Bio


I am a physician with post-graduate residency training in Radiation Oncology completed at University of São Paulo (USP), Brazil, in 2015. After a short period as Assistant Professor, I came to the United States to pursue a Postdoctoral Clinical Research Fellowship at the Department of Radiation Oncology, Stanford University. Since July 2015 I have had the opportunity to be mentored by Professor Albert Koong on clinical and translational research, and currently by Professor Daniel Chang, Vice-Chair of the Department of Radiation Oncology, with whom I have participated in clinical activities and conducted research with a special focus on SBRT efficacy and toxicity for treatment of liver and pancreatic tumors.

Honors & Awards


  • Investigator-Initiated Research Grant - Varian Research Collaborations Program, Varian Medical Systems Inc. (2017-2018)
  • Caywood Investigator Fund for Pancreatic Cancer, Stanford Cancer Institute, Division of Gastrointestinal Oncology (2016-2018)

Boards, Advisory Committees, Professional Organizations


  • Member-in-training, American Society of Radiation Oncology (2015 - Present)

Professional Education


  • Radiation Oncology Residency, University of São Paulo (2015)
  • General Surgery Residency, SES - São Paulo (2010)
  • Doctor of Medicine, Federal University of Mato Grosso do Sul (2007)

Stanford Advisors


Current Research and Scholarly Interests


Clinical and translational research in GI oncology. Development of projects focused on liver and pancreatic cancer, with a special interest on stereotactic body radiotherapy (SBRT) data, including imaging, treatment planning, treatment response, toxicity prediction and overall outcomes.

Lab Affiliations


  • Albert Ching-Wei Koong, Koong Lab (7/1/2015 - 6/30/2017)

All Publications


  • Strategies for prediction and mitigation of radiation-induced liver toxicity. Journal of radiation research Toesca, D. A., Ibragimov, B., Koong, A. J., Xing, L., Koong, A. C., Chang, D. T. 2018

    Abstract

    Although well described in the 1960s, liver toxicity secondary to radiation therapy, commonly known as radiation-induced liver disease (RILD), remains a major challenge. RILD encompasses two distinct clinical entities, a 'classic' form, composed of anicteric hepatomegaly, ascites and elevated alkaline phosphatase; and a 'non-classic' form, with liver transaminases elevated to more than five times the reference value, or worsening of liver metabolic function represented as an increase of 2 or more points in the Child-Pugh score classification. The risk of occurrence of RILD has historically limited the applicability of radiation for the treatment of liver malignancies. With the development of 3D conformal radiation therapy, which allowed for partial organ irradiation based on computed tomography treatment planning, there has been a resurgence of interest in the use of liver irradiation. Since then, a large body of evidence regarding the liver tolerance to conventionally fractionated radiation has been produced, but severe liver toxicities has continued to be reported. More recently, improvements in diagnostic imaging, radiation treatment planning technology and delivery systems have prompted the development of stereotactic body radiotherapy (SBRT), by which high doses of radiation can be delivered with high target accuracy and a steep dose gradient at the tumor - normal tissue interface, offering an opportunity of decreasing toxicity rates while improving tumor control. Here, we present an overview of the role SBRT has played in the management of liver tumors, addressing the challenges and opportunities to reduce the incidence of RILD, such as adaptive approaches and machine-learning-based predictive models.

    View details for DOI 10.1093/jrr/rrx104

    View details for PubMedID 29432550

  • Management of Borderline Resectable Pancreatic Cancer. International journal of radiation oncology, biology, physics Toesca, D. A., Koong, A. J., Poultsides, G. A., Visser, B. C., Haraldsdottir, S., Koong, A. C., Chang, D. T. 2018; 100 (5): 1155–74

    Abstract

    With the rapid development of imaging modalities and surgical techniques, the clinical entity representing tumors that are intermediate between resectable and unresectable pancreatic adenocarcinoma has been identified has been termed "borderline resectable" (BR). These tumors are generally amenable for resection but portend an increased risk for positive margins after surgery and commonly necessitate vascular resection and reconstruction. Although there is a lack of consensus regarding the appropriate definition of what constitutes a BR pancreatic tumor, it has been demonstrated that this intermediate category carries a particular prognosis that is in between resectable and unresectable disease. In order to downstage the tumor and increase the probability of clear surgical margins, neoadjuvant therapy is being increasingly utilized and studied. There is a lack of high-level evidence to establish the optimal treatment regimen for BR tumors. When resection with negative margins is achieved after neoadjuvant therapy, the prognosis for BR tumors approaches and even exceeds that for resectable disease. This review presents the current definitions, different treatment approaches, and the clinical outcomes of BR pancreatic cancer.

