Charles Chia-Chuen Hsu

Interests

Research

Clinical and research interests focus on thoracic, cutaneous, and gastrointestinal malignancies, stereotactic body radiotherapy, HDR brachytherapy, novel radiosensitizers, development of novel imaging modalities in assessing/predicting treatment response, immunotherapy / immune system function for tumors, treatment of oligometastatic disease, re-irradiation, cancer epidemiology, clinical trials, improving quality of life for patients, and outcomes research.

Teaching

Teaching interests focus on radiation oncology, epidemiology, public health, quality of life for cancer patients, and palliative care.

Courses

Scholarly Contributions

Journals/Publications

• Yi, S. K., Wang, S. J., Robbins, J. R., Julian, R., Hsu, C. C., Groysman, M., Bearelly, S., Bauman, J. E., & Baker, A. (2022). The impact of socioeconomic and geographic factors on access to transoral robotic/endoscopic surgery for early stage oropharyngeal malignancy.. American journal of otolaryngology, 43(1), 103243. doi:10.1016/j.amjoto.2021.103243
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  To evaluate the role of social and geographic factors on the likelihood of receiving transoral robotic surgery (TORS) or non-robotic transoral endoscopic surgery treatment in early stage oropharyngeal squamous cell carcinoma (OPSCC)..The National Cancer Database was queried to form a cohort of patients with T1-T2 N0-N1 M0 OPSCC (AJCC v.7) who underwent treatment from 2010 to 2016. Demographics, tumor characteristics, treatment type, social, and geographic factors were all collected. Univariate analysis and multivariate logistic regression were then performed..Among 9267 identified patients, 1774 (19.1%) received transoral robotic surgery (TORS), 1191 (12.9%) received transoral endoscopic surgery, and 6302 (68%) received radiation therapy. We found that lower cancer stage, lower comorbidity burden and HPV- positive status predicted a statistically significant increased likelihood of receiving surgery. Patients who reside in suburban or small urban areas (>1 million population), were low-to- middle income, or rely on Medicaid were less likely to receive surgery. Patients that reside in Medicaid-expansion states were more likely to receive TORS (p > .0001). Patients that reside in states that expanded Medicaid January 2014 and after were more likely to receive non-robotic transoral endoscopic surgery (p > .0001)..Poorer baseline health, lower socioeconomic status and residence in small urban areas may act as barriers to accessing minimally invasive transoral surgery while residence in a Medicaid-expansion state may improve access. Barriers to accessing robotic surgery may be greater than accessing non-robotic surgery.
• Goyal, U. D., Riegert, K., Davuluri, R., Ong, S., Yi, S. K., Dougherty, S. T., & Hsu, C. C. (2020). Prospective Study of Use of Edmonton Symptom Assessment Scale Versus Routine Symptom Management During Weekly Radiation Treatment Visits. JCO oncology practice, 16(9), e1029-e1035.
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  During radiotherapy (RT), patient symptoms are evaluated and managed weekly during physician on-treatment visits (OTVs). The Edmonton Symptom Assessment Scale (ESAS) is a 9-symptom validated self-assessment tool for reporting common symptoms in patients with cancer. We hypothesized that implementation and physician review of ESAS during weekly OTVs may result in betterment of symptom severity during RT for certain modifiable domains.
• Robbins, J. R., Robbins, J. R., Hsu, C. C., & Hirshberg, J. (2020). Abstract C001: Palliative radiation to bony metastases from GI tumors: Disparities, outcomes, and practice patterns. Cancer Epidemiology, Biomarkers & Prevention. doi:10.1158/1538-7755.disp19-c001
• Sawyer, D. M., Sawyer, T. W., Eshghi, N., Hsu, C., Hamilton, R. J., Garland, L. L., & Kuo, P. H. (2020). Pilot Study: Texture analysis of PET imaging demonstrates changes in F-FDG uptake of the brain after prophylactic cranial irradiation. Journal of nuclear medicine technology.
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  Prophylactic cranial irradiation (PCI) is used to decrease the probability of developing brain metastases in patients with small cell lung cancer and has been linked to deleterious cognitive effects. While no well-established imaging markers for these effects exist, previous studies have shown that structural and metabolic changes of the brain can be detected with magnetic resonance imaging and positron emission tomography (PET). This study utilized an image processing technique called texture analysis to explore whether global changes in brain glucose metabolism could be characterized in PET images. F-FDG PET images of the brain from patients with small cell lung cancer, obtained before and after the administration of PCI, were processed using texture analysis. Texture features were compared between the pre- and post-PCI images. Multiple texture features demonstrated statistically significant differences before and after PCI, when texture analysis was applied to the brain parenchyma as a whole. Regional differences were also seen but were not statistically significant. Global changes in brain glucose metabolism occur after PCI and are detectable using advanced image processing techniques. These changes may reflect radiation-induced damage and thus may provide a novel method for studying radiation-induced cognitive impairment.
• Han, J. E., Yi, S. K., Wang, S., Erman, A., Bearelly, S., Sindhu, S., Robbins, J. R., Bauman, J., & Hsu, C. C. (2019). Neoadjuvant chemotherapy improves survival compared with concurrent chemoradiation alone in nasopharyngeal carcinoma patients with N3 disease. Head & neck, 41(12), 4076-4087.
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  Neoadjuvant chemotherapy (NAC) trials in endemic regions of nasopharyngeal carcinoma (NPC) found improved survival, but studies are lacking in nonendemic regions. We assessed whether adding NAC to concurrent chemoradiation (CRT) improves overall survival (OS), especially in high-risk nonendemic patients.
• Kim, S., Bull, D. A., Garland, L., Khalpey, Z., Stea, B., Yi, S., & Hsu, C. C. (2019). Is There a Role for Cancer-Directed Surgery in Early-Stage Sarcomatoid or Biphasic Mesothelioma?. The Annals of thoracic surgery, 107(1), 194-201.
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  Benefits of surgical resection for early-stage nonepithelioid malignant pleural mesothelioma (MPM) have not been clearly elucidated. This study investigated whether cancer-directed surgery affects overall survival compared with nonsurgical therapies for T1-T2 N0 M0 sarcomatoid or biphasic MPM patients.
