University of Wisconsin–Madison
Grace Blitzer, MD

Grace Blitzer, MD

Radiation Oncology Resident

Department of Human Oncology

Education

Intern, University of Wisconsin Hospitals and Clinics, Internal Medicine (2018)

MD, Medical College of Wisconsin, Medicine (2017)

BS, University of Wisconsin--Madison, (2013)

Selected Honors and Awards

Michael J Dunn Summer Research Fellowship, Medical College of Wisconsin (2014)

Leadership Trust Award, University of Wisconsin College of Letters and Sciences (2012)

Phi Beta Kappa member (2012)

AACR-Thomas J. Bardos Science Education Award for Undergraduate Students (2012)

  • Results From a Free Oral Cancer Screening Clinic at a Major Academic Health Center: 10 Years of Free Oral Cancer Screening at an Academic Medical Center. Int J Radiat Oncol Biol Phys
    Blitzer GC, Rosenberg SA, Anderson BM, McCulloch TM, Wieland AM, Hartig GK, Bruce JY, Witek ME, Kimple RJ, Harari PM
    2018 Jul 03; :
  • Management of high-risk breast lesions found on mammogram or ultrasound: the value of contrast-enhanced MRI to exclude malignancy. Clin Imaging
    Hammersley JA, Partridge SC, Blitzer GC, Deitch S, Rahbar H
    2018 May - Jun; 49: 174-180
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      PURPOSE: To evaluate the performance of magnetic resonance imaging (MRI) to exclude malignancy in biopsy-proven high-risk breast lesions prior to surgical excision.

      MATERIAL AND METHODS: Breast MRIs performed after a core needle biopsy (CNB) yielding high-risk pathology were evaluated for the presence of suspicious enhancement. The diagnostic performance of MRI to exclude malignancy was calculated.

      RESULTS: The average reader sensitivity, specificity, negative predictive value, positive predictive value and accuracy of MRI were 92%, 51%, 98%, 22% and 56%, respectively.

      CONCLUSION: Lack of enhancement on MRI at the site of a high-risk lesion was useful for excluding malignancy.

      View details for PubMedID 29571172
  • Should functional renal scans be obtained prior to upper abdominal IMRT for pancreatic cancer? Pract Radiat Oncol
    Blitzer GC, Hall WA, Tsai S, Aldakkak M, Hellman RS, Evans DB, Christians KK, George B, Ritch PS, Erickson BA
    2017 Nov - Dec; 7 (6): e449-e455
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      BACKGROUND: Upper abdominal irradiation for pancreatic cancer is administered in close proximity to the radiation-sensitive kidneys. There is difficulty in defining dose-volume parameters to predict late renal toxicity after partial kidney irradiation. Less than 10% of the general population is estimated to have asymmetrical kidney function; however, there are no studies that examine this in patients with pancreatic cancer. The primary purpose of this study was to determine the prevalence of asymmetrical kidney function in patients with pancreatic cancer. A secondary aim was to determine if asymmetrical kidney function was associated with abnormal laboratory values or kidney size on computed tomography scans. Finally, we aimed to develop recommendations for when a functional renal scan in patients with pancreatic cancer should be ordered.

      METHODS AND MATERIALS: We performed a retrospective review of patients with resectable, borderline resectable, and locally advanced pancreatic cancer who received abdominal radiation therapy and had preradiation functional renal scans between 2009 and 2015. Asymmetrical kidney function was defined as a difference between the 2 kidneys that was ≥60%/40% on a functional renal scan. Serum studies (blood urea nitrogen [BUN], creatinine [Cr], and glomerular filtration rate [GFR]) and abdominal computed tomography scans were routinely obtained before simulation.

      RESULTS: Of the 204 patients examined, 23 (11.2%) had asymmetrical kidney function that was identified on preradiation functional renal scans. Elevated Cr or BUN, a GFR <60, or a medical history that suggested abnormal renal function were not significantly associated with asymmetrical kidney function. Only 6 of 23 patients (26%) with asymmetrical kidney function had a notable difference in kidney size.

      CONCLUSIONS: In our series, approximately 11% of patients with pancreatic cancer have asymmetrical kidney function that was not identified by kidney size, serum BUN, Cr, GFR, or a significant medical history. These data suggest that in cases in which renal radiation doses exceed a V18 of 20% to 30% or there is concern about baseline renal function, a functional renal scan should be considered.

