Grace Blitzer, MD

Grace Blitzer, MD

Assistant Professor (CHS)

Department of Human Oncology

I am an assistant professor in the Department of Human Oncology at the University of Wisconsin. I serve as the primary radiation oncologist at the UW Cancer Center in Johnson Creek, where I treat all types of cancer in adults. The UW Cancer Center Johnson Creek has a state-of-the-art linear accelerator that is the same as the machines at UW Carbone Cancer Center, which allows me to treat cancer using the same advanced techniques available to UWCCC. I work with our team of radiation therapists, nurses, front desk staff, medical oncologists, and other providers to best meet each patient’s individual needs. I am committed to serving the Johnson Creek community by building relationships with my patients, local healthcare providers, and community organizations. I participate in outreach and service, including providing education on cancer screening and treatment to community organizations.

In addition to my clinical pursuits, I am also a translational researcher. I am interested in designing clinical trials that bring research from the laboratory to the clinic in order to directly benefit my patients. I have written several clinical trials, including two investigating the use of mesenchymal stromal cells (MSCs) to treat radiation-induced dry mouth in patients who underwent radiation therapy for head and neck cancer. Additionally, my research includes examining the role of circulating tumor DNA in uterine cancer to improve our selection of treatments for patients. Through my partnership with my laboratory collaborators, I hope to bring improved treatments into the clinic for my patients.


Residency, University of Wisconsin–Madison, Radiation Oncology (2022)

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

MD, Medical College of Wisconsin, Medicine (2017)

BS, University of Wisconsin–Madison, Biology (2013)

Academic Appointments

Assistant Professor, Human Oncology (2022)

Selected Honors and Awards

American Society of Clinical Oncology Young Investigator Award (2021)

University of Wisconsin Carbone Cancer Center Trainee FlashTalk Winner (2020)

Radiological Society of North America Resident Research Grant (2019)

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

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)

American Association for Cancer Research Thomas J. Bardos Science Education Award for Undergraduate Students (2012)

Hilldale Scholar, University of Wisconsin–Madison (2011)

Boards, Advisory Committees and Professional Organizations

Member of the Wisconsin Cancer Council (2020-present)

Member of the Wisconsin Cancer Council Survivorship Committee (2020-2021)

Member of the American Society for Radiation Oncology (2017-present)

Member of the American Society of Clinical Oncology (2015-present)

Member of the American Association for Cancer Research (2011-present)

I am a translational researcher, partnering with basic science collaborators to bring laboratory innovations into the clinic to improve the lives of patients.

The goal of my research is to bridge the gap between the clinical problems I see daily and the laboratory solutions that could help my patients. I focus on designing and running clinical trials that translate basic science discoveries into clinical treatments.

  • YIA24-004: Liquid Biomarkers of Response to Radium-223 in Metastatic Prostate Cancer Journal of the National Comprehensive Cancer Network : JNCCN
    Zhao SG, Blitzer G, Sperger J, Yu M, Floberg J, Sharifi M, Lang J
    2024 Apr 5;22(2.5):YIA24-004. doi: 10.6004/jnccn.2023.7330.
  • A platform-independent AI tumor lineage and site (ATLAS) classifier Communications biology
    Rydzewski NR, Shi Y, Li C, Chrostek MR, Bakhtiar H, Helzer KT, Bootsma ML, Berg TJ, Harari PM, Floberg JM, Blitzer GC, Kosoff D, Taylor AK, Sharifi MN, Yu M, Lang JM, Patel KR, Citrin DE, Sundling KE, Zhao SG
    2024 Mar 13;7(1):314. doi: 10.1038/s42003-024-05981-5.
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      Histopathologic diagnosis and classification of cancer plays a critical role in guiding treatment. Advances in next-generation sequencing have ushered in new complementary molecular frameworks. However, existing approaches do not independently assess both site-of-origin (e.g. prostate) and lineage (e.g. adenocarcinoma) and have minimal validation in metastatic disease, where classification is more difficult. Utilizing gradient-boosted machine learning, we developed ATLAS, a pair of separate AI Tumor Lineage and Site-of-origin models from RNA expression data on 8249 tumor samples. We assessed performance independently in 10,376 total tumor samples, including 1490 metastatic samples, achieving an accuracy of 91.4% for cancer site-of-origin and 97.1% for cancer lineage. High confidence predictions (encompassing the majority of cases) were accurate 98-99% of the time in both localized and remarkably even in metastatic samples. We also identified emergent properties of our lineage scores for tumor types on which the model was never trained (zero-shot learning). Adenocarcinoma/sarcoma lineage scores differentiated epithelioid from biphasic/sarcomatoid mesothelioma. Also, predicted lineage de-differentiation identified neuroendocrine/small cell tumors and was associated with poor outcomes across tumor types. Our platform-independent single-sample approach can be easily translated to existing RNA-seq platforms. ATLAS can complement and guide traditional histopathologic assessment in challenging situations and tumors of unknown primary.

