, C, primary, Finkel, M, additional, Christos, PJ, additional, and Sinha, AA, additional
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- 2006
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8. Heartburn risk factors, knowledge, and prevention strategies: a population-based survey of individuals with heartburn.
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Oliveria SA, Christos PJ, Talley NJ, and Dannenberg AJ
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- 1999
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9. Clinical predictors of frequent patient telephone calls in Parkinson's disease.
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Liu AA, Boxhorn CE, Klufas MA, Christos PJ, Thorne JT, Shih AY, Tsankova NM, Dorfman BJ, Henchcliffe C, Piboolnurak P, Nirenberg MJ, Liu, Anli A, Boxhorn, Christine E, Klufas, Michael A, Christos, Paul J, Thorne, Jeffrey T, Shih, Angela Y, Tsankova, Nadejda M, Dorfman, Benjamin J, and Henchcliffe, Claire
- Abstract
Background: Patient telephone calls are a major form of unreimbursed healthcare utilization in Parkinson's disease (PD), yet little is known about potential risk factors for frequent calling behavior.Methods: Prospective cohort study of 175 non-demented outpatients with PD. Our primary outcome measure was the frequency of patient telephone calls over a three-month period relative to baseline demographics, State-Trait Anxiety Index (STAI) and Beck Anxiety Inventory (BAI) scores, Unified Parkinson's Disease Rating Scale (UPDRS) motor scores, and medication use. Based on the median call rate (1 call/3 months), subjects were dichotomized into frequent (≥2 calls) and infrequent (≤1 call) caller groups.Results: A total of 297 calls were received, of which 264 (89%) were from the frequent caller group (n = 63 subjects), and only 33 (11%) were from the infrequent caller group (n = 112 subjects). Compared with calls from infrequent callers, those from frequent callers more commonly related to somatic symptoms of PD (46.8% vs. 19.4%, p = 0.007). In multivariate logistic regression analysis, independent predictors of frequent calling were: anxiety (STAI ≥55; adjusted OR = 2.62, p = 0.02), sleep disorders (adjusted OR = 2.36, p = 0.02), dyskinesias (adjusted OR = 3.07, p = 0.03), and dopamine agonist use (adjusted OR = 2.27, p = 0.03). Baseline demographics, UPDRS motor scores, and levodopa use were similar in both groups.Conclusions: Frequent patient telephone calls in PD are independently associated with anxiety, sleep disorders, dyskinesias, and dopamine agonist use, with a minority of patients accounting for the majority of calls. Aggressive treatment of these non-motor symptoms and motor complications might potentially reduce the burden of patient telephone calls in PD. [ABSTRACT FROM AUTHOR]- Published
- 2011
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10. Determinants of radiation exposure during mobile cone-beam CT-guided robotic-assisted bronchoscopy.
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Kalchiem-Dekel O, Bergemann R, Ma X, Christos PJ, Miodownik D, Gao Y, Mahmood U, Adusumilli PS, Bott MJ, Dycoco J, Gelblum DY, Lee RP, Park BJ, Rocco G, Solomon SB, Jones DR, Chawla M, and Husta BC
- Subjects
- Humans, Male, Female, Middle Aged, Occupational Exposure adverse effects, Aged, Radiation Dosage, Phantoms, Imaging, Adult, Lung Neoplasms diagnostic imaging, Lung Neoplasms radiotherapy, Cone-Beam Computed Tomography methods, Bronchoscopy methods, Bronchoscopy adverse effects, Radiation Exposure adverse effects, Robotic Surgical Procedures adverse effects
- Abstract
Background and Objective: Robotic-assisted bronchoscopy (RAB) is an emerging modality to sample pulmonary lesions. Cone-beam computed tomography (CBCT) can be incorporated into RAB. We investigated the magnitude and predictors of patient and staff radiation exposure during mobile CBCT-guided shape-sensing RAB., Methods: Patient radiation dose was estimated by cumulative dose area product (cDAP) and cumulative reference air kerma (cRAK). Staff equivalent dose was calculated based on isokerma maps and a phantom simulation. Patient, lesion and procedure-related factors associated with higher radiation doses were identified by logistic regression models., Results: A total of 198 RAB cases were included in the analysis. The median patient cDAP and cRAK were 10.86 Gy cm
2 (IQR: 4.62-20.84) and 76.20 mGy (IQR: 38.96-148.38), respectively. Among staff members, the bronchoscopist was exposed to the highest median equivalent dose of 1.48 μSv (IQR: 0.85-2.69). Both patient and staff radiation doses increased with the number of CBCT spins and targeted lesions (p < 0.001 for all comparisons). Patient obesity, negative bronchus sign, lesion size <2.0 cm and inadequate sampling by on-site evaluation were associated with a higher patient dose, while patient obesity and inadequate sampling by on-site evaluation were associated with a higher bronchoscopist equivalent dose., Conclusion: The magnitude of patient and staff radiation exposure during CBCT-RAB is aligned with safety thresholds recommended by regulatory authorities. Factors associated with a higher radiation exposure during CBCT-RAB can be identified pre-operatively and solicit procedural optimization by reinforcing radiation protective measures. Future studies are needed to confirm these findings across multiple institutions and practices., (© 2024 Asian Pacific Society of Respirology.)- Published
- 2024
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11. Frequent potassium monitoring is associated with hyperkalemia that is clinically insignificant in females taking spironolactone for dermatologic conditions.
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Hill RC, Wang Y, Shaikh B, Christos PJ, and Lipner SR
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- Humans, Female, Middle Aged, Skin Diseases drug therapy, Skin Diseases diagnosis, Adult, Mineralocorticoid Receptor Antagonists therapeutic use, Mineralocorticoid Receptor Antagonists adverse effects, Hyperkalemia chemically induced, Hyperkalemia blood, Hyperkalemia diagnosis, Spironolactone therapeutic use, Spironolactone adverse effects, Potassium blood
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- 2024
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12. Sustained depression of B cell counts in lupus nephritis after treatment with rituximab and/or belimumab is associated with fewer disease flares.
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Zisa D, Zhang-Sun J, Christos PJ, and Kirou KA
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- Humans, Female, Retrospective Studies, Adult, Male, Lymphocyte Count, Middle Aged, Treatment Outcome, Immunosuppressive Agents therapeutic use, Young Adult, Symptom Flare Up, Immunologic Factors therapeutic use, Lupus Nephritis drug therapy, Lupus Nephritis immunology, Rituximab therapeutic use, Rituximab adverse effects, B-Lymphocytes drug effects, B-Lymphocytes immunology, Antibodies, Monoclonal, Humanized therapeutic use
- Abstract
Objective: To study the risk of lupus nephritis flare (LNF) or severe lupus flare (SLF) as a function of B cell count kinetics in lupus nephritis (LN) patients after they achieve at least a partial renal response (PRR) with induction treatment that includes rituximab (RTX) and/or belimumab (BLM)., Methods: We performed a retrospective analysis of a cohort of 19 patients with severe LN that received a B cell agent (BCA), RTX and/or BLM, as part of an initial treatment regimen for an LN flare and had subsequent CD19+ B cell measurements in peripheral blood. We then characterized the follow-up periods, after B cell depressions occurred and PRR were achieved, by the corresponding trajectories of B cell counts (BCC). Time periods with sustained low BCC were type 1 (T1) episodes, while those with repletion of BCC>100 cells/μL were called type 2 (T2) episodes. Time periods with rapid BCC repletion, defined as >50 cells/μL in ≤6 months, were called T2b episodes. Corresponding C3, C4, and anti-dsDNA levels were recorded for each episode. The time from PRR until an event, either a LNF or SLF, or to censoring, either at the end of the study period or the end of available patient follow-up, was assessed for each episode type. Kaplan-Meier survival analysis was used to compare time to flare between T1 and T2 episodes., Results: There were 26 episodes of B cell depression. Seventeen (65%) were T1 and 9 (35%) were T2. Compared to T1 episodes, T2 episodes were 9.0 times more likely to result in flare over the follow-up period (hazard ratio (HR) = 9.0, 95% CI for HR = 2.2-36.7); this risk was even larger for T2b vs T1 episodes. Median BCC was 14 cells/μL in T1 and 160 cells/μL in T2 episodes. Both C3 and C4 levels significantly increased over the duration of the episode in T1 episodes only., Conclusion: Sustained low BCC was associated with prolonged serologic and clinical response, whereas repletion, and particularly rapid repletion, of B cells after treatment with BCA was associated with subsequent disease flare., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Kyriakos Kirou received consultancy fees from Aurinia Pharmaceuticals, Astra Zeneca, and AMPEL BioSolutions LLC.
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- 2024
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13. Spironolactone treatment for dermatologic indications is not associated with hypotension in a single-center retrospective study.
- Author
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Hill RC, Wang Y, Shaikh B, Ong M, Christos PJ, and Lipner SR
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- Humans, Retrospective Studies, Female, Male, Middle Aged, Aged, Skin Diseases drug therapy, Mineralocorticoid Receptor Antagonists therapeutic use, Mineralocorticoid Receptor Antagonists adverse effects, Adult, Hypotension chemically induced, Spironolactone therapeutic use, Spironolactone adverse effects
- Abstract
Competing Interests: Conflicts of interest Ms Hill, Drs Wang and Shaikh, Mr Ong, Drs Christos and Lipner have no conflicts of interest.
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- 2024
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14. How accurate is the human olfactory system in detecting peanuts?
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Kim YE, Wang A, Christos PJ, Valente KE, and Reisacher WR
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- Humans, Allergens, Food, Arachis, Food Hypersensitivity
- Abstract
Key Points: This is the first study to quantify the accuracy, sensitivity, and specificity of the human olfactory system in detecting peanuts in common food items. With more competing sensory input, the human olfactory sensitivity to peanuts decreases; this is especially evident when peanuts are mixed in sauces. Metrics established in this study can be used to develop standards for determining the clinical utility of allergen detecting devices that are currently under development., (© 2023 ARS‐AAOA, LLC.)
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- 2024
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15. Timing to Surgery and Lymph Node Upstaging in Gastric Cancer: An NCDB Analysis.
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Riascos MC, Greenberg JA, Palacardo F, Edelmuth R, Lewis VC, An A, Najah H, Al Asadi H, Safe P, Finnerty BM, Christos PJ, Fahey TJ 3rd, and Zarnegar R
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- Humans, Neoplasm Staging, Lymph Nodes pathology, Proportional Hazards Models, Multivariate Analysis, Retrospective Studies, Lymph Node Excision, Stomach Neoplasms pathology
- Abstract
Background: Prior studies have shown tumor specificity on the impact of longer time interval from diagnosis to surgery, however in gastric cancer (GC) this remains unclear. We aimed to determine if a longer time interval from diagnosis to surgery had an impact on lymph node (LN) upstaging and overall survival (OS) outcomes among patients with clinically node negative (cN0) GC., Patients and Methods: Patients diagnosed with cN0 GC undergoing surgery between 2004-2018 were identified in the National Cancer Database (NCDB) and divided into intervals between time of diagnosis and surgery [short interval (SI): ≥ 4 days to < 8 weeks and long interval (LI): ≥ 8 weeks]. Multivariable regression analysis evaluated the independent impact of surgical timing on LN upstaging and a Cox proportional hazards analysis and Kaplan-Meier curves evaluated survival outcomes., Results: Of 1824 patients with cN0 GC, 71.8% had a SI to surgery and 28.1% had a LI to surgery. LN upstaging was seen more often in the SI group when compared to LI group (82% versus 76%, p = 0.004). LI to surgery showed to be an independent factor protective against LN upstaging [adjusted odds ratio = 0.62, 95% CI: (0.39-0.99)]. Multivariate Cox regression analysis indicated that time to surgery was not associated with a difference in overall survival [hazard ratio (HR) = 0.91, 95% CI: (0.71-1.17)], however uncontrolled Kaplan-Meier curves showed OS difference between the SI and LI to surgery groups (p = 0.037)., Conclusion: Timing to surgery was not a predictor of LN upstaging or overall survival, suggesting that additional medical optimization in preparation for surgery and careful preoperative staging may be appropriate in patients with node negative early stage GC without affecting outcomes., (© 2023. Society of Surgical Oncology.)