      View details for PubMedID 28886941
  • Adoptive cell therapy using PD-1+ myeloma-reactive T cells eliminates established myeloma in mice. J Immunother Cancer
    Jing W, Gershan JA, Blitzer GC, Palen K, Weber J, McOlash L, Riese M, Johnson BD
    2017; 5: 51
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      BACKGROUND: Adoptive cellular therapy (ACT) with cancer antigen-reactive T cells following lymphodepletive pre-conditioning has emerged as a potentially curative therapy for patients with advanced cancers. However, identification and enrichment of appropriate T cell subsets for cancer eradication remains a major challenge for hematologic cancers.

      METHODS: PD-1+ and PD-1- T cell subsets from myeloma-bearing mice were sorted and analyzed for myeloma reactivity in vitro. In addition, the T cells were activated and expanded in culture and given to syngeneic myeloma-bearing mice as ACT.

      RESULTS: Myeloma-reactive T cells were enriched in the PD-1+ cell subset. Similar results were also observed in a mouse AML model. PD-1+ T cells from myeloma-bearing mice were found to be functional, they could be activated and expanded ex vivo, and they maintained their anti-myeloma reactivity after expansion. Adoptive transfer of ex vivo-expanded PD-1+ T cells together with a PD-L1 blocking antibody eliminated established myeloma in Rag-deficient mice. Both CD8 and CD4 T cell subsets were important for eradicating myeloma. Adoptively transferred PD-1+ T cells persisted in recipient mice and were able to mount an adaptive memory immune response.

      CONCLUSIONS: These results demonstrate that PD-1 is a biomarker for functional myeloma-specific T cells, and that activated and expanded PD-1+ T cells can be effective as ACT for myeloma. Furthermore, this strategy could be useful for treating other hematologic cancers.

      View details for PubMedID 28642819
  • Xenograft assessment of predictive biomarkers for standard head and neck cancer therapies. Cancer Med
    Stein AP, Swick AD, Smith MA, Blitzer GC, Yang RZ, Saha S, Harari PM, Lambert PF, Liu CZ, Kimple RJ
    2015 May; 4 (5): 699-712
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      Head and neck squamous cell carcinoma (HNSCC) remains a challenging cancer to treat with overall 5-year survival on the order of 50-60%. Therefore, predictive biomarkers for this disease would be valuable to provide more effective and individualized therapeutic approaches for these patients. While prognostic biomarkers such as p16 expression correlate with outcome; to date, no predictive biomarkers have been clinically validated for HNSCC. We generated xenografts in immunocompromised mice from six established HNSCC cell lines and evaluated response to cisplatin, cetuximab, and radiation. Tissue microarrays were constructed from pre- and posttreatment tumor samples derived from each xenograft experiment. Quantitative immunohistochemistry was performed using a semiautomated imaging and analysis platform to determine the relative expression of five potential predictive biomarkers: epidermal growth factor receptor (EGFR), phospho-EGFR, phospho-Akt, phospho-ERK, and excision repair cross-complementation group 1 (ERCC1). Biomarker levels were compared between xenografts that were sensitive versus resistant to a specific therapy utilizing a two-sample t-test with equal standard deviations. Indeed the xenografts displayed heterogeneous responses to each treatment, and we linked a number of baseline biomarker levels to response. This included low ERCC1 being associated with cisplatin sensitivity, low phospho-Akt correlated with cetuximab sensitivity, and high total EGFR was related to radiation resistance. Overall, we developed a systematic approach to identifying predictive biomarkers and demonstrated several connections between biomarker levels and treatment response. Despite these promising initial results, this work requires additional preclinical validation, likely involving the use of patient-derived xenografts, prior to moving into the clinical realm for confirmation among patients with HNSCC.

      View details for PubMedID 25619980
  • Review of the clinical and biologic aspects of human papillomavirus-positive squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys
    Blitzer GC, Smith MA, Harris SL, Kimple RJ
    2014 Mar 15; 88 (4): 761-70
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      Human papillomavirus (HPV), a known etiology of a subset of head-and-neck squamous cell carcinomas (HNCs), causes numerous alterations in normal cellular functions. This article reviews the biology, detection, and treatment of HPV-positive HNC. The role of HPV oncoproteins in tumor development, the natural history of HPV infection, and risk factors for and prevention of transmission of oral HPV are considered. Commonly used methods for detecting HPV infection, including limitations of these methods, are discussed to aid the practicing clinician in using these tests in their clinical practice. Clinical characteristics of HPV-positive HNC, including potential explanations for the improved outcomes seen in patients with HPV-positive HNC, are assessed. Ongoing clinical trials specific for patients with HPV-positive HNC are described, and areas in need of additional research are summarized. Until the results of ongoing trials are known, treatment of HPV-positive HNC should not differ in clinical practice from treatment of similar non-HPV related cancers.

