Bio

Bio


Dr. Vitzthum is a radiation oncologist and clinical assistant professor of radiation oncology at Stanford University School of Medicine. He specializes in the treatment of gastrointestinal and thoracic cancers. He also has a clinical and research interest in oligometastatic cancer, which is cancer that has metastasized to a limited number of sites beyond its origin.

He began his career in biomedical engineering and is passionate aboutintegrating new technologies to advance patient care.

Dr. Vitzthum delivers treatment personalized to each patient’s condition, overall health, and goals. He believes clear communication between doctor and patient is vital to help patients make informed care decisions.

His research interests include clinical trial development, survivorship, and predictive modeling to personalize patient treatment. He is especially interested in pursuing research that can address unmet clinical needs.

Dr. Vitzthum has received research support through the Radiological Society of North America, the American Society of Clinical Oncology’s Conquer Cancer Foundation, and the UCSD Altman Clinical and Translational Research Institute. His work has appeared in International Journal of Radiation Oncology Biology Physics, Annals of Oncology, JAMA Oncology, Clinical Cancer Research, and other publications.

He is a member of the American College of Radiation Oncology, American Society for Radiation Oncology, American Society of Clinical Oncology, and Radiologic Society of North America.

Dr. Vitzthum is also interested in improving access to high-quality cancer care for under-served populations domestically and abroad.

Clinical Focus


  • Radiation Oncology
  • Gastrointestinal Cancers
  • Lung Cancers
  • Stereotactic Body Radiotherapy

Academic Appointments


Honors & Awards


  • Roentgen Research Award, RSNA (2020)
  • Endowed Young Investigator Award, American Society of Clinical Oncology (2019)
  • Resident Research Grant, RSNA (2019)
  • Alpha Omega Alpha Medical Honor Society, University of Minnesota (2014)
  • Dean's Merit Scholarship, University of Minnesota Medical School (2010-2015)

Professional Education


  • Residency: UCSD Radiation Oncology Residency Program (2020) CA
  • Internship: Hennepin County Medical Center Transitional Year Residency (2016) MN
  • Medical Education: University of Minnesota School of Medicine Registrar (2015) MN

Publications

All Publications


  • Comparison of Hematologic Toxicity and Bone Marrow Compensatory Response in Head and Neck vs. Cervical Cancer Patients Undergoing Chemoradiotherapy FRONTIERS IN ONCOLOGY Vitzthum, L. K., Heide, E. S., Park, H., Williamson, C. W., Sheridan, P., Huynh-Le, M., Sirak, I., Wei, L., Tarnawski, R., Mahantshetty, U., Nguyen, C., Mayadev, J., Yashar, C. M., Sacco, A. G., Mell, L. K. 2020; 10: 1179

    Abstract

    Background: Hematologic toxicity is a critical problem limiting treatment delivery in cancer patients undergoing concurrent chemoradiotherapy. However, the extent to which anatomic variations in radiation dose limit chemotherapy delivery is poorly understood. A unique natural experiment arises in patients with head and neck and cervical cancer, who frequently undergo identical chemotherapy but receive radiation to different regions of the body. Comparing these cohorts can help elucidate to what extent hematologic toxicity is attributable to marrow radiation as opposed to chemotherapy. Methods: In this longitudinal cohort study, we compared hematologic toxicity and bone marrow compensatory response in 148 patients (90 cervix, 58 head/neck) undergoing chemoradiotherapy with concurrent weekly cisplatin 40 mg/m2. We used linear mixed effect models to compare baseline and time-varying peripheral cell counts and hemoglobin levels between cohorts. To assess bone marrow compensatory response, we measured the change in metabolically active bone marrow (ABM) volume on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Results: We observed greater reductions in log-transformed lymphocyte, platelet, and absolute neutrophil counts (ANC) for cervix compared to head/neck cancer patients (fixed effects for time-cohort interaction [95% CI]: lymphocytes, -0.06 [-0.09, -0.031]; platelets,-0.028 [-0.051, -0.0047]; ANC, -0.043 [-0.075, -0.011]). Mean ANC nadirs were also lower for cervical vs. head/neck cancer cohorts (2.20 vs. 2.85 × 103 per μL, p < 0.01). Both cohorts exhibited reductions in ABM volume within the radiation field, and increases in ABM volume in out-of-field areas, indicating varying compensatory response to radiation injury. Conclusions: Cervical cancer patients had faster decreases in ANC, lymphocyte, and platelet counts, and lower ANC nadirs, indicating a significant effect of pelvic irradiation on acute peripheral blood cell counts. Both cohorts exhibited a compensatory response with increased out-of-field bone marrow activity.