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- 2024
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16. The use of thyroid isthmusectomy for management of well differentiated thyroid carcinoma - A systematic review and meta-analysis.
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Usman M, Yao P, Luckett K, Andreadis K, Thomas R, Hickner A, Christos PJ, Tassler A, Kutler D, Kuhel W, and Banuchi V
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- Humans, Prognosis, Survival Rate, Thyroid Neoplasms surgery, Thyroid Neoplasms pathology, Thyroidectomy standards, Thyroidectomy statistics & numerical data
- Abstract
Objective: With the growing global incidence of thyroid carcinomas, there is an increasing need for distinct guidelines for isthmus-confined carcinomas. Here, we performed the first systematic review on the topic to date, aiming to provide understanding to isthmusectomy as surgical management for well-differentiated thyroid carcinoma of the isthmus., Methods: We conducted a systematic review following the PRISMA guidelines, analyzing English-language studies from the past decade that report on thyroid isthmusectomy. Exclusion criteria included isthmusectomy performed alongside full thyroidectomy or partial thyroid lobectomy, lack of data on tumor characteristics or survival outcomes, and non-English publications where a translation was unavailable. Our review identified a total of 227 patients from seven studies., Results: The average 5-year overall survival and disease-free survival rates for patients with isthmus-confined PTC who underwent isthmusectomy were 100 % and 93.1 %, respectively. Similar to that of total thyroidectomy. 3.1 % of patients required completion thyroidectomy. Furthermore, isthmusectomy resulted in fewer surgical complications than total thyroidectomy., Conclusions: The scarcity of studies providing detailed tumor characteristics and patient outcomes limits our ability to fully evaluate the safety and efficacy of isthmusectomy for isthmus-confined PTC. Additionally, the variable sample sizes and restricted geographic distribution of the included studies calls into questions the generalizability of their findings. Despite these limitations, the data suggest that isthmusectomy may be a viable surgical option for select patients with small, isthmus-confined PTC. In the absence of a randomized controlled trial on the noninferiority of isthmusectomy, significantly more publications are needed before strong conclusions can be drawn., Competing Interests: Declaration of competing interest All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Moon Usman, Peter Yao, Kathleen Luckett, Katerina Andreadis, MS(,) Remil Thomas, Andy Hickner, Paul J Christos, Andrew Tassler, David Kutler, William Kuhel, and Vicky Banuchi disclose no conflicts., (Copyright © 2023. Published by Elsevier Ltd.)
- Published
- 2024
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17. Author Correction: Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I-III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial.
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Altorki NK, Walsh ZH, Melms JC, Port JL, Lee BE, Nasar A, Spinelli C, Caprio L, Rogava M, Ho P, Christos PJ, Saxena A, Elemento O, Bhinder B, Ager C, Amin AD, Sanfilippo NJ, Mittal V, Borczuk AC, Formenti SC, Izar B, and McGraw TE
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- 2024
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18. Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I-III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial.
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Altorki NK, Walsh ZH, Melms JC, Port JL, Lee BE, Nasar A, Spinelli C, Caprio L, Rogava M, Ho P, Christos PJ, Saxena A, Elemento O, Bhinder B, Ager C, Amin AD, Sanfilippo NJ, Mittal V, Borczuk AC, Formenti SC, Izar B, and McGraw TE
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- Humans, Antibodies, Monoclonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoadjuvant Therapy, Randomized Controlled Trials as Topic, Clinical Trials, Phase II as Topic, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Small Cell Lung Carcinoma drug therapy
- Abstract
We previously reported the results of a randomized phase II trial (NCT02904954) in patients with early-stage non-small cell lung cancer (NSCLC) who were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation (DRT). The trial met its primary endpoint of major pathological response, which was significantly higher following DRT with no new safety signals. Here, we report on the prespecified secondary endpoint of disease-free survival (DFS) regardless of treatment assignment and the prespecified exploratory analysis of DFS in each arm of the trial. DFS at 2 and 3 years across patients in both arms of the trial were 73% (95% CI: 62.1-84.5) and 65% (95% CI: 52.5-76.9) respectively. For the exploratory endpoint of DFS in each arm of the trial, three-year DFS was 63% (95% CI: 46.0-80.4) in the durvalumab monotherapy arm compared to 67% (95% CI: 49.6-83.4) in the dual therapy arm. In addition, we report post hoc exploratory analysis of progression-free survival as well as molecular correlates of response and recurrence through high-plex immunophenotyping of sequentially collected peripheral blood and gene expression profiles from resected tumors in both treatment arms. Together, our results contribute to the evolving landscape of neoadjuvant treatment regimens for NSCLC and identify easily measurable potential biomarkers of response and recurrence., (© 2023. The Author(s).)
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- 2023
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19. An Objective Structured Clinical Exam on Breaking Bad News for Clerkship Students: In-Person Versus Remote Standardized Patient Approach.
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Prasad L, Hockstein S, Safdieh JE, Harvey K, Christos PJ, and Kang Y
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- Humans, Educational Measurement methods, Clinical Competence, Curriculum, Students, Medical, Gynecology
- Abstract
Introduction: Telemedicine training for medical students is critical as that modality becomes integral to patient care. This formative standardized patient (SP) objective structured clinical exam (OSCE) lets students discuss miscarriage diagnosis and treatment virtually., Methods: The SP OSCE was a mandatory session during the obstetrics and gynecology clerkship. Students received immediate feedback and optional individual reviews with clerkship directors. Students completed a nonmandatory survey at the end to describe their experience. SPIKES protocol student responses (i.e., proportion of correct responses) from in-person and remote SP versions were compared., Results: Between July 2019 and March 2020, 79 students completed the in-person OSCE. Between July 2020 and June 2021, 149 students completed the remote SP encounter OSCE. Students who participated in the remote versus the in-person OSCE were more likely to admit their lack of knowledge when not equipped ( p = .02), be seated during the encounter ( p = .03), show listening body language ( p = .13), assess the SP's perception ( p = .19) and understanding ( p = .20), and correct the SP's misunderstandings ( p = .14). Of 84 students from eight rotations, including both in-person and remote formats, 99% believed learning objectives were clear, 91% felt preparation material was adequate, 95% thought the instructor summarized important points, 97% learned something in caring for gynecological patients, and 96% perceived the OSCE to be a worthwhile educational experience., Discussion: The remote OSCE was well received by students. Breaking bad news virtually met assessment goals. Telemedicine training should be incorporated into medical school curricula., (© 2023 Prasad et al.)
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- 2023
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20. Safety and efficacy of Cesium-131 brachytherapy for brain tumors.
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Bander ED, Kelly A, Ma X, Christos PJ, Wernicke AG, Stieg PE, Trichter S, Knisely JPS, Ramakrishna R, and Schwartz TH
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- Humans, Cesium Radioisotopes, Treatment Outcome, Retrospective Studies, Necrosis etiology, Neoplasm Recurrence, Local surgery, Meningioma surgery, Brachytherapy adverse effects, Brachytherapy methods, Brain Neoplasms surgery, Meningeal Neoplasms surgery, Lung Neoplasms, Glioma
- Abstract
Background: The introduction of Cesium-131 (Cs-131) as a radiation source has led to a resurgence of brachytherapy for central nervous system (CNS) tumors. The aim of this study was to evaluate the safety and efficacy of the largest cohort of Cs-131 patients to-date., Methods: A retrospective review of all CNS tumors treated with resection and adjuvant Cs-131 brachytherapy at New York-Presbyterian/Weill Cornell from 2010 to 2021 was performed. Overall survival (OS) and local control (LC) were assessed with Kaplan-Meier methodology. Univariable analysis was conducted to identify patient factors associated with local recurrence or radiation necrosis., Results: Adjuvant Cs-131 brachytherapy following resection was performed in 119 patients with a median follow-up time of 11.8 (IQR 4.7-23.6) months and a mean of 22.3 +/-30.3 months. 1-year survival rates were 53.3% (95%CI 41.9-64.6%) for brain metastases (BrM), 45.9% (95%CI 24.8-67.0%) for gliomas, and 73.3% (95%CI 50.9-95.7%) for meningiomas. 1-year local control rates were 84.7% for BrM, 34.1% for gliomas, and 83.3% for meningiomas (p < 0.001). For BrM, local control was superior in NSCLC relative to other BrM pathologies (90.8% versus 76.5%, p = 0.039). Radiographic radiation necrosis (RN) was identified in 10 (8.4%) cases and demonstrated an association with smaller median tumor size (2.4 [IQR 1.8-2.7 cm] versus 3.1 [IQR 2.4-3.8 cm], p = 0.034). Wound complications occurred in 14 (11.8%) patients., Conclusions: Cs-131 brachytherapy demonstrated a favorable safety and efficacy profile characterized by high rates of local control for all treated pathologies. The concept of brachytherapy has seen a resurgence given the excellent results when Cs-131 is used as a source., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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21. Association of neurotoxin treatment likelihood with sex of television journalists.
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Dave L, Christos PJ, and Lipner SR
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- Male, Humans, Female, Neurotoxins, Forehead, Television, Botulinum Toxins, Type A, Cosmetic Techniques, Skin Aging
- Abstract
Neurotoxin procedures have been increasing in popularity since they were approved for cosmetic use in 2002, with predominately women being treated. Our objectives were to determine likelihood of neurotoxin treatment in television journalists based on demographics and social media popularity. Likelihood of neurotoxin treatment was determined from by grading forehead and glabellar rhytides in videos using a standardized scale. A greater percentage of women vs. men were "likely/highly likely" to have had glabellar (23% vs. 17%, respectively) and forehead neurotoxins (42% vs. 13%, respectively) neurotoxins (both P < 0.05). A greater proportion of anchors vs. non-anchors were "likely/highly likely" to have had glabellar neurotoxins (37% vs. 11%; P < 0.05). In sum, we found that women broadcasters are more likely to pursue neurotoxin treatments compared to male broadcasters and uncovered potential gender-based aesthetic treatment biases in the media industry., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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22. Barriers to completion of cascade genetic testing: how can we improve the uptake of testing for hereditary breast and ovarian cancer syndrome?
