Yufan (Fred) Wu

All Publications

• Clinical LINAC-based electron FLASH: Pathway for practical translation to FLASH clinical trials: LINAC electron FLASH. International journal of radiation oncology, biology, physics No, H. J., Wu, Y. F., Dworkin, M. L., Manjappa, R., Skinner, L., Ashraf, M. R., Lau, B., Melemenidis, S., Viswanathan, V., Yu, A. S., Surucu, M., Schüler, E., Graves, E. E., Maxim, P. G., Loo, B. W. 2023

  Abstract

  Ultra-high dose rate (UHDR) radiotherapy (RT) has produced the FLASH effect in preclinical models: reduced toxicity with comparable tumor control compared to conventional dose rate RT. Early clinical trials focused on UHDR RT feasibility using specialized devices. We explore the technical feasibility of practical electron UHDR RT on a standard clinical linear accelerator (LINAC).We tuned the program board of a decommissioned electron energy for UHDR electron delivery on a clinical LINAC, without hardware modification. Pulse delivery was controlled using the respiratory gating interface. A short SSD electron set-up with a standard scattering foil was configured and tested on an anthropomorphic phantom using circular blocks with 3-20 cm field sizes. Dosimetry was evaluated using radiochromic film and an ion chamber profiler.UHDR open field mean dose rates at 100, 80, 70, and 59 cm SSD were 36.82, 59.52, 82.01, and 112.83 Gy/s, respectively. At 80 cm SSD, mean dose rate was ∼60 Gy/s for all collimated field sizes, with an R80 depth of 6.1 cm corresponding to an energy of 17.5 MeV. Heterogeneity was <5.0% with asymmetry of 2.2 to 6.2%. The short SSD set-up was feasible under realistic treatment conditions simulating broad clinical indications on an anthropomorphic phantom.Short SSD and tuning for high electron beam current on a standard clinical LINAC can deliver flat, homogenous UHDR electrons over a broad, clinically relevant range of field sizes and depths with practical working distances, in a configuration easily reversible to standard clinical use.

  View details for DOI 10.1016/j.ijrobp.2023.04.011

  View details for PubMedID 37105403

• Dosimetric Predictors of Local Control after Stereotactic Ablative Radiotherapy (SABR) for Lung Tumors: A Secondary Analysis of a Phase II Prospective Trial of Individualized SABR (iSABR) Wu, Y., Lau, B., Fu, J., Skinner, L., Gensheimer, M., Gee, H., Diehn, M., Loo, B., Chin, A., Vitzthum, L. LIPPINCOTT WILLIAMS & WILKINS. 2022: S16

  View details for Web of Science ID 000847787800034

• Sarcopenia and Abdominal Fat Distribution Are Prognostic for Overall Survival in Patients with Unresectable Pancreatic Cancer Undergoing Stereotactic Body Radiotherapy Wu, Y., Nwachukwu, C., Toesca, D., Liu, Y., Koong, A., von Eyben, R., Koong, A., Chang, D. LIPPINCOTT WILLIAMS & WILKINS. 2021: S58

  View details for Web of Science ID 000701779700097

• Pulmonary Hemorrhage in Patients Treated with Thoracic Stereotactic Ablative Radiotherapy and Anti-Angiogenic Agents. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Lau, B., Wu, Y. F., No, H. J., Ko, R. B., Devine, M., Das, M. S., Neal, J. W., Wakelee, H. A., Ramchandran, K., Gensheimer, M. F., Diehn, M., Chin, A. L., Loo, B. W., Vitzthum, L. K. 2023