    View details for DOI 10.3389/fonc.2020.01179

    View details for Web of Science ID 000558484800001

    View details for PubMedID 32793487

    View details for PubMedCentralID PMC7385402

  • Managing Cancer Pain During the Opioid Epidemic-Balancing Caution and Compassion JAMA ONCOLOGY Vitzthum, L. K., Riviere, P., Murphy, J. D. 2020; 6 (7): 1103–4

    View details for DOI 10.1001/jamaoncol.2020.0779

    View details for Web of Science ID 000552068600025

    View details for PubMedID 32379274

  • Predicting Persistent Opioid Use, Abuse, and Toxicity Among Cancer Survivors. Journal of the National Cancer Institute Vitzthum, L. K., Riviere, P., Sheridan, P., Nalawade, V., Deka, R., Furnish, T., Mell, L. K., Rose, B., Wallace, M., Murphy, J. D. 2020; 112 (7): 720–27

    Abstract

    BACKGROUND: Although opioids play a critical role in the management of cancer pain, the ongoing opioid epidemic has raised concerns regarding their persistent use and abuse. We lack data-driven tools in oncology to understand the risk of adverse opioid-related outcomes. This project seeks to identify clinical risk factors and create a risk score to help identify patients at risk of persistent opioid use and abuse.METHODS: Within a cohort of 106732 military veteran cancer survivors diagnosed between 2000 and 2015, we determined rates of persistent posttreatment opioid use, diagnoses of opioid abuse or dependence, and admissions for opioid toxicity. A multivariable logistic regression model was used to identify patient, cancer, and treatment risk factors associated with adverse opioid-related outcomes. Predictive risk models were developed and validated using a least absolute shrinkage and selection operator regression technique.RESULTS: The rate of persistent opioid use in cancer survivors was 8.3% (95% CI=8.1% to 8.4%); the rate of opioid abuse or dependence was 2.9% (95% CI=2.8% to 3.0%); and the rate of opioid-related admissions was 2.1% (95% CI=2.0% to 2.2%). On multivariable analysis, several patient, demographic, and cancer and treatment factors were associated with risk of persistent opioid use. Predictive models showed a high level of discrimination when identifying individuals at risk of adverse opioid-related outcomes including persistent opioid use (area under the curve [AUC] = 0.85), future diagnoses of opioid abuse or dependence (AUC=0.87), and admission for opioid abuse or toxicity (AUC=0.78).CONCLUSION: This study demonstrates the potential to predict adverse opioid-related outcomes among cancer survivors. With further validation, personalized risk-stratification approaches could guide management when prescribing opioids in cancer patients.

    View details for DOI 10.1093/jnci/djz200

    View details for PubMedID 31754696

  • Challenge of Directly Comparing Imaging-Based Diagnoses Made by Machine Learning Algorithms With Those Made by Human Clinicians JOURNAL OF CLINICAL ONCOLOGY Simon, A. B., Vitzthum, L. K., Mell, L. K. 2020; 38 (16): 1868-+

    View details for DOI 10.1200/JCO.19.03350

    View details for Web of Science ID 000537770500014

    View details for PubMedID 32271670

    View details for PubMedCentralID PMC7255980

  • Tobacco smoking and death from prostate cancer in US veterans PROSTATE CANCER AND PROSTATIC DISEASES Riviere, P., Kumar, A., Luterstein, E., Vitzthum, L. K., Nalawade, V., Sarkar, R. R., Bryant, A. K., Einck, J. P., Mundt, A. J., Murphy, J. D., Rose, B. S. 2020; 23 (2): 252–59

