University of Wisconsin–Madison
Huaising Cindy Ko

Huaising Cindy Ko, MD

Radiation Oncology Resident

Department of Human Oncology

Education

Intern, University of Wisconsin–Madison, Internal Medicine (2015)

MD, Mount Sinai School of Medicine, Medicine (2014)

BS, California Institute of Technology, Mechanical Engineering (2007)

Selected Honors and Awards

Doris Duke Clinical Research Fellowship at Mt. Sinai School of Medicine (2012–2013)

Thomas J. Watson Fellowship (2008–2009)

  • HPV impacts survival of stage IVC non-oropharyngeal HNSCC cancer patients. Otorhinolaryngol Head Neck Surg
    Burr AR, Harari PM, Ko HC, Chen S, Yu M, Baschnagel AM, Kimple RJ, Witek ME
    2018; 3 (1):
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      Objectives: Human papillomavirus (HPV) status is a favorable prognostic marker for patients with oropharyngeal squamous cell carcinoma (OPSCC) and non-metastatic head and neck non-OPSCC. We evaluated the impact of HPV status on overall survival (OS) for patients with Stage IVC non-OPSCC.

      Materials and methods: Patients diagnosed with Stage IVC non-OPSCC and known HPV status between 2010-2013 were identified in the National Cancer Database. Univariate and multivariate analyses were performed to determine factors associated with OS. Propensity score-weighted Kaplan-Meier estimation was used to adjust for confounders in OS analyses. Multiple imputation method was used for sensitivity analysis.

      Results: We identified 708 patients with Stage IVC non-OPSCC with 30% being HPV-positive. Unadjusted median survival was 10.3 months for HPV-negative patients and 21.4 months for HPV-positive patients (p<0.0001). Age ≥ 65 and tumor diameter were associated with worse OS (p<0.05) while treatment versus no treatment and HPV-positive status were associated with improved OS on multivariate analysis (p<0.001). Adjusted median survival for patients with HPV-negative and HPV-positive disease was 11.1 months and 23.8 months, respectively (p<0.001). On unadjusted subgroup analysis, patients with HPV-positive oral cavity disease exhibited improved outcomes (p<0.0001) while HPV-positive hypopharynx (p<0.06) and larynx (p<0.12) patients exhibited a trend for improved OS compared to HPV-negative patients. The survival advantage associated with HPV positivity was maintained on sensitivity analysis (p<0.01).

      Conclusion: These data demonstrate a clinically meaningful association between HPV status and OS in patients with non-OSPCC presenting with Stage IVC disease. In the absence of randomized data, these findings support active consideration of HPV status in clinical decision making, clinical trial design, and patient counseling regarding prognosis.

      View details for PubMedID 30271885
  • The Resident Individual Development Plan as a Guide for Radiation Oncology Mentorship. Int J Radiat Oncol Biol Phys
    Ko HC, Kimple RJ
    2018 Jul 15; 101 (4): 786-788
  • Novel use of ViewRay MRI guidance for high-dose-rate brachytherapy in the treatment of cervical cancer. Brachytherapy
    Ko HC, Huang JY, Miller JR, Das RK, Wallace CR, De Costa AA, Francis DM, Straub MR, Anderson BM, Bradley KA
    2018 May 14; :
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      PURPOSE: To characterize image quality and feasibility of using ViewRay MRI (VR)-guided brachytherapy planning for cervical cancer.

      METHODS AND MATERIALS: Cervical cancer patients receiving intracavitary brachytherapy with tandem and ovoids, planned using 0.35T VR MRI at our institution, were included in this series. The high-risk clinical target volume (HR-CTV), visible gross tumor volume, bladder, sigmoid, bowel, and rectum contours for each fraction of brachytherapy were evaluated for dosimetric parameters. Typically, five brachytherapy treatments were planned using the T2 sequence on diagnostic MRI for the first and third fractions, and a noncontrast true fast imaging with steady-state precession sequence on VR or CT scan for the remaining fractions. Most patients received 5.5 Gy × 5 fractions using high-dose-rate Ir-192 following 45 Gy of whole-pelvis radiotherapy. The plan was initiated at 5.5 Gy to point A and subsequently optimized and prescribed to the HR-CTV. The goal equivalent dose in 2 Gy fractions for the combined external beam and brachytherapy dose was 85 Gy. Soft-tissue visualization using contrast-to-noise ratios to distinguish normal tissues from tumor at their interface was compared between diagnostic MRI, CT, and VR.