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Kahn RM, Ahsan MD, Chapman-Davis E, Holcomb K, Nitecki R, Rauh-Hain JA, Fowlkes RK, Tubito F, Pires M, Christos PJ, Tkachuk K, Krinsky H, Sharaf RN, Offit K, Lipkin S, and Frey MK
- Subjects
- Female, Humans, Genetic Predisposition to Disease, Follow-Up Studies, Genetic Testing, Genetic Counseling methods, Hereditary Breast and Ovarian Cancer Syndrome diagnosis, Hereditary Breast and Ovarian Cancer Syndrome genetics, Breast Neoplasms diagnosis, Breast Neoplasms genetics, Ovarian Neoplasms diagnosis, Ovarian Neoplasms genetics
- Abstract
Cascade testing for familial cancer syndromes has historically been difficult to execute. As part of a facilitated cascade testing pathway, we evaluated barriers to completion of cascade testing. Our previously published study evaluated a facilitated cascade testing pathway whereby a genetics team facilitated at-risk relative (ARR) cascade testing through telephone genetic counseling and mailed saliva kit testing. This follow-up study evaluated barriers to completion of cascade genetic testing through six-month follow-up telephone interviews. Probands identified 114 ARRs, of whom 97 were successfully contacted by telephone. Among those contacted, 83 (86%) reported interest in genetic testing and 14 (14%) declined. Among those reporting interest in testing, 71% (69/83) completed testing. Follow-up telephone interviews revealed that 14 ARRs did not complete testing despite reporting interest for the following reasons: concern about genetic discrimination, fear of a positive result and belief that the pathogenic variant was not relevant to his/her health. Five ARRs reported that they remained interested in testing and the telephone call prompted completion of testing. Even when facilitated by a medical team with prioritization of relative convenience, significant barriers to cascade testing ARRs for hereditary breast and ovarian cancer syndrome persist due to concern about genetic discrimination, cost, and fear of positive test results., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2023
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23. Additive risk of surgical site infection from more than one risk factor following craniotomy for tumor.
- Author
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Maayan O, Tusa Lavieri ME, Babu C, Chua J, Christos PJ, and Schwartz TH
- Subjects
- Humans, Bevacizumab, Risk Factors, Craniotomy adverse effects, Retrospective Studies, Surgical Wound Infection epidemiology, Surgical Wound Infection etiology, Neoplasms complications
- Abstract
Purpose: This study seeks to expound upon risk factor etiologies for surgical site infection (SSI) and investigate their combinatorial effects on infection rate following craniotomy for neuro-oncologic pathology., Methods: Patients who underwent neuro-oncologic craniotomy between 2006 and 2020 were included. Medical records were reviewed to identify the occurrence of wound infection at ≤ 3 months postoperatively. Potential risk factors for infection included tumor pathology, location, anesthesia type, indication, ventricular entry, foreign body, brachytherapy, lumbar drain, prior operation, prior cranial radiation, prior infection, bevacizumab, and medical comorbidities (hypertension, obesity, diabetes, hyperlipidemia, other cancer, cirrhosis). Logistic regression was implemented to determine risk factors for SSI. Chi-square tests were used to assess whether the number of risk factors (e.g., 0, ≥ 1, ≥2, ≥ 3, ≥4) increases the risk of SSI compared to patients with fewer risk factors. The relative increase with each additional risk factor was also evaluated., Results: A total of 1209 patients were included. SSI occurred in 42 patients (3.5%) by 90 days after surgery. Significant risk factors on multivariate logistic regression were bevacizumab (OR 40.84; p < 0.001), cirrhosis (OR 14.20, p = 0.03), foreign body placement (OR 4.06; P < 0.0001), prior radiation (OR 2.20; p = 0.03), and prior operation (OR 1.92; p = 0.04). Infection rates in the combinatorial analysis were as follows: ≥1 risk factor = 5.9% (OR 2.74; p = 0.001), ≥ 2 = 6.7% (OR 2.28; p = 0.01), ≥ 3 = 19.0% (OR 6.5; p < 0.0001), ≥ 4 = 100% (OR 30.2; p < 0.0001)., Conclusions: Risk factors in aggregate incrementally increase the risk of postoperative SSI after craniotomy for tumor., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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24. Do people with hereditary cancer syndromes inform their at-risk relatives? A systematic review and meta-analysis.
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Ahsan MD, Levi SR, Webster EM, Bergeron H, Lin J, Narayan P, Nelson BB, Li X, Fowlkes RK, Brewer JT, Thomas C, Christos PJ, Chapman-Davis E, Cantillo E, Holcomb K, Sharaf RN, and Frey MK
- Abstract
Purpose: To evaluate rates of familial disclosure of hereditary cancer syndrome information., Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO no.: CRD42020134276). Key electronic databases were searched to identify studies evaluating hereditary cancer syndrome cascade relative disclosure. Eligible studies were subjected to meta-analysis., Results: Thirty-four studies met inclusion criteria. Among 11,711 included relatives, 70% (95% CI 60 - 78%) were informed of their risk of carrying a cancer-associated pathogenic variant; of 2,875 relatives informed of their risk who were evaluated for uptake of cascade testing, 43% (95% CI 27 - 61%) completed testing. Rates of disclosure were higher among female vs male relatives (79% [95% CI 73% - 84%] vs 67% [95% CI 57% - 75%]) and first-degree vs second-degree relatives (83% [95% CI 77% - 88%] vs 58% [95% CI 45 - 69%])., Conclusion: Nearly one-third of at-risk relatives remain uninformed of their risk of carrying a cancer-associated pathogenic variant. Even among those informed, fewer than half subsequently complete genetic testing, representing a critical missed opportunity for precision cancer prevention., Innovation: Five studies evaluating interventions to improve disclosure rates were generally ineffective. Urgent work is needed to elucidate barriers to relative disclosure by probands to develop targeted interventions that can optimize proband-mediated cascade genetic testing rates., Competing Interests: Kevin Holcomb reports a relationship with Johnson & Johnson that includes: consulting or advisory., (© 2023 The Authors.)
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- 2023
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25. Cascade Testing for Hereditary Cancer Syndromes: Should We Move Toward Direct Relative Contact? A Systematic Review and Meta-Analysis.
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Frey MK, Ahsan MD, Bergeron H, Lin J, Li X, Fowlkes RK, Narayan P, Nitecki R, Rauh-Hain JA, Moss HA, Baltich Nelson B, Thomas C, Christos PJ, Hamilton JG, Chapman-Davis E, Cantillo E, Holcomb K, Kurian AW, Lipkin S, Offit K, and Sharaf RN
- Subjects
- Humans, Genetic Counseling, Privacy, Genetic Predisposition to Disease, Neoplastic Syndromes, Hereditary
- Abstract
Purpose: Evidence-based guidelines recommend cascade genetic counseling and testing for hereditary cancer syndromes, providing relatives the opportunity for early detection and prevention of cancer. The current standard is for patients to contact and encourage relatives (patient-mediated contact) to undergo counseling and testing. Direct relative contact by the medical team or testing laboratory has shown promise but is complicated by privacy laws and lack of infrastructure. We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing in the first meta-analysis on this topic., Materials and Methods: We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42020134276). We searched key electronic databases to identify studies evaluating hereditary cancer cascade testing. Eligible trials were subjected to meta-analysis., Results: Eighty-seven studies met inclusion criteria. Among relatives included in the meta-analysis, 48% (95% CI, 38 to 58) underwent cascade genetic counseling and 41% (95% CI, 34 to 48) cascade genetic testing. Compared with the patient-mediated approach, direct relative contact resulted in significantly higher uptake of genetic counseling for all relatives (63% [95% CI, 49 to 75] v 35% [95% CI, 24 to 48]) and genetic testing for first-degree relatives (62% [95% CI, 49 to 73] v 40% [95% CI, 32 to 48]). Methods of direct contact included telephone calls, letters, and e-mails; respective rates of genetic testing completion were 61% (95% CI, 51 to 70), 48% (95% CI, 37 to 59), and 48% (95% CI, 45 to 50)., Conclusion: Most relatives at risk for hereditary cancer do not undergo cascade genetic counseling and testing, forgoing potentially life-saving medical interventions. Compared with patient-mediated contact, direct relative contact increased rates of cascade genetic counseling and testing, arguing for a shift in the care delivery paradigm, to be confirmed by randomized controlled trials.
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- 2022
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26. Proposed Risk Stratification and Patterns of Radioactive Iodine Therapy in Malignant Struma Ovarii.
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Egan C, Stefanova D, Thiesmeyer JW, Lee YJ, Greenberg J, Beninato T, Zarnegar R, Christos PJ, Klein IL, Fahey TJ 3rd, and Finnerty BM
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- Female, Humans, Iodine Radioisotopes therapeutic use, Risk Assessment, Thyroidectomy, Treatment Outcome, Ovarian Neoplasms radiotherapy, Ovarian Neoplasms surgery, Struma Ovarii pathology, Struma Ovarii radiotherapy, Struma Ovarii surgery, Thyroid Neoplasms pathology, Thyroid Neoplasms radiotherapy, Thyroid Neoplasms surgery
- Abstract
Introduction: Malignant struma ovarii (MSO) is a rare thyroid cancer arising within an ovarian teratoma. While surgical excision of the primary tumor is widely accepted as standard of care, recommendations for adjuvant treatment of MSO-whether or not to administer radioactive iodine (RAI)-are based largely on case reports and remain debated. In this study, we aimed to propose a risk stratification and analyze RAI utilization patterns in MSO cases. Methods: The National Cancer Database (NCDB) was queried for patients with MSO between 2004 and 2016. Demographic, oncological, and clinicopathologic data were compared between groups using Fisher's exact test. Kaplan-Meier curves were used to estimate overall survival (OS), and variables associated with OS were assessed via univariate Cox regression. We adapted the 2015 American Thyroid Association risk guidelines for MSO patients. We stratified patients into low-, intermediate-, and high-risk groups using metastasis, extraovarian extension, lymphovascular invasion, lymph node status, surgical margins, tumor size, and grade. Risk stratification, demographic, oncological, and clinicopathologic data were compared between the groups receiving and not receiving RAI therapy. We then queried the Surveillance, Epidemiology, and End Results (SEER) 18 registry for patients with MSO between 2000 and 2018 to confirm our risk stratification analysis. Results: In the NCDB analysis, a total of 158 patients were identified, and 19 received RAI. RAI therapy was associated with distant metastasis ( p = 0.005) and lymph node status ( p = 0.012). Twenty-one NCDB patients were stratified as high risk, and 30% of high-risk patients received RAI. High-risk stratification was associated with decreased OS via univariate Cox regression (hazard ratio = 4.0 [95% confidence interval 1.11-14.26], p = 0.034). In our subsequent analysis using the SEER registry, there were 95 MSO patients, and 18 received RAI. Again, the majority of high-risk patients did not receive RAI, with only 41% of high-risk patients receiving RAI. Conclusions: MSO is a rare malignancy with apparently variable and inconsistent patterns of postoperative RAI administration. The risk stratification described here provides a framework to identify patients potentially at risk for mortality, and utilization of RAI in this group should be studied further.
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- 2022
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27. Improved Water and Waste Management Practices Reduce Diarrhea Risk in Children under Age Five in Rural Tanzania: A Community-Based, Cross-Sectional Analysis.
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McClelland PH, Kenney CT, Palacardo F, Roberts NLS, Luhende N, Chua J, Huang J, Patel P, Sanchez LA, Kim WJ, Kwon J, Christos PJ, and Finkel ML
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- Cross-Sectional Studies, Diarrhea epidemiology, Diarrhea etiology, Diarrhea prevention & control, Humans, Infant, Rural Population, Sanitation, Tanzania epidemiology, Drinking Water, Waste Management
- Abstract
Diarrhea remains a significant cause of morbidity and mortality among children in developing countries. Water, sanitation, and hygiene practices (WASH) have demonstrated improved diarrhea-related outcomes but may have limited implementation in certain communities. This study analyzes the adoption and effect of WASH-based practices on diarrhea in children under age five in the rural Busiya chiefdom in northwestern Tanzania. In a cross-sectional analysis spanning July-September 2019, 779 households representing 1338 under-five children were surveyed. Among households, 250 (32.1%) reported at least one child with diarrhea over a two-week interval. Diarrhea prevalence in under-five children was 25.6%. In per-household and per-child analyses, the strongest protective factors against childhood diarrhea included dedicated drinking water storage (OR 0.25, 95% CI 0.18−0.36; p < 0.001), improved waste management (OR 0.37, 95% CI 0.27−0.51; p < 0.001), and separation of drinking water (OR 0.38, 95% CI 0.24−0.59; p < 0.001). Improved water sources were associated with decreased risk of childhood diarrhea in per-household analysis (OR 0.72, 95% CI 0.52−0.99, p = 0.04), but not per-child analysis (OR 0.83, 95% CI 0.65−1.05, p = 0.13). Diarrhea was widely treated (87.5%), mostly with antibiotics (44.0%) and oral rehydration solution (27.3%). Targeting water transportation, storage, and sanitation is key to reducing diarrhea in rural populations with limited water access.
