Bio


Dr. Dworkin graduated from The Ohio State University in 2012, where he studied mathematics and was inducted into Phi Beta Kappa. There, he developed a research interest in systems biology and oncology and won a Pelotonia Undergraduate Cancer Research Fellowship. He received his MD from Duke University School of Medicine in 2018. During medical school, he developed an interest in radiation oncology and researched psuedoprogression in patients with low-grade gliomas treated with proton radiotherapy. He completed a preliminary internal medicine internship at University of Kentucky in 2019. Currently, he is a resident physician in the Department of Radiation Oncology at Stanford. His work at Stanford has led to several abstracts and a first-authored publication on the use of a radiotherapy boost in patients undergoing hematopoietic stem cell transplant. He is interested in a career in academic radiation oncology focused on the development and implementation of radiobiologically informed and innovative radiotherapy treatment approaches and technologies that aim to deliver effective treatment while minimizing burden to patients with cancer.

Clinical Focus


  • Residency
  • Radiation Oncology

Honors & Awards


  • Pathology Retreat Poster Award, Harvard Medical School (2017)
  • Third Year Study Away Research Scholarship, Duke University School of Medicine (2016)
  • Pelotonia International Fellowship, The Ohio State University Foundation (2012)
  • Phi Beta Kappa, The Ohio State University (2012)
  • Pressey Honors Travel Grant, The Ohio State University (2012)
  • Henson Travel Grant, The Ohio State University (2011)
  • Pelotonia Undergraduate Cancer Research Fellowship, The Ohio State University Foundation (2011)
  • Symposium on Systems Biology of Influenza Travel Fellowship, Yale University (2011)
  • q-bio Conference Fellowship, , q-bio Summer School and Conference (2011)
  • Undergraduate Research Scholarship, The Ohio State University (2010)
  • Choose Ohio First Bioinformatics Scholarship, Ohio Department of Higher Education (2009 - 2011)

Boards, Advisory Committees, Professional Organizations


  • Member, Radiological Society of North America (2021 - Present)
  • Member, American Society of Clinical Oncology (2021 - Present)
  • Member, American Association for Cancer Research (2021 - Present)
  • Member, American Society for Radiation Oncology (2021 - Present)

Professional Education


  • Resident, Stanford Hospital and Clinics, Radiation Oncology (2023)
  • Resident, University of Kentucky, Preliminary Internal Medicine (2019)
  • MD, Duke University School of Medicine, Medicine (2018)
  • BS, The Ohio State University, Mathematics (2012)

Lab Affiliations


All Publications


  • Pathologic Response and Locoregional Control After Preoperative Pancreatic Stereotactic Body Radiation Therapy. International journal of radiation oncology, biology, physics Dworkin, M. L., Miller, J. A., Toesca, D. A., Baclay, J. R., Pollom, E., Chang, D. T. 2021; 111 (3S): e37