      RESULTS: One hundred and forty-two fractions of intracavitary brachytherapy were performed from April 2015 to January 2017 on 29 cervical cancer patients, ranging from stages IB1 to IVA. The median HR-CTV was 27.78 cc, with median D90 HR-CTV of 6.1 Gy. The median time from instrument placement to start of treatment using VR was 65 min (scan time 2 min), compared to 105 min using diagnostic MRI (scan time 11 min) (t-test, p < 0.01). The contrast-to-noise ratio of tumor to cervix in both diagnostic MRI and VR had significantly higher values compared to CT (ANOVA and t-tests, p < 0.01).

      CONCLUSIONS: We report the first clinical use of VR-guided brachytherapy. Time to treatment using this approach was shorter compared to diagnostic MRI. VR also provided significant advantage in visualizing the tumor and cervix compared to CT. This presents a feasible and reliable manner to image and plan gynecologic brachytherapy.

      View details for PubMedID 29773331
  • Impact of HPV Status on the Prognostic Potential of the AJCC Staging System for Larynx Cancer. Otolaryngol Head Neck Surg
    Davidson SM, Ko HC, Harari PM, Wieland AM, Chen S, Baschnagel AM, Kimple RJ, Witek AME
    2018 Apr 01; : 194599818766035
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      Objective We evaluated the ability of the American Joint Committee on Cancer (AJCC) seventh edition staging system to prognosticate the overall survival of patients with human papillomavirus (HPV)-positive laryngeal squamous cell carcinoma. Study Design Retrospective analysis. Setting National Cancer Database. Subjects and Methods Patients diagnosed with laryngeal squamous cell carcinoma who were treated with curative intent were identified in the National Cancer Database. Multivariate analysis was utilized to determine factors correlated with overall survival in the HPV-negative and HPV-positive cohorts. Unadjusted and propensity score-weighted Kaplan-Meier estimation was used to determine overall survival of HPV-negative and HPV-positive patients across AJCC stage groupings. Results We identified 3238 patients with laryngeal squamous cell carcinoma, of which 2812 were HPV negative and 426 were HPV positive. Overall survival adjusted for age, sex, and comorbidity status confirmed significant differences among all consecutive stage groupings (I vs II, P < .001; II vs III, P < .05; III vs IVA, P < .001; IVA vs IVB, P < .05) in the HPV-negative cohort, whereas only stages IVAs and IVB ( P < .01) exhibited a significant difference in overall survival for HPV-positive patients. Conclusion The current AJCC staging system does not accurately distinguish risk of mortality for patients with HPV-positive disease. These data support the consideration of HPV status in estimating prognosis as well as clinical trial design and clinical decision making for patients with laryngeal squamous cell carcinoma.

      View details for PubMedID 29611770
  • Survival Outcomes for Patients With T3N0M0 Squamous Cell Carcinoma of the Glottic Larynx. JAMA Otolaryngol Head Neck Surg
    Ko HC, Harari PM, Chen S, Wieland AM, Yu M, Baschnagel AM, Kimple RJ, Witek ME
    2017 Nov 01; 143 (11): 1126-1133
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      Importance: Radiotherapy (RT)-based organ preservation approaches for patients with advanced laryngeal cancer have been established stepwise through prospective randomized clinical trials. However, broad adoption of these approaches has stimulated discussion about long-term results challenging their applicability in a heterogeneous patient population, most recently for patients with T3 disease.

      Objective: To define outcomes in patients with clinical T3N0M0 glottic laryngeal cancer treated with definitive surgical and RT-based approaches.

      Design, Setting, and Participants: This retrospective cohort study included patients treated from January 1, 2004, through December 31, 2013, with a median follow-up time of 58 months (range, 0-126.6 months) in the National Cancer Database. Of the 4003 patients with T3N0M0 disease, 2622 received definitive therapy defined by the study protocol. Data were obtained from the clinical oncology database sourced from hospital registry data that are collected from more than 1500 Commission on Cancer-accredited facilities. Data were analyzed from September 14, 2016, through April 24, 2017.

      Interventions: Radiotherapy, chemoradiotherapy, surgery, surgery and RT, or surgery and chemoradiotherapy.

      Main Outcomes and Measures: Five-year overall survival (OS).