  Abstract

  Severe pulmonary hemorrhage can occur in patients treated with thoracic stereotactic ablative radiotherapy (SABR) and vascular endothelial growth factor inhibitors (VEGFi). There is limited understanding of which patients are at risk for toxicity with the combination of thoracic SABR and VEGFis or how the risk differs over either therapy alone.We evaluated a prospectively maintained cohort of 690 patients with 818 pulmonary tumors treated with highly conformal SABR. Rates of any grade and grade-three-plus (G3+) pulmonary hemorrhage were compared between patients treated with or without VEGFi therapy across tumor locations. Outcomes were compared between patients treated with SABR + VEGFi and a propensity-matched cohort of those treated with VEGFi therapy alone.Treatment with VEGFi + SABR was associated with higher rates of G3+ pulmonary hemorrhage compared to those treated with SABR alone for the overall cohort (3-year incidence: 7.9% vs 0.6%, p<0.01) and those with central tumors (19.1% vs 3.3%, p=0.04). When further subdivided, there were significantly higher toxicity rates with VEGFi for the ultracentral (9.0% vs 45.0%, p = 0.044), but not central non-abutting tumors (0.0% vs 1.3% p = 0.69). There was an increased incidence of G3+ hemorrhage in patients treated with VEGFi + SABR compared to VEGFi alone (9.6 vs 1.3%, p=0.04).The combination of VEGFi and SABR was associated with an increased risk of high-grade pulmonary hemorrhage over either therapy alone. Low rates of toxicity were observed when excluding patients with SABR to ultracentral tumors and applying highly conformal SABR techniques.

  View details for DOI 10.1016/j.jtho.2023.04.007

  View details for PubMedID 37085030

• Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma. Cureus Hui, C., Wu, Y. F., Liu, K., Sandhu, N., Blomain, E., Binkley, M. S., Gephart, M. H., Chang, S. D., Li, G. H., Reddy, S. A., Soltys, S. G., Pollom, E. 2022; 14 (11): e31838

  Abstract

  Purpose/Objectives Combination BRAF (vemurafenib, dabrafenib, or encorafenib) plus MEK (trametinib, cobimetinib, or binimetinib) inhibitor therapy is now widely used in the treatment of metastatic melanoma. However, data for intracranial response to these drugs are limited. We aimed to evaluate the intracranial efficacy of BRAF plus MEK inhibitors in patients with BRAF-mutant melanoma with brain metastases (BM) and to determine patterns of failure of these new agents to inform optimal integration of local intracranial therapy. Materials and methods We retrospectively reviewed charts of patients with BRAF-mutant melanoma with metastasis to the brain with at least one untreated brain metastasis at the time of initiation of BRAF plus MEK inhibitors at our institution from 2006 to 2020. We collected per-patient and per-lesion data on demographics, treatment modality, and outcomes. The cumulative incidence of local (LF), distant intracranial (DF), and extracranial failure (EF) were calculated with competing risk analysis with death as a competing risk and censored at the last brain MRI follow-up. LF was calculated on a per-lesion basis while DF and EF were calculated on a per-patient basis. DF was defined as any new intracranial lesions. Overall survival (OS) was analyzed using Kaplan-Meier. Logistic regression was used to identify predictors for LF. Results We identified 10 patients with 63 untreated brain metastases. The median age was 50.5 years. The median sum of the diameters of the five largest untreated brain metastases per patient was 20 mm (interquartile range 15-39 mm) and the median diameter for all measurable lesions was 4 mm. Median follow-up time was 9.0 months (range 1.4 months-46.2 months). Median OS was 13.6 months. The one-year cumulative incidence of LF, DF, and EF was 17.1%, 88.6, and 71.4%, respectively. The median time to LF, DF, and EF from the start of BRAF plus MEK inhibitors was 9.0 months, 4.7 months, and 7.0 months, respectively. The larger size of the BM was associated with LF on univariate analysis (odds ratio 1.13 per 1 mm increase in diameter, 95% confidence interval 1.019 to 1.308, p<0.02). Two (20%) patients eventually received stereotactic radiosurgery, and 2 (20%) received whole-brain radiotherapy for intracranial progression. Conclusion Although patients with BRAF-mutant melanoma with BM had fair local control on BRAF plus MEK inhibitors, the competing risk of death and distant intracranial and extracranial progression was high. Patients with larger brain metastases may benefit from local therapy.