      PMID:38480799 | PMC:PMC10937974 | DOI:10.1038/s42003-024-05981-5

      View details for PubMedID 38480799
  • Functionality of bone marrow mesenchymal stromal cells derived from head and neck cancer patients - A FDA-IND enabling study regarding MSC-based treatments for radiation-induced xerostomia Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
    Blitzer GC, Paz C, Glassey A, Ganz OR, Giri J, Pennati A, Meyers RO, Bates AM, Nickel KP, Weiss M, Morris ZS, Mattison RJ, McDowell KA, Croxford E, Chappell RJ, Glazer TA, Rogus-Pulia NM, Galipeau J, Kimple RJ
    2024 Mar;192:110093. doi: 10.1016/j.radonc.2024.110093. Epub 2024 Jan 13.
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      PURPOSE: Salivary dysfunction is a significant side effect of radiation therapy for head and neck cancer (HNC). Preliminary data suggests that mesenchymal stromal cells (MSCs) can improve salivary function. Whether MSCs from HNC patients who have completed chemoradiation are functionally similar to those from healthy patients is unknown. We performed a pilot clinical study to determine whether bone marrow-derived MSCs [MSC(M)] from HNC patients could be used for the treatment of RT-induced salivary dysfunction.

      METHODS: An IRB-approved pilot clinical study was undertaken on HNC patients with xerostomia who had completed treatment two or more years prior. Patients underwent iliac crest bone marrow aspirate and MSC(M) were isolated and cultured. Culture-expanded MSC(M) were stimulated with IFNγ and cryopreserved prior to reanimation and profiling for functional markers by flow cytometry and ELISA. MSC(M) were additionally injected into mice with radiation-induced xerostomia and the changes in salivary gland histology and salivary production were examined.

      RESULTS: A total of six subjects were enrolled. MSC(M) from all subjects were culture expanded to > 20 million cells in a median of 15.5 days (range 8-20 days). Flow cytometry confirmed that cultured cells from HNC patients were MSC(M). Functional flow cytometry demonstrated that these IFNγ-stimulated MSC(M) acquired an immunosuppressive phenotype. IFNγ-stimulated MSC(M) from HNC patients were found to express GDNF, WNT1, and R-spondin 1 as well as pro-angiogenesis and immunomodulatory cytokines. In mice, IFNγ-stimulated MSC(M) injection after radiation decreased the loss of acinar cells, decreased the formation of fibrosis, and increased salivary production.

      CONCLUSIONS: MSC (M) from previously treated HNC patients can be expanded for auto-transplantation and are functionally active. Furthermore IFNγ-stimulated MSC(M) express proteins implicated in salivary gland regeneration. This study provides preliminary data supporting the feasibility of using autologous MSC(M) from HNC patients to treat RT-induced salivary dysfunction.

      PMID:38224919 | PMC:PMC10922976 | DOI:10.1016/j.radonc.2024.110093

      View details for PubMedID 38224919
  • Empowering the Radiation Oncology Triage Nurse Role: A Single-Center Analysis Clinical journal of oncology nursing
    Weber BW, Blitzer GC, Harari CM, Ruesga SL, Huenerberg KJ, Anderson B, Schuster JM
    2023 Nov 16;27(6):637-643. doi: 10.1188/23.CJON.637-643.
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      BACKGROUND: Triage nurses play a crucial role in addressing patient telephone calls. However, topics that radiation oncology (RO) triage nurses encounter have not been thoroughly investigated.

      OBJECTIVES: This project established baseline patient issues addressed via telephone by RO triage nurses in a clinically busy academic RO department; identified themes and potential areas for workflow improvement; and evaluated interprofessional perceptions of RO triage from nurses, physicians, and radiation therapists.

      METHODS: This two-part study was conducted from September through November 2021 using a retrospective chart review that analyzed patient communications to the RO nurse triage line. Physicians, nurses, and radiation therapists completed an online survey about their experiences with nurse triage.

      FINDINGS: Analysis revealed 13 message themes, with scheduling questions being the most common theme. Survey results indicated that average provider satisfaction with the effectiveness of triage was 3 of 5, perceived triage nurse preparedness to resolve encounters was 3 of 5, and perception of the triage program by physicians was 2.4 of 5.

      PMID:38009877 | DOI:10.1188/23.CJON.637-643

      View details for PubMedID 38009877
  • The role of ctDNA in endometrial cancer: A tool for risk stratification and disease monitoring Gynecologic oncology
    Blitzer GC, Zhao SG, Bradley KA, Hartenbach EM
    2023 Nov;178:170-171. doi: 10.1016/j.ygyno.2023.08.008. Epub 2023 Aug 28.
  • Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): A pilot, first-in-human study of interferon gamma-stimulated marrow mesenchymal stromal cells for treatment of radiation-induced xerostomia Cytotherapy
    Blitzer GC, Glazer T, Burr A, Gustafson S, Ganz O, Meyers R, McDowell KA, Nickel KP, Mattison RJ, Weiss M, Chappell R, Rogus-Pulia NM, Galipeau J, Kimple RJ
    2023 Nov;25(11):1139-1144. doi: 10.1016/j.jcyt.2023.07.009. Epub 2023 Aug 15.
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      BACKGROUND AIMS: Xerostomia, or the feeling of dry mouth, is a significant side effect of radiation therapy for patients with head and neck cancer (HNC). Preliminary data suggest that mesenchymal stromal/stem cells (MSCs) can improve salivary function. We performed a first-in-human pilot study of interferon gamma (IFNγ)-stimulated autologous bone marrow-derived MSCs, or MSC(M), for the treatment of radiation-induced xerostomia (RIX). Here we present the primary safety and secondary efficacy endpoints.