      Results: A total of 2622 patients (2251 men [85.9%] and 371 women [14.1%]; median age, 64 years [range, 19-90 years]) were included in the analytic cohort. In the overall patient cohort, the adjusted 5-year survival probability was 53%. No statistical differences were observed between the primary surgery (53%; 95% CI, 48%-57%) and primary RT (54%; 95% CI, 52%-57%) cohorts. In multivariate analysis, patient factors associated with decreased OS included age (hazard ratio [HR], 1.04; 95% CI, 1.03-1.04), insurance status (HR, 1.26; 95% CI, 1.06-1.50), and increasing comorbidity (HR, 1.20; 95% CI, 1.02-1.42).

      Conclusions and Relevance: Current management of T3N0M0 glottic laryngeal cancer relies largely on RT-based organ preservation approaches. The present study substantiates randomized clinical trial data supporting the use of RT-based organ preservation approaches for patients with T3N0M0 glottic laryngeal cancer without compromising OS.

      View details for PubMedID 29049434
  • Prognostic implications of human papillomavirus status for patients with non-oropharyngeal head and neck squamous cell carcinomas. J Cancer Res Clin Oncol
    Ko HC, Harari PM, Sacotte RM, Chen S, Wieland AM, Yu M, Baschnagel AM, Bruce JY, Kimple RJ, Witek ME
    2017 Nov; 143 (11): 2341-2350
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      PURPOSE: We examined overall survival in a large cohort of patients with human papillomavirus (HPV)-positive and HPV-negative non-oropharyngeal squamous cell carcinoma of the head and neck (non-OPSCC).

      METHODS: Patients diagnosed with non-OPSCC and known HPV status were identified in the National Cancer Database (NCDB). Multivariate logistic regression was applied to examine factors associated with HPV status. Multivariate analysis was utilized to determine factors correlated with overall survival. Propensity score-weighted Kaplan-Meier estimation was used to adjust for confounders in survival analyses. Multiple imputation method was used for sensitivity analysis.

      RESULTS: We identified 19,993 non-OPSCC patients with 5070 being positive for HPV in the NCDB. Median follow-up was 23.5 months. HPV-positive patients were more commonly male, white, with a lower comorbidity index score, presenting with T-stage <2, and N-stage ≥1. Unadjusted 3-year overall survival was 62% and 80% for HPV-negative and HPV-positive patients, respectively (p < 0.0001). On multivariate analysis, mortality was reduced for HPV-positive patients with early stage (HR = 0.68) and locally advanced disease (HR = 0.46). Adjusted 3-year overall survival was 65% for HPV-negative and 76% for HPV-positive patients (p < 0.0001). The survival advantage of HPV was maintained in all subsites and robust on sensitivity analysis.

      CONCLUSIONS: Patients with HPV-positive non-OPSCC exhibit similar characteristics as HPV-positive OPSCC. Overall survival was significantly higher for patients with HPV-positive versus HPV-negative non-OPSCC. These data reveal that HPV-positive non-OPSCC represent a favorable cohort that warrants recognition in the design of future clinical trial investigation.

      View details for PubMedID 28752235
  • Clinical outcomes for patients presenting with N3 head and neck squamous cell carcinoma: Analysis of the National Cancer Database. Head Neck
    Ko HC, Chen S, Wieland AM, Yu M, Baschnagel AM, Hartig GK, Harari PM, Witek ME
    2017 Nov; 39 (11): 2159-2170
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      BACKGROUND: There is a paucity of data regarding head and neck squamous cell carcinomas (HNSCCs) and N3 nodal disease.

      METHODS: Retrospective analysis of patients with N3 HNSCC identified in the National Cancer Database (NCDB) was performed.

      RESULTS: We identified 4867 patients with N3 HNSCC treated with primary surgery or chemoradiotherapy (CRT). Propensity-adjusted median survival was 54.2 and 44.8 months for surgery and CRT, respectively (P = .06). Oropharyngeal primary subsite demonstrated a survival advantage with surgery versus CRT with propensity-adjusted median survivals of 86.0 and 61.9 months, respectively (P < .05).

      CONCLUSION: Management of N3 HNSCC relies largely on CRT. Patients with N3 nodal disease with nonoropharyngeal primary tumors exhibit 5-year overall survival approaching 30% independent of initial treatment modality. Patients with oropharyngeal primaries exhibit improved outcomes with surgery largely influenced by the human papillomavirus (HPV)-negative subset. These data represent the most comprehensive analysis of N3 HNSCC outcomes and serves as a foundation for future research and clinical management.

      View details for PubMedID 28737019
  • Small cell carcinoma of the head and neck: An analysis of the National Cancer Database. Oral Oncol
    Pointer KB, Ko HC, Brower JV, Witek ME, Kimple RJ, Lloyd RV, Harari PM, Baschnagel AM
    2017 Jun; 69: 92-98
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      PURPOSE/OBJECTIVE(S): To evaluate treatment trends and overall survival of patients with small cell carcinoma of the head and neck region.