• Eshghi, N., Garland, L. L., Choudhary, G., Hsu, C. C., Eshghi, A., Han, J., Hamilton, R. J., Krupinski, E., & Kuo, P. H. (2018). Regional Changes in Brain F-FDG Uptake After Prophylactic Cranial Irradiation and Chemotherapy in Small Cell Lung Cancer May Reflect Functional Changes. Journal of nuclear medicine technology, 46(4), 355-358.
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  Chemotherapy followed by prophylactic cranial irradiation (PCI) is associated with increased survival in patients with small cell lung cancer but is associated with fatigue and cognitive impairment. This retrospective study evaluated regional differences in F-FDG uptake by the brain before and after PCI. The null hypothesis was that direct toxic effects on the brain from PCI and chemotherapy are symmetric; thus, asymmetric deviations may reflect functional changes due to therapy. Electronic medical records from 2013 to 2016 were reviewed for patients with small cell lung cancer, MRI of brain negative for metastasis, and F-FDG PET/CT scans before and after PCI. As the standard of care, patients received first-line chemotherapy or chemoradiation to the thorax followed by PCI. The F-FDG PET/CT scans nearest the PCI were selected. Sixteen patients met these initial criteria. Commercially available PET software was used to register and subtract the PET scans before and after PCI to obtain difference maps. Occipital and cerebellar regions were excluded from the final statistical analysis given the known high variability and misregistration. The χ test was used to analyze the data. Two patients had F-FDG uptake differences only in the occipital and cerebellar regions. The software registration failed on 1 patient's scans. Therefore, 13 patients were included in the final analysis. Nine of 13 patients demonstrated significant unilateral changes in only 1 region of the brain, and 3 of 13 showed significant changes unilaterally in 2 regions. The χ test revealed a significant unilateral regional difference on a patient level (χ = 6.24, = 0.025). The most commonly affected brain region was the frontal lobe. Significantly more patients had unilateral than bilateral regional differences (both increases and decreases) in F-FDG uptake in the brain before and after PCI. This finding suggests that differences in unilateral distribution are related to functional changes, since direct toxicity alone from PCI and chemotherapy would be symmetric. The frontal region was the most commonly affected, suggesting a potential contributing etiology for cognitive impairment and decreased executive function after therapy.
• Fang, P., Jiang, W., Davuluri, R., Xu, C., Krishnan, S., Mohan, R., Koong, A. C., Hsu, C. C., & Lin, S. H. (2018). High lymphocyte count during neoadjuvant chemoradiotherapy is associated with improved pathologic complete response in esophageal cancer. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 128(3), 584-590.
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  Neoadjuvant chemoradiation (nCRT) can reduce tumor infiltrating lymphocytes. We examined absolute lymphocyte count (ALC) nadir during nCRT for esophageal cancer (EC) and pathologic complete response (pCR).
• Herman, J. M., Jabbour, S. K., Lin, S. H., Deek, M. P., Hsu, C. C., Fishman, E. K., Kim, S., Cameron, J. L., Chekmareva, M., Laheru, D. A., Narang, A. K., Pawlik, T. M., Hruban, R. H., Wolfgang, C. L., & Iacobuzio-Donahue, C. A. (2018). Smad4 Loss Correlates With Higher Rates of Local and Distant Failure in Pancreatic Adenocarcinoma Patients Receiving Adjuvant Chemoradiation. Pancreas, 47(2), 208-212.
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  The tumor suppressor gene SMAD4 (DPC4) is genetically inactivated in approximately half of pancreatic ductal adenocarcinomas (PDAs). We examined whether Smad4 tumor status was associated with outcomes after adjuvant chemoradiation (CRT) for resected PDAs.
• Hsu, C., Yi, S. K., Stea, B., Khalpey, Z. I., Garland, L. L., Bull, D. A., Kim, S. S., Hsu, C., Yi, S. K., Stea, B., Khalpey, Z. I., Garland, L. L., Bull, D. A., & Kim, S. S. (2018). Is there a role for cancer directed surgery in early stage sarcomatoid or biphasic mesothelioma. Ann Thorac Surg. doi:10.1016/j.athoracsur.2018.07.081
• Okunieff, P., Casey-Sawicki, K., Lockney, N. A., Hoppe, B. S., Enderling, H., Pinnix, C., Welsh, J., Krishnan, S., Yothers, G., Brown, M., Knox, S., Bristow, R., Spellman, P., Mitin, T., Nabavizadeh, N., Jaboin, J., Manning, H. C., Feng, F., Galbraith, S., , Solanki, A. A., et al. (2018). Report from the SWOG Radiation Oncology Committee: Research Objectives Workshop 2017. Clinical cancer research : an official journal of the American Association for Cancer Research, 24(15), 3500-3509.
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  The Radiation Therapy Committee of SWOG periodically evaluates its strategic plan in an effort to maintain a current and relevant scientific focus, and to provide a standard platform for future development of protocol concepts. Participants in the 2017 Strategic Planning Workshop included leaders in cancer basic sciences, molecular theragnostics, pharmaceutical and technology industries, clinical trial design, oncology practice, and statistical analysis. The committee discussed high-priority research areas, such as optimization of combined modality therapy, radiation oncology-specific drug design, identification of molecular profiles predictive of radiation-induced local or distant tumor responses, and methods for normal tissue-specific mitigation of radiation toxicity. The following concepts emerged as dominant questions ready for national testing: (i) what is the role of radiotherapy in the treatment of oligometastatic, oligorecurrent, and oligoprogressive disease? (ii) How can combined modality therapy be used to enhance systemic and local response? (iii) Can we validate and optimize liquid biopsy and other biomarkers (such as novel imaging) to supplement current response criteria to guide therapy and clinical trial design endpoints? (iv) How can we overcome deficiencies of randomized survival endpoint trials in an era of increasing molecular stratification factors? And (v) how can we mitigate treatment-related side effects and maximize quality of life in cancer survivors? The committee concluded that many aspects of these questions are ready for clinical evaluation and example protocol concepts are provided that could improve rates of cancer cure and quality of survival. .
