Publications by authors named "Fauzia Arif"

5 Publications

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A prospective clinical and transcriptomic feasibility study of oral-only hormonal therapy with radiation for unfavorable prostate cancer in men 70 years of age and older or with comorbidity.

Cancer 2021 Apr 21. Epub 2021 Apr 21.

Department of Radiation and Cellular Oncology, University of Chicago Medicine, Chicago, Illinois.

Background: Androgen deprivation therapy (ADT) improves outcomes in unfavorable-risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing hormone-releasing hormone (LHRH) agonists with a 5-α-reductase inhibitor (5-ARI) would improve hormonal health-related quality of life (HRQOL) without differentially suppressing androgen-responsive (AR) gene expression.

Methods: Patients with localized unfavorable-risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5-ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long-term LHRH agonist with RT. RNA sequencing was performed from matched pre-/post-ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment.

Results: Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow-up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6-month hormonal decline was 1% (oADT) versus 12% (SOC; P = .04). The 4-year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P = .48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold-change = 2; false-discovery rate-adjusted P ≤ .05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling.

Conclusions: For men with PCa undergoing RT, oral versus standard ADT may improve 6-month QOL and appears to have a similar impact on androgen-responsive gene expression.
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http://dx.doi.org/10.1002/cncr.33556DOI Listing
April 2021

A prospective trial of stereotactic body radiation therapy for unresectable pancreatic cancer testing ablative doses.

J Gastrointest Oncol 2020 Dec;11(6):1399-1407

Department of Medical Oncology, University of Chicago Medical Center, Chicago, IL, USA.

Background: We explored the safety and efficacy of ablative doses of stereotactic body radiation therapy (SBRT) for unresectable pancreatic cancer.

Methods: This phase I/II trial included patients with unresectable pancreatic cancer previously treated with any number of cycles of induction chemotherapy. Patients were enrolled according to a 3+3 dose escalation design at 10, 12.5, and 15 Gy ×3, with subsequent patients at the maximally tolerated dose (MTD). Treatment was delivered to gross tumor delineated with MRI fusion using image-guidance to fiducial markers. Dose-limiting toxicity (DLT) was defined as grade 3+ toxicity within 30 days. Secondary endpoints included late gastrointestinal (GI) toxicity, freedom from local failure (FFLF), and survival.

Results: Fifteen patients received a median 10 cycles of chemotherapy. There were no DLTs, and the MTD was 15 Gy ×3. Thirty-day toxicity included grade 2 nausea (46%) and grade 2 diarrhea (7%). Median survival after SBRT was 12.8 months (23 months after diagnosis) and median relapse-free survival was 7 months. At 1-year, FFLF was 80%. Four patients had grade 3+ GI bleeding after 30 days (median 6 months). Grade 3+ GI bleeding was associated with tumor volume (P=0.01), heterogeneity of dose within the planning target volume (PTV) (V120, P=0.03), and duodenal dose (V26-30 Gy, P<0.2).

Conclusions: This aggressive SBRT regimen demonstrated limited 30-day morbidity, a moderate degree of local control, and a moderate risk for late GI bleeding. Further work is necessary to define the most appropriate hypofractionated radiation therapy (RT) regimen in the ablative dose range.
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http://dx.doi.org/10.21037/jgo-20-187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807259PMC
December 2020

A Phase 1 Trial Assessing the Safety and Tolerability of a Therapeutic DNA Vaccination Against HPV16 and HPV18 E6/E7 Oncogenes After Chemoradiation for Cervical Cancer.

Int J Radiat Oncol Biol Phys 2020 07 7;107(3):487-498. Epub 2020 Mar 7.

Department of Radiation and Cellular Oncology, University of Chicago, Chicago Illinois.

Purpose: This study assessed the safety and tolerability of therapeutic immunization against the human papillomavirus (HPV) viral oncoproteins E6 and E7 in patients with cervical cancer after chemoradiation.

Methods And Materials: MEDI0457 (INO-3112) is a DNA-based vaccine targeting E6 and E7 of HPV-16/18 that is coinjected with an IL-12 plasmid followed by electroporation with the CELLECTRA 5P device. At 2 to 4 weeks after chemoradiation, patients with newly diagnosed stage IB1-IVA (cohort 1) or persistent/recurrent (cohort 2) cervical cancers were treated with 4 immunizations of MEDI0457 every 4 weeks. The primary endpoints were incidence of adverse events and injection site reactions. Immune responses against HPV antigens were measured by ELISpot for interferon-γ (IFNγ), enzyme-linked immunosorbent assay for antibody responses and multiplexed immunofluorescence for immune cells in cervical biopsy specimens.

