OR.52. Phase I Evaluation of Therapeutic, E7-targeted DNA Vaccination in Women with HPV16+ High Grade Cervical Dysplasia (CIN2/3)

2008 ◽  
Vol 127 ◽  
pp. S22
Author(s):  
Cornelia Trimble ◽  
Shiwen Peng ◽  
Richard Roden ◽  
Patti Gravitt ◽  
Drew Pardoll ◽  
...  
Keyword(s):  
Phase I ◽  
Cervical Dysplasia ◽  
Dna Vaccination ◽  
High Grade

Low Utility in Colposcopy-directed Biopsies for Non-high Grade Cytological Abnormalities on PAP Smear

2020 ◽  
Vol 16 (1) ◽  
pp. 18-22
Author(s):  
Eronmwon E. Gbinigie ◽  
Joshua Fogel ◽  
Maggie Tetrokalashvili
Keyword(s):  
Pap Smear ◽  
Multinomial Logistic Regression ◽  
Cervical Dysplasia ◽  
Outcome Variable ◽  
Low Grade ◽  
High Grade ◽  
Squamous Intraepithelial Lesion ◽  
Intraepithelial Lesion ◽  
Cytologic Abnormalities ◽  
Cytology Screening

Background: Clinicians commonly perform colposcopy directed biopsies on patients with low grade squamous intraepithelial lesion (LSIL) on PAP cytology even when not consistent with clinical guidelines. Objective: We study the association of PAP cytology screening results with cervical intra-epithelia neoplasia (CIN) 2-3 high-grade dysplasia, as confirmed by colposcopy-directed biopsy. Methods: A retrospective study of 263 women with an abnormality on the PAP smear. Multinomial logistic regression was performed with predictors of PAP cytology screening results with the outcome variable of colposcopy-directed biopsy. Results: High grade squamous intraepithelial lesion (HSIL) had significantly increased relative risk for CIN 2-3 (RR: 9.85, 95% CI: 1.84, 52.79, p=0.008). LSIL was not significantly associated with CIN 2-3. In the comparisons of negative with CIN-1, both HSIL and LSIL were not significantly associated with a negative biopsy. Conclusion: HSIL is associated with cervical dysplasia of CIN 2-3 while LSIL is not associated with cervical dysplasia of CIN 2-3. We do not recommend routine biopsies in patients with LSIL cytologic abnormalities unless additional compelling factors exist.

scholarly journals EPCT-19. A PHASE I STUDY OF RIBOCICLIB AND EVEROLIMUS FOLLOWING RADIATION THERAPY IN CHILDREN WITH NEWLY DIAGNOSED NON-BIOPSIED DIFFUSE PONTINE GLIOMAS (DIPG) AND RB+ BIOPSIED DIPG AND HIGH GRADE GLIOMAS (HGG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii307-iii307
Author(s):  
Mariko DeWire ◽  
James Leach ◽  
Christine Fuller ◽  
Peter de Blank ◽  
Trent Hummel ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
High Grade ◽  
Newly Diagnosed ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Expansion Cohort

Abstract Genomic aberrations in the cell cycle and mTOR pathways have been reported in diffuse pontine gliomas (DIPG) and high-grade gliomas (HGG). Dual inhibition of CDK4/6 (ribociclib) and mTOR (everolimus) has strong biologic rationale, non-overlapping single-agent toxicities, and adult clinical experience. The maximum tolerated dose (MTD) and/or recommended phase two dose (RP2D) of ribociclib and everolimus administered during maintenance therapy following radiotherapy was determined in the phase I study as a rolling 6 design. Ribociclib and everolimus were administered once daily for 21 days and 28 days, respectively starting two-four weeks post completion of radiotherapy. All HGG patients and any DIPG patient who had undergone biopsy were screened for RB protein by immunohistochemistry. Eighteen eligible patients enrolled (median age 8 years; range: 2–18). Six patients enrolled at dose levels 1,2, and 3 without dose limiting toxicities (DLT). Currently, five patients are enrolled at dose level 3 expansion cohort. The median number of cycles are 4.5 (range: 1–20+). Among the expansion cohort, one dose limiting toxicity included a grade 3 infection and one patient required a dose reduction in course 3 due to grade 3 ALT and grade 4 hypokalemia. The most common grade 3/4 adverse events included neutropenia. Preliminary pharmacokinetic studies on 12 patients suggest an impact of ribociclib on everolimus pharmacokinetics. The MTD/RP2D of ribociclib and everolimus following radiotherapy in newly diagnosed DIPG and HGG is anticipated to be 170 mg/m2/day x 21 days and 1.5 mg/ m2/day every 28 days which is equivalent to the adult RP2D.