• Rao, A. D., Liu, Y., von Eyben, R., Hsu, C. C., Hu, C., Rosati, L. M., Parekh, A., Ng, K., Hacker-Prietz, A., Zheng, L., Pawlik, T. M., Laheru, D. A., Jaffee, E. M., Weiss, M. J., Le, D. T., Hruban, R. H., De Jesus-Acosta, A., Wolfgang, C. L., Narang, A. K., , Chang, D. T., et al. (2018). Multiplex Proximity Ligation Assay to Identify Potential Prognostic Biomarkers for Improved Survival in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy. International journal of radiation oncology, biology, physics, 100(2), 486-489.
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  To explore seromarker levels for associations with outcomes in locally advanced pancreatic cancer (LAPC) patients who received chemotherapy and stereotactic body radiation therapy (SBRT).
• Stea, B., Skrepnik, T., Hsu, C. C., & Abendroth, R. (2018). The role of radiation therapy in the treatment of metastatic cancer. Clinical & experimental metastasis, 35(5-6), 535-546.
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  Radiation therapy continues to play an important role in the management of cancer. In this review, we discuss the use of radiation therapy to target and control micrometastatic disease (adjuvant use of radiation), or using stereotactic radiation therapy to address small volumes of gross disease, such as oligometastases, and finally the use of radiation therapy in the era of immunotherapy. Radiation therapy is commonly used to treat nodal basins suspected of harboring microscopic disease. More recently, computer and technical innovations have allowed radiation oncologists to treat small volumes of gross disease within the brain and also in the body with great success, adding to the cancer armamentarium. This modality of cancer treatment that began shortly after the discovery of X-rays by William Roentgen continues to evolve and finds new clinical applications which minimize toxicity while increasing effectiveness. The newly discovered interactions of high dose/fraction radiation (stereotactic radiosurgery) with immune check point inhibitors in melanoma is the latest example of how synergism can be achieved between two different modalities thus increasing the therapeutic ratio to control metastatic cancer.
• Yom, S. S., Schwartz, G. K., Salama, J. K., Munster, P. N., Luke, J. J., Kozloff, M., Hsu, C. C., Chmura, S. J., Allred, J. B., & Al-hallaq, H. A. (2018). A randomized phase II study of anti-PD1 antibody [MK-3475 (Pembrolizumab)] alone versus anti-PD1 antibody plus stereotactic body radiation therapy in advanced merkel cell carcinoma (Alliance A091605).. Journal of Clinical Oncology, 36(15_suppl), TPS9599-TPS9599. doi:10.1200/jco.2018.36.15_suppl.tps9599
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  TPS9599Background: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy associated with ultraviolet light exposure, advanced age and infection with the Merkel cell polyomavirus (MCP). Histori...
• Davuluri, R., Jiang, W., Fang, P., Xu, C., Komaki, R., Gomez, D. R., Welsh, J., Cox, J. D., Crane, C. H., Hsu, C. C., & Lin, S. H. (2017). Lymphocyte Nadir and Esophageal Cancer Survival Outcomes After Chemoradiation Therapy. International journal of radiation oncology, biology, physics, 99(1), 128-135.
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  Host immunity may affect the outcome in patients with esophageal cancer. We sought to identify factors that influenced absolute lymphocyte count (ALC) nadir during chemoradiation therapy (CRT) for esophageal cancer (EC) and looked for clinically relevant associations with survival.
• Jones, K. M., Stuehm, C. A., Hsu, C. C., Kuo, P. H., Pagel, M. D., & Randtke, E. A. (2017). Imaging Lung Cancer by Using Chemical Exchange Saturation Transfer MRI With Retrospective Respiration Gating. Tomography (Ann Arbor, Mich.), 3(4), 201-210.
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  Performing chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) in lung tissue is difficult because of motion artifacts. We, therefore, developed a CEST MRI acquisition and analysis method that performs retrospective respiration gating. Our method used an acquisition scheme with a short 200-millisecond saturation pulse that can accommodate the timing of the breathing cycle, and with saturation applied at frequencies in 0.03-ppm intervals. The Fourier transform of each image was used to calculate the difference in phase angle between adjacent pixels in the longitudinal direction of the respiratory motion. Additional digital filtering techniques were used to evaluate the breathing cycle, which was used to construct CEST spectra from images during quiescent periods. Results from CEST MRI with and without respiration gating analysis were used to evaluate the asymmetry of the magnetization transfer ratio (MTR), a measure of CEST, for an egg white phantom that underwent cyclic motion, in the liver of healthy patients, as well as liver and tumor tissues of patients diagnosed with lung cancer. Retrospective respiration gating analysis produced more precise measurements in all cases with significant motion compared with nongated analysis methods. Finally, a preliminary clinical study with the same respiration-gated CEST MRI method showed a large increase in MTR after radiation therapy, a small increase or decrease in MTR after chemotherapy, and mixed results with combined chemoradiation therapy. Therefore, our retrospective respiration-gated method can improve CEST MRI evaluations of tumors and organs that are affected by respiratory motion.
• Kim, S. S., Khalpey, Z., Hsu, C., & Little, A. G. (2017). Changes in Tracheostomy- and Intubation-Related Tracheal Stenosis: Implications for Surgery. The Annals of thoracic surgery, 104(3), 964-970.
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  This study sought to identify the changing characteristic patterns and locations of stenosis after tracheostomy or intubation and to assess the risk factors associated with perioperative complication and restenosis after primary resection and reconstruction.
• Davuluri, R., Jiang, W., Fang, P., Xu, C., Komaki, R. U., Lin, S. H., Welsh, J. W., Cox, J. D., Crane, C. H., & Hsu, C. C. (2016). Absolute Lymphocyte Count Nadir During Chemoradiation as a Prognostic Indicator of Esophageal Cancer Survival Outcomes. International Journal of Radiation Oncology*Biology*Physics.