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- 2022
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28. Familial colloid cysts: not a chance occurrence.
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Giantini-Larsen AM, Garton ALA, Villamater FN, Kuzan-Fischer CM, Savage NJ, Cunniff CM, Ross ME, Christos PJ, Stieg PE, and Souweidane MM
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- Child, Cohort Studies, Humans, Retrospective Studies, Colloid Cysts epidemiology, Colloid Cysts genetics, Colloid Cysts surgery, Hydrocephalus complications, Third Ventricle pathology
- Abstract
Purpose: Colloid cysts are rare, benign brain tumors of the third ventricle with an estimated population prevalence of 1 in 5800. Sudden deterioration and death secondary to obstructive hydrocephalus are well-described presentations in patients with a colloid cyst. Although historically conceptualized as driven by sporadic genetic events, a growing body of literature supports the possibility of an inherited predisposition., Methods: A prospective registry of patients with colloid cysts was maintained between 1996 and 2021. Data pertaining to a family history of colloid cyst was collected retrospectively; self-reporting was validated in each case by medical record or imaging review. Frequency of patients with a documented first-degree family member with a colloid cyst based on self-reporting was calculated. The rate of familial co-occurrence within our series was then compared to a systematic literature review and aggregation of familial case studies, as well as population-based prevalence rates of sporadic colloid cysts., Results: Thirteen cases with affected first-degree relatives were identified in our series. Of the entire cohort, 19/26 were symptomatic from the lesion (73%), 12/26 (46.2%) underwent resection, and 2/26 (7.7%) had sudden death from presumed obstructive hydrocephalus. The majority of transmission patterns were between mother and child (9/13). Compared with the estimated prevalence of colloid cysts, our FCC rate of 13 cases in 383 (3.4%) estimates a greater-than-chance rate of co-occurrence., Conclusion: Systematic screening for FCCs may facilitate early recognition and treatment of indolent cysts, thereby preventing the rapid deterioration that can occur with an unrecognized third ventricular tumor. Furthermore, identifying a transmission pattern may yield more insight into the molecular and genetic underpinnings of colloid cysts., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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29. Combined use of vancomycin powder and betadine irrigation lowers the incidence of postcraniotomy wound infection in low-risk cases: a single-center risk-stratified cohort analysis.
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Maayan O, Babu C, Tusa Lavieri ME, Chua J, Christos PJ, and Schwartz TH
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- Anti-Bacterial Agents therapeutic use, Antibiotic Prophylaxis methods, Cohort Studies, Humans, Incidence, Powders, Retrospective Studies, Surgical Wound Infection epidemiology, Surgical Wound Infection etiology, Surgical Wound Infection prevention & control, Povidone-Iodine therapeutic use, Vancomycin therapeutic use
- Abstract
Purpose: Postoperative surgical site infections (SSIs) constitute a significant source of morbidity for neurosurgical patients. Protocols that minimize postoperative wound infections are integral to improving outcomes and curtailing expenditures. The present study seeks to identify risk factors for infection and assess the efficacy of prophylactic betadine irrigation and vancomycin powder in addition to standard antibiotic irrigation., Methods: We reviewed craniotomies performed by THS at Weill Cornell/New York Presbyterian Hospital to treat neuro-oncologic pathology. Patients were divided into three groups: group 1 - antibiotic irrigation, group 2 - antibiotic irrigation and betadine irrigation, group 3 - antibiotic irrigation, betadine irrigation, and vancomycin powder. SSI was confirmed with bacterial culture. Risk factor identification and assessment of treatment paradigms was performed using chi-square tests and univariate logistic regression., Results: Among 1209 total patients, the 30- and 90-day SSI rates were 1.7% and 3.5%, respectively. Significant predictors of SSI included preoperative use of bevacizumab (OR 40.84; p < 0.0001), foreign body (OR 4.06; p < 0.0001), prior radiation (OR 2.20; p = 0.03), and prior operation/biopsy (OR 1.92; p = 0.04). Risk of infection was 2.1% in low-risk cases and 6.9% in high-risk cases. A significant, incremental decrement in SSIs was identified between the prophylaxis groups, although only among low-risk cases: group 1: 4.53%, group 2: 1.39%, group 3: 0.42% (p = 0.02). Neither vancomycin powder nor betadine significantly reduced the risk of SSI in patients with one or more risk factors., Conclusion: Vancomycin powder with betadine irrigation decreased SSI rates following neuro-oncologic cranial procedures in patients at low risk of infection (i.e., no preoperative risk factors)., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
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- 2022
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30. Dual Biologic or Small Molecule Therapy for Treatment of Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.
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Ahmed W, Galati J, Kumar A, Christos PJ, Longman R, Lukin DJ, Scherl E, and Battat R
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- Cohort Studies, Humans, Ustekinumab therapeutic use, Biological Products therapeutic use, Crohn Disease drug therapy, Inflammatory Bowel Diseases chemically induced, Inflammatory Bowel Diseases drug therapy
- Abstract
Background and Aims: We conducted a systematic review and meta-analysis to summarize emerging data on the safety and effectiveness of dual biologic therapy in combination or with tofacitinib in patients with refractory inflammatory bowel disease (IBD)., Methods: Through a systematic search of multiple electronic databases through November 9, 2020, we identified cohort studies or case series (>10 patients) reporting the safety and effectiveness of simultaneous use of biologic agents in combination or with tofacitinib in patients with IBD. Rates of adverse events, clinical remission, and endoscopic remission were synthesized using pooled data, and we identified factors associated with successful dual therapy., Results: We identified 30 studies reporting 288 trials of dual biologic or small molecule therapy in 279 patients (76% Crohn's disease; median duration of treatment 24 weeks (IQR
25 -IQR75 1332)). The main indications for dual therapy included medically refractory IBD (81%) and concurrent extra-intestinal manifestations or rheumatologic disease (12%). The most common combinations of dual therapy included tumor necrosis factor-α antagonists & anti-integrins (48%), ustekinumab & anti-integrins (19%); 61% of patients had previously failed at least one of the two therapies used in combination. Over a median follow-up of 32 weeks (IQR25 -IQR75 24-52), pooled rates of adverse and serious adverse events were 31% (95% CI, 13%-54%) and 6.5% (95% CI, 2.1%-13.1%); pooled rates of clinical and endoscopic remission were 59% (95% CI, 42%-74%), and 34% (95% CI, 23%-46%), respectively. 12% (95% CI, 4%-24%) of patients required surgery. Rates of success were higher in patients on dual therapy due to EIM. Heterogeneity was not significant for endoscopic response (P = .88, I2 = 0%), endoscopic remission (P = .44, I2 = 0%), and malignancy (P = .87, I2 = 0%). However, significant heterogeneity existed for other outcomes., Conclusions: Dual biologic or small molecule therapy may be a possible option in highly selected, refractory IBD patients at specialized centers. Higher quality combination of therapies with a significant improvement in the quality of data is required prior to more widespread use., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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31. Pilot study of the diagnostic utility of 89 Zr-df-IAB2M and 68 Ga-PSMA-11 PET imaging and multiparametric MRI in localized prostate cancer.
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Vlachostergios PJ, Niaz MJ, Thomas C, Christos PJ, Osborne JR, Margolis DJA, Khani F, Bander NH, Scherr DS, and Tagawa ST
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- Aged, Antibodies, Monoclonal, Humans, Male, Middle Aged, Pilot Projects, Prostatectomy, Sensitivity and Specificity, Antigens, Surface immunology, Gallium Radioisotopes, Glutamate Carboxypeptidase II immunology, Multiparametric Magnetic Resonance Imaging, Positron Emission Tomography Computed Tomography methods, Prostatic Neoplasms diagnostic imaging, Radioisotopes, Zirconium
- Abstract
Background: Accurate diagnosis of localized prostate cancer (PCa) is limited by inadequacy of multiparametric (mp) MRI to fully identify and differentiate localized malignant tissue from benign pathologies. Prostate-specific membrane antigen (PSMA) represents an excellent target for molecular imaging. IAB2M, an 85-kD minibody derived from a de-immunized monoclonal antibody directed at the extracellular domain of human PSMA (huJ591), and PSMA-11, a small molecule ligand have been previously tested as probes for visualization of recurrent/metastatic PCa with PET/CT. This pilot, non-randomized trial studied their diagnostic utility in patients (pts) with localized PCa., Methods: Pts planned for radical prostatectomy (RP) were enrolled and underwent mpMRI and PET/CT imaging with
89 Zr-df-IAB2M and/or68 Ga-PSMA-PET/CT. Image results were read by a radiologist blinded to clinical information and pathology results, mapped and compared to corresponding histopathology findings from all lesions, both clinically significant and nonsignificant. The detection rates of all three imaging modalities were measured and correlated., Results: 20 pts with median age of 64.5 (46-79) years and PSA level of 7.5 (1.6-36.56) ng/ml were enrolled. 19 pts underwent RP and were imaged pre-operatively with89 Zr-Df-IAB2M PET/CT and mpMRI. Nine of those were imaged using68 Ga-PSMA-11 as well. Out of 48 intraprostatic lesions verified on surgical pathology, IAB2M PET/CT was able to detect 36 (75%). A similar proportion of pathologically confirmed, clinically significant lesions (22/29, 76%) was detected. IAB2M PET/CT was also able to identify 14/19 (74%) extraprostatic lesions. The performance of mpMRI was inferior, with 24/48 detectable lesions (50%) and 18/29 clinically significant intraprostatic lesions (62%). Compared to the current standard (mpMRI), IAB2M PET/CT had a sensitivity of 88%, specificity 38%, positive predictive value 58%, and accuracy 63%. In 9 pts who underwent Ga-PSMA-11 as well, the latter yielded a detection rate of 70% (14/20), which was also seen in clinically significant lesions (10/14, 71%). Ga-PSMA-11 PET/CT also detected 4/6 (67%) extraprostatic lesions., Conclusions: In this pilot study, the performance of89 Zr-df-IAB2M was superior to mpMRI and similar to68 Ga-PSMA-11 PET/CT. The higher detection rate of PSMA-PET supports its use as a diagnostic tool with consequent management change implications in men with localized PCa., (© 2022 Wiley Periodicals LLC.)- Published
- 2022
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32. Room for improvement in capturing cancer family history in a gynecologic oncology outpatient setting.
