All Publications

  • Disseminated cryptococcosis with gastrointestinal involvement and false-negative cryptococcal antigen testing due to postzone phenomenon: a case report and review of the literature. BMC infectious diseases Zimmet, A. N., Cullen, G. D., Mische, L., Deftos, M., Bogler, Y., Nguyen, N. L., Ray, M. 2023; 23 (1): 217


    BACKGROUND: Cryptococcosis is an increasingly common infection given the growing immunocompromised population worldwide. Cryptococcal antigen (CrAg) testing demonstrates excellent sensitivity and specificity and is the mainstay of diagnosis. However, there may be rare instances in which false-negative CrAg results can delay diagnosis and early treatment, which are critical to ensure positive outcomes.CASE PRESENTATION: A 31-year-old man living with HIV/AIDS who was not taking antiretroviral therapy was hospitalized with fever, diarrhea, and headaches. CD4 count on presentation was 71 cells/uL, and HIV viral load was 3,194,949 copies/mL. Serum CrAg testing was initially negative, however CSF CrAg performed several days later was positive at 1:40 and blood and CSF cultures grew Cryptococcus neoformans. Colonoscopy revealed mucosal papules throughout the sigmoid colon, and tissue biopsy showed yeast within the lamina propria consistent with GI cryptococcosis. Given the high burden of disease, the original serum CrAg specimen was serially diluted and subsequently found to be positive at 1:2,560, confirming the postzone phenomenon.CONCLUSION: Cryptococcosis has a wide array of presentations including intraluminal GI disease, as seen in this patient. While serum CrAg testing displays excellent test characteristics, it is important for clinicians to be aware of the rare instances in which false-negative results may occur in the presence of excess antigen, as in this case.

    View details for DOI 10.1186/s12879-023-08141-y

    View details for PubMedID 37024821

  • Evolving standards of care and new challenges in the management of HER2-positive breast cancer CA-A CANCER JOURNAL FOR CLINICIANS Choong, G. M., Cullen, G. D., O'Sullivan, C. C. 2020; 70 (5): 355-374


    The management of human epidermal growth factor receptor (HER2)-positive breast cancer (BC) has rapidly evolved over the last 20 years. Major advances have led to US Food and Drug Administration approval of 7 HER2-targeted therapies for the treatment of early-stage and/or advanced-stage disease. Although oncologic outcomes continue to improve, most patients with advanced HER2-positive BC ultimately die of their disease because of primary or acquired resistance to therapy, and patients with HER2-positive early BC who have residual invasive disease after preoperative systemic therapy are at a higher risk of distant recurrence and death. The concept of treatment de-escalation and escalation is increasingly important to optimally tailor therapy for patients with HER2-positive BC and is a major focus of the current review. Research efforts in this regard are discussed as well as updates regarding the evolving standard of care in the (neo)adjuvant and metastatic settings, including the use of novel combination therapies. The authors also briefly discuss ongoing challenges in the management of HER2-positive BC (eg, intrinsic vs acquired drug resistance, the identification of predictive biomarkers, the integration of imaging techniques to guide clinical practice), and the treatment of HER2-positive brain metastases. Research aimed at superseding these challenges will be imperative to ensure continued progress in the management of HER2-positive BC going forward.

    View details for DOI 10.3322/caac.21634

    View details for Web of Science ID 000560498600001

    View details for PubMedID 32813307

  • Long-term quality of life in older patients with HPV-related oropharyngeal cancer HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Baxi, S. S., Cullen, G., Xiao, H., Atoria, C. L., Sherman, E. J., Ho, A., Lee, N. Y., Elkin, E. B., Pfister, D. G. 2018; 40 (11): 2321-2328


    We explored if age affects quality of life (QOL) in survivors of locally advanced human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC).In a cross-sectional survey of 185 patients, at least 12 months from radiation, we evaluated generic (EuroQOL-5D questionnaire [EQ-5D]) and head and neck specific (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35-questions [EORTC-QLQ-H&N35]) QOL questionnaires and compared differences between younger (<65) and older (≥65) patients.The median age was 57.0 years (range 25-77 years), and 31 patients (16.8%) were ≥65 years old. There was no significant difference in EQ-5D global QOL scores by age (P = .53). Patients ≥65 years reported more immobility (P < .01), problems with social eating (P < .0001), and coughing (P < .01). Patients ≥65 years were not more likely to ever require a gastrostomy (P = .24) but were more likely to remain gastrostomy-dependent at the time of the survey (P = .02).Despite similar generic QOL, older survivors may have more mobility problems and issues with social eating compared with younger survivors deserving of further evaluation.