• Davuluri, R., Krase, J. M., Cui, H., Goyal, U. D., Cheung, M. K., Hsu, C. C., & Yi, S. K. (2016). Image guided volumetric response during chemoradiotherapy for head and neck squamous cell carcinoma as a predictor of disease outcomes. American journal of otolaryngology, 37(4), 304-10.
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  The goal of this study was to correlate volumetric image guided disease response to clinical outcomes in patients receiving chemoradiation therapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC).
• Hsu, C. C., Paciorek, A. T., Cooperberg, M. R., Roach, M., Hsu, I. J., & Carroll, P. R. (2015). Postoperative radiation therapy for patients at high-risk of recurrence after radical prostatectomy: does timing matter?. BJU international, 116(5), 713-20.
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  To evaluate among radical prostatectomy (RP) patients at high-risk of recurrence whether the timing of postoperative radiation therapy (RT) (adjuvant, early salvage with detectable post-RP prostate-specific antigen [PSA], or 'late' salvage with a PSA level of >1.0 ng/mL) is significantly associated with overall survival (OS), prostate-cancer specific survival or metastasis-free survival, in a longitudinal cohort.
• Moningi, S., Walker, A. J., Hsu, C. C., Reese, J. B., Wang, J., Fan, K. Y., Rosati, L. M., Laheru, D. A., Weiss, M. J., Wolfgang, C. L., Pawlik, T. M., & Herman, J. M. (2015). Correlation of clinical stage and performance status with quality of life in patients seen in a pancreas multidisciplinary clinic. Journal of oncology practice / American Society of Clinical Oncology, 11(2), e216-21.
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  The objectives of this study were to evaluate quality of life (QoL) in patients presenting to the Johns Hopkins Pancreas Multidisciplinary Clinic (PMDC), and to examine associations between disease status, performance status, and QoL in order to identify patient subgroups that are most at risk for reduced QoL.
• Wang, J., Narang, A. K., Sugar, E. A., Luber, B., Rosati, L. M., Hsu, C. C., Fuller, C. D., Pawlik, T. M., Miller, R. C., Czito, B. G., Tuli, R., Crane, C. H., Ben-Josef, E., Thomas, C. R., & Herman, J. M. (2015). Evaluation of Adjuvant Radiation Therapy for Resected Gallbladder Carcinoma: A Multi-institutional Experience. Annals of surgical oncology, 22 Suppl 3, 1100-6.
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  The role of adjuvant radiation for gallbladder carcinoma (GBC) is uncertain. We combine the experience of six National Cancer Institute-designated cancer centers to explore the impact of adjuvant radiation following oncologic resection of GBC.
• Crehange, G., Izaguirre, A., Weinberg, V., Hsu, C. C., Gottschalk, A. R., Hsu, I., Shinohara, K., Carroll, P., & Roach, M. (2014). Long-term Outcomes Following Radiation Therapy For Prostate Cancer Patients With Lymph Node Metastases at Diagnosis Treated With and Without Surgery. American journal of clinical oncology.
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  To evaluate the long-term outcomes for prostate cancer (PCa) patients with lymph node involvement (LNI) treated with radiotherapy at the University of California San Francisco.
• Fan, K. Y., Dholakia, A. S., Wild, A. T., Su, Z., Hacker-Prietz, A., Kumar, R., Hodgin, M., Hsu, C. C., Le, D. T., De Jesus-Acosta, A., Diaz, L. A., Laheru, D. A., Hruban, R. H., Fishman, E. K., Brown, T. D., Pawlik, T. M., Wolfgang, C. L., Tran, P. T., & Herman, J. M. (2014). Baseline hemoglobin-A1c impacts clinical outcomes in patients with pancreatic cancer. Journal of the National Comprehensive Cancer Network : JNCCN, 12(1), 50-7.
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  An association between diabetes mellitus and pancreatic ductal adenocarcinoma (PDA) has long been recognized. This article assesses the effect of the baseline hemoglobin-A1c (HbA1c) value on the clinical outcomes of patients with PDA. HbA1c values were prospectively collected on 656 consecutive patients presenting to a pancreas multidisciplinary cancer clinic from 2009 to 2012. Patients were diagnosed with benign pancreatic disease (BPD) or biopsy-confirmed resectable (R), borderline/locally advanced (BL), or metastatic (M) PDA. Excluded were those with prior treatment for PDA or a history of chronic diabetes mellitus (>1-year or unknown duration), resulting in a final cohort of 284 patients. Of 284 patients, 44 had benign disease, 62 had R-PDA, 115 had BL-PDA, and 63 had M-PDA. Patients with malignant disease (R-, BL-, and M-PDA) collectively had a higher average HbA1c value than patients with BPD (6.1% vs 5.6%; P
• Hsu, C. C., Hsu, H., Pickett, B., Crehange, G., Hsu, I. J., Dea, R., Weinberg, V., Gottschalk, A. R., Kurhanewicz, J., Shinohara, K., & Roach, M. (2013). Feasibility of MR imaging/MR spectroscopy-planned focal partial salvage permanent prostate implant (PPI) for localized recurrence after initial PPI for prostate cancer. International journal of radiation oncology, biology, physics, 85(2), 370-7.
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  To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease.
• Créhange, G., Chen, C. P., Hsu, C. C., Kased, N., Coakley, F. V., Kurhanewicz, J., & Roach, M. (2012). Management of prostate cancer patients with lymph node involvement: a rapidly evolving paradigm. Cancer treatment reviews, 38(8), 956-67.
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  Although widespread PSA screening has inevitably led to increased diagnosis of lower risk prostate cancer, the number of patients with nodal involvement at baseline remains high (nearly 40% of high risk patients initially staged cN0). These rates probably do not reflect the true incidence of prostate cancer with lymph node involvement among patients selected for external beam radiotherapy (EBRT), as patients selected for surgery often have more favorable prognostic features. At many institutions, radical treatment directed only at the prostate is considered standard and patients known to have regional disease are often managed palliatively with androgen deprivation therapy (ADT) for presumed systemic disease. New imaging tools such as MR lymphangiography, choline-based PET imaging or combined SPECT/CT now allow surgeons and radiation oncologists to identify and target nodal metastasis and/or lymph nodes with a high risk of occult involvement. Recent advances in the field of surgery including the advent of extended nodal dissection and sentinel node procedures have suggested that cancer-specific survival might be improved for lymph-node positive patients with a low burden of nodal involvement when managed with aggressive interventions. These new imaging tools can provide radiation oncologists with maps to guide delivery of high dose conformal radiation to a target volume while minimizing radiation toxicity to non-target normal tissue. This review highlights advances in imaging and reports how they may help to define a new paradigm to manage node-positive prostate cancer patients with a curative-intent.