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Lin J, Wolfe I, Ahsan MD, Krinsky H, Lackner AI, Pelt J, Bolouvi K, Gamble C, Thomas C, Christos PJ, Cantillo E, Holcomb K, Chapman-Davis E, Sharaf R, Lipkin SM, Blank SV, and Frey MK
- Abstract
The literature demonstrates that the quality of cancer family history (CFH) as currently collected in the outpatient setting is inadequate to assess disease risk. Prior to implementation of a web-based application for cancer family history collection, we aimed to review the quality of collected CFH in a gynecologic oncology outpatient clinic and determine contributing patient factors. Medical records were reviewed for 200 new patients presenting between 4/2019-7/2019. CFH was collected during the patient interview and evaluated for inclusion of eight elements based on standards set by the genetics community. Univariate and multivariable linear regression analyses were utilized to evaluate the effect of patient characteristics on the number of relatives included in the CFH. Among our cohort of 200 patients, CFH was documented for 185 patients (92.5%). On univariate analysis, patients with a family history of cancer and prior genetic testing had significantly greater median number of relatives included in the CFH. On multivariable analysis, patients with family members with cancer had significantly more relatives included. Our data are consistent with the literature, suggesting that the current collection methods may not adequately capture all measures of a high quality CFH. Patients reporting no family history of cancer and those without prior genetic testing were least likely to have CFH that included key quality elements and these patients might benefit from health information technology CFH collection tools., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Inc.)
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- 2022
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33. Stereotactic radiosurgery for vestibular schwannomas in neurofibromatosis type 2 patients: a systematic review and meta-analysis.
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Tosi U, Maayan O, An A, Lavieri MET, Guadix SW, DeRosa AP, Christos PJ, Pannullo S, Stieg PE, Brandmaier A, Knisely JPS, and Ramakrishna R
- Subjects
- Hearing Loss epidemiology, Humans, Treatment Outcome, Neurofibromatosis 2 complications, Neuroma, Acoustic etiology, Neuroma, Acoustic radiotherapy, Radiosurgery adverse effects, Radiosurgery methods
- Abstract
Introduction: Neurofibromatosis type 2 (NF2) is characterized by often bilateral vestibular schwannomas (VS) that result in progressive hearing loss and compression of nearby brainstem structures causing cranial nerve palsies. Treatment of these tumors remains challenging, as both surgical removal and expectant management can result in symptom progression. Stereotactic radiosurgery (SRS) has been investigated for the management of NF2-associated VS; however, the role, promises, and pitfalls of this treatment modality remain unclear., Methods: Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Reviews were searched for studies assessing SRS outcome in NF2-associated VS only. Primary endpoints included tumor control, serviceable hearing, presence of tinnitus, and cranial nerve V and VII symptoms., Results: A total of 16 studies (589 patients harboring 750 tumors) were analyzed. Clinical tumor control was achieved in 88% of cases (95% CI 80-95%); salvage surgery was needed in 8% (95% CI 4-13%) of cases. Treatment resulted in a worsening of pre-treatment serviceable hearing (OR = 0.26, p < 0.01), increased facial nerve (OR = 1.62, p < 0.01) and trigeminal nerve (OR = 1.42, p = 0.07) impairment. The incidence of vestibular symptoms and hydrocephalus were not consistently reported and thus could not be assessed., Conclusions: The treatment of NF2-associated VS continues to pose a challenge, as current SRS regimens result in impaired hearing and worse cranial nerve comorbidities, despite achieving high tumor control. It remains unclear if these findings have to be regarded as treatment complications or, rather, continued disease progression., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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34. An Assessment of Race as a Risk Factor for Doxorubicin-Related Cardiotoxicity in Diffuse Large B-Cell Lymphoma.
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Toure A, Luan D, Wu Y, Christos PJ, Leonard JP, and Martin P
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- Aged, Aged, 80 and over, Cardiotoxicity physiopathology, Female, Humans, Incidence, Lymphoma, Large B-Cell, Diffuse pathology, Male, Racial Groups, Retrospective Studies, Risk Assessment, Risk Factors, Cardiotoxicity etiology, Doxorubicin adverse effects, Heart Failure chemically induced, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
Background: Doxorubicin carries a risk of congestive heart failure (CHF). Black race has been suggested as a risk factor for doxorubicin-related cardiotoxicity, but data are limited. We assessed whether HF occurs at higher rates in Black patients compared to White patients who receive doxorubicin for DLBCL, and evaluated race as an independent risk factor for the development of HF after adjusting for known risk factors., Patients and Methods: We used SEER-Medicare to identify patients 66 years and older with DLBCL. We excluded patients with CHF documented prior to diagnosis with DLBCL. We assessed for hypertension, type 2 diabetes, coronary artery disease, and arrhythmias prior to diagnosis with DLBCL. The primary outcome was documented CHF at any point following DLBCL diagnosis. Secondary outcomes included CHF in the first year following diagnosis and death. We performed analyses additionally stratified by cumulative dose of doxorubicin., Results: Our study population consisted of 8,604 patients (White 96.8%, Black 3.2%). In both Kaplan-Meier and competing risk analyses, we observed no significant difference in the incidence of CHF between Black and White patients, both before and after adjusting for covariates. Finally, we observed no significant differences in the incidence of CHF by race after stratification by cumulative doxorubicin dose., Conclusions: CHF is common following doxorubicin chemotherapy for DLBCL in older patients. No association was observed between Black race and the onset of heart failure in this setting. Rigorous screening for known clinical risk factors is likely more relevant than race in treatment selection and optimization., (Copyright © 2021. Published by Elsevier Inc.)
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- 2022
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35. Achieving universal genetic assessment for women with ovarian cancer: Are we there yet? A systematic review and meta-analysis.
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Lin J, Sharaf RN, Saganty R, Ahsan D, Feit J, Khoury A, Bergeron H, Chapman-Davis E, Cantillo E, Holcomb K, Blank SV, Liu Y, Thomas C, Christos PJ, Wright DN, Lipkin S, Offit K, and Frey MK
- Subjects
- BRCA1 Protein genetics, BRCA2 Protein genetics, DNA Mutational Analysis statistics & numerical data, Female, Genetic Counseling statistics & numerical data, Humans, Ovarian Neoplasms genetics, Ovarian Neoplasms prevention & control, Referral and Consultation statistics & numerical data, Telemedicine organization & administration, Telemedicine statistics & numerical data, Early Detection of Cancer statistics & numerical data, Genetic Counseling organization & administration, Genetic Testing statistics & numerical data, Ovarian Neoplasms diagnosis, Referral and Consultation organization & administration
- Abstract
Purpose: Several professional organizations recommend universal genetic assessment for people with ovarian cancer as identifying pathogenic variants can affect treatment, prognosis, and all-cause mortality for patients and relatives. We sought to evaluate the literature on genetic assessment for women with ovarian cancer and determine if any interventions or patient characteristics drive utilization of services., Methods: We searched key electronic databases to identify trials that evaluated genetic assessment for people with ovarian cancer. Trials with the primary aim to evaluate utilization of genetic assessment with or without interventions were included. Eligible trials were subjected to meta-analysis and the moderating influence of health interventions on rates of genetic assessment were examined., Results: A total of 35 studies were included (19 report on utilization of genetic services without an intervention, 7 with an intervention, and 9 with both scenarios). Without an intervention, pooled estimates for referral to genetic counseling and completion of genetic testing were 39% [CI 27-53%] and 30% [CI 19-44%]. Clinician-facilitated interventions included: mainstreaming of genetic services (99% [CI 86-100%]), telemedicine (75% [CI 43-93%]), clinic-embedded genetic counselor (76% [CI 32-95%]), reflex tumor somatic genetic assessment (64% [CI 17-94%]), universal testing (57% [28-82%]), and referral forms (26% [CI 10-53%]). Random-effects pooled proportions demonstrated that Black vs. White race was associated with a lower rate of genetic testing (26%[CI 17-38%] vs. 40% [CI 25-57%]) as was being un-insured vs. insured (23% [CI 18-28%] vs. 38% [CI 26-53%])., Conclusions: Reported rates of genetic testing for people with ovarian cancer remain well below the goal of universal testing. Interventions such as mainstreaming can improve testing uptake. Strategies aimed at improving utilization of genetic services should consider existing disparities in race and insurance status., Competing Interests: Declaration of Competing Interest Kevin Holcomb serves as a consultant for Johnson and Johnson and receives research support from Fujirebio Diagnostics, outside the submitted work. The other authors made no disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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36. Financial toxicity, mental health, and gynecologic cancer treatment: The effect of the COVID-19 pandemic among low-income women in New York City.
- Author
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Chen YS, Zhou ZN, Glynn SM, Frey MK, Balogun OD, Kanis M, Holcomb K, Gorelick C, Thomas C, Christos PJ, and Chapman-Davis E
- Subjects
- Adult, Aged, Aged, 80 and over, COVID-19 economics, Female, Financial Stress etiology, Genital Neoplasms, Female economics, Genital Neoplasms, Female psychology, Humans, Medicaid, Mental Health, Middle Aged, New York City, Pilot Projects, Poverty, Surveys and Questionnaires, Telemedicine, United States, Young Adult, COVID-19 psychology, Financial Stress epidemiology, Genital Neoplasms, Female therapy, Pandemics economics
- Abstract
Background: New York City (NYC) emerged as an epicenter of the COVID-19 pandemic, and marginalized populations were affected at disproportionate rates. The authors sought to determine the impact of COVID-19 on cancer treatment, anxiety, and financial distress among low-income patients with gynecologic cancer during the peak of the NYC pandemic., Methods: Medicaid-insured women who were receiving gynecologic oncology care at 2 affiliated centers were contacted by telephone interviews between March 15 and April 15, 2020. Demographics and clinical characteristics were obtained through self-report and retrospective chart review. Financial toxicity, anxiety, and cancer worry were assessed using modified, validated surveys., Results: In total, 100 patients completed the telephone interview. The median age was 60 years (range, 19-86 years), and 71% had an annual income <$40,000. A change in employment status and early stage cancer (stage I and II) were associated with an increase in financial distress (P < .001 and P = .008, respectively). Early stage cancer and telehealth participation were significantly associated with increased worry about future finances (P = .017 and P = .04, respectively). Lower annual income (<$40,000) was associated with increased cancer worry and anxiety compared with higher annual income (>$40,000; P = .036 and P = .017, respectively). When controlling for telehealth participation, income, primary language, and residence in a high COVID-19 prevalence area, a delay in medical care resulted in a 4-fold increased rate of anxiety (P = .023, 95% CI, 1.278-14.50). Race was not significantly associated with increased financial distress, cancer worry, or anxiety., Conclusions: Low socioeconomic status was the most common risk factor for increased financial distress, cancer worry, and anxiety. Interventions aimed at improving access to timely oncology care should be implemented during this ongoing pandemic., (© 2021 American Cancer Society.)
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- 2021
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37. Outcomes in CLL patients with NOTCH1 regulatory pathway mutations.
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Helbig DR, Abu-Zeinah G, Bhavsar E, Christos PJ, Furman RR, and Allan JN
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chromosomes, Human, Pair 12, DNA-Binding Proteins physiology, F-Box-WD Repeat-Containing Protein 7 physiology, Follow-Up Studies, Humans, Immunotherapy, Kaplan-Meier Estimate, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Mediator Complex physiology, Neoplasm Proteins physiology, Prognosis, Progression-Free Survival, RNA-Binding Proteins physiology, Receptor, Notch1 physiology, Time-to-Treatment, Treatment Outcome, Trisomy, Watchful Waiting, DNA-Binding Proteins genetics, F-Box-WD Repeat-Containing Protein 7 genetics, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Mediator Complex genetics, Neoplasm Proteins genetics, RNA-Binding Proteins genetics, Receptor, Notch1 genetics, Signal Transduction genetics
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- 2021
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38. Leveraging Health Information Technology to Collect Family Cancer History: A Systematic Review and Meta-Analysis.