Results: Ten patients (cohort 1, n = 7; cohort 2, n = 3) with HPV16 (n = 7) or HPV18 (n = 3) cervical cancers received MEDI0457 after chemoradiation. Treatment-related adverse events were all grade 1, primarily related to the injection site. Eight of 10 patients had detectable cellular or humoral immune responses against HPV antigens after chemoradiation and vaccination: 6 of 10 patients generated anti-HPV antibody responses and 6 of 10 patients generated IFNγ-producing T cell responses. At the completion of chemoradiation and vaccination, cervical biopsy specimens had detectable CD8 T cells and decreased PD-1CD8, PD-L1CD8, and PD-L1CD68 subpopulations. All patients cleared detectable HPV DNA in cervical biopsies by completion of chemoradiation and vaccination.

Conclusions: Adjuvant MEDI0457 is safe and well tolerated after chemoradiation for locally advanced or recurrent cervical cancers, supporting further investigation into combining tumor-specific vaccines with radiation therapy.
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http://dx.doi.org/10.1016/j.ijrobp.2020.02.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705948PMC
July 2020

Pretreatment multiparametric MRI is independently associated with biochemical outcome in men treated with radiation therapy for prostate cancer.

Urol Oncol 2018 10 16;36(10):471.e11-471.e18. Epub 2018 Aug 16.

Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL. Electronic address:

Purpose: The purpose of this study was to investigate the utility of pre-treatment multiparametric magnetic resonance imaging (mpMRI) in a modern cohort of intermediate and high-risk prostate cancer patients treated with primary radiotherapy.

Methods And Materials: One hundred twenty three men with National Comprehensive Cancer Network (NCCN) intermediate or high-risk prostate cancer were treated with primary EBRT and/or brachytherapy and had evaluable pre-treatment mpMRI with endorectal coil. Images were assessed for the presence of radiographic extraprostatic extension (rEPE), seminal vesicle invasion (rSVI), lymph node involvement (LNI), sextant involvement, and largest axial tumor diameter. Imaging characteristics were analyzed along with clinical risk factors against freedom from biochemical failure (FFBF). Median follow-up time was 50 months.

Results: Fourteen (11%) men developed biochemical failure. The 5-year FFBF was 94% in intermediate-risk patients and 82% in high-risk patients (p < 0.01). mpMRI findings including rEPE (29% vs. 66%, p < 0.01), rSVI (6% vs. 25%, p < 0.01), LNI (1% vs. 30%, p < 0.01), and largest axial tumor size> 15 mm (27% vs. 48%, p = 0.02) were identified in men with intermediate vs. high risk prostate cancer, respectively. mpMRI features associated with 5-y FFBF biochemical failure on univariate analysis included rEPE (80% vs 98%), rSVI (55% vs. 96%), LNI (65% vs. 93%), and largest axial tumor size >15mm (81% vs. 94%, all p < 0.01). Men without any high risk MRI finding had a 5-y FFBF of 100% vs. 81% (p < 0.01). Adverse imaging features (HR 8.9, p < 0.01) were independently associated with biochemical failure in a bivariate model analyzed alongside clinical risk category (HR 3.2, p = 0.04).

Conclusions: Pre-treatment mpMRI findings are strongly associated with biochemical outcomes in a modern cohort of intermediate and high-risk patients treated with primary radiotherapy. mpMRI may aid risk stratification beyond clinical risk factors in men treated with radiation therapy; further study is warranted to better understand how mpMRI can be used to individualize therapy.
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http://dx.doi.org/10.1016/j.urolonc.2018.07.004DOI Listing
October 2018

Appropriate and inappropriate use of fresh frozen plasma.

J Pak Med Assoc 2006 Aug;56(8):356-9

Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi.

Objective: To analyze the current situation of use and misuse of fresh frozen plasma (FFP) in various clinical situations.

Methods: This was a cross sectional study done at Liaquat National Hospital (LNH) during a period of 4 months from December 2002 to March 2003. About 300 file records of those patients who received fresh frozen plasma were studied. Each file record was checked for the diagnosis of the patient, coagulation profile and doctor's trigger for blood transfusion. The indications of FFP were checked according to guidelines set by British Committee of Standards and Haematology.

Results: Of 1486 units of FFP that were transfused to 300 patients, it was observed that 78.6% (1169 / 1486) of FFP was appropriately transfused while the remaining 21.3% (317/1486 units) was used without any supportive evidence.

Conclusion: Although majority of the plasma was used appropriately, a considerable volume of plasma was also wasted.
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August 2006