      METHODS: A single-center pilot clinical trial was conducted investigating the safety and tolerability of autologous IFNγ-stimulated MSC(M). The study was conducted under an approved Food and Drug Administration Investigational New Drug application using an institutional review board-approved protocol (NCT04489732). Patients underwent iliac crest bone marrow aspirate and MSC(M) were isolated, cultured, stimulated with IFNγ and cryopreserved for later use. Banked cells were thawed and allowed to recover in culture before patients received a single injection of 10 × 106 MSC(M) into the right submandibular gland under ultrasound guidance. The primary objective was determination of safety and tolerability by evaluating dose-limiting toxicity (DLT). A DLT was defined as submandibular pain >5 on a standard 10-point pain scale or any serious adverse event (SAE) within 1 month after injection. Secondary objectives included analysis of efficacy as measured by salivary quantification and using three validated quality of life instruments. Quantitative results are reported as mean and standard deviation.

      RESULTS: Six patients with radiation-induced xerostomia who had completed radiation at least 2 years previously (average 7.8 years previously) were enrolled in the pilot study. The median age was 71 (61-74) years. Five (83%) patients were male. Five patients (83%) were treated with chemoradiation and one patient (17%) with radiation alone. Grade 1 pain was seen in 50% of patients after submandibular gland injection; all pain resolved within 4 days. No patients reported pain 1 month after injection, with no SAE or other DLTs reported 1 month after injection. The analysis of secondary endpoints demonstrated a trend of increased salivary production. Three patients (50%) had an increase in unstimulated saliva at 1 and 3 months after MSC(M) injection. Quality of life surveys also showed a trend toward improvement.

      CONCLUSIONS: Injection of autologous IFNγ-stimulated MSC(M) into a singular submandibular gland of patients with RIX is safe and well tolerated in this pilot study. A trend toward an improvement in secondary endpoints of salivary quantity and quality of life was observed. This first-in-human study provides support for further investigation into IFNγ-stimulated MSC(M) injected in both submandibular glands as an innovative approach to treat RIX and improve quality of life for patients with HNC.

      PMID:37589639 | PMC:PMC10615723 | DOI:10.1016/j.jcyt.2023.07.009

      View details for PubMedID 37589639
  • Toxicity and Patient-Reported Quality-of-Life Outcomes After Prostate Stereotactic Body Radiation Therapy With Focal Boost to Magnetic Resonance Imaging-Identified Prostate Cancer Lesions: Results of a Phase 2 Trial International journal of radiation oncology, biology, physics
    Morris BA, Holmes EE, Anger NJ, Cooley G, Schuster JM, Hurst N, Baschnagel AM, Bassetti MF, Blitzer GC, Chappell RJ, Bayliss RA, Morris ZS, Ritter MA, Floberg JM
    2023 Nov 1;117(3):613-623. doi: 10.1016/j.ijrobp.2023.05.004. Epub 2023 May 12.
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      PURPOSE: In this prospective phase 2 trial, we investigated the toxicity and patient-reported quality-of-life outcomes in patients treated with stereotactic body radiation therapy (SBRT) to the prostate gland and a simultaneous focal boost to magnetic resonance imaging (MRI)-identified intraprostatic lesions while also de-escalating dose to the adjacent organs at risk.

      METHODS AND MATERIALS: Eligible patients included low- or intermediate-risk prostate cancer (Gleason score ≤7, prostate specific antigen ≤20, T stage ≤2b). SBRT was prescribed to 40 Gy in 5 fractions delivered every other day to the prostate, with any areas of high disease burden (MRI-identified prostate imaging reporting and data system 4 or 5 lesions) simultaneously escalated to 42.5 to 45 Gy and areas overlapping organs at risk (within 2 mm of urethra, rectum, and bladder) constrained to 36.25 Gy (n = 100). Patients without a pretreatment MRI or without MRI-identified lesions were treated to dose of 37.5 Gy with no focal boost (n = 14).

      RESULTS: From 2015 to 2022, a total of 114 patients were enrolled with a median follow-up of 42 months. No acute or late grade 3+ gastrointestinal (GI) toxicity was observed. One patient developed late grade 3 genitourinary (GU) toxicity at 16 months. In patients treated with focal boost (n = 100), acute grade 2 GU and GI toxicity was seen in 38% and 4% of patients, respectively. Cumulative late grade 2+ GU and GI toxicities at 24 months were 13% and 5% respectively. Patient-reported outcomes showed no significant long-term change from baseline in urinary, bowel, hormonal, or sexual quality-of-life scores after treatment.

      CONCLUSIONS: SBRT to a dose of 40 Gy to the prostate gland with a simultaneous focal boost up to 45 Gy is well tolerated with similar rates of acute and late grade 2+ GI and GU toxicity as seen in other SBRT regimens without intraprostatic boost. Moreover, no significant long-term changes were seen in patient-reported urinary, bowel, or sexual outcomes from pretreatment baseline.

