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Sangjune Laurence Lee, MD

Eric Wolfe Clinical Research Fellow

Department of Human Oncology

I am a Canadian-board certified radiation oncologist currently training as a Wolfe Clinical Fellow in the Department of Human Oncology. I am pursuing a career in academic radiation oncology with the goal of characterizing and solving oncology problems at the intersection between medicine and engineering. As a clinical fellow, I specialize in treating patients with gastrointestinal malignancies. My research interests are to improve the therapeutic ratio through the use of real-time MRI-guided radiation therapy. I am currently a co-principal investigator of an RSNA funded clinical protocol investigating the use of MRI to identify biomarkers in esophageal cancer patients. In addition to my clinical and research activities, I regularly teach medical residents.

Education

Resident, University of Toronto, Radiation Oncology (2019)

MD, University of Toronto, Medicine (2010)

MS, Johns Hopkins University, Biomedical Engineering (2010)

BASc, University of Waterloo, Electrical Engineering (2007)

Academic Appointments

Selected Honors and Awards

Radiologic Society of North America (RSNA) Fellow Research Grant (2019)

Robert V. Brady Award for Exemplary Compassion, Advocacy, and Patient Care (2018)

Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21) (2016-2018)

International Society for Magnetic Resonance in Medicine (ISMRM) Educational Stipend and Summa Cum Laude Merit Award (2012)

University of Waterloo Graduation with Distinction and Dean's Honours List (2007)

University of Waterloo George J. Dufault Award (for excellence in written communication) (2006)

University of Waterloo Natural Sciences and Engineering Research Council Undergraduate Student Research Award (NSERC USRA) (2005)

Research Focus

Gastrointestinal cancers

Improving the therapeutic ratio through the use of real-time MRI guided radiation therapy

The combined MRI and linear accelerator treatment unit, also known as the MR-linac, provides real-time MRI guidance during radiation therapy. This allows radiation oncologists to have greater confidence that the radiation treatment is delivered correctly to the tumor and avoids the surrounding normal organs. The radiation plan can be adapted daily according to changes in the tumor and surrounding organ anatomy, and the treatment delivery can be timed so that radiation is only delivered during part of the respiratory cycle when the tumor is within a safe location. My research focuses on improving the MR-linac workflow and using MRI for more personalized radiation treatment.

Identifying MRI biomarkers of tumor response and cardiac toxicity in patients undergoing concurrent chemoradiation for esophageal cancer:

Concurrent chemoradiation improves the survival of patients with locally advanced esophageal cancer. In patients who undergo surgical resection after chemoradiation, 30% achieve a complete pathological response. Although chemoradiation is an effective local treatment, because esophageal tumors are often adjacent to the heart, chemoradiation is also associated with a 10% chance of symptomatic cardiac toxicity. Under the supervision of Dr. Michael Bassetti, I am investigating the use of additional diagnostic tests to measure the response of esophageal cancer to chemoradiation and to detect acute signs of cardiac toxicity. Quantitative MRI techniques, ECGs, and blood cardiac markers will be taken throughout the normal chemoradiation treatment schedule. Changes in the tumor as seen on MRI will be correlated with rates of pathologic tumor regression. Final diagnostic tests to detect chronic heart disease 1.5 years after completion of chemoradiation will be correlated with signs of acute cardiac toxicity. The findings from this study will inform dose modification for improved therapeutic ratios and will guide appropriate cardiac follow up care.

  • Improved dosimetric accuracy with semi-automatic contour propagation of organs-at-risk in glioblastoma patients undergoing chemoradiation. J Appl Clin Med Phys
    Lee S, Stewart J, Lee Y, Myrehaug S, Sahgal A, Ruschin M, Tseng CL
    2019 Oct 31; :
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      BACKGROUND: We study the changes in organs-at-risk (OARs) morphology as contoured on serial MRIs during chemoradiation therapy (CRT) of glioblastoma (GBM). The dosimetric implication of assuming non-deformable OAR changes and the accuracy and feasibility of semi-automatic OAR contour propagation are investigated.

      METHODS: Fourteen GBM patients who were treated with adjuvant CRT for GBM prospectively underwent MRIs on fractions 0 (i.e., planning), 10, 20, and 1 month post last fraction of CRT. Three sets of OAR contours - (a) manual, (b) rigidly registered (static), and (c) semi-automatically propagated - were compared using Dice similarity coefficient (DSC) and Hausdorff distance (HD). Dosimetric impact was determined by comparing the minimum dose to the 0.03 cc receiving the highest dose (D0.03 cc) on a clinically approved reference, non-adapted radiation therapy plan.

      RESULTS: The DSC between the manual contours and the static contours decreased significantly over time (fraction 10: [mean ± 1 SD] 0.78 ± 0.17, post 1 month: 0.76 ± 0.17, P = 0.02) while the HD (P = 0.74) and the difference in D0.03cc did not change significantly (P = 0.51). Using the manual contours as reference, compared to static contours, propagated contours have a significantly higher DSC (propagated: [mean ± 1 SD] 0.81 ± 0.15, static: 0.77 ± 0.17, P < 0.001), lower HD (propagated: 3.77 ± 1.8 mm, static: 3.96 ± 1.6 mm, P = 0.002), and a significantly lower absolute difference in D0.03cc (propagated: 101 ± 159 cGy, static: 136 ± 243 cGy, P = 0.019).