  View details for DOI 10.7759/cureus.31838

  View details for PubMedID 36579260

  View details for PubMedCentralID PMC9788920

• Measures of Body Composition Obtainable from a Computed Tomography Scan Are Predictive of Overall Survival in Patients with Unresectable Pancreatic Cancer Undergoing Stereotactic Body Radiotherapy Wu, Y., Nwachukwu, C., Toesca, D., Liu, Y., Koong, A., Von Eyben, R., Koong, A., Chang, D. LIPPINCOTT WILLIAMS & WILKINS. 2022: S3-S4

  View details for Web of Science ID 000847787800011

• Design and validation of a dosimetric comparison scheme tailored for ultra-high dose-rate electron beams to support multicenter FLASH preclinical studies. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Gonçalves Jorge, P., Melemenidis, S., Grilj, V., Buchillier, T., Manjappa, R., Viswanathan, V., Gondré, M., Vozenin, M. C., Germond, J. F., Bochud, F., Moeckli, R., Limoli, C., Skinner, L., Joshua No, H., Fred Wu, Y., Surucu, M., Yu, A. S., Lau, B., Wang, J., Schüler, E., Bush, K., Graves, E. E., Maxim, P. G., Loo, B. W., Bailat, C. 2022

  Abstract

  We describe a multicenter cross validation of ultra-high dose rate (UHDR) (>= 40 Gy/s) irradiation in order to bring a dosimetric consensus in absorbed dose to water. UHDR refers to dose rates over 100-1000 times those of conventional clinical beams. UHDR irradiations have been a topic of intense investigation as they have been reported to induce the FLASH effect in which normal tissues exhibit reduced toxicity relative to conventional dose rates. The need to establish optimal beam parameters capable of achieving the in vivo FLASH effect has become paramount. It is therefore necessary to validate and replicate dosimetry across multiple sites conducting UHDR studies with distinct beam configurations and experimental set-ups.Using a custom cuboid phantom with a cylindrical cavity (5 mm diameter by 10.4 mm length) designed to contain three type of dosimeters (thermoluminescent dosimeters (TLDs), alanine pellets, and Gafchromic films), irradiations were conducted at expected doses of 7.5 to 16 Gy delivered at UHDR or conventional dose rates using various electron beams at the Radiation Oncology Departments of the CHUV in Lausanne, Switzerland and Stanford University, CA.Data obtained between replicate experiments for all dosimeters were in excellent agreement (+/- 3 %). In general, films and TLDs were in closer agreement with each other, while alanine provided the closest match between the expected and measured dose, with certain caveats related to absolute reference dose.In conclusion, successful cross-validation of different electron beams operating under different energies and configurations lays the foundation for establishing dosimetric consensus for UHDR irradiation studies, and, if widely implemented, decrease uncertainty between different sites investigating the mechanistic basis of the FLASH effect.

  View details for DOI 10.1016/j.radonc.2022.08.023

  View details for PubMedID 36030934

• A Randomized Split-Body Feasibility Trial of Single-Fraction FLASH Vs Conventional Electron Radiotherapy Using a Standard Clinical Linear Accelerator for Adults with Multilesional Primary Cutaneous Lymphomas Physica Medica Dworkin, M. L., No, H. J., Wu, Y. F., Binkley, M., Rieger, K., Graves, E., Barcellos-Hoff, M., von Eyben, R., Ashraf, R., Manjappa, R., Yu, A., Skinner, L., Surucu, M., Kim, Y., Loo, B., Hoppe, R. 2022: S94-S95

  View details for DOI 10.1016/S1120-1797(22)01654-4

• A Six Minute Brachytherapy Waste Audit: A Feasible, Efficient Method for Identifying Opportunities to Enhance the Environmental Sustainability of a Radiation Oncology Department Practices American Brachytherapy Society (ABS) Annual Meeting Baniel, C., Lichter, K., Frick, M., Oladipo, E., Wu, Y., Blomain, E., Chan, J., Lee, M., Kimball, E., Singer, L., Kidd, E., Buyyounouski, M., Mohamad, O., Bagshaw, H. 2022
• Implementing Environmentally Sustainable Practices in an Outpatient Oncology Clinic Vizient Connections Summit Frick, M., Baniel, C., Blomain, E., Yu, A., Skinner, L., Chin, A., Oladipo, E., Wu, Y., Shieh, L., Bagshaw, H. 2022
• FLASH Radiation Therapy Principles, Technology, and Clinical Translation American Association of Medical Dosimetrists 47th Meeting Wu, Y., No, H., Loo, B., et al 2022
• FLASH Radiation Therapy Principles, Technology, and Clinical Translation American Association of Medical Dosimetrists Fall Virtual Symposium Wu, Y., No, H., Breitkreutz, D., Mascia, A., Moeckli, R., Bourhis, J., Schuler, E., Maxim, P., Loo, B. 2022
• Chest Wall Toxicity after Individualized Stereotactic Ablative Radiotherapy for Lung Tumors IASLC World Conference on Lung Cancer Lau, B., Wu, Y., Fu, J., Cui, S., Pham, D., Gee, H., Skinner, L., Shirato, H., Taguchi, H., Chin, A., Gensheimer, M., Diehn, M., Loo, B., Vitzthum, L. 2022
• Dosimetric predictors of local control after SABR for lung tumors: a secondary analysis of a phase II prospective trial of individualized SABR American Radium Society (ARS) Annual Meeting Wu, Y., Lau, B., Fu, J., Skinner, L., Gensheimer, M., Gee, H., Diehn, M., Loo, B., Chin, A., Vitzthum, L. 2022
• Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma Cureus Hui, C., Wu, Y., et al 2022; 14 (11)