    View details for DOI 10.1016/j.ijrobp.2017.12.287

    View details for PubMedID 29722658

  • Assessment of hepatic function decline after stereotactic body radiation therapy for primary liver cancer. Practical radiation oncology Toesca, D. A., Osmundson, E. C., von Eyben, R., Shaffer, J. L., Koong, A. C., Chang, D. T. 2017; 7 (3): 173-182

    Abstract

    This study aims to determine how the albumin-bilirubin (ALBI) score compares with the Child-Pugh (CP) score for assessing liver function following stereotactic body radiation therapy (SBRT).In total, 60 patients, 40 with hepatocellular carcinoma (HCC) and 20 with cholangiocarcinoma (CCA), were treated with SBRT. Liver function panels were obtained before and at 1, 3, 6, and 12 months after SBRT. Laboratory values were censored after locoregional recurrence, further liver-directed therapies, or liver transplant.A significant decline in hepatic function occurred after SBRT for HCC patients only (P = .001 by ALBI score; P < .0001 by CP score). By converting radiation doses to biologically equivalent doses by using a standard linear quadratic model using α/β of 10, the strongest dosimetric predictor of liver function decline for HCC was the volume of normal liver irradiated by a dose of 40 Gy when assessing liver function by the ALBI score (P = .07), and the volume of normal liver irradiated by a dose of 20 Gy by using the CP score (P= .0009). For CCA patients, the volume of normal liver irradiated by a dose of 40 Gy remained the strongest dosimetric predictor when using the ALBI score (P = .002), but no dosimetric predictor was significant using the CP score. Hepatic function decline correlated with worse overall survival for HCC (by ALBI, P = .0005; by CP, P < .0001) and for CCA (by ALBI, P = NS; by CP, P = .008).ALBI score was similarly able to predict hepatic function decline compared with CP score, and both systems correlated with survival.

    View details for DOI 10.1016/j.prro.2016.10.003

    View details for PubMedID 28343896

  • Central liver toxicity after SBRT: An expanded analysis and predictive nomogram. Radiotherapy and oncology Toesca, D. A., Osmundson, E. C., Eyben, R. v., Shaffer, J. L., Lu, P., Koong, A. C., Chang, D. T. 2017; 122 (1): 130-136

    Abstract

    To further explore the correlation of central biliary tract (cHBT) radiation doses with hepatobiliary toxicity (HBT) after stereotactic body radiation therapy (SBRT) in a larger patient dataset.We reviewed the treatment and outcomes of all patients who received SBRT for primary liver cancer (PLC) and metastatic liver tumors between July 2004 and November 2015 at our institution. The cHBT was defined as isotropic expansions (5, 10, 15, 20 and 25mm) from the portal vein (PV). Doses were converted to biologically effective doses by using the standard linear quadratic model with α/β of 10 (BED10). HBT was graded according to the Common Terminology Criteria for Adverse Events v4.03.Median follow-up was 13months. Out of the 130 patients with complete follow-up records analyzed, 60 (46.1%) had liver metastases, 40 (30.8%) had hepatocellular carcinoma (HCC), 26 (20%) had cholangiocarcinoma (CCA) and 4 (3.1%) patients other PLC histologies. Thirty-three (25.4%) grade 2+ and 28 (21.5%) grade 3+ HBT were observed. Grade 3+ HBT was seen in 13 patients (50%) with CCA, 7 patients (17.5%) with HCC and 7 (11.7%) patients with liver metastases. SBRT doses to the cHBT were highly associated with HBT, but only for PLC patients when analyzed by histological subtype. The 15mm expansion from the PV (cHBT15) proved to be an appropriate surrogate for the cHBT. The strongest cHBT15 dose predictors for G3+ HBT for PLC were the VBED1040⩾37cc (p<0.0001) and the VBED1030⩾45cc (p<0.0001).SBRT doses to the cHBT are associated with occurrence of HBT only in PLC patients. Limiting the dose to the cHBT to VBED1040<37cc and VBED1030<45cc when treating PLC patients with SBRT may reduce the risk of HBT.