    Abstract

    Cigarette smoking is a risk factor for mortality in several genitourinary cancers, likely due to accumulation of carcinogens in urine. However, in prostate cancer (PC) the link has been less studied. We evaluated differences in prostate cancer-specific mortality (PCSM) between current smokers, past smokers, and never smokers diagnosed with PC.This was a retrospective cohort study of PCSM in men diagnosed with PC between 2000 and 2015 treated in the US Veterans Affairs health care system, using competing risk regression analyses.The cohort included 73,668 men (current smokers: 22,608 (30.7%), past smokers: 23,695 (32.1%), and never smokers: 27,365 (37.1%)). Median follow-up was 5.9 years. Current smoker patients were younger at presentation (median age current: 63, never: 66; p < 0.001), and had more advanced disease stage (stage IV disease current: 5.3%, never: 4.3%; p < 0.04). The 10-year incidence of PCSM was 5.2%, 4.8%, and 4.5% for current, past, and never smokers, respectively. On competing risk regression, current smoking was associated with increased PCSM (subdistribution hazard ratio: 1.14, 95% confidence interval: (1.05-1.24), p = 0.002), whereas past smoking was not. Hierarchical regression suggests that this increased risk was partially attributable to tumor characteristics.Smoking at the time of diagnosis is associated with a higher risk of dying from PC as well as other causes of death. In contrast, past smoking was not associated with PCSM suggesting that smoking may be a modifiable risk factor. PC diagnosis may be an important opportunity to discuss smoking cessation.

    View details for DOI 10.1038/s41391-019-0178-6

    View details for Web of Science ID 000534552900005

    View details for PubMedID 31624316

  • African-American men with low-risk prostate cancer treated with radical prostatectomy in an equal-access health care system: implications for active surveillance PROSTATE CANCER AND PROSTATIC DISEASES Deka, R., Parsons, J., Simpson, D. R., Riviere, P., Nalawade, V., Vitzthum, L. K., Kader, A., Kane, C. J., Rock, C. S., Murphy, J. D., Rose, B. S. 2020

    Abstract

    There is concern that African-American men (AA) with low-risk prostate cancer may present with more aggressive disease and thus may not be candidates for active surveillance (AS). However, it is uncertain if poorer outcomes are due to disparities in access to medical care rather than true biological differences.Observational cohort study of patients diagnosed with low-risk PC-Gleason score ≤6, clinical tumor stage ≤2A, and prostate specific antigen (PSA) level ≤10-at US Department of Veterans Affairs between January 1, 2001 and October 31, 2015 and treated with radical prostatectomy. Outcomes included upgrading to Gleason Grade Group 2 (GG2), GG ≥ 3, PSA recurrence, pathologic tumor stage ≥3, positive surgical margins, and all-cause mortality.A total of 2857 men (AA: 835 White: 2022) with a median follow-up of 7.1 years. Overall, there was no significant difference between AA and White men in upgrading to GG ≥ 3 (RR = 1.18, p = 0.43), tumor stage ≥3 (RR = 0.95, p = 0.74), positive surgical margins (RR = 1.14, p = 0.20), PSA recurrence (SHR = 1.26, p = 0.06), and all-cause mortality (SHR = 1.26, p = 0.16). However, there was a significant increase in upgrading for AA to GG2 (RR = 1.49, p < 0.01).There was no significant difference in most adverse pathologic outcomes between AA and White patients. However, GG2 upgrading was more common in AA men. The implication is that AA may need to undergo additional evaluation, such as a biopsy MRI, before initiating AS. Whether the increase in GG2 upgrading will lead to poorer long-term clinical outcomes such as metastasis and PCSM also requires further investigation.

    View details for DOI 10.1038/s41391-020-0230-6

    View details for Web of Science ID 000528293600001

    View details for PubMedID 32327702

  • Risk of Pelvic Fracture With Radiation Therapy in Older Patients INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Vitzthum, L. K., Park, H., Zakeri, K., Heide, E. S., Nalawade, V., Mundt, A. J., Vaida, F., Murphy, J. D., Mell, L. K. 2020; 106 (3): 485–92