• Hsu, C. C., Wolfgang, C. L., Laheru, D. A., Pawlik, T. M., Swartz, M. J., Winter, J. M., Robinson, R., Edil, B. H., Narang, A. K., Choti, M. A., Hruban, R. H., Cameron, J. L., Schulick, R. D., & Herman, J. M. (2012). Early mortality risk score: identification of poor outcomes following upfront surgery for resectable pancreatic cancer. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 16(4), 753-61.
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  Identifying pancreatic cancer patients at high risk of early mortality following pancreaticoduodenectomy (PD) is important for treatment decisions in a multidisciplinary setting. This study examines the preoperative predictors of early mortality following PD and combines these variables into an early mortality risk score (EMRS).
• Horowitz, D. P., Hsu, C. C., Wang, J., Makary, M. A., Winter, J. M., Robinson, R., Schulick, R. D., Cameron, J. L., Pawlik, T. M., & Herman, J. M. (2011). Adjuvant chemoradiation therapy after pancreaticoduodenectomy in elderly patients with pancreatic adenocarcinoma. International journal of radiation oncology, biology, physics, 80(5), 1391-7.
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  To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients ≥ 75 years of age.
• Hsu, C. C., Kao, W. L., Steffes, M. W., Gambir, T., Brancati, F. L., Heilig, C. W., Shuldiner, A. R., Boerwinkle, E. A., & Coresh, J. (2011). Genetic variation of glucose transporter-1 (GLUT1) and albuminuria in 10,278 European Americans and African Americans: a case-control study in the Atherosclerosis Risk in Communities (ARIC) study. BMC medical genetics, 12, 16.
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  Evidence suggests glucose transporter-1 (GLUT1) genetic variation affects diabetic nephropathy and albuminuria. Our aim was to evaluate associations with albuminuria of six GLUT1 single nucleotide polymorphisms(SNPs), particularly XbaI and the previously associated Enhancer-2 (Enh2) SNP.
• Narang, A. K., Miller, R. C., Hsu, C. C., Bhatia, S., Pawlik, T. M., Laheru, D., Hruban, R. H., Zhou, J., Winter, J. M., Haddock, M. G., Donohue, J. H., Schulick, R. D., Wolfgang, C. L., Cameron, J. L., & Herman, J. M. (2011). Evaluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Radiation oncology (London, England), 6, 126.
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  The role of adjuvant chemoradiation therapy for ampullary carcinoma is unknown. Previous literature suggests that certain populations with high risk factors for recurrence may benefit from adjuvant chemoradiation. We combined the experience of two institutions to better delineate which patients may benefit from adjuvant chemoradiation.
• Seo, Y., Aparici, C. M., Chen, C. P., Hsu, C., Kased, N., Schreck, C., Costouros, N., Hawkins, R., Shinohara, K., & Roach Iii, M. (2011). Mapping of lymphatic drainage from the prostate using filtered 99mTc-sulfur nanocolloid and SPECT/CT. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 52(7), 1068-72.
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  We have developed a practice procedure for prostate lymphoscintigraphy using SPECT/CT and filtered (99m)Tc-sulfur nanocolloid, as an alternative to the proprietary product (99m)Tc-Nanocoll, which is not approved in the United States.
• Hsu, C. C., Herman, J. M., Corsini, M. M., Winter, J. M., Callister, M. D., Haddock, M. G., Cameron, J. L., Pawlik, T. M., Schulick, R. D., Wolfgang, C. L., Laheru, D. A., Farnell, M. B., Swartz, M. J., Gunderson, L. L., & Miller, R. C. (2010). Adjuvant chemoradiation for pancreatic adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Annals of surgical oncology, 17(4), 981-90.
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  Survival for pancreatic ductal adenocarcinoma is low, the role of adjuvant therapy remains controversial, and recent data suggest adjuvant chemoradiation (CRT) may decrease survival compared with surgery alone. Our goal was to examine efficacy of adjuvant CRT in resected pancreatic adenocarcinoma compared with surgery alone.
• Swartz, M. J., Hsu, C. C., Pawlik, T. M., Winter, J., Hruban, R. H., Guler, M., Schulick, R. D., Cameron, J. L., Laheru, D. A., Wolfgang, C. L., & Herman, J. M. (2010). Adjuvant chemoradiotherapy after pancreatic resection for invasive carcinoma associated with intraductal papillary mucinous neoplasm of the pancreas. International journal of radiation oncology, biology, physics, 76(3), 839-44.
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  Intraductal papillary mucinous neoplasms are mucin-producing cystic neoplasms of the pancreas. One-third are associated with invasive carcinoma. We examined the benefit of adjuvant chemoradiotherapy (CRT) for this cohort.
• Vaccarella, S., Franceschi, S., Clifford, G. M., Touzé, A., Hsu, C. C., de Sanjosé, S., Pham, T. H., Nguyen, T. H., Matos, E., Shin, H. R., Sukvirach, S., Thomas, J. O., Boursaghin, L., Gaitan, J., Snijders, P. J., Meijer, C. J., Muñoz, N., Herrero, R., Coursaget, P., & , I. H. (2010). Seroprevalence of antibodies against human papillomavirus (HPV) types 16 and 18 in four continents: the International Agency for Research on Cancer HPV Prevalence Surveys. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 19(9), 2379-88.
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  Few human papillomavirus (HPV) seroprevalence studies have been carried out in women from low-resource countries.