      MATERIALS/METHODS: Patients from 2004 to 2012 were identified from the National Cancer Database. Patient demographics and overall survival were analyzed. Multivariable analysis was used to identify predictors of survival.

      RESULTS: Among 347,252 head and neck patients a total of 1042 (0.3%) patients with small cell carcinoma were identified. 17% of patients were diagnosed as stage I/II, 61% as stage III/IVA/IVB and 22% as stage IVC disease. The distribution by anatomic site was 9% oral cavity, 12% oropharynx, 35% larynx, 4% hypopharynx, 10% nasopharynx and 30% nasal cavity and paranasal sinuses. The median overall survival by anatomical site was 20.8months for oral cavity, 23.7months for oropharynx, 17.9months for larynx/hypopharynx, 15.1months for nasopharynx and 36.4months for nasal cavity primary tumors. On multivariable analysis across stage, patients with nasal cavity and paranasal sinuses tumors had the best survival and patients with nasopharynx primaries had the worst survival. In stage I/II patients, type of treatment delivered resulted in no overall survival difference (p=0.78). In patients with locally advanced disease, there was no difference in survival between those treated with combined surgery, radiotherapy and chemotherapy compared to those treated only with radiotherapy and chemotherapy (p=0.46). The addition of radiotherapy to chemotherapy in the metastatic setting did not result in improved survival (p=0.14).

      CONCLUSIONS: Small cell carcinoma of the head and neck is a rare malignancy with a poor prognosis. The addition of surgery to radiotherapy and chemotherapy did not improve survival in patients with locally advanced disease.

      View details for PubMedID 28559027
  • Lhermitte's Sign following VMAT-Based Head and Neck Radiation-Insights into Mechanism. PLoS One
    Ko HC, Powers AR, Sheu RD, Kerns SL, Rosenstein BS, Krieger SC, Mourad WF, Hu KS, Gupta V, Bakst RL
    2015; 10 (10): e0139448
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      PURPOSE/OBJECTIVES: We observed a number of patients who developed Lhermitte's sign (LS) following radiation to the head and neck (H/N), since instituting volumetric modulated arc therapy (VMAT). We aimed to investigate the incidence of LS following VMAT-based RT without chemotherapy, and determine the dosimetric parameters that predict its development. We explored whether the role of inhomogeneous dose distribution across the spinal cord, causing a "bath-and-shower" effect, explains this finding.

      METHODS AND MATERIALS: From 1/20/2010-12/9/2013, we identified 33 consecutive patients receiving adjuvant RT using VMAT to the H/N without chemotherapy at our institution. Patients' treatment plans were analyzed for dosimetric parameters, including dose gradients along the anterior, posterior, right, and left quadrants at each cervical spine level. Institutional Review Board approval was obtained.

      RESULTS: 5 out of 33 (15.2%) patients developed LS in our patient group, all of whom had RT to the ipsilateral neck only. LS patients had a steeper dose gradient between left and right quadrants across all cervical spine levels (repeated-measures ANOVA, p = 0.030). Within the unilateral treatment group, LS patients received a higher mean dose across all seven cervical spinal levels (repeated-measures ANOVA, p = 0.046). Dose gradients in the anterior-posterior direction and mean doses to the cord were not significant between LS and non-LS patients.

      CONCLUSIONS: Dose gradients along the axial plane of the spinal cord may contribute to LS development; however, a threshold dose within the high dose region of the cord may still be required. This is the first clinical study to suggest that inhomogeneous dose distributions in the cord may be relevant in humans. Further investigation is warranted to determine treatment-planning parameters associated with development of LS.

      View details for PubMedID 26448647
  • A contouring guide for head and neck cancers with perineural invasion. Pract Radiat Oncol
    Ko HC, Gupta V, Mourad WF, Hu KS, Harrison LB, Som PM, Bakst RL
    2014 Nov-Dec; 4 (6): e247-58
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      PURPOSE: Perineural invasion (PNI) is a frequent pathological finding in head and neck cancers. When adjuvant radiation to cranial nerves at risk in head and neck cancers with PNI is considered, there is a need for consensus on which nerves are at risk and how to contour these nerves. This contouring guide attempts to address this need.