  View details for DOI 10.7759/cureus.31838

• Pulmonary Hemorrhage in Patients Treated With Thoracic Stereotactic Ablative Radiotherapy and Anti-Angiogenic Agents Lau, B., No, H. J., Wu, Y. F., Ko, R. B., Devine, M., Das, M., Neal, J. W., Ramchandran, K. J., Wakelee, H. A., Shaheen, S., Diehn, M., Chin, A. L., Loo, B. W., Vitzthum, L. ELSEVIER SCIENCE INC. 2021: E423

  View details for Web of Science ID 000715803800868

• Feasibility of Clinically Practical Ultra-High Dose Rate (FLASH) Radiation Delivery by a Reversible Configuration of a Standard Clinical-Use Linear Accelerator No, H. J., Wu, Y. F., Manjappa, R., Skinner, L., Lau, B., Melemenidis, S., Yu, S. J., Surucu, M., Schueler, E., Bush, K., Graves, E. E., Maxim, P. G., Loo, B. W. ELSEVIER SCIENCE INC. 2021: S32

  View details for Web of Science ID 000715803801402

• Validation of a Novel Cone-Less Set-up for Electron FLASH Radiation Delivery on a Clinical-Use Linear Accelerator Wu, Y. F., No, H. J., Manjappa, R., Skinner, L., Yu, S. J., Lau, B., Surucu, M., Schueler, E., Bush, K., Graves, E. E., Maxim, P. G., Loo, B. W. ELSEVIER SCIENCE INC. 2021: S139

  View details for Web of Science ID 000715803801616

• Intracranial Response to Combination BRAF and MEK Inhibitor Therapy in Patients with Metastatic Melanoma Hui, C., Wu, Y., Liu, K., Sandhu, N., Blomain, E., Binkley, M., Gephart, M., Chang, S., Li, G., Reddy, S., Gibbs, I., Soltys, S., Pollom, E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S48-S49

  View details for Web of Science ID 000701779700077

• Pulmonary Hemorrhage in Patients Treated with Thoracic Stereotactic Ablative Radiotherapy and Anti-Angiogenic Agents Lau, B., No, H., (Fred) Wu, Y., Devine, M., Ko, R., Loo, B., Diehn, M., Chin, A., Vitzthum, L. LIPPINCOTT WILLIAMS & WILKINS. 2021: S105

  View details for Web of Science ID 000701779700169

• Radiation Therapy for Primary Cutaneous Gamma Delta Lymphoma Prior to Stem Cell Transplantation. Cancer investigation Wu, Y. F., Skinner, L., Lewis, J., Khodadoust, M. S., Kim, Y. H., Kwong, B. Y., Weng, W., Hoppe, R. T., Sodji, Q., Hui, C., Kastelowitz, N., Fernandez-Pol, S., Hiniker, S. M. 2021: 1–11

  Abstract

  We present a patient with widespread PCGD-TCL of the bilateral arms and legs, who underwent radiotherapy with 34Gy in 17 fractions using circumferential VMAT and 3-D printed bolus to the 4 extremities prior to planned stem cell transplant, who was then found to have progression in the liver, lung, and skin, followed by drastic regression of all in and out-of-field lesions on imaging 1.5months later. The cause of regression may be related to a radiation-induced abscopal effect from the immunomodulatory effects of radiation, or related to immune reactivation in the setting of cessation of systemic immunosuppressive agents.