    View details for DOI 10.1016/j.radonc.2016.10.024

    View details for PubMedID 27865544

  • Prediction of pancreatic cancer surgical outcomes and prognosis based on an objective resectability scoring system 2018 Gastrointestinal Cancers Sysmposium (GI-ASCO) Toesca, D. A., Jeffrey, B., von Eyben, R., Poullos, P. D., Poultsides, G. A., Fisher, G. A., Visser, B. C., Koong, A. C., Chang, D. T. : 446
  • Can looking at density differences between liver parenchyma and oligometastatic lesions predict outcomes and toxicities in patients receiving stereotactic body radiation therapy for metastatectomy? 2018 Gastrointestinal Cancers Symposium (GI-ASCO) Jin, W., Toesca, D. A., Osmundson, E., Shaffer, J. L., Koong, A. C., Chang, D. T. : 479
  • Reirradiation with stereotactic body radiation therapy after prior conventional fractionation radiation for locally recurrent pancreatic adenocarcinoma. Advances in radiation oncology Koong, A. J., Toesca, D. A., von Eyben, R., Pollom, E. L., Chang, D. T. ; 2 (1): 27–36

    Abstract

    Locally recurrent pancreatic cancer after prior radiotherapy is a therapeutic challenge with limited treatment options. This study examines the safety and efficacy of stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma after prior conventional fractionation radiotherapy (CRT).Outcomes from all patients treated with SBRT for locally recurrent pancreatic adenocarcinoma after prior CRT at our institution were reviewed. A total of 23 patients were identified. Prior CRT median dose was 50.4 Gy (range, 30-60 Gy). Twelve patients (52%) had previously undergone surgery and received CRT as neo- or adjuvant treatment. Nine patients (39.1%) were reirradiated with SBRT with a dose of 25 Gy in a single fraction, and 14 patients (60.8%) received a 5-fraction SBRT schedule with a median dose of 25 Gy (range, 20-33 Gy) in 5 fractions (1-5 fractions).Median follow-up time was 28 months (range, 9-77 months). The median planning target volume was 46 cm(3) (range, 14-89 cm(3)). Median overall survival from diagnosis and from reirradiation were 27.5 months (range, 10-77 months) and 8.5 months (range, 1 month to not reached) respectively. The cumulative incidence of local failures at the last follow-up was 19%. For the 4 patients who presented with local failure, one was treated with a single fraction of 25 Gy, and the other 3 were treated with 25 Gy in 5 fractions. Three patients presented regional failure, with a cumulative incidence of 14%, all with concurrent distant progression. The cumulative incidence of distant progression was 64% at last follow-up. After reirradiation, 6 patients (26.1%) developed a grade 2 or 3 gastrointestinal toxicity, 4 of them occurring among patients treated with a single-fraction SBRT regimen.Our report shows that SBRT for reirradiation of locally recurrent pancreas adenocarcinoma is a feasible option with good local control and acceptable toxicity rates, especially with a multifraction schedule.

    View details for DOI 10.1016/j.adro.2017.01.003

    View details for PubMedID 28740913

    View details for PubMedCentralID PMC5514250

  • Outcomes after Stereotactic Body Radiotherapy for Treatment of Hepatocellular Carcinoma 59th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Toesca, D. A., Osmundson, E., Shaffer, J., von Eyben, R., Koong, A. C., Chang, D. T. : E192–E193
  • Efficacy and Safety of Stereotactic Body Radiation Therapy for Treatment of Inoperable Intrahepatic and Perihilar Cholangiocarcinoma 59th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Toesca, D. A., Osmundson, E., Shaffer, J., von Eyben, R., Koong, A. C., Chang, D. T. : E192
  • The Impact of Chemotherapy Regimen and Radiation Dose of Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Adenocarcinoma 59th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Toesca, D. A., Pollom, E. L., von Eyben, R., Koong, A. C., Chang, D. T. : E193
  • Deep Learning-Based Autosegmentation of Portal Vein for Prediction of Central Liver Toxicity After SBRT 59th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Ibragimov, B., Toesca, D. A., Chang, D. T., Koong, A. C., Xing, L. : E672
  • Resectable and Borderline Resectable Pancreatic Cancer Gastrointestinal Malignancies - A Practical Guide on Treatment Techniques Toesca, D. A., Chang, D. T., Kim, E., Herman, J., Koong, A. C., Russo, S. Springer International Publishing. 2018; 1: 199–229
  • A Human Genome-wide RNAi Screen Reveals Diverse Modulators that Mediate IRE1α-XBP1 Activation. Molecular cancer research : MCR Yang, Z., Zhang, J., Jiang, D., Khatri, P., Solow-Cordero, D. E., Toesca, D. A., Koumenis, C., Denko, N. C., Giaccia, A. J., Le, Q. T., Koong, A. C. 2018