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Li X, Kahn RM, Wing N, Zhou ZN, Lackner AI, Krinsky H, Badiner N, Fogla R, Wolfe I, Bergeron H, Baltich Nelson B, Thomas C, Christos PJ, Sharaf RN, Cantillo E, Holcomb K, Chapman-Davis E, and Frey MK
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- Humans, Medical Informatics, Neoplasms diagnosis, Neoplasms epidemiology, Neoplasms genetics
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Purpose: Collection of family cancer histories (FCHs) can identify individuals at risk for familial cancer syndromes. The aim of this study is to evaluate the literature on existing strategies whereby providers use information technology to assemble FCH., Methods: A systematic search of online databases (Ovid MEDLINE, Cochrane, and Embase) between 1980 and 2020 was performed. Statistical heterogeneity was assessed through the chi-square test (ie, Cochrane Q test) and the inconsistency statistic (I
2 ). A random-effects analysis was used to calculate the pooled proportions and means., Results: The comprehensive search produced 4,005 publications. Twenty-eight studies met inclusion criteria. Twenty-seven information technology tools were evaluated. Eighteen out of 28 studies were electronic surveys administered before visits (18, 64.3%). Five studies administered tablet surveys in offices (5, 17.8%). Four studies collected electronic survey via kiosk before visits (4, 14.3%), and one study used animated virtual counselor during visits (1, 3.6%). Among the studies that use an FCH tool, the pooled estimate of the overall completion rate was 86% (CI, 72% to 96%), 84% (CI, 65% to 97%) for electronic surveys before visits, 89% (CI, 0.74 to 0.98) for tablet surveys, and 85% (CI, 0.66 to 0.98) for surveys via kiosk. Mean time required for completion was 31.0 minutes (CI, 26.1 to 35.9), and the pooled estimate of proportions of participants referred to genetic testing was 12% (CI, 4% to 23%)., Conclusion: Our review found that electronic FCH collection can be completed successfully by patients in a time-efficient manner with high rates of satisfaction., Competing Interests: Charlene ThomasTravel, Accommodations, Expenses: Inovio Pharmaceuticals, Nektar, Pfizer Kevin HolcombResearch Funding: Fujirebio DiagnosticsExpert Testimony: Johnson and Johnson Inc Melissa K. FreyResearch Funding: InvitaeNo other potential conflicts of interest were reported.- Published
- 2021
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39. Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial.
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Altorki NK, McGraw TE, Borczuk AC, Saxena A, Port JL, Stiles BM, Lee BE, Sanfilippo NJ, Scheff RJ, Pua BB, Gruden JF, Christos PJ, Spinelli C, Gakuria J, Uppal M, Binder B, Elemento O, Ballman KV, and Formenti SC
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- Adolescent, Adult, Aged, Antibodies, Monoclonal adverse effects, B7-H1 Antigen antagonists & inhibitors, B7-H1 Antigen immunology, Carcinoma, Non-Small-Cell Lung immunology, Carcinoma, Non-Small-Cell Lung pathology, Combined Modality Therapy, Female, Humans, Male, Middle Aged, Neoadjuvant Therapy adverse effects, Neoplasm Staging, Radiosurgery methods, Young Adult, Antibodies, Monoclonal administration & dosage, B7-H1 Antigen genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung radiotherapy
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Background: Previous phase 2 trials of neoadjuvant anti-PD-1 or anti-PD-L1 monotherapy in patients with early-stage non-small-cell lung cancer have reported major pathological response rates in the range of 15-45%. Evidence suggests that stereotactic body radiotherapy might be a potent immunomodulator in advanced non-small-cell lung cancer (NSCLC). In this trial, we aimed to evaluate the use of stereotactic body radiotherapy in patients with early-stage NSCLC as an immunomodulator to enhance the anti-tumour immune response associated with the anti-PD-L1 antibody durvalumab., Methods: We did a single-centre, open-label, randomised, controlled, phase 2 trial, comparing neoadjuvant durvalumab alone with neoadjuvant durvalumab plus stereotactic radiotherapy in patients with early-stage NSCLC, at NewYork-Presbyterian and Weill Cornell Medical Center (New York, NY, USA). We enrolled patients with potentially resectable early-stage NSCLC (clinical stages I-IIIA as per the 7th edition of the American Joint Committee on Cancer) who were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients were randomly assigned (1:1) to either neoadjuvant durvalumab monotherapy or neoadjuvant durvalumab plus stereotactic body radiotherapy (8 Gy × 3 fractions), using permuted blocks with varied sizes and no stratification for clinical or molecular variables. Patients, treating physicians, and all study personnel were unmasked to treatment assignment after all patients were randomly assigned. All patients received two cycles of durvalumab 3 weeks apart at a dose of 1·12 g by intravenous infusion over 60 min. Those in the durvalumab plus radiotherapy group also received three consecutive daily fractions of 8 Gy stereotactic body radiotherapy delivered to the primary tumour immediately before the first cycle of durvalumab. Patients without systemic disease progression proceeded to surgical resection. The primary endpoint was major pathological response in the primary tumour. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrial.gov, NCT02904954, and is ongoing but closed to accrual., Findings: Between Jan 25, 2017, and Sept 15, 2020, 96 patients were screened and 60 were enrolled and randomly assigned to either the durvalumab monotherapy group (n=30) or the durvalumab plus radiotherapy group (n=30). 26 (87%) of 30 patients in each group had their tumours surgically resected. Major pathological response was observed in two (6·7% [95% CI 0·8-22·1]) of 30 patients in the durvalumab monotherapy group and 16 (53·3% [34·3-71·7]) of 30 patients in the durvalumab plus radiotherapy group. The difference in the major pathological response rates between both groups was significant (crude odds ratio 16·0 [95% CI 3·2-79·6]; p<0·0001). In the 16 patients in the dual therapy group with a major pathological response, eight (50%) had a complete pathological response. The second cycle of durvalumab was withheld in three (10%) of 30 patients in the dual therapy group due to immune-related adverse events (grade 3 hepatitis, grade 2 pancreatitis, and grade 3 fatigue and thrombocytopaenia). Grade 3-4 adverse events occurred in five (17%) of 30 patients in the durvalumab monotherapy group and six (20%) of 30 patients in the durvalumab plus radiotherapy group. The most frequent grade 3-4 events were hyponatraemia (three [10%] patients in the durvalumab monotherapy group) and hyperlipasaemia (three [10%] patients in the durvalumab plus radiotherapy group). Two patients in each group had serious adverse events (pulmonary embolism [n=1] and stroke [n=1] in the durvalumab monotherapy group, and pancreatitis [n=1] and fatigue [n=1] in the durvalumab plus radiotherapy group). No treatment-related deaths or deaths within 30 days of surgery were reported., Interpretation: Neoadjuvant durvalumab combined with stereotactic body radiotherapy is well tolerated, safe, and associated with a high major pathological response rate. This neoadjuvant strategy should be validated in a larger trial., Funding: AstraZeneca., Competing Interests: Declaration of interests NKA reports stock options from TMRW, Angiocrine Bioscience, and View Point Medical; and is on the research advisory committee for AstraZeneca. AS reports personal fees from AstraZeneca, Blueprint Medicines, Genentech, Medtronic, and Takeda. JLP reports leadership and stock options from TMRW, Angiocrine Bioscience, and View Point Medical. BMS reports personal fees from AstraZeneca, Pfizer, Flame Biosciences, Gala Therapeutics, Bristol Myers Squibb, and Ribon Therapeutics; and is on the board of directors for the Lung Cancer Research Foundation. BEL reports personal fees from AstraZeneca. KVB reports personal fees from Janssen, Eli Lilly, Takeda, Johnson and Johnson, Sanfoi, and Ariad. SCF has received grants from Bristol Myers Squibb, Varian, Merck, Eisai, Eli Lilly, Janssen, and Regeneron; and personal fees from Accuray, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Elekta, EMD Serono/Merck, GlaxoSmithKline, Janssen, MedImmune, Merck US, Regeneron, Varian, and ViewRay. PJC was partially supported by a grant from the Clinical and Translational Science Center at Weill Cornell Medical College (grant number 1-UL1-TR002384-01). All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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40. Time to administration of stereotactic radiosurgery to the cavity after surgery for brain metastases: a real-world analysis.
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Roth O'Brien DA, Kaye SM, Poppas PJ, Mahase SS, An A, Christos PJ, Liechty B, Pisapia D, Ramakrishna R, Wernicke AG, Knisely JPS, Pannullo SC, and Schwartz TH
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Objective: Publications on adjuvant stereotactic radiosurgery (SRS) are largely limited to patients completing SRS within a specified time frame. The authors assessed real-world local recurrence (LR) for all brain metastasis (BM) patients referred for SRS and identified predictors of SRS timing., Methods: The authors retrospectively identified BM patients undergoing resection and referred for SRS between 2012 and 2018. Patients were categorized by time to SRS, as follows: 1) ≤ 4 weeks, 2) > 4-8 weeks, 3) > 8 weeks, and 4) never completed. The relationships between timing of SRS and LR, LR-free survival (LRFS), and survival were investigated, as well as predictors of and reasons for specific SRS timing., Results: In a cohort of 159 patients, the median age at resection was 64.0 years, 56.5% of patients were female, and 57.2% were in recursive partitioning analysis (RPA) class II. The median preoperative tumor diameter was 2.9 cm, and gross-total resection was achieved in 83.0% of patients. All patients were referred for SRS, but 20 (12.6%) did not receive it. The LR rate was 22.6%, and the time to SRS was correlated with the LR rate: 2.3% for patients receiving SRS at ≤ 4 weeks postoperatively, 14.5% for SRS at > 4-8 weeks (p = 0.03), and 48.5% for SRS at > 8 weeks (p < 0.001). No LR difference was seen between patients whose SRS was delayed by > 8 weeks and those who never completed SRS (48.5% vs 50.0%; p = 0.91). A similar relationship emerged between time to SRS and LRFS (p < 0.01). Non-small cell lung cancer pathology (p = 0.04), earlier year of treatment (p < 0.01), and interval from brain MRI to SRS (p < 0.01) were associated with longer intervals to SRS. The rates of receipt of systemic therapy also differed significantly between patients by category of time to SRS (p = 0.02). The most common reasons for intervals of > 4-8 weeks were logistic, whereas longer delays or no SRS were caused by management of systemic disease or comorbidities., Conclusions: Available data on LR rates after adjuvant SRS are often obtained from carefully preselected patients receiving timely treatment, whereas significantly less information is available on the efficacy of adjuvant SRS in patients treated under "real-world" conditions. Management of these patients may merit reconsideration, particularly when SRS is not delivered within ≤ 4 weeks of resection. The results of this study indicate that a substantial number of patients referred for SRS either never receive it or are treated > 8 weeks postoperatively, at which time the SRS-treated patients have an LR risk equivalent to that of patients who never received SRS. Increased attention to the reasons for prolonged intervals from surgery to SRS and strategies for reducing them is needed to optimize treatment. For patients likely to experience delays, other radiotherapy techniques may be considered.
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- 2021
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41. Timing of Adjuvant Fractionated Stereotactic Radiosurgery Affects Local Control of Resected Brain Metastases.