      PMID:37179035 | DOI:10.1016/j.ijrobp.2023.05.004

      View details for PubMedID 37179035
  • A clinical-grade liquid biomarker detects neuroendocrine differentiation in prostate cancer The Journal of clinical investigation
    Zhao SG, Sperger JM, Schehr JL, McKay RR, Emamekhoo H, Singh A, Schultz ZD, Bade RM, Stahlfeld CN, Gilsdorf CS, Hernandez CI, Wolfe SK, Mayberry RD, Krause HM, Bootsma M, Helzer KT, Rydzewski N, Bakhtiar H, Shi Y, Blitzer G, Kyriakopoulos CE, Kosoff D, Wei XX, Floberg J, Sethakorn N, Sharifi M, Harari PM, Huang W, Beltran H, Choueiri TK, Scher HI, Rathkopf DE, Halabi S, Armstrong AJ, Beebe DJ, Yu M, Sundling KE, Taplin M, Lang JM
    2022 Nov 1;132(21):e161858. doi: 10.1172/JCI161858.
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      BackgroundNeuroendocrine prostate cancer (NEPC) is an aggressive subtype, the presence of which changes the prognosis and management of metastatic prostate cancer.MethodsWe performed analytical validation of a Circulating Tumor Cell (CTC) multiplex RNA qPCR assay to identify the limit of quantification (LOQ) in cell lines, synthetic cDNA, and patient samples. We next profiled 116 longitudinal samples from a prospectively collected institutional cohort of 17 patients with metastatic prostate cancer (7 NEPC, 10 adenocarcinoma) as well as 265 samples from 139 patients enrolled in 3 adenocarcinoma phase II trials of androgen receptor signaling inhibitors (ARSIs). We assessed a NEPC liquid biomarker via the presence of neuroendocrine markers and the absence of androgen receptor (AR) target genes.ResultsUsing the analytical validation LOQ, liquid biomarker NEPC detection in the longitudinal cohort had a per-sample sensitivity of 51.35% and a specificity of 91.14%. However, when we incorporated the serial information from multiple liquid biopsies per patient, a unique aspect of this study, the per-patient predictions were 100% accurate, with a receiver-operating-curve (ROC) AUC of 1. In the adenocarcinoma ARSI trials, the presence of neuroendocrine markers, even while AR target gene expression was retained, was a strong negative prognostic factor.ConclusionOur analytically validated CTC biomarker can detect NEPC with high diagnostic accuracy when leveraging serial samples that are only feasible using liquid biopsies. Patients with expression of NE genes while retaining AR-target gene expression may indicate the transition to neuroendocrine differentiation, with clinical characteristics consistent with this phenotype.FundingNIH (DP2 OD030734, 1UH2CA260389, R01CA247479, and P30 CA014520), Department of Defense (PC190039 and PC200334), and Prostate Cancer Foundation (Movember Foundation - PCF Challenge Award).

      PMID:36317634 | PMC:PMC9621140 | DOI:10.1172/JCI161858

      View details for PubMedID 36317634
  • Considering Lumpectomy Cavity PTV Expansions: Characterization of Intrafraction Lumpectomy Cavity Motion Practical radiation oncology
    Merfeld EC, Blitzer GC, Kuczmarska-Haas A, Witt JS, Wojcieszynski AP, Mittauer KM, Hill PM, Bayouth JE, Yadav P, Anderson BM
    2023 Jan-Feb;13(1):e14-e19. doi: 10.1016/j.prro.2022.08.011. Epub 2022 Sep 9.
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      PURPOSE: Accelerated partial breast irradiation and lumpectomy cavity boost radiation therapy plans generally use volumetric expansions from the lumpectomy cavity clinical target volume to the planning target volume (PTV) of 1 to 1.5 cm, substantially increasing the volume of irradiated breast tissue. The purpose of this study was to quantify intrafraction lumpectomy cavity motion during external beam radiation therapy to inform the indicated clinical target volume to PTV expansion.

      METHODS AND MATERIALS: Forty-four patients were treated with a whole breast irradiation using traditional linear accelerator-based radiation therapy followed by lumpectomy cavity boost using magnetic resonance (MR)-guided radiation therapy on a prospective registry study. Two-dimensional cine-MR images through the center of the surgical cavity were acquired during each boost treatment to define the treatment position of the lumpectomy cavity. This was compared with the reference position to quantify intrafraction cavity motion. Free-breathing technique was used during treatment. Clinical outcomes including toxicity, cosmesis, and rates of local control were additionally analyzed.

      RESULTS: The mean maximum displacement per fraction in the anterior-posterior (AP) direction was 1.4 mm. Per frame, AP motion was <5 mm in 92% of frames. The mean maximum displacement per fraction in the superior-inferior (SI) direction was 1.2 mm. Per frame, SI motion was <5 mm in 94% of frames. Composite motion was <5 mm in 89% of frames. Three-year local control was 97%. Eight women (18%) developed acute G2 radiation dermatitis. With a median follow-up of 32.4 months, cosmetic outcomes were excellent (22/44, 50%), good (19/44, 43%), and fair (2/44, 5%).

      CONCLUSIONS: In approximately 90% of analyzed frames, intrafraction displacement of the lumpectomy cavity was <5 mm, with even less motion expected with deep inspiratory breath hold. Our results suggest reduced PTV expansions of 5 mm would be sufficient to account for lumpectomy cavity position, which may accordingly reduce late toxicity and improve cosmetic outcomes.