  View details for DOI 10.1080/07357907.2021.1919696

  View details for PubMedID 33899635

• Technological Basis for Clinical Trials in FLASH Radiation Therapy: A Review Applied Radiation Oncology Wu, Y., No, H. J., Breitkreutz, D. Y., Mascia, A. E., Moeckli, R., Bourhis, J., Schüler, E., Maxim, P. G., Loo Jr., B. W. 2021; 10 (2): 6-14
• A Lung Mass that Vanishes Journal of Hospital Medicine (2020 Virtual Competition) Crawford, D. L., Wu, Y. F., Peng, F. B., Musher, D. M. 2020
• The impact of postoperative therapy on primary cardiac sarcoma. The Journal of thoracic and cardiovascular surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018; 156 (6): 2194-2203

  Abstract

  Primary cardiac sarcomas (PCS) are extremely rare, portend a very poor prognosis, and have limited outcomes data to direct management. This study evaluated the impact of postoperative chemotherapy and/or radiotherapy on survival for PCS.A retrospective chart review was conducted of 12 patients diagnosed with and who underwent resection for PCS at a single institution between 2000 and 2016. Data were collected on patient/tumor characteristics and analyzed with respect to treatment and outcome using Kaplan-Meier methods.Median age was 43 (range 21-73 years) with a 50:50 male-to-female ratio. The most common subtype was angiosarcoma (42%), and 25% presented with distant metastases (DMs). The initial treatment modality for all patients was surgery, with 58% having macroscopically positive (R2) margins. In total, 75% received postoperative chemotherapy and/or radiotherapy. Median progression-free survival (PFS) was 5.9 months, and median overall survival (OS) was 12.0 months. Achieving negative or microscopically positive margins (R0/R1) as compared with R2 resection significantly improved PFS (12.6 vs 2.7 months, P = .008) and OS (21.8 vs 7.2 months, P = .006). DM at presentation demonstrated a significantly shorter OS (7.0 vs 16.9 months, P = .04) and PFS (0.7 vs 7.9 months, P = .003) compared with localized disease. Patients given postoperative therapy had longer OS compared with surgery only, but this difference was not statistically significant (15.5 vs 2.6 months, P = .12).Gross total surgical resection can significantly improve PFS and OS in PCS, but DM at diagnosis is an extremely poor prognostic sign. Postoperative therapy should be considered, although this study was likely underpowered to demonstrate a statistically significant benefit.

  View details for DOI 10.1016/j.jtcvs.2018.04.127

  View details for PubMedID 30454911

• Worsening of Child-Pugh Score after Stereotactic Body Radiation Therapy Significantly Impacts Survival of Patients Treated for Hepatocellular Carcinoma Toesca, D. S., Wu, Y., Koong, A., Von Eyben, R., Osmundson, E. C., Shaffer, J., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2018: E64

  View details for DOI 10.1016/j.ijrobp.2018.07.498

  View details for Web of Science ID 000447811600149

• The Impact of Post-Operative Therapy on Primary Cardiac Sarcoma The Journal of Thoracic and Cardiovascular Surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018

  View details for DOI 10.1016/j.jtcvs.2018.04.127

• Patient-Centered Care Challenges and Surprises: Through the Clerkship Students' Eyes. Family medicine Boggiano, V. L., Wu, Y., Bruce, J. S., Merrell, S. B., Schillinger, E. 2017; 49 (1): 57-61

  Abstract

  The patient-centered care model for health care delivery encourages medical providers to respect patients' preferences and give patients more autonomy over their health care decisions. This approach has gained importance within US medical school curricula. Yet, little is known about student perspectives on both patient-centered care and the benefits and challenges that lie therein. This manuscript explores the greatest impediments to, as well as the benefits from, student engagement in patient-centered care from the perspectives of students participating in their family medicine outpatient clerkship.Clerkship students on their core family medicine clerkship at Stanford University School of Medicine were provided the following open-ended prompt: "Describe a patient-centered care challenge or surprise in the family medicine core clerkship." Free-text responses were collected and analyzed using content and thematic analysis.A total of 326 responses from 216 students were analyzed for frequency and patient-centered themes. Nine final themes emerged and were grouped into three domains: student definitions of patient-centered care, patient-centered care impact on patients, and patient-centered care impact on medical professionals.Our study suggests that students find the patient-centered care model for health care delivery to be challenging but worthwhile. We highlight that students find communication with patients in a patient-centered manner challenging and discuss the need for improved medical education about patient-centered care in order to better prepare students to implement the model in a variety of psychosocial and medical contexts.