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Roth O'Brien DA, Poppas P, Kaye SM, Mahase SS, An A, Christos PJ, Liechty B, Pisapia D, Ramakrishna R, Wernicke AG, Knisely JPS, Pannullo S, and Schwartz TH
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- Humans, Middle Aged, Neoplasm Recurrence, Local surgery, Prospective Studies, Retrospective Studies, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Radiosurgery
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Purpose: For resected brain metastases (BMs), stereotactic radiosurgery (SRS) is often offered to minimize local recurrence (LR). Although the aim is to deliver SRS within a few weeks of surgery, a variety of socioeconomic, medical, and procedural issues can cause delays. We evaluated the relationship between timing of postoperative SRS and LR., Methods and Materials: We retrospectively identified a consecutive series of patients with BM managed with resection and SRS or fractionated SRS at our institution from 2012 to 2018. We assessed the correlation of time to SRS and other demographic, disease, and treatment variables with LR, local recurrence-free survival, distant recurrence, distant recurrence-free survival, and overall survival., Results: A total of 133 patients met inclusion criteria. The median age was 64.5 years. Approximately half of patients had a single BM, and median BM size was 2.9 cm. Gross total resection was achieved in 111 patients (83.5%), and more than 90% of patients received fractionated SRS. The median time to SRS was 37.0 days, and the LR rate was 16.4%. Time to SRS was predictive of LR. The median time from surgery to SRS was 34.0 days for patients without LR versus 61.0 days for those with LR (P < .01). The LR rate was 2.3% with SRS administered ≤4 weeks postoperatively, compared with 23.6% if SRS was administered >4 weeks postoperatively (P < .01). Local recurrence-free survival was also improved for patients who underwent SRS at ≤4 weeks (P = .02). Delayed SRS was also predictive of distant recurrence (P = .02) but not overall survival., Conclusions: In this retrospective study, the strongest predictor of LR after postoperative SRS for BM was time to SRS, and a cutoff of 4 weeks was a reliable predictor of recurrence. These findings merit investigation in a prospective, randomized trial., (Copyright © 2021. Published by Elsevier Inc.)
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- 2021
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42. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted β-emitting radionuclide therapies in metastatic castration-resistant prostate cancer.
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Vlachostergios PJ, Niaz MJ, Skafida M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, and Tagawa ST
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- Adult, Aged, Aged, 80 and over, Antigens, Surface metabolism, Glutamate Carboxypeptidase II metabolism, Humans, Lutetium administration & dosage, Lutetium metabolism, Male, Middle Aged, Neoplasm Metastasis diagnostic imaging, Positron Emission Tomography Computed Tomography methods, Prospective Studies, Prostate-Specific Antigen blood, Prostatic Neoplasms, Castration-Resistant diagnostic imaging, Prostatic Neoplasms, Castration-Resistant metabolism, Radiopharmaceuticals therapeutic use, Single Photon Emission Computed Tomography Computed Tomography methods, Antigens, Surface analysis, Glutamate Carboxypeptidase II analysis, Lutetium therapeutic use, Neoplasm Metastasis radiotherapy, Prostatic Neoplasms, Castration-Resistant radiotherapy, Radioisotopes therapeutic use, Radiotherapy methods
- Abstract
Background: Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) has demonstrated efficacy and tolerability with a dose-response effect in phase I/II trials in men with metastatic castration-resistant prostate cancer (mCRPC). The need for positive PSMA imaging before PSMA-TRT to select patients is largely practiced, but its utility is not proven. Given target heterogeneity, developing a biomarker to identify the optimal patient population remains an unmet need. The aim of this study was to assess PSMA uptake by imaging and response to PSMA-TRT., Methods: We performed an analysis of men with mCRPC enrolled in sequential prospective phase I/II trials of PSMA-TRT. Each patient had baseline PSMA imaging by planar
111 In and/or177 Lu SPECT (N = 171) or68 Ga-PSMA-11 PET/CT (N = 44), but the results were not used to include/exclude treatment. Semiquantitative imaging scores (IS) on a 0-4 scale were assigned based on PSMA uptake in tumors compared to liver uptake. We compared the ≥50% PSA decline response proportions between low (0-1) and high (2-4) PSMA IS using the χ2 -test. We used multivariable logistic regression analysis to understand the relationship between independent and dependent variables, including IS, radionuclide activity (dose) administered, CALGB (Halabi) prognostic risk score, prior taxane use., Results: 215 men with progressive mCRPC received PSMA-TRT as follows:177 Lu-J591 (n = 137),177 Lu-PSMA-617 (n = 44),90 Y-J591 (n = 28),177 Lu-J591 +177 Lu-PSMA-617 (n = 6). High PSMA expression (IS 2-4) was found in 160 (74.4%) patients and was significantly associated with more frequent ≥ 50% PSA reduction (26.2 vs. 7.3%, p = .006). On multivariate logistic regression analysis, higher IS was associated with a ≥50% decrease in PSA, even after accounting for CALGB (Halabi) prognostic score, the dose administered, and previous taxane use (OR, 4.72; 95% CI, 1.71-16.85; p = .006). Patients with low PSMA expression (N = 55, 24.7%) were less likely to respond. Thirteen of 26 (50%) with no PSMA uptake (IS = 0) had post-PSMA-TRT PSA decline with 2 (7.7%) having ≥ 50% PSA declines., Conclusion: Collectively, the data provide evidence in favor of the hypothesis that patients with high PSMA uptake and high administered radionuclide dose correlate with a higher chance of response., (© 2021 Wiley Periodicals LLC.)- Published
- 2021
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43. Optimal lead follicle size for human chorionic gonadotropin trigger in clomiphene citrate and intrauterine insemination cycles: an analysis of 1,676 treatment cycles.
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Hancock KL, Pereira N, Christos PJ, Petrini AC, Hughes J, Chung PH, and Rosenwaks Z
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- Adult, Cell Size drug effects, Female, Humans, Infertility diagnostic imaging, Infertility therapy, Insemination, Artificial standards, Male, Ovarian Follicle drug effects, Pregnancy, Chorionic Gonadotropin administration & dosage, Clomiphene administration & dosage, Fertility Agents, Female administration & dosage, Insemination, Artificial methods, Ovarian Follicle physiology, Pregnancy Rate trends
- Abstract
Objective: To identify the optimal lead follicle size for hCG trigger in clomiphene citrate (CC)-intrauterine insemination (IUI) cycles., Design: Retrospective cohort study., Setting: University-affiliated center., Patient(s): Patients <40 years of age with ovulatory dysfunction or unexplained infertility undergoing their first CC-IUI cycle., Intervention(s): Ovulation induction, hCG trigger, and IUI., Main Outcome Measure(s): Clinical pregnancy rate (CPR) was the primary outcome and was plotted against lead follicle size in increments of 1 mm. Odds ratios with 95% confidence intervals for associations between lead follicle size and CPR were calculated from a multivariable logistic regression model. A receiver operating characteristic (ROC) curve was generated for CPR as a function of lead follicle size., Result(s): 1,676 cycles were included. The overall CPR was 13.8% (232/1,676). There was no difference in baseline demographics or ovulation induction parameters of patients who did or did not conceive. The odds of clinical pregnancy were 2.3 and 2.2 times higher with lead follicle sizes of 21.1-22.0 mm and >22.0 mm, respectively, compared with the referent category of 19.1-20.0 mm. Lead follicle size was an independent predictor of CPR, even after accounting for confounders. A lead follicle size of 22.1 mm corresponded to a sensitivity and specificity of 80.1% and 90.4% for clinical pregnancy, respectively, with an area under the ROC curve of 0.89., Conclusion(s): hCG administration at a lead follicle size of 21.1-22.0 mm is associated with higher odds of clinical pregnancy in patients undergoing their first CC-IUI cycles for ovulatory dysfunction or unexplained infertility., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
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- 2021
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44. Multispectral Imaging for Metallic Biopsy Marker Detection During MRI-Guided Breast Biopsy: A Feasibility Study for Clinical Translation.
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Eskreis-Winkler S, Simon K, Reichman M, Spincemaille P, Nguyen TD, Christos PJ, Drotman M, Prince MR, Pinker K, Sutton EJ, Morris EA, and Wang Y
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Purpose: To assess the feasibility and diagnostic accuracy of multispectral MRI (MSI) in the detection and localization of biopsy markers during MRI-guided breast biopsy., Methods: This prospective study included 20 patients undergoing MR-guided breast biopsy. In 10 patients (Group 1), MSI was acquired following tissue sampling and biopsy marker deployment. In the other 10 patients (Group 2), MSI was acquired following tissue sampling but before biopsy marker deployment (to simulate deployment failure). All patients received post-procedure mammograms. Group 1 and Group 2 designations, in combination with the post-procedure mammogram, served as the reference standard. The diagnostic performance of MSI for biopsy marker identification was independently evaluated by two readers using two-spectral-bin MR and one-spectral-bin MR. The κ statistic was used to assess inter-rater agreement for biopsy marker identification., Results: The sensitivity, specificity, and accuracy of biopsy marker detection for readers 1 and 2 using 2-bin MSI were 90.0% (9/10) and 90.0% (9/10), 100.0% (10/10) and 100.0% (10/10), 95.0% (19/20) and 95.0% (19/20); and using 1-bin MSI were 70.0% (7/10) and 80.0% (8/10), 100.0% (8/8) and 100.0% (10/10), 85.0% (17/20) and 90.0% (18/20). Positive predictive value was 100% for both readers for all numbers of bins. Inter-rater agreement was excellent: κ was 1.0 for 2-bin MSI and 0.81 for 1-bin MSI., Conclusion: MSI is a feasible, diagnostically accurate technique for identifying metallic biopsy markers during MRI-guided breast biopsy and may eliminate the need for a post-procedure mammogram., Competing Interests: YW and PS are inventors on QSM-related patents issued to Cornell University and hold equity in Medimagemetric LLC. KP received payment for activities not related to the present article including lectures including service on speakers bureaus and for travel/accommodations/meeting expenses unrelated to activities listed from the European Society of Breast Imaging (MRI educational course, annual scientific meeting), and the IDKD 2019 (educational course). EM has received a grant from GRAIL, Inc. for research not related to the present article. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Eskreis-Winkler, Simon, Reichman, Spincemaille, Nguyen, Christos, Drotman, Prince, Pinker, Sutton, Morris and Wang.)
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- 2021
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45. Prostate-Specific Membrane Antigen Uptake and Survival in Metastatic Castration-Resistant Prostate Cancer.
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Vlachostergios PJ, Niaz MJ, Sun M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, and Tagawa ST
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Background: Prostate-specific membrane antigen (PSMA) imaging has been suggested as highly sensitive modality for detection of metastases in patients with biochemically recurrent or advanced prostate cancer (PCa). PSMA expression is associated with grade and stage and has a relationship with androgen receptor signaling. The aim of this study was to evaluate the prognostic utility of radiographic PSMA expression in men with metastatic castration-resistant prostate cancer (mCRPC)., Methods: Patients with mCRPC and available baseline PSMA imaging were studied. Images by planar/single-photon emission computed tomography (SPECT) or positron emission tomography (PET)/CT were reviewed. Planar/SPECT images were scored semi-quantitatively and PET/CT scored quantitatively with comparison of tumor uptake to liver uptake on a scale of 0-4 in order to determine an imaging score (IS). The IS (high: 2-4 versus low: 0-1), subsequent receipt of life-prolonging systemic therapies (taxane chemotherapy, potent androgen receptor pathway inhibitors, sipuleucel-T, and radium-223), and the CALGB prognostic risk stratification of patients were analyzed according to overall survival (OS) in univariate and multivariate Cox's proportional hazards models., Results: High PSMA expression (IS 2-4) was found in 179 (75.21%) patients, and 59 (24.79%) patients had low PSMA uptake. The median OS of the entire cohort was 16.8 (95%CI: 14.9-19.3) months. Patients with a high IS had a significantly shorter OS of 15.8 (95%CI 13.0-18.1) months compared to those with low expression [22.7 (95%CI: 17.7-30.7) months, p = 0.002]. After accounting for use of life-prolonging therapies (p<0.001) and CALGB prognostic groups (p = 0.001), high PSMA IS emerged as an independent prognostic factor for OS [HR(95%CI): 1.7 (1.2-2.2); p = 0.003]., Conclusion: Presence of high radiographic PSMA expression on SPECT or PET/CT may portend a poor prognosis in patients with mCRPC treated with standard systemic therapies. This provides implications for therapeutic targeting of PSMA-avid disease as a means to improve outcomes., Competing Interests: ST certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: NB is an inventor of patents assigned to the Cornell Center for Technology Licensing for the J591 antibody described in this article. He is also a paid consultant for and holds equity in BZL Biologics, LLC, the company to which these patents were licensed for further research and development and is a SAB member and holds equity in Telix Pharmaceuticals, Ltd, sub-licensed to develop J591-Lu177. ST has served as a paid consultant to Endocyte/AAA/Novartis and Blue Earth, as an unpaid consultant to Atlab and Telix, and Weill Cornell Medicine has received research funding from Endocyte/AAA/Novartis, Progenics, and Atlab/Telix. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vlachostergios, Niaz, Sun, Mosallaie, Thomas, Christos, Osborne, Molina, Nanus, Bander and Tagawa.)