    View details for DOI 10.1002/hed.25159

    View details for Web of Science ID 000454204600001

    View details for PubMedID 30421835

    View details for PubMedCentralID PMC6681446

  • Phase 2 study evaluating the combination of sorafenib and temsirolimus in the treatment of radioactive iodine-refractory thyroid cancer CANCER Sherman, E. J., Dunn, L. A., Ho, A. L., Baxi, S. S., Ghossein, R. A., Fury, M. G., Haque, S., Sima, C. S., Cullen, G., Fagin, J. A., Pfister, D. G. 2017; 123 (21): 4114-4121


    Patients with recurrent and/or metastatic, radioactive iodine-refractory thyroid carcinoma have limited treatment options. Sorafenib, an oral kinase inhibitor, is approved by the US Food and Drug Administration for the treatment of radioactive iodine-refractory thyroid carcinoma, although it demonstrated low response rates (12.2%) as a single agent in the first-line setting. The objective of the current study was to determine whether adding the mammalian target of rapamycin inhibitor temsirolimus to sorafenib could improve on these results.In this single-institution, phase 2 study, 36 patients with metastatic, radioactive iodine-refractory thyroid carcinoma of follicular origin received treatment with the combination of oral sorafenib (200 mg twice daily) and intravenous temsirolimus (25 mg weekly). The receipt of prior systemic treatment with cytotoxic chemotherapy and targeted therapy, including sorafenib, was permitted. The primary endpoint was the radiographic response rate.The best response was a partial response in 8 patients (22%), stable disease in 21 (58%), and progressive disease in 1 (3%). Six patients were not evaluable for a response. Patients who had received any prior systemic treatment had a response rate of 10% compared with 38% of those who had not received prior systemic treatment. One of 2 patients with anaplastic thyroid cancer had an objective response. The progression-free survival rate at 1 year was 30.5%. The most common grade 3 and 4 toxicities associated with sorafenib and temsirolimus included hyperglycemia, fatigue, anemia, and oral mucositis.Sorafenib and temsirolimus appear to be an active combination in patients with radioactive iodine-refractory thyroid carcinoma, especially in patients who received no prior treatment compared with historic data from single-agent sorafenib. Activity is also observed in patients who previously received sorafenib. This regimen warrants further investigation. Cancer 2017;123:4114-4121. © 2017 American Cancer Society.

    View details for DOI 10.1002/cncr.30861

    View details for Web of Science ID 000413478900006

    View details for PubMedID 28662274

    View details for PubMedCentralID PMC5650535

  • A phase II study of axitinib (AG-013736) in patients with incurable adenoid cystic carcinoma ANNALS OF ONCOLOGY Ho, A. L., Dunn, L., Sherman, E. J., Fury, M. G., Baxi, S. S., Chandramohan, R., Dogan, S., Morris, L. T., Cullen, G. D., Haque, S., Sima, C. S., Ni, A., Antonescu, C. R., Katabi, N., Pfister, D. G. 2016; 27 (10): 1902-1908


    Recurrent/metastatic adenoid cystic carcinoma (ACC) is an incurable disease with no standard treatments. The majority of ACCs express the oncogenic transcription factor MYB (also c-myb), often in the context of a MYB gene rearrangement. This phase II trial of the tyrosine kinase inhibitor (TKI) axitinib (Pfizer) tested the hypothesis that targeting pathways activated by MYB can be therapeutically effective for ACC.This is a minimax two-stage, phase II trial that enrolled patients with incurable ACC of any primary site. Progressive or symptomatic disease was required. Patients were treated with axitinib 5 mg oral twice daily; dose escalation was allowed. The primary end point was best overall response (BOR). An exploratory analysis correlating biomarkers to drug benefit was conducted, including next-generation sequencing (NGS) in 11 patients.Thirty-three patients were registered and evaluable for response. Fifteen patients had the axitinib dose increased. Tumor shrinkage was achieved in 22 (66.7%); 3 (9.1%) had confirmed partial responses. Twenty-five (75.8%) patients had stable disease, 10 of whom had disease stability for >6 months. The median progression-free survival (PFS) was 5.7 months (range 0.92-21.8 months). Grade 3 axitinib-related toxicities included hypertension, oral pain and fatigue. A trend toward superior PFS was noted with the MYB/NFIB rearrangement, although this was not statistically significant. NGS revealed three tumors with 4q12 amplification, producing increased copies of axitinib-targeted genes PDGFR/KDR/KIT. Two 4q12 amplified patients achieved stable disease for >6 months, including one with significant tumor reduction and the longest PFS on study (21.8 months).Although the primary end point was not met, axitinib exhibited clinical activity with tumor shrinkage achieved in the majority of patients with progressive disease before trial enrollment. Analysis of MYB biomarkers and genomic profiling suggests the hypothesis that 4q12 amplified ACCs are a disease subset that benefit from TKI therapy.

    View details for DOI 10.1093/annonc/mdw287

    View details for Web of Science ID 000386018200013

    View details for PubMedID 27566443

    View details for PubMedCentralID PMC5035791