    Abstract

    PURPOSE/OBJECTIVE(S): In light of ALLIANCE02150, the role of preoperative stereotactic body radiotherapy (SBRT) for pancreatic cancer is controversial. We studied patients who had surgery after preoperative SBRT to assess pathologic and clinical outcomes, and evaluate if elective nodal irradiation (ENI) decreases locoregional failure (LRF).MATERIALS/METHODS: Patients with pancreatic cancer who received SBRT at one center from 2007 to 2020 followed by oncologic surgery were reviewed. Local (primary tumor), regional (peripancreatic or perivascular per RTOG consensus), and distant failures were coded. Pathologic treatment response per College of American Pathologists was reviewed. Incidence of LRF with death as competing risk was assessed. Time to overall (OS) and progression-free survival (PFS) from date of pathologic diagnosis was assessed via Kaplan-Meier. Association testing via Cox analysis for OS/PFS and Gray test for LRF was performed.RESULTS: Twenty-eight patients were evaluable. Median (range) ECOG was 1 (0-2). Tumor stage was cT4 in 19 (67.9%) patients. Nodal stage was cN1 in 10 (35.7 %) patients. There were 7 and 21 patients with initially unresectable and borderline resectable disease respectively. Chemotherapy (CT) was given prior to SBRT in 27 (96.4%) patients, with FOLFIRINOX and gemcitabine-paclitaxel in 21 and 4 patients, respectively. Median (range) duration of CT was 5 (0-12) cycles. Median (range) dose, BED10, and fractionation were 40 Gy (25 - 50 Gy), 72 Gy (54.78 - 100 Gy), and 5 (1-5) respectively. The median (range) time between SBRT and surgery was 6.7 (2.6 - 21.9) weeks. Whipple, Appleby, and distal pancreatectomy was performed in 22, 4, and 2 patients respectively. The R0 rate was 23/28 (82.1%). Pathologic complete, near complete, partial, and poor/no treatment response was seen in 1 (3.6%), 10 (35.7%), 15 (53.6%), and 2 (7.1%) patients, respectively. The pN1 rate was 12/28 (42.3%). Median (range) follow up was 21.5 months (6.9 - 67.2 months). The 18-month (95% CI) overall survival (OS) and LRF were 66.6% (50.0 - 88.6%), and 7.8% (0.0 - 48.4%) respectively. Complete or near complete pathologic response was associated with improved OS (HR = 0.21, P = 0.022) and PFS (HR = 0.25, P = 0.021), but not LRC (P = 0.780). Longer (≥8 weeks) time between end of SBRT and surgery was associated with improved complete or near complete response rate (P = 0.024) but not OS, PFS, or LRF. BED10 did not predict for pathologic treatment response or margin status. Sixteen patients received ENI. There were no other statistically significant differences in the above baseline characteristics, OS, PFS, or pathology outcomes, with vs without ENI. The 18-month (95% CI) LRF with vs without ENI was 0.0% (0.0 - 0.0%) vs 12.8% (0.0 - 38.8%), P = 0.29.CONCLUSION: Our cohort of patients with pancreatic cancer treated with preoperative SBRT and surgery showed good pathologic response and R0 rate. ENI was associated with numerically lower LRF. Increased BED10 was not associated with improved pathologic treatment response.

    View details for DOI 10.1016/j.ijrobp.2021.07.356

    View details for PubMedID 34701293

  • Pathologic Response and Locoregional Control After Preoperative Pancreatic Stereotactic Body Radiation Therapy Dworkin, M. L., Miller, J. A., Toesca, D. S., Baclay, J. R., Pollom, E., Chang, D. T. ELSEVIER SCIENCE INC. 2021: E37
  • Outcomes of adults with lymphoma treated with nonmyeloablative TLI-ATG and radiation boost to high risk or residual disease before allogeneic hematopoietic cell transplant. Bone marrow transplantation Dworkin, M. L., Jiang, A. L., Von Eyben, R., Spinner, M. A., Advani, R. H., Lowsky, R., Hiniker, S. M., Hoppe, R. T. 2021

    Abstract

    We evaluated the impact on survival of antithymocyte globulin conditioning (TLI-ATG) with radiation (RT) boost to high risk or residual disease before allogeneic hematopoietic cell transplant (allo-HCT) for adults with lymphoma (excluding mycosis fungoides and low-grade NHL other than SLL/CLL). Of 251 evaluable patients, 36 received an RT boost within 3 months of allo-HCT at our institution from 2001 to 2016. At the time of TLI-ATG, patients who received boost vs no boost had a lower rate of CR (11% vs 47%, p = 0.0003), higher rates of bulky disease (22% vs 4%, p < 0.0001), extranodal disease (39% vs 5%, p < 0.0001), and positive PET (75% vs 28%, p < 0.00001). In the boost group, the median (range) largest axial lesion diameter was 5.2 cm (1.8-22.3). Median follow-up was 50.2 months (range: 1-196). There was no significant difference in OS, time to recurrence, or time to graft failure with vs without boost. A trend toward higher percent donor CD3+ chimerism was seen with vs without boost (p = 0.0819). The worst boost-related toxicity was grade 2 dermatitis. RT boost may help successfully mitigate the risk of high risk or clinically evident residual disease in adults with lymphoma undergoing allo-HCT.

