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Melanoma: HELP
Articles by Haris Zahoor
Based on 3 articles published since 2010
(Why 3 articles?)

Between 2010 and 2020, Haris Zahoor wrote the following 3 articles about Melanoma.
+ Citations + Abstracts
1 Clinical Trial Pro-Inflammatory Cytokines Predict Relapse-Free Survival after One Month of Interferon-α but Not Observation in Intermediate Risk Melanoma Patients. 2015

Tarhini, Ahmad A / Lin, Yan / Zahoor, Haris / Shuai, Yongli / Butterfield, Lisa H / Ringquist, Steven / Gogas, Helen / Sander, Cindy / Lee, Sandra / Agarwala, Sanjiv S / Kirwood, John M. ·University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America. · University of Pittsburgh Cancer Institute Biostatistics Facility, Pittsburgh, Pennsylvania, United States of America. · Hellenic Cooperative Oncology Group, Athens, Greece. · Dana Farber Cancer Institute, Boston, Massachusetts, United States of America. · St. Luke's Cancer Center, Bethlehem, Pennsylvania, United States of America; Temple University, Philadelphia, Pennsylvania, United States of America. ·PLoS One · Pubmed #26192408.

ABSTRACT: BACKGROUND: E1697 was a phase III trial of adjuvant interferon (IFN)-α2b for one month (Arm B) versus observation (Arm A) in patients with resected melanoma at intermediate risk. We evaluated the levels of candidate serum cytokines, the HLA genotype, polymorphisms of CTLA4 and FOXP3 genes and the development of autoantibodies for their association with relapse free survival (RFS) in Arm A and Arm B among 268 patients with banked biospecimens. METHODS: ELISA was used to test 5 autoantibodies. Luminex/One Lambda LABTypeRSSO was used for HLA Genotyping. Selected CTLA4 and FOXP3 Single nucleotide polymorphisms (SNPs) and microsatellites were tested for by polymerase chain reaction (PCR). Sixteen serum cytokines were tested at baseline and one month by Luminex xMAP multiplex technology. Cox Proportional Hazards model was applied and the Wald test was used to test the marginal association of each individual marker and RFS. We used the Lasso approach to select the markers to be included in a multi-marker Cox Proportional Hazards model. The ability of the resulting models to predict one year RFS was evaluated by the time-dependent ROC curve. The leave-one-out method of cross validation (LOOCV) was used to avoid over-fitting of the data. RESULTS: In the multi-marker modeling analysis conducted in Arm B, one month serum IL2Rα, IL-12p40 and IFNα levels predicted one year RFS with LOOCV AUC = 82%. Among the three markers selected, IL2Rα and IFNα were the most stable (selected in all the cross validation cycles). The risk score (linear combination of the 3 markers) separated the RFS curves of low and high risk groups well (p = 0.05). This model did not hold for Arm A, indicating a differential marker profile in Arm B linked to the intervention (adjuvant therapy). CONCLUSIONS: Early on-treatment proinflammatory serum markers (IL2Rα, IL-12p40, IFNα) significantly predict RFS in our cohort of patients treated with adjuvant IFN-α2b and warrant further study.

2 Article Tumor associated PD-L1 expression pattern in microscopically tumor positive sentinel lymph nodes in patients with melanoma. 2015

Tarhini, Ahmad A / Zahoor, Haris / Yearley, Jennifer H / Gibson, Christopher / Rahman, Zahra / Dubner, Rachel / Rao, Uma N M / Sander, Cindy / Kirkwood, John M. ·University of Pittsburgh, Pittsburgh, PA, USA. tarhiniaa@upmc.edu. · University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. tarhiniaa@upmc.edu. · University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. zahoor@upmc.edu. · Merck, Philadelphia, PA, USA. jennifer.yearley@merck.com. · Merck, Philadelphia, PA, USA. christopher.gibson2@merck.com. · University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. rahman23@upmc.edu. · University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. racheldubner2018@u.northwestern.edu. · University of Pittsburgh, Pittsburgh, PA, USA. raounm@upmc.edu. · University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. raounm@upmc.edu. · University of Pittsburgh, Pittsburgh, PA, USA. sandca@upmc.edu. · University of Pittsburgh, Pittsburgh, PA, USA. kirkwoodjm@upmc.edu. · University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. kirkwoodjm@upmc.edu. ·J Transl Med · Pubmed #26419843.