      METHODS AND MATERIALS: Representative patient diagnostic computed tomographic (CT) scans with contrast of the neck were used to create example contours. The cranial nerves V2, V3, VII, and XII, and sample primary tumor sites were initially delineated using the Varian Eclipse planning system by 5 radiation oncologists. All of the images were then reviewed with a diagnostic radiologist to establish consensus for delineating the cranial nerves.

      RESULTS: We provided detailed contouring and planning guidelines on a CT atlas, with figures to help illustrate internerve connections, based on clinical experience, literature-based patterns of failure, and established anatomic connections between cranial nerves. Tumor bed, cranial nerve, and elective target volumes are depicted.

      CONCLUSIONS: These planning guidelines and atlas provide anatomic, clinical, and technical recommendations for guiding radiation oncologists in the planning and delivery of intensity modulated radiation therapy for head and neck cancer with PNI.

      View details for PubMedID 25407876
  • Antibiotic prophylaxis for preventing recurrent cellulitis: a systematic review and meta-analysis. J Infect
    Oh CC, Ko HC, Lee HY, Safdar N, Maki DG, Chlebicki MP
    2014 Jul; 69 (1): 26-34
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      IMPORTANCE: A significant proportion of patients who have had a first episode of erysipelas or uncomplicated cellulitis will subsequently develop a recurrence. There is disagreement about how effective antibiotic prophylaxis is for preventing recurrent cellulitis.

      OBJECTIVE: To determine if antibiotic prophylaxis is effective in preventing recurrent cellulitis compared to no prophylaxis using a systematic review and meta-analysis.

      DATA SOURCES: Studies in any language identified by searching Medline, EMBASE, Cochrane Library, CINAHL, TRIP database, clinical practice guidelines websites, and ongoing trials databases up to 31st August 2012. Search terms included cellulitis, erysipelas, controlled clinical trial, randomized, placebo, clinical trials, randomly, and trial.

      STUDY SELECTION: Only controlled trials comparing antibiotic prophylaxis to no antibiotic prophylaxis in patients age 16 years and above, and after 1 or more episodes of cellulitis, were included.

      DATA EXTRACTION AND SYNTHESIS: Independent extraction of articles was done by 2 investigators using predefined data extraction templates, including study quality indicators. PROSPERO registration number: CRD42012002528. Meta-analyses were done using random-effects models.

      MAIN OUTCOMES AND MEASURES: The primary outcome was the number of patients with a recurrence of cellulitis. Secondary outcomes were (1) the time to next episode of recurrence, (2) quality of life measures, and (3) adverse events (e.g. allergic reactions, nausea).

      RESULTS: Five randomized controlled trials (n = 535), with 260 patients in the intervention arm and 275 in the comparator group met our inclusion criteria. 44 patients (8%) in the antibiotic prophylaxis group and 97 patients (18%) in the comparator group had an episode of cellulitis. Antibiotic prophylaxis significantly reduced the number of patients having recurrent cellulitis, with a risk ratio (RR) of 0.46 (95% CI 0.26-0.79). None of the studies reported severe adverse effects to antibiotics. There was methodological heterogeneity amongst the studies in terms of types of antibiotic used, delivery modes, number of recurrences of cellulitis at study entry, and study quality.

      CONCLUSION AND RELEVANCE: Antibiotic prophylaxis can prevent recurrent cellulitis. Future research should aim to identify the ideal type, dosage, and duration of antibiotics for prophylaxis, as well as to identify the group of patients who will benefit most from antibiotic prophylaxis.

      View details for PubMedID 24576824
  • Concise review: drug discovery in the age of the induced pluripotent stem cell. Stem Cells Transl Med
    Ko HC, Gelb BD
    2014 Apr; 3 (4): 500-9
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      For decades, the paradigm of drug discovery and development has relied on immortalized cell lines, animal models of human disease, and clinical trials. With the discovery of induced pluripotent stem cell (iPSC) technology in 2007, a new human in vitro drug testing platform has potentially augmented this set of tools by providing additional ways to screen compounds for safety and efficacy. The growing number of human disease models made with patient-specific iPSCs has made it possible to conduct research on a wide range of disorders, including rare diseases and those with multifactorial origin, as well as to simulate drug effects on difficult-to-obtain tissues such as brain and cardiac muscle. Toxicity and teratogenicity assays developed with iPSC-derived cells can also provide an additional layer of safety before advancing drugs to clinical trials. The incorporation of iPSC technology into drug therapy development holds promise as a more powerful and nuanced approach to personalized medicine.

      View details for PubMedID 24493856

Contact Information

Huaising Cindy Ko, MD

600 Highland Avenue,
Madison, WI 53792
Email