      View details for PubMedID 24606845
  • Enhanced radiation sensitivity in HPV-positive head and neck cancer. Cancer Res
    Kimple RJ, Smith MA, Blitzer GC, Torres AD, Martin JA, Yang RZ, Peet CR, Lorenz LD, Nickel KP, Klingelhutz AJ, Lambert PF, Harari PM
    2013 Aug 01; 73 (15): 4791-800
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      Patients with human papillomavirus (HPV+)-associated head and neck cancer (HNC) show significantly improved survival outcome compared with those with HPV-negative (HPV-) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV- HNC cell lines using in vitro and in vivo techniques. HPV+ HNCs exhibited greater intrinsic radiation sensitivity (average SF2 HPV-: 0.59 vs. HPV+: 0.22; P < 0.0001), corresponding with a prolonged G2-M cell-cycle arrest and increased apoptosis following radiation exposure (percent change 0% vs. 85%; P = 0.002). A genome-wide microarray was used to compare gene expression 24 hours following radiation between HPV+ and HPV- cell lines. Multiple genes in TP53 pathway were upregulated in HPV+ cells (Z score 4.90), including a 4.6-fold increase in TP53 (P < 0.0001). Using immortalized human tonsillar epithelial (HTE) cells, increased radiation sensitivity was seen in cell expressing HPV-16 E6 despite the effect of E6 to degrade p53. This suggested that low levels of normally functioning p53 in HPV+ HNC cells could be activated by radiation, leading to cell death. Consistent with this, more complete knockdown of TP53 by siRNA resulted in radiation resistance. These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV- HNC. This issue is under active investigation in a series of clinical trials attempting to de-escalate radiation (and chemotherapy) in selected patients with HPV+ HNC in light of their favorable overall survival outcome.

      View details for PubMedID 23749640
  • Development and characterization of HPV-positive and HPV-negative head and neck squamous cell carcinoma tumorgrafts. Clin Cancer Res
    Kimple RJ, Harari PM, Torres AD, Yang RZ, Soriano BJ, Yu M, Armstrong EA, Blitzer GC, Smith MA, Lorenz LD, Lee D, Yang DT, McCulloch TM, Hartig GK, Lambert PF
    2013 Feb 15; 19 (4): 855-64
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      PURPOSE: To develop a clinically relevant model system to study head and neck squamous cell carcinoma (HNSCC), we have established and characterized a direct-from-patient tumorgraft model of human papillomavirus (HPV)-positive and HPV-negative cancers.

      EXPERIMENTAL DESIGN: Patients with newly diagnosed or recurrent HNSCC were consented for donation of tumor specimens. Surgically obtained tissue was implanted subcutaneously into immunodeficient mice. During subsequent passages, both formalin-fixed/paraffin-embedded as well as flash-frozen tissues were harvested. Tumors were analyzed for a variety of relevant tumor markers. Tumor growth rates and response to radiation, cisplatin, or cetuximab were assessed and early passage cell strains were developed for rapid testing of drug sensitivity.

      RESULTS: Tumorgrafts have been established in 22 of 26 patients to date. Significant diversity in tumorgraft tumor differentiation was observed with good agreement in degree of differentiation between patient tumor and tumorgraft (Kappa 0.72). Six tumorgrafts were HPV-positive on the basis of p16 staining. A strong inverse correlation between tumorgraft p16 and p53 or Rb was identified (Spearman correlations P = 0.085 and P = 0.002, respectively). Significant growth inhibition of representative tumorgrafts was shown with cisplatin, cetuximab, or radiation treatment delivered over a two-week period. Early passage cell strains showed high consistency in response to cancer therapy between tumorgraft and cell strain.

      CONCLUSIONS: We have established a robust human tumorgraft model system for investigating HPV-positive and HPV-negative HNSCC. These tumorgrafts show strong correlation with the original tumor specimens and provide a powerful resource for investigating mechanisms of therapeutic response as well as preclinical testing.

      View details for PubMedID 23251001

Contact Information

Grace C. Blitzer, MD

600 Highland Avenue,
Madison, WI 53792
Email