High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes

2021 ◽  
Author(s):  
Giorgio Bogani ◽  
Francesco Sopracordevole ◽  
Violante Di Donato ◽  
Andrea Ciavattini ◽  
Alessandro Ghelardi ◽  
...  
Keyword(s):  
High Risk ◽  
Cervical Dysplasia ◽  
High Grade ◽  
High Risk Hpv

Su.98. Mechanisms of Immune Privilege in High Grade Cervical Dysplasia

2008 ◽  
Vol 127 ◽  
pp. S156
Author(s):  
Cornelia Trimble ◽  
Christopher Thoburn ◽  
Ferdynand Kos ◽  
Shiwen Peng ◽  
Raphael Viscidi ◽  
...  
Keyword(s):  
Cervical Dysplasia ◽  
Immune Privilege ◽  
High Grade

A phase I study of temozolomide and lapatinib combination in patients with recurrent high-grade gliomas

2013 ◽  
Vol 260 (6) ◽  
pp. 1469-1480 ◽  
Author(s):  
Vasilios Karavasilis ◽  
Vassiliki Kotoula ◽  
George Pentheroudakis ◽  
Despina Televantou ◽  
Sofia Lambaki ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
High Grade ◽  
High Grade Gliomas

CTNI-41. INITIAL RESULTS OF A PHASE I WINDOW OF OPPORTUNITY TRIAL EVALUATING A FIRST-IN-CLASS CD29 INHIBITOR, OS2966, IN RECURRENT HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi69-vi69
Author(s):  
James Liu ◽  
Chibueze D Nwagwu ◽  
Amanda V Immidisetti ◽  
Gabriela Bukanowska ◽  
Anne-Marie Carbonell ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Underlying Disease ◽  
Tissue Level ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Tumor Biopsy ◽  
Safety Issues

Abstract BACKGROUND OS2966 is a first-in-class, humanized and deimmunized monoclonal antibody which antagonizes CD29/β1integrin, a mechanosignaling receptor prominently upregulated in glioblastoma. Preclinical studies in mice and non-human primates have demonstrated safety and encouraging efficacy. A two-part, ascending concentration, phase I clinical trial was therefore initiated to evaluate the safety and feasibility of delivering OS2966 directly to the site of disease via convection-enhanced delivery (CED) in recurrent high-grade glioma patients. METHODS This study has a 2-part design: In part 1, patients undergo stereotactic tumor biopsy followed by placement of a multiport CED catheter for delivery of OS2966 to the bulk contrast enhancing tumor. Subsequently, patients undergo a clinically-indicated tumor resection followed by placement of two CED catheters and delivery of OS2966 to the surrounding tumor-infiltrated brain. A unique concentration-based accelerated titration design is utilized for dose escalation. Given availability of pre and post infusion samples, pharmacodynamic data will be analyzed to explore mechanism of action of OS2966. RESULTS Two subjects have been treated at two corresponding dose levels (0.2mg/mL and 0.4 mg/mL). No dose-limiting toxicity or unexpected safety issues have been identified. To date, reported adverse events were mild (i.e., grade 1) and consistent with underlying disease and surgical procedures. No adverse events were attributed to OS2966 or CED catheter placement. Further, no clinically significant changes from baseline neurological exam have been noted for either patient through initial follow-up. Maximal tumor coverage and concomitant gross total resection were achieved for both patients. Tumor volume measured 1.63 cm3 and 16 cm3 for Patient 1 and 2 respectively with an intratumoral Vd/Vi ratio of 1.3. and 0.94. Pharmacodynamic analysis via tissue-level biomarkers is ongoing and will be presented. CONCLUSION Initial data demonstrates the safety and feasibility of direct intracranial delivery of OS2966.

scholarly journals Significance of survivin immunoreactivity and morphometric analysis of HPV-induced cervical dysplasia

2014 ◽  
Vol 66 (1) ◽  
pp. 429-436
Author(s):  
Biserka Vukomanovic-Djurdjevic ◽  
Gordana Basta-Jovanovic ◽  
N. Baletic ◽  
Milica Berisavac ◽  
D. Nenadic ◽  
...  
Keyword(s):  
High Risk ◽  
Human Papilloma Virus ◽  
Morphometric Analysis ◽  
Cervical Dysplasia ◽  
Epithelial Dysplasia ◽  
Control Group ◽  
High Grade ◽  
Squamous Intraepithelial Lesion ◽  
Papilloma Virus ◽  
Intraepithelial Lesion

Genomic integration of high-risk human papilloma virus in the nucleus of cervical epithelial mucosal cells leads to epithelial dysplasia. The aim of this study was to determine the relevance of correlation between epithelial survivin expression and the degree of human papilloma virus (HPV)-induced cervical epithelial dysplasia, and to establish the significance of morphometric analysis of the nuclear area in the assessment of the degree of cervical dysplasia. This retrospective study included 99 women with primary, previously untreated lesions, and colposcopic findings indicating dysplasia, in whom a cytological test by Papanicolaou method was interpreted according to the Bethesda criteria as lowgrade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and atypical squamous cells of undetermined significance (ASCUS). We performed human papilloma virus (HPV) typing by PCR for evidence of viruse types 16, 18, 31, 33. After biopsy of the cervical mucosa, we performed hematoxylin-eosin (H-E) and Periodic Acid Schiff (PAS) staining, and immunohistochemical and morphometric analysis of tissue samples. The control group consisted of 12 women without dysplasia and without a verified infection of cervical high-risk HPV. A high statistical correlation between the degree of dysplasia and expression of survivin was found in patients with different types of cervical dysplasia (p = 0.003). We observed a high statistical difference between the area of nuclei at different degrees of cervical dysplasias (p = 0.000). The high-grade cervical dysplasia had a more than 2-fold higher level of ranking in comparison to low-grade dysplasia, and a more than 10-fold higher ranking than the control group without cervical dysplasia.

Sign in / Sign up

Export Citation Format

Share Document