      PMID:36089252 | DOI:10.1016/j.prro.2022.08.011

      View details for PubMedID 36089252
  • Quantification of very late xerostomia in head and neck cancer patients after irradiation Laryngoscope investigative otolaryngology
    Blitzer GC, Rogus-Pulia NM, Paz C, Nickel KP, Cannaday VL, Kelm-Nelson CA, Sudakaran S, Chappell RJ, Glazer T, Kimple RJ
    2022 Jul 12;7(4):1018-1024. doi: 10.1002/lio2.864. eCollection 2022 Aug.
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      OBJECTIVE: Radiation therapy (RT) for head and neck cancer (HNC) can result in severe xerostomia, or the subjective feeling of dry mouth. Characterizing xerostomia is critical to designing future clinical trials investigating how to improve HNC patients' quality of life (QoL). Few studies have investigated the very late (>5 years post-RT) effects of RT for HNC. We undertook preliminary studies quantifying very late xerostomia.

      METHODS: Six adults who underwent RT for HNC at least 5 years prior and reported xerostomia were enrolled. Five healthy adults without a self-reported history of HNC or xerostomia were enrolled as controls. All participants completed three validated surveys to measure xerostomia-related QoL. Salivary production rates were measured and compositional analysis of the saliva and oral microbiome was completed.

      RESULTS: The QoL survey scores for the HNC participants were significantly worse as compared to the control participants. The HNC participants produced less unstimulated saliva (p = .02) but not less stimulated saliva. The median salivary mucin significantly higher in HNC participants than in control participants (p = .02). There was no significant difference between the pH, amylase, or total protein. Microbiome analysis revealed alpha diversity to be significantly lower in the HNC participants.

      CONCLUSION: In the survivors of HNC who suffer from late toxicities, multiple means of measuring toxicity may be useful. We found that in patients with radiation-induced xerostomia over 5 years after therapy, not only were the QoL surveys significantly worse, as expected, but other measurements such as mucin and oral microbiome diversity were also significantly different.


      PMID:36000048 | PMC:PMC9392383 | DOI:10.1002/lio2.864

      View details for PubMedID 36000048
  • Use of Stereotactic Magnetic Resonance-Guided Online Adaptive Radiation Therapy for Treatment of a Pelvic Recurrence of Prostate Cancer in a Patient With an Orthotopic Neobladder Advances in radiation oncology
    Floberg JM, Blitzer GC, Yadav P
    2022 Apr 8;7(5):100958. doi: 10.1016/j.adro.2022.100958. eCollection 2022 Sep-Oct.
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      PMID:35647410 | PMC:PMC9130090 | DOI:10.1016/j.adro.2022.100958

      View details for PubMedID 35647410
  • Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma Journal of clinical oncology : official journal of the American Society of Clinical Oncology
    Bootsma M, McKay RR, Emamekhoo H, Bade RM, Schehr JL, Mannino MC, Singh A, Wolfe SK, Schultz ZD, Sperger J, Xie W, Signoretti S, Kyriakopoulos CE, Kosoff D, Abel EJ, Helzer KT, Rydzewski N, Bakhtiar H, Shi Y, Blitzer G, Bassetti M, Floberg J, Yu M, Sethakorn N, Sharifi M, Harari PM, Choueiri TK, Lang JM, Zhao SG
    2022 Nov 1;40(31):3633-3641. doi: 10.1200/JCO.22.00219. Epub 2022 May 26.
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      PURPOSE: Liquid biopsies in metastatic renal cell carcinoma (mRCC) provide a unique approach to understand the molecular basis of treatment response and resistance. This is particularly important in the context of immunotherapies, which target key immune-tumor interactions. Unlike metastatic tissue biopsies, serial real-time profiling of mRCC is feasible with our noninvasive circulating tumor cell (CTC) approach.

      METHODS: We collected 457 longitudinal liquid biopsies from 104 patients with mRCC enrolled in one of two studies, either a prospective cohort or a phase II multicenter adaptive immunotherapy trial. Using a novel CTC capture and automated microscopy platform, we profiled CTC enumeration and expression of HLA I and programmed cell death-ligand 1 (PD-L1). Given their diametric immunological roles, we focused on the HLA I to PD-L1 ratio (HP ratio).

      RESULTS: Patients with radiographic responses showed significantly lower CTC abundances throughout treatment. Furthermore, patients whose CTC enumeration trajectory was in the highest quartile (> 0.12 CTCs/mL annually) had shorter overall survival (median 17.0 months v 21.1 months, P < .001). Throughout treatment, the HP ratio decreased in patients receiving immunotherapy but not in patients receiving tyrosine kinase inhibitors. Patients with an HP ratio trajectory in the highest quartile (≥ 0.0012 annually) displayed significantly shorter overall survival (median 18.4 months v 21.2 months, P = .003).

      CONCLUSION: In the first large longitudinal CTC study in mRCC to date to our knowledge, we identified the prognostic importance of CTC enumeration and the change over time of both CTC enumeration and the HP ratio. These insights into changes in both tumor burden and the molecular profile of tumor cells in response to different treatments provide potential biomarkers to predict and monitor response to immunotherapy in mRCC.