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46. Outcomes of stereotactic radiosurgery for large vestibular schwannomas: a systematic review and meta-analysis.
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Tosi U, Lavieri MET, An A, Maayan O, Guadix SW, DeRosa AP, Christos PJ, Pannullo S, Stieg PE, Brandmaier A, Knisely JPS, and Ramakrishna R
- Abstract
Background: Large vestibular schwannomas (VS) pose a treatment challenge for both microsurgery (MS) and stereotactic radiosurgery (SRS). Technical developments have allowed for safer irradiation of large tumors. It remains unclear if SRS can achieve appropriate tumor control and acceptable cranial nerve toxicities. In this study, we assess outcomes of irradiation for large VS., Methods: PubMed MEDLINE, EMBASE, Web of Science, and Cochrane were searched for all the studies assessing SRS outcome in large VS. Primary endpoints included clinical and radiographic tumor control, need for salvage surgery, serviceable hearing, cranial nerve V and VII impairment, presence of hydrocephalus requiring shunting, and presence of vertigo/dizziness., Results: Twenty-two studies were identified that met selection criteria for analysis from an initial pool of 1272 reports. They were evaluated according to treatment protocol: 1) single-dose SRS (13 studies, 483 patients), 2) combination of MS and SRS (7 studies, 182 patients), and 3) fractionated SRS (3 studies, 82 patients). Tumor control was achieved in 89%, 94%, and 91% of patients, respectively. Odds ratios (ORs) of post- over pretreatment serviceable hearing were 0.42 ( P < .01), 0.47 ( P = .05), and 0.60 ( P = .22); for facial nerve impairment, these ORs were 1.08 ( P = .69), 3.45 ( P = .28), and 0.87 ( P = .71), respectively., Conclusions: The management of large VS remains challenging. All treatment modalities resulted in high tumor control rates and worsening of pretreatment hearing. None, however, caused significant facial nerve impairment, suggesting that management strategies incorporating focal irradiation can be successful., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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47. Efficacy and comorbidities of hypofractionated and single-dose radiosurgery for vestibular schwannomas: a systematic review and meta-analysis.
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Tosi U, Guadix S, An A, Wright D, Christos PJ, Pannullo S, Brandmaier A, Knisely JPS, Stieg PE, and Ramakrishna R
- Abstract
Background: Vestibular schwannomas (VS) are tumors of the cerebellopontine angle with significant morbidity, causing hearing loss, tinnitus, and trigeminal and facial nerve compromise. An effective alternative to microsurgical resection is stereotactic radiosurgery (SRS), which can be delivered in either single-fraction (SRS) or hypofractionated stereotactic radiotherapy (hSRT) (3-5 treatments) regimens. It remains unclear which fractionation regimen provides superior outcomes., Methods: Ovid MEDLINE, EMBASE, CINAHL, and Cochrane Reviews were searched for studies either comparing hSRT with SRS or focusing on hSRT alone in treating VS. Primary endpoints included tumor control, serviceable hearing, tinnitus, and cranial nerve V and VII symptoms. A random-effects analysis was employed to compare pre- and post-treatment effects (hSRT alone) or SRS and hSRT outcomes (two-arm studies)., Results: This analysis included 21 studies focusing on hSRT alone and 13 studies comparing SRS and hSRT. Significant heterogeneity was observed. Overall, when hSRT was analyzed alone, crude tumor control was achieved in 94% (95% CI: 88%, 99%) of 1571 patients. There was no difference between pre- and post-treatment odds ratios (OR) of tinnitus, facial, or trigeminal impairment. Serviceable hearing was diminished following hSRT (OR = 0.60, 95% CI: 0.44, 0.83). Comparison with SRS showed no difference with respect to tumor control, serviceable hearing, trigeminal or facial nerve impairment., Conclusions: hSRT achieved excellent tumor control and, with the exception of serviceable hearing, did not result in worse post-treatment cranial nerve symptomatology. Analysis of comparative studies between hSRT and SRS did not reveal any significant difference in either tumor control or treatment morbidities., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
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48. Adapting and avoiding coping strategies for women with ovarian cancer during the COVID-19 pandemic.
- Author
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Frey MK, Chapman-Davis E, Glynn SM, Lin J, Ellis AE, Tomita S, Fowlkes RK, Thomas C, Christos PJ, Cantillo E, Zeligs K, Holcomb K, and Blank SV
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Middle Aged, Ovarian Neoplasms therapy, Adaptation, Psychological, COVID-19 epidemiology, Ovarian Neoplasms psychology, SARS-CoV-2
- Abstract
Background: The COVID-19 pandemic has resulted in unprecedented challenges for people living with cancer, impacting not only physical health but psychological well-being. The psychological response affects the individual as well as the community and can persist long after the outbreak. We aim to assess coping strategies employed by women with ovarian cancer during the COVID-19 pandemic., Methods: Women with a current or prior diagnosis of ovarian cancer completed an online survey which included a query about coping strategies during the COVID-19 pandemic. The survey was distributed from March 30th through April 13, 2020 through survivor networks and social media., Results: Six hundred and three women visited the survey website during the study period and 555 (92.0%) completed the survey. Four hundred and eight (73.5%) provided information on coping strategies utilized during COVID-19. Among those who responded, the median age was 58 years (range 20-85) and 150 participants (40.8%) were undergoing active cancer treatment. Commonly utilized adaptive coping strategies included emotional support (159, 39.0%), self care (148, 36.3%), hobbies (139, 34.1%), planning (87, 21.3%), positive reframing (54, 13.2%), religion (50, 12.3%) and instrumental support (38, 9.3%). Many participants also relied on avoidance coping strategies including self distraction (111, 27.2%) and substance use (19, 4.7%)., Conclusions: Most ovarian cancer survivors are using adaptive, problem-focused coping strategies during the COVID-19 pandemic, however many are practicing avoidance strategies as well. As coping mechanisms profoundly impact quality of life, oncology providers must assist patients in identifying coping strategies that optimize physical and psychological well-being., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2021
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49. Basal cell carcinomas of the ear are more aggressive and have higher discordance rates between biopsy and Mohs histopathology.
- Author
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Navrazhina K, Parra CE, Cressey BD, Xanthos C, Christos PJ, and Minkis K
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- Aged, Biopsy statistics & numerical data, Carcinoma, Basal Cell pathology, Carcinoma, Basal Cell surgery, Ear pathology, Ear Neoplasms pathology, Ear Neoplasms surgery, Facial Neoplasms pathology, Facial Neoplasms surgery, Female, Humans, Male, Margins of Excision, Middle Aged, Neoplasm Invasiveness, Observer Variation, Retrospective Studies, Skin pathology, Skin Neoplasms pathology, Skin Neoplasms surgery, Carcinoma, Basal Cell diagnosis, Ear Neoplasms diagnosis, Facial Neoplasms diagnosis, Mohs Surgery statistics & numerical data, Skin Neoplasms diagnosis
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- 2020
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50. Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank.
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Kolin DA, Kulm S, Christos PJ, and Elemento O
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- Adult, Aged, Betacoronavirus, Biological Specimen Banks, COVID-19, Comorbidity, Coronavirus Infections blood, Depression epidemiology, Female, Humans, Longitudinal Studies, Male, Middle Aged, Myocardial Ischemia epidemiology, Pandemics, Pneumonia, Viral blood, Prospective Studies, Pulmonary Disease, Chronic Obstructive epidemiology, Risk Factors, SARS-CoV-2, United Kingdom epidemiology, ABO Blood-Group System, Black People, Coronavirus Infections epidemiology, Coronavirus Infections genetics, Pneumonia, Viral epidemiology, Pneumonia, Viral genetics
- Abstract
Background: Coronavirus disease 2019 (Covid-19) has rapidly infected millions of people worldwide. Recent studies suggest that racial minorities and patients with comorbidities are at higher risk of Covid-19. In this study, we analyzed the effects of clinical, regional, and genetic factors on Covid-19 positive status., Methods: The UK Biobank is a longitudinal cohort study that recruited participants from 2006 to 2010 from throughout the United Kingdom. Covid-19 test results were provided to UK Biobank starting on March 16, 2020. The main outcome measure in this study was Covid-19 positive status, determined by the presence of any positive test for a single individual. Clinical risk factors were derived from UK Biobank at baseline, and regional risk factors were imputed using census features local to each participant's home zone. We used robust adjusted Poisson regression with clustering by testing laboratory to estimate relative risk. Blood types were derived using genetic variants rs8176719 and rs8176746, and genomewide tests of association were conducted using logistic-Firth hybrid regression., Results: This prospective cohort study included 397,064 UK Biobank participants, of whom 968 tested positive for Covid-19. The unadjusted relative risk of Covid-19 for Black participants was 3.66 (95% CI 2.83-4.74), compared to White participants. Adjusting for Townsend deprivation index alone reduced the relative risk to 2.44 (95% CI 1.86-3.20). Comorbidities that significantly increased Covid-19 risk included chronic obstructive pulmonary disease (adjusted relative risk [ARR] 1.64, 95% CI 1.18-2.27), ischemic heart disease (ARR 1.48, 95% CI 1.16-1.89), and depression (ARR 1.32, 95% CI 1.03-1.70). There was some evidence that angiotensin converting enzyme inhibitors (ARR 1.48, 95% CI 1.13-1.93) were associated with increased risk of Covid-19. Each standard deviation increase in the number of total individuals living in a participant's locality was associated with increased risk of Covid-19 (ARR 1.14, 95% CI 1.08-1.20). Analyses of genetically inferred blood types confirmed that participants with type A blood had increased odds of Covid-19 compared to participants with type O blood (odds ratio [OR] 1.16, 95% CI 1.01-1.33). A meta-analysis of genomewide association studies across ancestry groups did not reveal any significant loci. Study limitations include confounding by indication, bias due to limited information on early Covid-19 test results, and inability to accurately gauge disease severity., Conclusions: When assessing the association of Black race with Covid-19, adjusting for deprivation reduced the relative risk of Covid-19 by 33%. In the context of sociological research, these findings suggest that discrimination in the labor market may play a role in the high relative risk of Covid-19 for Black individuals. In this study, we also confirmed the association of blood type A with Covid-19, among other clinical and regional factors., Competing Interests: OE reports grants from the National Institutes of Health and the Emerson Research Collective. The funders had no role in any aspect of study design, analysis, writing, or other aspects related to the submitted work. There are no relationships or activities that have influenced the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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- 2020
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