• Voong, K. R., Davison, J., Pawlik, T. M., Uy, M. O., Hsu, C. C., Winter, J., Hruban, R. H., Laheru, D., Rudra, S., Swartz, M. J., Nathan, H., Edil, B. H., Schulick, R., Cameron, J. L., Wolfgang, C. L., & Herman, J. M. (2010). Resected pancreatic adenosquamous carcinoma: clinicopathologic review and evaluation of adjuvant chemotherapy and radiation in 38 patients. Human pathology, 41(1), 113-22.
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  Pancreatic adenosquamous carcinoma is a rare morphological variant of pancreatic adenocarcinoma with an especially poor prognosis. The purpose of this study is to identify clinicopathologic features associated with prognosis, assess whether the percentage of squamous differentiation in pancreatic adenosquamous carcinoma is associated with an inferior prognosis, and examine the impact of adjuvant chemoradiation therapy on overall survival. Forty-five (1.2%) of 3651 patients who underwent pancreatic resection at the Johns Hopkins Hospital, Baltimore, MD, between 1986 and 2007 were identified with adenocarcinoma of the pancreas with any squamous differentiation. All pathologic specimens were re-reviewed. Statistical analyses were performed on the 38 patients amenable to adjuvant chemoradiation therapy for whom clinical outcome data could be obtained. Median age was 68 years (61% male). Sixty-one percent underwent pancreaticoduodenectomy. Median tumor size was 5.0 cm. Seventy-six percent of carcinomas were node positive, 37% were margin-positive resections, and 68% had 30% or more squamous differentiation. Median overall survival of the pancreatic adenosquamous carcinoma cohort was 10.9 months (range, 2.1-140.6 months; 95% confidence interval, 8.2-12.5 months). Adjuvant chemoradiation therapy was associated with superior overall survival in patients with pancreatic adenosquamous carcinoma (P = .005). Adjuvant chemoradiation therapy was associated with improved survival in patients with tumors 3 cm or larger and vascular or perineural invasion (P = .02, .03, .02, respectively). The proportion of squamous differentiation was not associated with median overall survival (< 30% versus > or = 30%, P = .82). Survival after pancreatic resection of pancreatic adenosquamous carcinoma is poor. Treatment with adjuvant chemoradiation therapy is associated with improved survival. The proportion of squamous differentiation in resected pancreatic adenosquamous carcinoma specimens does not appear to impact overall survival.
• Hsu, C. C., Brancati, F. L., Astor, B. C., Kao, W. H., Steffes, M. W., Folsom, A. R., & Coresh, J. (2009). Blood pressure, atherosclerosis, and albuminuria in 10,113 participants in the atherosclerosis risk in communities study. Journal of hypertension, 27(2), 397-409.
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  Albuminuria predicts cardiovascular risk, but its function as a marker of endothelial damage and atherosclerosis is uncertain, as is the complex relationship with hypertension and diabetes.
• Zhou, J., Hsu, C. C., Winter, J. M., Pawlik, T. M., Laheru, D., Hughes, M. A., Donehower, R., Wolfgang, C., Akbar, U., Schulick, R., Cameron, J., & Herman, J. M. (2009). Adjuvant chemoradiation versus surgery alone for adenocarcinoma of the ampulla of Vater. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 92(2), 244-8.
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  To examine the role of adjuvant chemoradiation (CRT) in patients with resected ampullary adenocarcinoma.
• Herman, J. M., Swartz, M. J., Hsu, C. C., Winter, J., Pawlik, T. M., Sugar, E., Robinson, R., Laheru, D. A., Jaffee, E., Hruban, R. H., Campbell, K. A., Wolfgang, C. L., Asrari, F., Donehower, R., Hidalgo, M., Diaz, L. A., Yeo, C., Cameron, J. L., Schulick, R. D., & Abrams, R. (2008). Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 26(21), 3503-10.
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  To examine the efficacy of adjuvant chemoradiotherapy after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PC) in patients undergoing resection at Johns Hopkins Hospital (JHH; Baltimore, MD).
• Köttgen, A., Hsu, C. C., Coresh, J., Shuldiner, A. R., Berthier-Schaad, Y., Gambhir, T. R., Smith, M. W., Boerwinkle, E., & Kao, W. H. (2008). The association of podocin R229Q polymorphism with increased albuminuria or reduced estimated GFR in a large population-based sample of US adults. American journal of kidney diseases : the official journal of the National Kidney Foundation, 52(5), 868-75.
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  Rare mutations in nephrosis 2 (NPHS2), encoding podocin, are found in patients with familial and sporadic steroid-resistant nephrotic syndrome and focal segmental glomerular sclerosis. The objective of this study is to assess the contribution of the commonly reported functional podocin polymorphism R229Q to kidney disease in the population at large and replicate a prior study of an association of R229Q and albuminuria in the general population.
• Moore, L. E., Hung, R., Karami, S., Boffetta, P., Berndt, S., Hsu, C. C., Zaridze, D., Janout, V., Kollarova, H., Bencko, V., Navratilova, M., Szeszenia-Dabrowska, N., Mates, D., Mukeria, A., Holcatova, I., Yeager, M., Chanock, S., Garcia-Closas, M., Rothman, N., , Chow, W., et al. (2008). Folate metabolism genes, vegetable intake and renal cancer risk in central Europe. International journal of cancer. Journal international du cancer, 122(8), 1710-5.