    Abstract

    Older patients undergoing radiation therapy (RT) for pelvic malignancies are at increased risk for pelvic fracture, which is associated with significant morbidity and mortality. RT techniques such as brachytherapy or intensity modulated RT (IMRT) allow for more conformal dose distributions, but it is not known whether the risk for pelvic fracture varies by RT modality.This observational cohort study involved 28,354 patients ≥65 years old, treated with RT for pelvic malignancies. We evaluated the relative risk of pelvic fracture by type of RT when accounting for baseline factors. To test for nonspecific effects, we also evaluated risk of nonpelvic fractures in the same population.The 5-year incidence of pelvic fractures was 12.7% (95% confidence interval [CI], 11.6%-13.8%), 11.8% (10.8%-12.8%), and 3.7% (3.4%-4.0%) for patients with gastrointestinal, gynecologic, and prostate cancer, respectively. On multivariable analysis, being treated with IMRT (hazard ratio, 0.85; 95% CI, 0.73-0.99) or brachytherapy therapy alone (hazard ratio, 0.43; 95% CI, 0.34-0.54) was associated with a reduced hazard for pelvic fractures compared with 3D conformal radiation therapy in female patients. In contrast, there was no association with RT modality and the hazard for nonpelvic fractures among females. There was no significant association between pelvic fractures and IMRT or brachytherapy for male patients. White race, advanced age, and higher comorbidity were associated with an increased hazard for pelvic fracture.IMRT and brachytherapy were associated with a reduced risk of pelvic fractures in older women undergoing RT for pelvic malignancies. Pelvic insufficiency fracture risk should be considered when treating with pelvic RT.

    View details for DOI 10.1016/j.ijrobp.2019.10.006

    View details for Web of Science ID 000510861900009

    View details for PubMedID 31610251

  • Associations among statins, preventive care, and prostate cancer mortality PROSTATE CANCER AND PROSTATIC DISEASES Kumar, A., Riviere, P., Luterstein, E., Nalawade, V., Vitzthum, L., Sarkar, R. R., Bryant, A. K., Einck, J. P., Mundt, A. J., Murphy, J. D., Rose, B. S. 2020; 23 (3): 475–85

    Abstract

    Increasing evidence indicates an association between statins and reduced prostate cancer-specific mortality (PCSM). However, significant bias may exist in these studies. One particularly challenging bias to assess is the healthy user effect, which may be quantified by screening patterns. We aimed to evaluate the association between statin use, screening, and PCSM in a dataset with detailed longitudinal information.We used the Veterans Affairs Informatics and Computing Infrastructure to assemble a cohort of patients diagnosed with prostate cancer (PC) between 2000 and 2015. We collected patient-level demographic, comorbidity, and tumor data. We also assessed markers of preventive care utilization including cholesterol and prostate specific antigen (PSA) screening rates. Patients were considered prediagnosis statin users if they had at least one prescription one or more years prior to PC diagnosis. We evaluated PCSM using hierarchical Fine-Gray regression models and all-cause mortality (ACM) using a cox regression model.The final cohort contained 68,432 men including 40,772 (59.6%) prediagnosis statin users and 27,660 (40.4%) nonusers. Prediagnosis statin users had higher screening rates than nonusers for cholesterol (90 vs. 69%, p < 0.001) and PSA (76 vs. 67%, p < 0.001). In the model which excluded screening, prediagnosis statin users had improved PCSM (SHR 0.90, 95% CI 0.84-0.97; p = 0.004) and ACM (HR 0.96, 95% CI 0.93-0.99; p = 0.02). However, after including cholesterol and PSA screening rates, prediagnosis statin users and nonusers showed no differences in PCSM (SHR 0.98, 95% CI 0.91-1.06; p = 0.59) or ACM (HR 1.02, 95% CI 0.98-1.05; p = 0.25).We found that statin users tend to have more screening than nonusers. When we considered screening utilization, we observed no relationship between statin use before a prostate cancer diagnosis and prostate cancer mortality.

