Jacob Witt, Post Grad Trainee

Jacob Witt, MD

Radiation Oncology Resident

Department of Human Oncology

Education

MD, Washington University School of Medicine in St. Louis, (2016)

BS, Washington University in St. Louis, Biology (2012)

Selected Honors and Awards

Missouri State Medical Association Scholarship (2013)

Denardo Summer Scholar (2013)

T35 NIH Training Grant (2012)

Sigma Xi (2012)

Howard Hughes Medical Institute Summer Undergraduate Research Fellowship (2010)

Washington University Student Associate (2009–2010)

National Merit Commended Scholar (2007)

  • Impact of adjuvant fractionated stereotactic radiotherapy dose on local control of brain metastases. J Neurooncol
    Musunuru HB, Witt JS, Yadav P, Francis DM, Kuczmarska-Haas A, Labby ZE, Bassetti MF, Howard SP, Baschnagel AM
    2019 Oct 12; :
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      PURPOSE: The aim of this study was to determine whether a higher biological effective dose (BED) would result in improved local control in patients treated with fractionated stereotactic radiotherapy (FSRT) for their resected brain metastases.

      METHODS: Patients with newly diagnosed brain metastases without previous brain radiotherapy were retrospectively reviewed. Patients underwent surgical resection of at least one brain metastasis and were treated with adjuvant FSRT, delivering 25-36 Gy in 5-6 fractions. Outcomes were computed using Kaplan-Meier survival analysis and univariate analysis.

      RESULTS: Fifty-four patients with 63 post-operative cavities were included. Median follow-up was 16 months (3-60). Median metastasis size at diagnosis was 2.9 cm (0.6-8.1) and median planning target volume was 19.7 cm3 (6.3-68.1). Two-year local control (LC) was 83%. When stratified by dose, 2 years LC rate was 95.1% in those treated with 30-36 Gy in 5-6 fractions (BED10 of 48-57.6 Gy10) versus 59.1% lesions treated with 25 Gy in 5 fractions (BED10 of 37.5 Gy10) (p < 0.001). LC was not associated with resection cavity size. One year overall survival was 68.7%, and was independent of BED10. Symptomatic radiation necrosis occurred in 7.9% of patients and was not associated with dose.

      CONCLUSION: In the post-operative setting, high-dose FSRT (BED10 > 37.5 Gy10) were associated with a significantly higher rate of LC compared to lower BED regimens. Overall, 25 Gy in 5 fractions is not an adequate dose to control microscopic disease. If selecting a 5-fraction regimen, 30 Gy in five fractions appears to provide excellent tumor bed control.

      View details for PubMedID 31606876
  • Dosimetric study for spine stereotactic body radiation therapy: magnetic resonance guided linear accelerator versus volumetric modulated arc therapy. Radiol Oncol
    Yadav P, Musunuru HB, Witt JS, Bassetti M, Bayouth J, Baschnagel AM
    2019 Sep 24; 53 (3): 362-368
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      Background Stereotactic body radiation therapy (SBRT) given in 1-5 fractions is an effective treatment for vertebral metastases. Real-time magnetic resonance-guided radiotherapy (MRgRT) improves soft tissue contrast, which translates into accurate delivery of spine SBRT. Here we report on clinical implementation of MRgRT for spine SBRT, the quality of MRgRT plans compared to TrueBeam based volumetric modulated arc therapy (VMAT) plans in the treatment of spine metastases and benefits of MRgRT MR scan. Patients and methods Ten metastatic lesions were included in this study for plan comparison. Lesions were spread across thoracic spine and lumbosacral spine. Three fraction spine SBRT plans: 27Gy to planning target volume (PTV) and 30Gy to gross tumor volume (GTV) were generated on the ViewRay MRIdian Linac system and compared to TrueBeamTM STx based VMAT plans. Plans were compared using metrics such as minimum dose, maximum dose, mean dose, ratio of the dose to 50% of the volume (R50), conformity index, homogeneity index and dose to the spinal cord. Results MRIdian plans achieved equivalent target coverage and spinal cord dose compared to VMAT plans. The maximum and minimum PTV doses and homogeneity index were equivalent for both planning systems. R50 was lower for MRIdian plans compared to VMAT plans, indicating a lower spread of intermediate doses with MRIdian system (5.16 vs. 6.11, p = 0.03). Conclusions MRgRT can deliver high-quality spine SBRT plans comparable to TrueBeam volumetric modulated arc therapy (VMAT) plans.