    View details for DOI 10.1038/s41409-021-01495-4

    View details for PubMedID 34671121

  • Outcomes Of Adult Patients With Lymphoma Treated With Nonmyeloablative Total Lymphoid Irradiation For Stem Cell Transplant (SCT) Conditioning With A Boost To High Risk Or Gross Disease Dworkin, M. L., Hiniker, S. M., Von Eyben, R., Spinner, M. A., Advani, R. H., Lowsky, R., Hoppe, R. T. ELSEVIER SCIENCE INC. 2020: E752–E753
  • Long-term outcomes and late adverse effects of a prospective study on proton radiotherapy for patients with low-grade glioma RADIOTHERAPY AND ONCOLOGY Tabrizi, S., Yeap, B. Y., Sherman, J. C., Nachtigall, L. B., Colvin, M. K., Dworkin, M., Fullerton, B. C., Daartz, J., Royce, T. J., Oh, K. S., Batchelor, T. T., Curry, W. T., Loeffler, J. S., Shih, H. A. 2019; 137: 95-101

    Abstract

    Patients with low-grade gliomas (LGG) can survive years with their illness. Proton radiotherapy (PRT) can reduce off-target dose and decrease the risk of treatment-related morbidity. We examined long-term morbidity following proton therapy in this updated prospective cohort of patients with LGG.Twenty patients with LGG were enrolled prospectively and received PRT to 54 Gy(RBE) in 30 fractions. Comprehensive baseline and longitudinal assessments of toxicity, neurocognitive and neuroendocrine function, quality of life, and survival outcomes were performed up to 5 years following treatment.Six patients died (all of disease) and six had progression of disease. Median follow-up was 6.8 years for the 14 patients alive at time of reporting. Median progression-free survival (PFS) was 4.5 years. Of tumors tested for molecular markers, 71% carried the IDH1-R132H mutation and 29% had 1p/19q co-deletion. There was no overall decline in neurocognitive function; however, a subset of five patients with reported cognitive symptoms after radiation therapy had progressively worse function by neurocognitive testing. Six patients developed neuroendocrine deficiencies, five of which received Dmax ≥20 Gy(RBE) to the hypothalamus-pituitary axis (HPA). Most long-term toxicities developed within 2 years after radiation therapy.The majority of patients with LGG who received proton therapy retained stable cognitive and neuroendocrine function. The IDH1-R132H mutation was present in the majority, while 1p/19q loss was present in a minority. A subset of patients developed neuroendocrine deficiencies and was more common in those with higher dose to the HPA.

    View details for DOI 10.1016/j.radonc.2019.04.027

    View details for Web of Science ID 000475782600013

    View details for PubMedID 31082632

    View details for PubMedCentralID PMC6642836

  • Patterns of Failure Among Patients With Low-grade Glioma Treated With Proton Radiation Therapy PRACTICAL RADIATION ONCOLOGY Kamran, S. C., Dworkin, M., Niemierko, A., Bussiere, M., Oh, K. S., Loeffler, J. S., Shih, H. A. 2019; 9 (4): E356-E361

    Abstract

    Proton treatment may be a useful radiation therapy modality for long-term surviving patients with glioma to reduce normal tissue toxicities. Photon studies demonstrate that most low-grade glioma (LGG) failures occur within the radiation field, supporting the use of more conformal treatment plans, yet it is unclear whether this can be translated to proton radiation therapy (PRT). Our objective is to examine our institutional experience to determine patterns of failure in patients with LGG with respect to the volume irradiated with PRT.Patients with World Health Organization 2007 grade I to II or isocitrate dehydrogenase 1-positive mutation grade III LGG treated with PRT between 2005 and 2015 were retrospectively reviewed. Patients with documented local recurrences on magnetic resonance imaging after receipt of PRT underwent a comparison with the initial treatment plan dosimetry to evaluate patterns of failure. A total of 141 patients were included in the final cohort.The median follow-up time was 46.7 months (range, 2.8-144 months), and 5-year overall survival was 84%. The median PRT dose delivered was 54 Gy (relative biological effectiveness) (range, 45-60 Gy). There were 42 failures after PRT (30%). The median time to progression after treatment was 32.7 months (range, 4.8-93.6 months). Thirty-one patients (74%) failed in-field (defined as within the 95% isodose volume), 5 patients (12%) failed out-of-field, and 5 patients (12%) had marginal failures (defined as within the 50%-95% isodose volume). The 5-year freedom from progression after PRT was 60.1% (95% confidence interval, 48.7-70.0). The 5-year cumulative incidence of overall survival was 33% among those with recurrence after PRT and 96% among those without recurrence after PRT (P < .001).Of the patients with LGG who had documented failures after PRT, most recurred within the radiation field with few marginal failures, indicating that even with PRT, which often can have steeper dose gradients, coverage is adequate. Survival was poor for patients whose tumors recurred.