    Abstract

    Activation of the unfolded protein response (UPR) signaling pathways is linked to multiple human diseases including cancer. The inositol-requiring kinase 1 (IRE1)-X-box binding protein 1 (XBP1) pathway is the most evolutionarily conserved of the three major signaling branches of the UPR. Here, we performed a genome-wide siRNA screen to obtain a systematic assessment of genes integrated in the IRE1-XBP1 axis. We monitored the expression of an XBP1-luciferase chimeric protein in which luciferase was fused in-frame with the spliced (active) form of XBP1. Using cells expressing this reporter construct, we identified 162 genes for which siRNA inhibition resulted in alteration in XBP1 splicing. These genes express diverse types of proteins modulating a wide range of cellular processes. Pathway analysis identified a set of genes implicated in the pathogenesis of breast cancer. Several genes including BCL10, GCLM, and IGF1R correlated with worse relapse-free survival (RFS) in an analysis of patients with triple negative breast cancer (TNBC). However, in this cohort of 1908 patients, only high GCLM expression correlated with worse RFS in both TNBC and non-TNBC patients. Altogether, our study revealed unidentified roles of novel pathways regulating the UPR and these findings may serve as a paradigm for exploring novel therapeutic opportunities based on modulating the UPR.Genome-wide RNAi screen identifies novel genes/pathways that modulate IRE1-XBP1 signaling in human tumor cells and leads to the development of improved therapeutic approaches targeting the UPR.

    View details for DOI 10.1158/1541-7786.MCR-17-0307

    View details for PubMedID 29440447

  • Assessing local progression after stereotactic body radiation therapy for unresectable pancreatic adenocarcinoma: CT versus PET. Practical radiation oncology Toesca, D. A., Pollom, E. L., Poullos, P. D., Flynt, L., Cui, Y., Quon, A., von Eyben, R., Koong, A. C., Chang, D. T. 2017; 7 (2): 120-125

    Abstract

    Evaluation of local tumor progression (LP) has typically been defined by contrast-enhanced computed tomography (CT) imaging after stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (PDAC). The purpose of this study is to determine the benefit of adding 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging to CT for LP assessment of PDAC after SBRT.We retrospectively reviewed pretreatment, follow-up images, and outcomes of all patients treated with definitive SBRT for unresectable PDAC between December 2002 and December 2015 at our institution. For each patient, we independently analyzed LP both by CT and by FDG-PET criteria, using the Response Evaluation Criteria In Solid Tumors version 1.1 and the FDG-PET Response Evaluation Criteria In Solid Tumors version 1.0, respectively.Among 206 patients treated with definitive SBRT for unresectable PDAC, we identified 30 with LP on follow-up. Four did not undergo follow-up FDG-PET. Median time to LP after SBRT was 7.5 months (range, 2-25 months). Of the 26 patients with LP who had follow-up FDG-PET, 21 were diagnosed by FDG-PET (80.7%), 14 by CT (53.8%), and 9 by both FDG-PET and CT (34.6%). Use of CT alone revealed only 53.8% of cases of LP detected when FDG-PET and CT were combined. The cumulative incidence of LP, based on competing risk of death, at 1 and 2 years after SBRT was 9.6% and 16.7% by CT and 11% and 29.1% by FDG-PET, respectively.FDG-PET increases the chance of detecting LP of unresectable PDAC after SBRT and can have an important impact on reported outcomes. We recommend obtaining FDG-PET to assess treatment response when evaluating efficacy of SBRT and taking its use into account when comparing clinical data.