      View details for PubMedID 31553704
  • Cardiac Toxicity in Operable Esophageal Cancer Patients Treated With or Without Chemoradiation. Am J Clin Oncol
    Witt JS, Jagodinsky JC, Liu Y, Yadav P, Kuczmarska-Haas A, Yu M, Maloney JD, Ritter MA, Bassetti MF, Baschnagel AM
    2019 Jul 15; :
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      PURPOSE: The purpose of this study was to evaluate predictors of cardiac events in esophageal cancer patients treated with neoadjuvant chemoradiotherapy (NA CRT) followed by surgery compared with surgery alone.

      MATERIALS AND METHODS: We retrospectively identified patients treated for esophageal cancer between 2006 and 2016. A total of 123 patients were identified; 70 were treated with surgery alone, and 53 were treated with NA CRT. Cardiac events were scored based on Common Terminology Criteria for Adverse Events (version 4.03), and dosimetric data was compiled for all patients who received radiation. Univariate analysis and multivariable analysis (MVA) were performed to identify predictors of cardiac events. Competing risk of death regression was performed to a model the cumulative incidence of cardiac events.

      RESULTS: The overall rates of grade ≥3 cardiac events were 24.5% in the NA CRT group versus 10% in the surgery group (P=0.04). On MVA, use of NA CRT (P<0.01, hazard ratio [HR]: 3.45, 95% confidence interval [CI]: 1.35-9.09) predicted for grade ≥3 cardiac events, though no dosimetric variable predicted for grade ≥3 cardiac events or overall survival. On MVA, NA CRT predicted for pericardial effusions of any grade (P<0.01, HR: 3.70, 95% CI: 1.67-8.33). The V45 Gy was the most significant predictor of pericardial effusions (P=0.012, HR: 1.03, 95% CI: 1.01-1.06) CONCLUSIONS:: NA CRT significantly increased the rate of grade ≥3 cardiac events compared with patients treated with surgery alone. Although no dosimetric parameter predicted for grade ≥3 cardiac events or survival, the V45 Gy predicted for pericardial effusions.

      View details for PubMedID 31313677
  • Indications for and efficacy of postmastectomy radiotherapy for patients with a favorable response to neoadjuvant chemotherapy. Cancer
    Francis DM, Witt JS, Anderson BM
    2018 Dec 03; :
  • Large volume re-irradiation for recurrent meningioma with pulsed reduced dose rate radiotherapy. J Neurooncol
    Witt JS, Musunuru HB, Bayliss RA, Howard SP
    2019 Jan; 141 (1): 103-109
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      PURPOSE: Meningiomas comprise up to 30% of primary brain tumors. The majority of meningioma patients enjoy high rates of control after conventional therapies. However, patients with recurrent disease previously treated with radiotherapy have few options for salvage treatment, and systemic interventions have proven largely ineffective. The aim of this study was to determine whether pulsed reduced dose rate radiotherapy (PRDR) was well tolerated in a small cohort of patients with recurrent meningioma.

      METHODS: We retrospectively identified eight patients with recurrent intracranial meningioma treated with PRDR from April 2013 to August of 2017 at a single institution. All patients had radiographic and/or pathologic evidence of progression prior to treatment and had previously completed conventional radiotherapy. Acute and late toxicities were graded based on CTCAE 4.0.

      RESULTS: Of eight patients, six had histologically confirmed atypical meningiomas upon recurrence. All patients were re-treated with IMRT at an apparent dose rate of 0.0667 Gy/min. Median time between radiation courses was 7.7 years. Median PRDR dose was 54 Gy in 27 fractions to a median volume of 261.6 cm3. Two patients (25%) had in field failure with a median follow up of 23.3 months. PFS at 6 months was 100%. All but one (87.5%) patient was still alive at last follow up. No patient experienced grade ≥ 2 acute or late toxicities.