  View details for PubMedID 28166582

• Patient-Centered Care Challenges and Surprises FAMILY MEDICINE Boggiano, V. L., Wu, Y., Bruce, J. S., Merrell, S. B., Schillinger, E. 2017; 49 (1): 57-61

  Abstract

  The patient-centered care model for health care delivery encourages medical providers to respect patients' preferences and give patients more autonomy over their health care decisions. This approach has gained importance within US medical school curricula. Yet, little is known about student perspectives on both patient-centered care and the benefits and challenges that lie therein. This manuscript explores the greatest impediments to, as well as the benefits from, student engagement in patient-centered care from the perspectives of students participating in their family medicine outpatient clerkship.Clerkship students on their core family medicine clerkship at Stanford University School of Medicine were provided the following open-ended prompt: "Describe a patient-centered care challenge or surprise in the family medicine core clerkship." Free-text responses were collected and analyzed using content and thematic analysis.A total of 326 responses from 216 students were analyzed for frequency and patient-centered themes. Nine final themes emerged and were grouped into three domains: student definitions of patient-centered care, patient-centered care impact on patients, and patient-centered care impact on medical professionals.Our study suggests that students find the patient-centered care model for health care delivery to be challenging but worthwhile. We highlight that students find communication with patients in a patient-centered manner challenging and discuss the need for improved medical education about patient-centered care in order to better prepare students to implement the model in a variety of psychosocial and medical contexts.

  View details for Web of Science ID 000397087700010

• Predictors of Toxicity Associated With Stereotactic Body Radiation Therapy to the Central Hepatobiliary Tract INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Osmundson, E. C., Wu, Y., Luxton, G., Bazan, J. G., Koong, A. C., Chang, D. T. 2015; 91 (5): 986-994

  Abstract

  To identify dosimetric predictors of hepatobiliary (HB) toxicity associated with stereotactic body radiation therapy (SBRT) for liver tumors.We retrospectively reviewed 96 patients treated with SBRT for primary (53%) or metastatic (47%) liver tumors between March 2006 and November 2013. The central HB tract (cHBT) was defined by a 15-mm expansion of the portal vein from the splenic confluence to the first bifurcation of left and right portal veins. Patients were censored for toxicity upon local progression or additional liver-directed therapy. HB toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0. To compare different SBRT fractionations, doses were converted to biologically effective doses (BED) by using the standard linear quadratic model α/β = 10 (BED10).Median follow-up was 12.7 months after SBRT. Median BED10 was 85.5 Gy (range: 37.5-151.2). The median number of fractions was 5 (range: 1-5), with 51 patients (53.1%) receiving 5 fractions and 29 patients (30.2%) receiving 3 fractions. In total, there were 23 (24.0%) grade 2+ and 18 (18.8%) grade 3+ HB toxicities. Nondosimetric factors predictive of grade 3+ HB toxicity included cholangiocarcinoma (CCA) histology (P<.0001), primary liver tumor (P=.0087), and biliary stent (P<.0001). Dosimetric parameters most predictive of grade 3+ HB toxicity were volume receiving above BED10 of 72 Gy (VBED1072) ≥ 21 cm(3) (relative risk [RR]: 11.6, P<.0001), VBED1066 ≥ 24 cm(3) (RR: 10.5, P<.0001), and mean BED10 (DmeanBED10) cHBT ≥14 Gy (RR: 9.2, P<.0001), with VBED1072 and VBED1066 corresponding to V40 and V37.7 for 5 fractions and V33.8 and V32.0 for 3 fractions, respectively. VBED1072 ≥ 21 cm(3), VBED1066 ≥ 24 cm(3), and DmeanBED10 cHBT ≥14 Gy were consistently predictive of grade 3+ toxicity on multivariate analysis.VBED1072, VBED1066, and DmeanBED10 to cHBT are associated with HB toxicity. We suggest VBED1072 < 21 cm(3) (5-fraction: V40 < 21 cm(3); 3-fraction: V33.8 < 21 cm(3)), VBED1066 < 24 cm(3) (5-fraction: V37.7 < 24 cm(3); 3-fraction: V32 < 24 cm(3)) as potential dose constraints for the cHBT when clinically indicated.