    View details for DOI 10.1016/j.prro.2019.02.002

    View details for Web of Science ID 000472574100002

    View details for PubMedID 30790717

  • Increase of pseudoprogression and other treatment related effects in low-grade glioma patients treated with proton radiation and temozolomide JOURNAL OF NEURO-ONCOLOGY Dworkin, M., Mehan, W., Niemierko, A., Kamran, S. C., Lamba, N., Dietrich, J., Martinez-Lage, M., Oh, K. S., Batchelor, T. T., Wen, P. Y., Loeffler, J. S., Shih, H. A. 2019; 142 (1): 69-77

    Abstract

    Concurrent radiotherapy and temozolomide (TMZ) is associated with radiographic pseudoprogression (PsP) in glioblastoma. The occurrence of PsP and other treatment effects is less well understood in low-grade gliomas (LGG). The purpose of this study is to evaluate whether the addition of TMZ to radiotherapy increases the incidence of PsP in adults with LGG treated with proton radiotherapy (PRT).Chart review and volumetric MRI-analysis was performed on radiotherapy-naive adults with WHO grade II or IDH mutant WHO grade III gliomas treated with PRT between 2005 and 2015. Progression was defined by histology, new chemotherapy initiation, or progressive increase in lesion volume beyond 40% from baseline. Post treatment related effects (PTRE) were defined as new/increased T2/FLAIR or abnormal enhancement which eventually resolved or stabilized without evidence of progression for a period of 6-12 months. PsP was defined as the subset of PRTE suspicious for progression or volumetrically increased at least 40% from baseline. Pearson's chi-squared test and Cox-proportional hazards models were used for statistical analysis.There were 119 patients meeting inclusion criteria. There was an increased risk of PsP following PRT + TMZ versus PRT-alone (HR = 2.2, p = 0.006, on Cox univariate analysis). Presence of PsP was associated with improved OS (p = 0.02 with PsP as time-varying covariate).TMZ use, when added to PRT, was associated with increased PsP in patients with LGG; however, patients with PsP tended to achieve longer survival.

    View details for DOI 10.1007/s11060-018-03063-1

    View details for Web of Science ID 000461075200007

    View details for PubMedID 30488294

  • Long-term Outcomes and Imaging Response for Image-Guided Stereotactic Radiosurgery (IG-SRS) of Brain Arteriovenous Malformations (AVM) Trotter, J., Kirkpatrick, J. P., McSherry, F., Rodrigues, A., Dworkin, M. L., Zomorodi, A., Gonzalez, L. F., Herndon, J., Hauck, E. F. ELSEVIER SCIENCE INC. 2018: E363
  • Patterns of Failure and Risk Factors for Recurrence Among Low-Grade Glioma Patients Treated With Proton Radiation Therapy Kamran, S. C., Dworkin, M. L., Niemierko, A., Oh, K. S., Loeffler, J. S., Shih, H. A. ELSEVIER SCIENCE INC. 2017: E82-E83
  • In Silico Modeling of Itk Activation Kinetics in Thymocytes Suggests Competing Positive and Negative IP4 Mediated Feedbacks Increase Robustness PLOS ONE Mukherjee, S., Rigaud, S., Seok, S., Fu, G., Prochenka, A., Dworkin, M., Gascoigne, N. J., Vieland, V. J., Sauer, K., Das, J. 2013; 8 (9): e73937