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  In a multicenter case-control study of renal cell carcinoma (RCC) conducted in central and eastern Europe, we reported a strong inverse association with high vegetable intake and RCC risk. The odds ratio (OR) for high compared to the lowest tertile of vegetable intake was OR = 0.67; (95% confidence interval (CI): 0.53-0.83; p-trend < 0.001). We hypothesized that variation in key folate metabolism genes may modify this association. Common variation in 5 folate metabolism genes (CBS: Ex9+33C > T (rs234706), Ex13 +41C > T (rs1801181), Ex18 -391 G > A (rs12613); MTHFR: A222V Ex5+79C > T (rs1801133), Ex8-62A > C (rs1801131); MTR: Ex26 20A > G (rs1805087), MTRR: Ex5+136 T > C (rs161870), and TYMS:IVS2-405 C > T (rs502396), Ex8+157 C > T (rs699517), Ex8+227 A > G (rs2790)) were analyzed among 1,097 RCC cases and 1,555 controls genotyped in this study. Having at least 1 variant T allele of MTHFR A222V was associated with higher RCC risk compared to those with 2 common (CC) alleles (OR = 1.44; 95% CI: 1.17-1.77; p = 0.001). After stratification by tertile of vegetable intake, the higher risk associated with the variant genotype was only observed in the low and medium tertiles (p-trend = 0.001), but not among those in the highest tertile (p-interaction = 0.22). The association remained robust after calculation of the false discovery rate (FDR = 0.05). Of the 3 TYMS SNPs examined, only the TYMS IVS2 -405 C (rs502396) variant was associated with a significantly lower risk compared to the common genotype (OR = 0.73; 95% CI: 0.57-0.93). Vegetable intake modified the association between all 3 TYMS SNPs and RCC risk (p-interaction < 0.04 for all). In summary, these findings suggest that common variation in MTHFR and TYMS genes may be associated with RCC risk, particularly when vegetable intake is low.
• Winter, J. M., Swartz, M. J., Pawlik, T. M., Miller, R. C., Hsu, C. C., Herman, J. M., Gunderson, L. L., Corsini, M. M., Cameron, J. L., Callister, M. D., & Callister, C. (2008). Adjuvant Chemoradiation Therapy after Surgical Resection for 1092 Cases of Pancreatic Adenocarcinoma: The Johns Hopkins Hospital - Mayo Clinic Collaborative Study of Pancreatic Cancer. International Journal of Radiation Oncology Biology Physics, 72(1), S13. doi:10.1016/j.ijrobp.2008.06.795
• Hsu, C. C., Chow, W., Boffetta, P., Moore, L., Zaridze, D., Moukeria, A., Janout, V., Kollarova, H., Bencko, V., Navratilova, M., Szeszenia-Dabrowska, N., Mates, D., & Brennan, P. (2007). Dietary risk factors for kidney cancer in Eastern and Central Europe. American journal of epidemiology, 166(1), 62-70.
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  The authors examined the role of diet in the high-risk population of Central Europe among 1,065 incident kidney cancer cases and 1,509 controls in Russia, Romania, Poland, and the Czech Republic. They observed an increased association with kidney cancer for consumption of milk (odds ratio (OR) = 1.46, 95% confidence interval (CI): 1.15, 1.84) and yogurt (OR = 1.34, 95% CI: 1.07, 1.67), as well as all meat (OR = 1.27, 95% CI: 1.06, 1.51 compared with the lowest tertile). High consumption of all vegetables (OR = 0.64, 95% CI: 0.51, 0.80) and cruciferous vegetables (OR = 0.68, 95% CI: 0.55, 0.84) was inversely associated with kidney cancer. In addition, high consumption of preserved vegetables increased the risk of kidney cancer (OR = 1.66, 95% CI: 1.24, 2.21). Alcohol consumption did not appear to be associated with kidney cancer. This 1999-2003 study provides further evidence that diet may play a role in the development of kidney cancer, with a particularly strong protective association for high vegetable intake. The increased risk associated with dairy products, preserved vegetables, and red meat provides clues to the high rates of kidney cancer in this population.
• Hsu, C. C., Bray, M. S., Kao, W. H., Pankow, J. S., Boerwinkle, E., & Coresh, J. (2006). Genetic variation of the renin-angiotensin system and chronic kidney disease progression in black individuals in the atherosclerosis risk in communities study. Journal of the American Society of Nephrology : JASN, 17(2), 504-12.
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  The renin-angiotensin system (RAS) regulates BP and may affect chronic kidney disease (CKD) through induction of tissue growth and fibrosis. The angiotensinogen (AGT) promoter G(-6) allele lowers transcription and is inversely associated with hypertension. In white individuals, the A1166C 3'-UTR variant of angiotensin II type 1 receptor (AT1R) has been associated with CKD. CKD associations with these RAS genes are uncertain in high-risk black populations. A prospective population-based study of CKD risk was conducted among 3706 black individuals without severe renal dysfunction at baseline (serum creatinine > or =177 micromol/L [2.0 mg/dl] for men, > or =159 micromol/L [1.8 mg/dl] for women) to examine associations with AGT and AT1R. Incident CKD progression was defined as kidney disease hospitalization or increase in serum creatinine level > or =35 micromol/L (0.4 mg/dl) above baseline. During mean follow-up of 10.2 yr, CKD progression incidence rate (per 1000 person-years) was 8.2 (n = 312 cases). Risk was lower for AGT G(-6) carriers compared with A(-6) (incidence 6.9 versus 9.0; log-rank P = 0.03) and nonsignificantly higher among AT1R C1166 carriers. Adjusting for hypertension and major CKD risk factors, AGT G(-6)decreased risk (relative risk 0.75; 95% confidence interval 0.57 to 0.98). AT1R C1166 increased risk only among those with hypertension (relative risk 1.65; 95% confidence interval 1.14 to 2.39). The AGT G(-6)A polymorphism may play a role in CKD progression in black individuals, consistent with in vitro effects on AGT levels and renal remodeling but independent of BP. The AT1R C1166 allele may increase susceptibility but only in the presence of hypertension.
• Kida, Y., Kao, W. H., Hsu, C. C., & Coresh, J. (2006). Apolipoprotein E and progression of chronic kidney disease. Authors' reply. JAMA, 295(1), 35-36.
• Brennan, P., Hsu, C. C., Moullan, N., Szeszenia-Dabrowska, N., Lissowska, J., Zaridze, D., Rudnai, P., Fabianova, E., Mates, D., Bencko, V., Foretova, L., Janout, V., Gemignani, F., Chabrier, A., Hall, J., Hung, R. J., Boffetta, P., & Canzian, F. (2005). Effect of cruciferous vegetables on lung cancer in patients stratified by genetic status: a mendelian randomisation approach. Lancet (London, England), 366(9496), 1558-60.