      CONCLUSIONS: PRDR re-irradiation was well tolerated and appeared effective for a small cohort of patients with recurrent meningioma previously treated with radiotherapy. A phase II trial to assess this prospectively is in development.

      View details for PubMedID 30392090
  • Low cardiac and left anterior descending coronary artery dose achieved with left-sided multicatheter interstitial-accelerated partial breast irradiation. Brachytherapy
    Witt JS, Gao RW, Sudmeier LJ, Rosenberg SA, Francis DM, Wallace CR, Das RK, Anderson BM
    2019 Jan - Feb; 18 (1): 50-56
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      PURPOSE: Studies have shown that an additional mean dose of 1 Gy to the heart can increase the relative risk of cardiac events. The purpose of this study was to quantify the dose delivered to the heart and left anterior descending artery (LAD) in a series of patients with left-sided breast cancer (BC) or ductal carcinoma in situ treated with multicatheter-accelerated partial breast irradiation (MC-APBI) at a single institution.

      METHODS AND MATERIALS: Patients with left-sided BC or ductal carcinoma in situ treated consecutively from 2005 to 2011 with MC-APBI were retrospectively identified. Cardiac and LAD contours were generated for each patient. Cardiac dosimetry and distance to the planning target volume were recorded. Patient health records were reviewed and cardiac events were recorded based on Common Terminology Criteria for Adverse Events version 4.0.

      RESULTS: Twenty consecutive patients with left-sided BC treated with MC-APBI were retrospectively identified. Median followup was 41.4 months. Mean equivalent dose in 2 Gy fractions delivered to the heart and LAD were 1.3 (standard deviation: 0.7, range: 0.2-2.9) and 3.8 (standard deviation: 3.0, range: 0.4-11.3) Gy, respectively. There was an inverse linear relationship (R2 = 0.52) between heart-to-lumpectomy cavity distance and mean heart equivalent dose in 2 Gy fractions. One patient (5%) experienced symptomatic cardiac toxicity.

      CONCLUSIONS: MC-APBI consistently delivers average doses to the heart and LAD that are similar to those achieved in most series with deep inspiration breath-hold and lower than free-breathing radiotherapy techniques. Distance from the heart to the lumpectomy cavity and the availability of other heart-sparing technologies should be considered to minimize the risk of cardiac toxicity.

      View details for PubMedID 30262411
  • Geminin regulates the transcriptional and epigenetic status of neuronal fate-promoting genes during mammalian neurogenesis. Mol Cell Biol
    Yellajoshyula D, Lim JW, Thompson DM, Witt JS, Patterson ES, Kroll KL
    2012 Nov; 32 (22): 4549-60
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      Regulating the transition from lineage-restricted progenitors to terminally differentiated cells is a central aspect of nervous system development. Here, we investigated the role of the nucleoprotein geminin in regulating neurogenesis at a mechanistic level during both Xenopus primary neurogenesis and mammalian neuronal differentiation in vitro. The latter work utilized neural cells derived from embryonic stem and embryonal carcinoma cells in vitro and neural stem cells from mouse forebrain. In all of these contexts, geminin antagonized the ability of neural basic helix-loop-helix (bHLH) transcription factors to activate transcriptional programs promoting neurogenesis. Furthermore, geminin promoted a bivalent chromatin state, characterized by the presence of both activating and repressive histone modifications, at genes encoding transcription factors that promote neurogenesis. This epigenetic state restrains the expression of genes that regulate commitment of undifferentiated stem and neuronal precursor cells to neuronal lineages. However, maintaining geminin at high levels was not sufficient to prevent terminal neuronal differentiation. Therefore, these data support a model whereby geminin promotes the neuronal precursor cell state by modulating both the epigenetic status and expression of genes encoding neurogenesis-promoting factors. Additional developmental signals acting in these cells can then control their transition toward terminal neuronal or glial differentiation during mammalian neurogenesis.

      View details for PubMedID 22949506

 

 

Contact Information

Jacob Witt, MD

600 Highland Avenue,
Madison, WI 53792
Email