    Abstract

    The inositol-phosphate messenger inositol(1,3,4,5)tetrakisphosphate (IP4) is essential for thymocyte positive selection by regulating plasma-membrane association of the protein tyrosine kinase Itk downstream of the T cell receptor (TCR). IP4 can act as a soluble analog of the phosphoinositide 3-kinase (PI3K) membrane lipid product phosphatidylinositol(3,4,5)trisphosphate (PIP3). PIP3 recruits signaling proteins such as Itk to cellular membranes by binding to PH and other domains. In thymocytes, low-dose IP4 binding to the Itk PH domain surprisingly promoted and high-dose IP4 inhibited PIP3 binding of Itk PH domains. However, the mechanisms that underlie the regulation of membrane recruitment of Itk by IP4 and PIP3 remain unclear. The distinct Itk PH domain ability to oligomerize is consistent with a cooperative-allosteric mode of IP4 action. However, other possibilities cannot be ruled out due to difficulties in quantitatively measuring the interactions between Itk, IP4 and PIP3, and in generating non-oligomerizing Itk PH domain mutants. This has hindered a full mechanistic understanding of how IP4 controls Itk function. By combining experimentally measured kinetics of PLCγ1 phosphorylation by Itk with in silico modeling of multiple Itk signaling circuits and a maximum entropy (MaxEnt) based computational approach, we show that those in silico models which are most robust against variations of protein and lipid expression levels and kinetic rates at the single cell level share a cooperative-allosteric mode of Itk regulation by IP4 involving oligomeric Itk PH domains at the plasma membrane. This identifies MaxEnt as an excellent tool for quantifying robustness for complex TCR signaling circuits and provides testable predictions to further elucidate a controversial mechanism of PIP3 signaling.

    View details for DOI 10.1371/journal.pone.0073937

    View details for Web of Science ID 000324494000069

    View details for PubMedID 24066087

    View details for PubMedCentralID PMC3774804

  • Dramatic reduction of dimensionality in large biochemical networks owing to strong pair correlations JOURNAL OF THE ROYAL SOCIETY INTERFACE Dworkin, M., Mukherjee, S., Jayaprakash, C., Das, J. 2012; 9 (73): 1824-1835

    Abstract

    Large multi-dimensionality of high-throughput datasets pertaining to cell signalling and gene regulation renders it difficult to extract mechanisms underlying the complex kinetics involving various biochemical compounds (e.g. proteins and lipids). Data-driven models often circumvent this difficulty by using pair correlations of the protein expression levels to produce a small number (fewer than 10) of principal components, each a linear combination of the concentrations, to successfully model how cells respond to different stimuli. However, it is not understood if this reduction is specific to a particular biological system or to nature of the stimuli used in these experiments. We study temporal changes in pair correlations, described by the covariance matrix, between concentrations of different molecular species that evolve following deterministic mass-action kinetics in large biologically relevant reaction networks and show that this dramatic reduction of dimensions (from hundreds to less than five) arises from the strong correlations between different species at any time and is insensitive to the form of the nonlinear interactions, network architecture, and to a wide range of values of rate constants and concentrations. We relate temporal changes in the eigenvalue spectrum of the covariance matrix to low-dimensional, local changes in directions of the system trajectory embedded in much larger dimensions using elementary differential geometry. We illustrate how to extract biologically relevant insights such as identifying significant timescales and groups of correlated chemical species from our analysis. Our work provides for the first time, to our knowledge, a theoretical underpinning for the successful experimental analysis and points to a way to extract mechanisms from large-scale high-throughput datasets.

    View details for DOI 10.1098/rsif.2011.0896

    View details for Web of Science ID 000305810200012

    View details for PubMedID 22378749

    View details for PubMedCentralID PMC3385761

  • Competing positive and negative feedbacks mediated by PH domain ligand interactions regulate Itk activation kinetics in T Cells Das, J., Mukherjee, S., Rigaud, S., Seok, S., Fu, G., Prochenka, A., Dworkin, M., Gascoigne, N., Vieland, V., Sauer, K. AMER ASSOC IMMUNOLOGISTS. 2012
  • Extracting Mechanistic Insight from Large Biochemical Networks via Statistical Analysis Dworkin, M., Mukherjee, S., Jayaprakash, C., Das, J. CELL PRESS. 2011: 166