ABSTRACT: BACKGROUND: Characterization of PD-L1 expression within clinically/radiologically negative but microscopically tumor positive sentinel lymph nodes (SLN) is important to our understanding of the relevance of this immune checkpoint pathway for adjuvant therapy. METHODS: Patients included had primary cutaneous melanoma, Breslow thickness of 2.01-4.0 or >4 mm with or without tumor ulceration (T3a, T3b, T4a, T4b). All patients had microscopically tumor positive SLN. Hematoxylin and eosin (H&E) staining was performed, followed by PD-L1 immunohistochemical (IHC) staining using a preliminary IHC assay with anti-PD-L1 antibody clone 22C3. The slides were separately evaluated by two pathologists (JY and CG). Samples containing metastatic melanoma lesions were scored separately for PD-L1 expression in intratumoral and peritumoral locations, by utilizing two scoring methods. RESULTS: Twenty-four patients where metastatic melanoma presence in the SLN was confirmed by H&E review of the cut sections were included in the final analysis of PD-L1 expression. SLN tumor size ranged from 1 to 2 mm. For three patients, the melanin content was too high to confidently assign a PD-L1 score. For the remaining 21 patients, all had some evidence of either intratumoral or peritumoral PD-L1 expression. The frequency of intratumoral tumor-associated PD-L1 expression was: 0 % of tumor cells (3 pts, 14 %); <1 % (5 pts, 24 %); 1-10 % (6 pts, 29 %) and >10 % (7 pts, 33 %). CONCLUSIONS: Tumor-associated PD-L1 expression is readily detectable within melanoma micrometastases in the SLN of the majority of patients. These results support the testing of a therapeutic role for PD1/PD-L1 inhibition in the adjuvant setting, targeting melanoma micrometastases.

3 Article Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma. 2015

Tarhini, Ahmad A / Zahoor, Haris / Lin, Yan / Malhotra, Usha / Sander, Cindy / Butterfield, Lisa H / Kirkwood, John M. ·University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue (555), Pittsburgh, PA 15232 USA. ·J Immunother Cancer · Pubmed #26380086.

ABSTRACT: BACKGROUND: We evaluated candidate circulating serum cytokines, chemokines and growth factors in patients with locally/regionally advanced melanoma receiving neoadjuvant ipilimumab with toxicity and clinical outcome. METHODS: Patients were treated with ipilimumab (10 mg/kg IV every 3 weeks, 2 doses) before and after surgery. xMAP multiplex serum testing for 36 functionally selected cytokines and chemokines was performed at baseline and at six weeks (following ipilimumab). Based on our prior data, the association of IL-17 and immune related colitis was tested. Serum cytokines were divided into functional groups (Th1, Th2, Regulatory, Proinflammatory) and were assessed at baseline and week 6 using sparse-group Lasso modeling to assess the association of various cytokine groups with progression free survival (PFS). The linear combination of the cytokines/chemokines in this model was then used as a risk score and a Kaplan-Meier curve was generated to examine the association of the dichotomized score and PFS. RESULTS: Thirty-five patients were enrolled whose staging was: IIIB (3; N2b), IIIC (30; N2c, N3), IV (2). Median follow-up was 18 months. Among 33 evaluable patients, median PFS was 11 months (95 % CI = 6.2-19.2). IL-17 was found to correlate significantly with the incidence of grade 3 diarrhea/colitis when measured at baseline (p = 0.02) with a trend towards significance at 6 weeks (p = 0.06). In the modeling analysis, at baseline, the linear combination of 2 regulatory cytokines [TGF- β1 (ρ = 0.19) and IL-10 (ρ = -0.34)] was significantly associated with PFS (HR 2.66; p = 0.035). No significant correlations with clinical outcomes were found in examining the week 6 cytokines. CONCLUSIONS: Baseline IL-17 level was significantly associated with the later development of severe diarrhea/colitis while the combination of baseline TGF- β1 and IL-10 levels were associated with therapeutic clinical outcome after neoadjuvant ipilimumab. These findings warrant further investigation and validation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00972933.