      PMID:35617646 | PMC:PMC9622626 | DOI:10.1200/JCO.22.00219

      View details for PubMedID 35617646
  • The Role of MRI-Guided Radiotherapy for Soft Tissue Sarcomas Journal of clinical medicine
    Blitzer GC, Yadav P, Morris ZS
    2022 Feb 17;11(4):1042. doi: 10.3390/jcm11041042.
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      Soft tissue sarcomas (STS) are a rare class of tumors that originate from mesenchymal tissues and occur most frequently in the extremities, trunk, and retroperitoneum. Surgical resection with R0 margins is the primary curative treatment for most localized STS. In this setting, radiation therapy is used either pre-operatively or post-operatively to reduce the rate of local recurrence. Modern pre- or post-operative radiation therapy rely on the use of MRI sequences to guide target delineation during treatment planning. MRI-guided radiotherapy also offers unique advantages over CT-guided approaches in differentiating STS from surrounding normal soft tissues and enabling better identification of target volumes on daily imaging. For patients with unresectable STS, radiation therapy may offer the best chance for local tumor control. However, most STS are relatively radioresistant with modest rates of local control achieved using conventionally fractionated radiation. Specialized techniques such as hypofractionated radiation may allow for dose intensification and may increase rates of local control for STS. In these settings, MRI becomes even more critical for the delineation of targets and organs at risk and management of tumor and organ at risk motion during and between radiotherapy treatment fractions.

      PMID:35207317 | PMC:PMC8880805 | DOI:10.3390/jcm11041042

      View details for PubMedID 35207317
  • Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): Study protocol for a phase 1 dose-escalation trial of patients with xerostomia after radiation therapy for head and neck cancer: MARSH: Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction Cytotherapy
    Blitzer GC, Rogus-Pulia NM, Mattison RJ, Varghese T, Ganz O, Chappell R, Galipeau J, McDowell KA, Meyers RO, Glazer TA, Kimple RJ
    2022 May;24(5):534-543. doi: 10.1016/j.jcyt.2021.11.003. Epub 2022 Feb 16.
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      BACKGROUND: Xerostomia, or dry mouth, is a common side effect of head and neck radiation. Current treatment options for radiation-induced xerostomia are generally supportive in nature. Adult stem cells are the ultimate source for replenishment of salivary gland tissue. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are a viable cell-based therapy for xerostomia. We have undertaken studies enabling U.S. Food and Drug Administration Investigational New Drug status, demonstrating the normal phenotype, intact functionality, and pro-growth secretome of interferon-γ (IFNγ)-stimulated BM-MSCs taken from patients with head and neck cancer who have undergone radiation ± chemotherapy. Here we present the protocol of MARSH, a first-in-human clinical trial of bone marrow-derived, IFNγ-activated BM-MSCs for the treatment of radiation-induced xerostomia.

      METHODS: This single-center phase 1 dose-escalation with expansion cohort, non-placebo-controlled study will assess the safety and tolerability of BM-MSCs for the treatment of radiation-induced xerostomia in patients who had head and neck cancer. The phase 1 dose-escalation study will be a 3 + 3 design with staggered enrollment. A total of 21 to 30 subjects (9 to 18 in phase 1 study, 12 in expansion cohort) will be enrolled. The primary endpoint is determining the recommended phase 2 dose (RP2D) of IFNγ-stimulated BM-MSCs to enable further studies on the efficacy of BM-MSCs. Patients' bone marrow will be aspirated, and BM-MSCs will be expanded, stimulated with IFNγ, and injected into the submandibular gland. The RP2D will be determined by dose-limiting toxicities occurring within 1 month of BM-MSC injection. Secondary outcomes of saliva amounts and composition, ultrasound of salivary glands, and quality of life surveys will be taken at 3-, 6-, 12-, and 24-month visits.

      DISCUSSION: Autotransplantation of IFNγ-stimulated BM-MSCs in salivary glands after radiation therapy or chemoradiation therapy may provide an innovative remedy to treat xerostomia and restore quality of life. This is the first therapy for radiation-induced xerostomia that may be curative.

      TRIAL REGISTRATION: World Health Organization International Clinical Trials Registry Platform: NCT04489732.

      PMID:35183442 | PMC:PMC9038658 | DOI:10.1016/j.jcyt.2021.11.003

      View details for PubMedID 35183442
  • Women Oncologists' Perceptions and Factors Associated With Decisions to Pursue Academic vs Nonacademic Careers in Oncology JAMA network open
    Merfeld EC, Blitzer GC, Kuczmarska-Haas A, Pitt SC, Chino F, Le T, Allen-Rhoades WA, Cole S, Marshall AL, Carnes M, Jagsi R, Duma N
    2021 Dec 1;4(12):e2141344. doi: 10.1001/jamanetworkopen.2021.41344.
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      IMPORTANCE: Women outnumber men in US medical school enrollment, but they represent less than 40% of academic oncology faculty.

      OBJECTIVE: To identify the key factors associated with female oncologists' decision to pursue academic or nonacademic oncology practice and to characterize their perceptions about their current career.

      DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study was distributed through email and social media to female physicians in academic and nonacademic oncology practice in the United States. The survey was open for 3 months, from August 1 to October 31, 2020.