    View details for DOI 10.1016/j.prro.2016.09.002

    View details for PubMedID 28274396

  • Nonoperative Management of Rectal Cancer: A Modern Perspective. Oncology (Williston Park, N.Y.) Qian, Y., Chin, A. L., Toesca, D. A., Koong, A. C., Chang, D. T. 2017; 31 (10): e13–e22

    Abstract

    Nonoperative management of rectal cancer is an emerging treatment approach that aims to enable carefully selected patients to avoid the morbidity of radical surgical resection, while benefiting from the same excellent rates of tumor control achieved with radical surgery-based combined-modality therapy. The success of nonoperative management in this setting is based on the accurate assessment of tumor eradication after chemoradiotherapy, without pathologic verification. Therefore, clinical evidence of complete response-based on physical examination, endoscopic procedures, and imaging-must be utilized as a marker to predict for pathologic complete response and thus help select the patients who are most appropriate for nonoperative management. Initial evidence from retrospective and prospective single-arm and cohort studies has demonstrated high rates of local control and disease-free survival with nonoperative management of rectal cancer, compared with historical results of combined-modality therapy. Several trials and registries are prospectively investigating nonoperative management vs standard treatment of rectal cancer. At this time, combined-modality therapy with total mesorectal excision remains the standard of care for patients with locally advanced rectal cancer; nonoperative management should not be routinely offered outside of clinical trials.

    View details for PubMedID 29083469

  • Combining deep learning with anatomy analysis for segmentation of portal vein for liver SBRT planning. Physics in medicine and biology Ibragimov, B., Toesca, D., Chang, D., Koong, A., Xing, L. 2017

    Abstract

    Automated segmentation of portal vein (PV) for liver radiotherapy planning is a challenging task due to potentially low vasculature contrast, complex PV anatomy and image artifacts originated from fiducial markers and vasculature stents. In this paper, we propose a novel framework for automated PV segmentation from computed tomography (CT) images. We apply convolutional neural networks (CNN) to learn consistent appearance patterns of PV using a training set of CT images with reference annotations and then enhance PV in previously unseen CT images. Markov Random Fields (MRF) were further used to smooth the CNN enhancement results and remove isolated mis-segmented regions. Finally, CNN-MRF-based enhancement was augmented with PV centerline detection that was based on PV anatomical properties such as tubularity and branch composition. The framework was validated on a clinical database with 72 CT images of patients scheduled to liver stereotactic body radiation therapy. The obtained segmentation accuracy was DSC = 0.83 and η = 1.08 in terms of the median Dice coefficient and mean symmetric surface distance, respectively, when segmentation is encompassed into the PV region of interest. The obtained results indicate that CNN can be used for accurate segmentation of PV and potentially integrated into liver radiation therapy planning.

    View details for DOI 10.1088/1361-6560/aa9262

    View details for PubMedID 28994665

  • Increased Visceral to Subcutaneous Fat Ratio Is Associated With Decreased Overall Survival in Pancreatic Cancer 58th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Nwachukwu, C. R., Toesca, D. A., Liu, Y., Koong, A., von Eyben, R., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2016: E220–E220
  • Hepatobiliary Toxicity Association With Central Biliary Tract Dose After Stereotactic Body Radiation Therapy: An Expanded Analysis 58th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Toesca, D. A., Osmundson, E., Shaffer, J., von Eyben, R., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2016: S141–S142
  • Reirradiation With Stereotactic Body Radiation Therapy After Prior Conventional Fractionation Radiation for Locally Recurrent Pancreatic Adenocarcinoma 58th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Toesca, D. A., Pollom, E., Nwachukwu, C. R., von Eyben, R., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2016: E205–E205
  • Stereotactic Body Radiation Therapy After Surgical Resection for Locally Recurrent Pancreatic Adenocarcinoma 58th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Nwachukwu, C. R., Toesca, D. A., Pollom, E., von Eyben, R., Chang, D. T., Koong, A. C. ELSEVIER SCIENCE INC. 2016: E158–E158
  • The Impact of FDG Positron Emission Tomography for Assessment of Local Progression of Unresectable Pancreatic Adenocarcinoma After Stereotactic Body Radiation Therapy 58th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Toesca, D. A., Pollom, E., Nwachukwu, C. R., von Eyben, R., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2016: E205–E205
  • Assessment of Hepatic Function Decline After Stereotactic Body Radiation Therapy for Primary Liver Tumors Using the Albumin-Bilirubin (ALBI) Score 58th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Toesca, D. A., Osmundson, E., Shaffer, J., von Eyben, R., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2016: E203–E204