  View details for DOI 10.1016/j.ijrobp.2014.11.028

  View details for PubMedID 25659885

• Dosimetric Modeling of Central Liver Toxicity After SBRT to the Liver 56th Annual Meeting of the American-Society-for-Radiation-Oncology Osmundson, E., Wu, Y., Bazan, J. G., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2014: S382–S382

  View details for Web of Science ID 000342331401326

• Statin-associated Autoimmune Myopathies: A Pathophysiologic Spectrum CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES Wu, Y., Lach, B., Provias, J. P., Tarnopolsky, M. A., Baker, S. K. 2014; 41 (5): 638-647

  Abstract

  Statins have recently been reported to cause a rare autoimmune inflammatory and/or necrotic myopathy that begins or persists after drug cessation.We report on 26 patients seen at a neuromuscular centre between 2005 and 2011 who demonstrated muscle weakness/myalgias and creatine kinase elevations during or after statin treatment with continuation of signs and symptoms despite statin withdrawal.All patients were treated with immunosuppressive therapy with good response; all improved biochemically and 86% improved clinically. Sixty-five percent of patients who attempted to taper off immunosuppressive therapy relapsed. We report on a novel finding whereby five of the seven patients who underwent multiple biopsies throughout their disease demonstrated a transformation of their histological diagnosis, with four progressing from having myofibre necrosis with minimal or no inflammation to a diagnosis of polymyositis.This study offers preliminary evidence that statin-associated necrotizing myopathy and statin-associated polymyositis may not be separate entities but are part of the same pathophysiological spectrum. Both entities respond well to immunosuppression.

  View details for DOI 10.1017/cjn.2014.22

  View details for Web of Science ID 000347654100016

  View details for PubMedID 25373816

• Practice-Based Challenges and Improvement Opportunities: Clerkship Students’ Perceptions Western Group on Educational Affairs Regional Conference Wu, Y., Boggiano, V., Bereknyei, S., Bruce, J., Rydel, T., Schillinger, E. 2014
• Six novel mutations in the myophosphorylase gene in patients with McArdle disease and a family with pseudo-dominant inheritance pattern MOLECULAR GENETICS AND METABOLISM Wu, Y., Weber, J. L., Vladutiu, G. D., Tarnopolsky, M. A. 2011; 104 (4): 587-591

  Abstract

  McArdle disease is an autosomal recessive glycogenosis due to deficiency of the enzyme myophosphorylase. It results from homozygous or compound heterozygous mutations in the gene for this enzyme, PYGM. We report six novel mutations in the PYGM gene based upon sequencing data including three missense mutations (p.D51G, p.P398L, and p.N648Y), one nonsense mutation (p.Y75X), one frame-shift mutation (p.Y114SfsX181), and one amino acid deletion (p.Y53del) in six patients with McArdle disease. We also report on a Caucasian family that appeared to transmit McArdle disease in an autosomal dominant manner. In order to evaluate the potential pathogenicity of the sequence variants, we performed in silico analysis using PolyPhen-2 and SIFT BLink, along with species conservation analysis using UCSC Genome Browser. The above mutations were all predicted to be disease associated with high probability and with at least the same level of certainty as several confirmed mutations. The current data add to the list of pathogenic mutations in the PYGM gene associated with McArdle disease.

  View details for DOI 10.1016/j.ymgme.2011.08.012

  View details for Web of Science ID 000298021400023

  View details for PubMedID 21880526

• Age-Related Effects of Diet-Induced Obesity on Skeletal Muscle Regeneration Ontario Exercise Physiology Conference Trajcevski, K., Wang, D., Wu, Y., Hawke, T. 2011