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  Whether consumption of cruciferous vegetables protects against lung cancer is unclear, largely because of potential confounding factors. We therefore studied the role of cruciferous vegetables in lung cancer after stratifying by GSTM1 and GSTT1 status, two genes implicated in the elimination of isothiocyanates, the likely chemopreventative compound. In 2141 cases and 2168 controls, weekly consumption of cruciferous vegetables protected against lung cancer in those who were GSTM1 null (odds ratio=0.67, 95% CI 0.49-0.91), GSTT1 null (0.63, 0.37-1.07), or both (0.28, 0.11-0.67). No protective effect was seen in people who were both GSTM1 and GSTT1 positive (0.88, 0.65-1.21). Similar protective results were noted for consumption of cabbage and a combination of broccoli and brussels sprouts. These data provide strong evidence for a substantial protective effect of cruciferous vegetable consumption on lung cancer.
• Hsu, C. C., Kao, W. H., Coresh, J., Pankow, J. S., Marsh-Manzi, J., Boerwinkle, E., & Bray, M. S. (2005). Apolipoprotein E and progression of chronic kidney disease. JAMA, 293(23), 2892-9.
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  Apolipoprotein E (APOE) genetic variation has been implicated in diabetic nephropathy with the epsilon2 allele increasing and the epsilon4 allele decreasing risk. APOE allelic associations with chronic kidney disease beyond diabetic nephropathy are unknown, with no studies reported in high-risk African American populations.
• Hsu, C. C., Hwang, L. H., Huang, Y. W., Chi, W. K., Chu, Y. D., & Chen, D. S. (1998). An ELISA for RNA helicase activity: application as an assay of the NS3 helicase of hepatitis C virus. Biochemical and biophysical research communications, 253(3), 594-9.
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  A convenient enzyme-linked immunosorbent assay (ELISA) for RNA helicase activity was developed with principles similar to the standard assay. The helicase ELISA utilizes a non-radioactive double-stranded substrate with a biotin-labeled template (long) strand hybridized to a digoxigenin (DIG)-labeled release (short) strand. The template strand binds to the wells of streptavidin-coated microtiter plates (SA-MTP) where the helicase catalyzes the unwinding reaction. Substrate not unwound retains the DIG-labeled release strand and is detected using anti-DIG coupled to horseradish peroxidase. Chromogenic detection follows. Absorbance measurement allows determination of unwinding efficiency of reactions. To demonstrate effectiveness, the ELISA-based assay was used to study the unwinding activity of the hepatitis C virus (HCV) NS3 helicase. Using a known inhibitor of NS3 helicase activity and two mutant HCV helicases, the ability of the assay to screen potential anti-helicase drugs and putative helicases is illustrated. The helicase ELISA is more convenient than the standard helicase assay and is especially suited for the testing of large numbers of samples.

Presentations

• Jiang, W., Davuluri, R., Fang, P., Xu, C., Welsh, J. W., Crane, C. H., Komaki, R. U., Cox, J. D., Hsu, C. C., & Lin, S. H. (2016, Fall). Circulating Lymphocyte Count During Neoadjuvant Chemoradiation Therapy for Esophageal Cancer as a Predictive Biomarker of Pathologic Complete Response. International Journal of Radiation Oncology*Biology*Physics.
• Rosati, L. M., Liu, Y., Rao, A. D., Hsu, C. C., Parekh, A., Ng, K., Hacker-Prietz, A., Zheng, L., Laheru, D. A., Jaffee, E. M., Le, D. T., Jesus-Acosta, A. D., Hruban, R. H., Pawlik, T. M., Weiss, M. J., Wolfgang, C. L., Chang, D. T., Herman, J. M., & Koong, A. C. (2016, Fall). Serum Protein Expression and Associations With Conversion to Resectable Status Following Chemotherapy and Stereotactic Body Radiation Therapy in Locally Advanced Pancreatic Adenocarcinoma. International Journal of Radiation Oncology*Biology*Physics.
• Davuluri, R., Krase, J. M., Cui, H., Goyal, U. D., Cheung, M. K., Hsu, C. C., & Yi, S. K. (2015, May). Image Guided Volumetric Response During Chemoradiotherapy for Head and Neck Squamous Cell Carcinoma as a Predictor of Disease Outcomes. American Radium Society 97th Annual Meeting.
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  Oral presentation

Poster Presentations

• Cao, Y., Chen, L., Guss, Z. D., Moore, J., Mian, O. Y., Hsu, C. C., Robertson, S. P., Rosati, L. M., Cheng, Z., Narang, A., Hacker-Prietz, A., McNutt, T. R., & Herman, J. M. (2016, Fall). Pancreas Stereotactic Body Radiation Therapy Demonstrates Minimal Acute Treatment-Related Toxicity. International Journal of Radiation Oncology*Biology*Physics.
• Goyal, U., O'Donnell, K., Ong, S., Hayman, J., Yi, S. K., Dougherty, S. T., & Hsu, C. C. (2016, Fall). Prospective Study of Nonrandomized Intervention Based on Review of Edmonton Symptom Assessment Scales Versus Routine Symptom Management During Weekly On-Treatment Visits. International Journal of Radiation Oncology*Biology*Physics.
• Guss, Z. D., Rosati, L. M., Hsu, C. C., Hacker-Prietz, A., He, J., Pawlik, T. M., Makary, M. A., Hirose, K., Jesus-Acosta, A. D., Le, D. T., Zheng, L., Laheru, D. A., Cameron, J. L., Wolfgang, C. L., Weiss, M. J., & Herman, J. M. (2016, Fall). Neoadjuvant Stereotactic Body Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: Prognostic Factors for Local Recurrence and Survival. International Journal of Radiation Oncology*Biology*Physics.
• Rosati, L. M., Hsu, C. C., Hacker-Prietz, A., Rao, A. D., He, J., Pawlik, T. M., Cameron, J. L., Makary, M. A., Hirose, K., Jesus-Acosta, A. D., Le, D. T., Zheng, L., Laheru, D. A., Wolfgang, C. L., Weiss, M. J., & Herman, J. M. (2016, Fall). Predictive Factors of Pathologic Response in Patients With Localized Pancreatic Cancer Treated With Induction Chemotherapy and Stereotactic Body Radiation Therapy. International Journal of Radiation Oncology*Biology*Physics.