      MAIN OUTCOMES AND MEASURES: No single primary study outcome was established because of the cross-sectional nature of the survey. Data were collected anonymously and analyzed using t tests for continuous variables and χ2 tests for categorical variables.

      RESULTS: Among the 667 female respondents, 422 (63.2%) identified as academic oncologists and 245 (36.8%) identified as nonacademic oncologists. Approximately 25% of respondents reported that their spouse or partner (156 [23.5%]) and/or family (176 [26.4%]) extremely or moderately affected their decision to pursue academic practice. Academic oncologists perceived the biggest sacrifice of pursuing academics to be time with loved ones (181 [42.9%]). Nonacademic oncologists perceived the biggest sacrifice of pursuing academics to be pressure for academic promotion (102 [41.6%]). Respondents had different perceptions of how their gender affected their ability to obtain a chosen job, with 116 academic oncologists (27.6%) and 101 nonacademic oncologists (41.2%) reporting a positive or somewhat positive impact (P = .001). More than half of the women surveyed (54.6% academic oncologists [230]; 50.6% nonacademic oncologists [123]; P = .61) believed they were less likely to be promoted compared with male colleagues. Academic and nonacademic oncologists reported rarely or never having a sense of belonging in their work environment (33 [7.9%] and 5 [2.0%]; P < .001). Most respondents reported that they would choose the same career path again (301 academic oncologists [71.3%]; 168 nonacademic oncologists [68.6%]); however, 92 academic oncologists (21.9%) reported they were likely to pursue a career outside of academic oncology in the next 5 years.

      CONCLUSIONS AND RELEVANCE: This survey study found that a spouse or partner and/or family were factors in the career choice of both academic and nonacademic oncologists and that female gender was largely perceived to adversely affect job promotion. Given that more than 20% of female academic oncologists were considering leaving academia, gender inequality is at high risk of continuing if the culture is not addressed.

      PMID:34967880 | PMC:PMC8719237 | DOI:10.1001/jamanetworkopen.2021.41344

      View details for PubMedID 34967880
  • Why an Increasing Number of Unmatched Residency Positions in Radiation Oncology? A Survey of Fourth-Year Medical Students Advances in radiation oncology
    Blitzer GC, Parekh AD, Chen S, Taparra K, Kahn JM, Fields EC, Stahl JM, Rosenberg SA, Buatti JM, Laucis AM, Wang Y, Mayhew DL, McDonald AM, Harari PM, Brower JV
    2021 Jun 24;6(5):100743. doi: 10.1016/j.adro.2021.100743. eCollection 2021 Sep-Oct.
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      PURPOSE: The number of US fourth-year medical students applying to radiation oncology has decreased during the past few years. We conducted a survey of fourth-year medical students to examine factors that may be influencing the decision to pursue radiation oncology.

      METHODS AND MATERIALS: An anonymous online survey was sent to medical students at 9 participating US medical schools.

      RESULTS: A total of 232 medical students completed the survey. Of the 153 students who stated they were never interested in radiation oncology, 77 (50%) reported never having been exposed to the specialty as their reason for not pursuing radiation oncology. The job market was the most commonly cited factor among students who said they were once interested in but ultimately chose not to pursue radiation oncology. Conversely, the recent low pass rates for board examinations and a perception of a lack of diversity within radiation oncology had the least influence.

      CONCLUSIONS: Despite discussion of potential measures to address this disquieting trend, there have been minimal formal attempts to characterize and address potential causes of a decreasing interest in radiation oncology. This study's data are consistent with previous research regarding the trend of decreased medical student interest in radiation oncology and may be used as part of ongoing introspective assessment to inform future change within radiation oncology.

      PMID:34466713 | PMC:PMC8385400 | DOI:10.1016/j.adro.2021.100743

      View details for PubMedID 34466713
  • Four Ways to Decrease Late Toxicity From Pelvic Radiation Therapy in Children and Young Adults Practical radiation oncology
    Blitzer GC, Bradley KA
    2021 Nov-Dec;11(6):434-440. doi: 10.1016/j.prro.2021.07.001. Epub 2021 Jul 16.
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      The use of curative-intent multimodality therapy with chemotherapy, surgery, and radiation results in late toxicities in almost two-thirds of patients with pediatric cancer. When pelvic radiation is used for pediatric malignancies such as rhabdomyosarcoma, lymphoma, neuroblastoma, Ewing sarcoma, and Wilms tumor, the associated late toxicities can affect many normal tissues and may include growth asymmetries, cystitis, infertility, and sexual dysfunction. We describe 4 recommendations of how to prevent or minimize late toxicities from pelvic radiation and review the literature of these pediatric late toxicities.