      CONCLUSIONS: Nonrigid changes in OARs over time lead to different maximum doses than planned. By using semi-automatic OAR contour propagation, OARs are more accurately delineated on subsequent fractions, with corresponding improved accuracy of the reported dose to the OARs.

      View details for PubMedID 31670900
  • Extensive Unpredictable Pancreas Cancer Inter-fraction Motion: A Case Report. Cureus
    Lee SL, Velec M, Munoz-Schuffenegger P, Stanescu T, Dawson L
    2019 Jun 30; 11 (6): e5047
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      We present a case of locally advanced pancreatic cancer with duodenal invasion treated with consolidative chemoradiation, where extensive unpredictable interfraction motion was observed. Initially, two attempts were made to treat with volumetric modulated arc therapy technique. However, due to substantial interfractional motion of the pancreatic head mass relative to the regional nodal areas, the patient was eventually replanned and treated with a four-field box technique. This case highlights the difficulty in delivering conformal radiation to the pancreas and quantifies the movement of the target, the adjacent biliary stent, and regional nodes.

      View details for PubMedID 31501738
  • Computer-assisted image analysis of the tumor microenvironment on an oral tongue squamous cell carcinoma tissue microarray. Clin Transl Radiat Oncol
    Lee SL, Cabanero M, Hyrcza M, Butler M, Liu FF, Hansen A, Huang SH, Tsao MS, Song Y, Lu L, Xu W, Chepeha DB, Goldstein DP, Weinreb I, Bratman SV
    2019 Jul; 17: 32-39
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      Oral tongue squamous cell carcinoma (OTSCC) displays variable levels of immune cells within the tumor microenvironment. The quantity and localization of tumor infiltrating lymphocytes (TILs), specific functional TIL subsets (e.g., CD8+), and biomarker-expressing cells (e.g., PD-L1+) may have prognostic and predictive value. The purpose of this study was to evaluate the robustness and utility of computer-assisted image analysis tools to quantify and localize immunohistochemistry-based biomarkers within the tumor microenvironment on a tissue microarray (TMA). We stained a 91-patient OTSCC TMA with antibodies targeting CD3, CD4, CD8, FOXP3, IDO, and PD-L1. Cell populations were segmented into epithelial (tumor) or stromal compartments according to a mask derived from a pan-cytokeratin stain. Definiens Tissue Studio was used to enumerate marker-positive cells or to quantify the staining intensity. Automated methods were validated against manual tissue segmentation, cell count, and stain intensity quantification. Univariate associations of cell count and stain intensity with smoking status, stage, overall survival (OS), and disease-free survival (DFS) were determined. Our results revealed that the accuracy of automated tissue segmentation was dependent on the distance of the tissue section from the cytokeratin mask and the proportion of the tissue containing tumor vs. stroma. Automated and manual cell counts and stain intensities were highly correlated (Pearson coefficient range: 0.46-0.90; p < 0.001). Within this OTSCC cohort, smokers had significantly stronger PD-L1 stain intensity and higher numbers of CD3+, CD4+ and FOXP3+ TILs. In the subset of patients who had received adjuvant radiotherapy, a higher number of CD8+ TILs was associated with inferior OS and DFS. Taken together, this proof-of-principle study demonstrates the robustness and utility of computer-assisted image analysis for high-throughput assessment of multiple IHC markers on TMAs, with potential implications for studies on prognostic and predictive biomarkers.

      View details for PubMedID 31193592
  • Changes in ADC and T2-weighted MRI-derived radiomic features in patients treated with focal salvage HDR prostate brachytherapy for local recurrence after previous external-beam radiotherapy. Brachytherapy
    Lee SL, Ravi A, Morton G, Loblaw A, Tseng CL, Haider M, Murgic J, Nicolae A, Semple M, Chung HT
    2019 Sep - Oct; 18 (5): 567-573
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      PURPOSE: To explore the changes in T2-weighted (T2w) and apparent diffusion coefficient (ADC) magnetic resonance imaging -derived radiomic features of the gross tumor volume (GTV) from focal salvage high-dose-rate prostate brachytherapy (HDRB) and to correlate with clinical parameters.

      MATERIALS AND METHODS: Eligible patients included those with biopsy-confirmed local recurrence that correlated with MRI (T2w, ADC). Patients received 27 Gy in 2 fractions separated by 1 week to a quadrant consisting of the GTV. The MRI was repeated 1 year after HDRB. GTVs, planning target volumes, and normal prostate tissue control volumes were identified on the pre- and post-HDRB MRIs. Radiomic features from each GTV were extracted, and principle component analysis identified features with the highest variance.

      RESULTS: Pre- and post-HDRB MRIs were obtained from 14 trial patients. Principle component analysis showed that 18 and 17 features contributed to 93% and 86% of the variance observed in the T2w and ADC data, respectively. Sixteen T2w features and 1 ADC GTV feature were different from the control volumes in the pre-HDRB images (p < 0.05). Ten T2w and 7 ADC GTV post-HDRB features were different from those of pre-HDRB (p < 0.05).

      CONCLUSIONS: Exploratory analysis reveals several radiomic features in the T2w and ADC image GTVs that distinguish the GTV from healthy prostate tissue and change significantly after salvage HDRB.

      View details for PubMedID 31126856

Contact Information

Sangjune Laurence Lee, MD

600 Highland Ave.,
K4/B59
Madison, WI 53792