      PMID:34274520 | DOI:10.1016/j.prro.2021.07.001

      View details for PubMedID 34274520
  • Combining Stereotactic Body Radiotherapy and Microwave Ablation Appears Safe and Feasible for Renal Cell Carcinoma in an Early Series Clinical genitourinary cancer
    Blitzer GC, Wojcieszynski A, Abel EJ, Best S, Lee FT, Hinshaw JL, Wells S, Ziemlewicz TJ, Lubner MG, Alexander M, Yadav P, Bayouth JE, Floberg J, Cooley G, Harari PM, Bassetti MF
    2021 Oct;19(5):e313-e318. doi: 10.1016/j.clgc.2021.04.010. Epub 2021 Apr 20.
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      Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) are both used in treating inoperable renal cell carcinoma (RCC). MW ablation and SBRT have potentially complementary advantages and limitations. Combining SBRT and MW ablation may optimize tumor control and toxicity for patients with larger (> 5 cm) RCCs or those with vascular involvement. Seven patients with RCC were treated at our institution with combination of SBRT and MW ablation, median tumor size of 6.4 cm. Local control was 100% with a median follow-up of 15 months. Four patients experienced grade 2 nausea during SBRT. Three patients experienced toxicities after MW ablation, 2 with grade 1 hematuria and 1 with grade 3 retroperitoneal bleed/collecting system injury. Median eGFR (estimated glomerular filtration rate) preceding and following SBRT and MW ablation was 69 mL/min/1.73 m2 and 68 mL/min/1.73 m2 (P = .19), respectively. In patients who are not surgical candidates, larger RCCs or those with vascular invasion are challenging to treat. Combination treatment with SBRT and MW ablation may balance the risks and benefits of both therapies and demonstrates high local control in our series. MW ablation and SBRT have potentially complementary advantages and limitations.

      PMID:34024743 | DOI:10.1016/j.clgc.2021.04.010

      View details for PubMedID 34024743
  • Evaluating dose constraints for radiation induced liver damage following magnetic resonance image guided Stereotactic Body radiotherapy Physics and imaging in radiation oncology
    Yadav P, Kuczmarska-Haas A, Musunuru HB, Witt J, Blitzer G, Mahler P, Bassetti MF
    2021 Feb 6;17:91-94. doi: 10.1016/j.phro.2021.01.009. eCollection 2021 Jan.
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      This study reports dose corresponding to visible radiation induced liver damage following Stereotactic Body Radiation Therapy (SBRT) for liver metastasis, and the optimal time for follow up scans using post radiation imaging. Diagnostic magnetic resonance scans of nine patients treated with liver SBRT using a 0.35 T MRI-guided radiotherapy system were analyzed. The dice coefficients between the region of visible liver damage and the delivered dose were calculated. A median dose of 35 Gy correlated most closely with the visible radiation induced liver damage. We compared scans over two to nine months and observed maximal dice coefficients at two to five months post radiation. We have presented a new method for developing treatment planning guidelines for liver SBRT.

      PMID:33898785 | PMC:PMC8058022 | DOI:10.1016/j.phro.2021.01.009

      View details for PubMedID 33898785
  • Declining Medical Student Interest in Radiation Oncology: Wake-Up Call With a Silver Lining? International journal of radiation oncology, biology, physics
    Brower JV, Blitzer GC, Vapiwala N, Harari PM
    2021 Jun 1;110(2):274-277. doi: 10.1016/j.ijrobp.2021.02.035. Epub 2021 Mar 12.
  • Results From 10 Years of a Free Oral Cancer Screening Clinic at a Major Academic Health Center International journal of radiation oncology, biology, physics
    Blitzer GC, Rosenberg SA, Anderson BM, McCulloch TM, Wieland AM, Hartig GK, Bruce JY, Witek ME, Kimple RJ, Harari PM
    2018 Sep 1;102(1):146-148. doi: 10.1016/j.ijrobp.2018.05.007. Epub 2018 Jul 3.
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      PMID:29980415 | PMC:PMC6089656 | DOI:10.1016/j.ijrobp.2018.05.007

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  • Management of high-risk breast lesions found on mammogram or ultrasound: the value of contrast-enhanced MRI to exclude malignancy Clinical imaging
    Hammersley JA, Partridge SC, Blitzer GC, Deitch S, Rahbar H
    2018 May-Jun;49:174-180. doi: 10.1016/j.clinimag.2018.03.011. Epub 2018 Mar 13.
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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.

      PMID:29571172 | DOI:10.1016/j.clinimag.2018.03.011

      View details for PubMedID 29571172
  • Should functional renal scans be obtained prior to upper abdominal IMRT for pancreatic cancer? Practical radiation oncology
    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. doi: 10.1016/j.prro.2017.06.013. Epub 2017 Jun 29.
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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.

      PMID:28886941 | DOI:10.1016/j.prro.2017.06.013

      View details for PubMedID 28886941
  • Adoptive cell therapy using PD-1<sup>+</sup> myeloma-reactive T cells eliminates established myeloma in mice Journal for immunotherapy of cancer
    Jing W, Gershan JA, Blitzer GC, Palen K, Weber J, McOlash L, Riese M, Johnson BD
    2017 Jun 20;5:51. doi: 10.1186/s40425-017-0256-z. eCollection 2017.
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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.

      PMID:28642819 | PMC:PMC5477110 | DOI:10.1186/s40425-017-0256-z

      View details for PubMedID 28642819
  • Xenograft assessment of predictive biomarkers for standard head and neck cancer therapies Cancer medicine
    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. doi: 10.1002/cam4.387. Epub 2015 Jan 26.
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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.

      PMID:25619980 | PMC:PMC4430263 | DOI:10.1002/cam4.387

      View details for PubMedID 25619980

Contact Information

Grace C. Blitzer, MD

600 Highland Avenue,
3139 WIMR
Madison, WI 53792