    View details for DOI 10.1038/s41391-020-0207-5

    View details for Web of Science ID 000511538100001

    View details for PubMedID 32029930

  • Survival of African American and non-Hispanic white men with prostate cancer in an equal-access health care system. Cancer Riviere, P., Luterstein, E., Kumar, A., Vitzthum, L. K., Deka, R., Sarkar, R. R., Bryant, A. K., Bruggeman, A., Einck, J. P., Murphy, J. D., Martínez, M. E., Rose, B. S. 2020; 126 (8): 1683–90

    Abstract

    African American (AA) men in the general US population are more than twice as likely to die of prostate cancer (PC) compared with non-Hispanic white (NHW) men. The authors hypothesized that receiving care through the Veterans Affairs (VA) health system, an equal-access medical system, would attenuate this disparity.A longitudinal, centralized database of >20 million veterans was used to assemble a cohort of 60,035 men (18,201 AA men [30.3%] and 41,834 NHW men [69.7%]) who were diagnosed with PC between 2000 and 2015.AA men were more likely to live in regions with a lower median income ($40,871 for AA men vs $48,125 for NHW men; P < .001) and lower high school graduation rates (83% for AA men vs 88% for NHW men; P < .001). At the time of diagnosis, AA men were younger (median age, 63.0 years vs 66.0 years; P < .001) and had a higher prostate-specific antigen level (median, 6.7 ng/mL vs 6.2 ng/mL; P < .001), but were less likely to have Gleason score 8 to 10 disease (18.8% among AA men vs 19.7% among NHW men; P < .001), a clinical T classification ≥3 (2.2% vs 2.9%; P < .001), or distant metastatic disease (2.7% vs 3.1%; P = 0.01). The 10-year PC-specific mortality rate was slightly lower for AA men (4.4% vs 5.1%; P = .005), which was confirmed in multivariable competing-risk analysis (subdistribution hazard ratio, 0.85; 95% CI, 0.78-0.93; P < .001).AA men diagnosed with PC in the VA health system do not appear to present with more advanced disease or experience worse outcomes compared with NHW men, in contrast to national trends, suggesting that access to care is an important determinant of racial equity.

    View details for DOI 10.1002/cncr.32666

    View details for PubMedID 31984482

  • Selection of Head and Neck Cancer Patients for Intensive Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Vitzthum, L. K., Park, H., Zakeri, K., Bryant, A. K., Feng, C., Shen, H., Cohen, E. W., Murphy, J. D., Mell, L. K. 2020; 106 (1): 157–66

    Abstract

    Previous studies have found that patients with head and neck cancer (HNC) with a higher relative hazard for recurrence versus competing mortality (ω+ ratio) are more likely to benefit from intensive therapy. Nomograms to predict this ratio (ω scores) can be useful to guide clinical management; however, comorbidity and other risk factors are frequently lacking from trial samples.In this study of 7117 US veterans, we evaluated the ability of a ω score nomogram developed from clinical trial data to stratify patients with HNC treated with radiation therapy by their relative risk of cancer progression versus competing mortality. We then fit generalized competing event models to determine the effect of comorbidity and other covariates on the ω+ ratio.The ω score was effective in stratifying patients with HNC according to their risk for cancer recurrence relative to competing mortality, especially among patients aged >70 years. Patients with ω score ≥0.80 were more likely to receive intensive therapy compared with patients with a ω score <0.80 (66 vs. 54%; P < .001). On multivariable generalized competing event regression, T2-4 category (relative hazard ratio [RHR], 1.08; 95% confidence interval [CI], 1.01-1.16), N2-3 category (RHR, 1.07; 95% CI, 1.01-1.15), and being employed (RHR, 1.11; 95% CI, 1.03-1.20) were associated with increased ω+ ratio, and increasing age (RHR, 0.83; 95% CI, 0.78-0.89), Charlson comorbidity index ≥2 (RHR, 0.85; 95% CI, 0.79-0.91), being a current smoker (RHR, 0.90; 95% CI, 0.84-0.96), and lower body mass index (RHR, 0.89; 95% CI, 0.84-0.95) were associated with a decreased ω+ ratio.The ω scores are effective in stratifying patients with HNC and are correlated with the intensity of treatment given. The ω scores incorporating comorbidity and other risk factors could help identify patients with HNC most likely to benefit from intensive therapy.

    View details for DOI 10.1016/j.ijrobp.2019.09.011

    View details for Web of Science ID 000502338300030

    View details for PubMedID 31580929

  • Combined Androgen Blockade in Localized Prostate Cancer Treated With Definitive Radiation Therapy JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Vitzthum, L. K., Straka, C., Sarkar, R. R., Mckay, R., Randall, J., Sandhu, A., Murphy, J. D., Rose, B. S. 2019; 17 (12): 1497-+

    Abstract

    The addition of androgen deprivation therapy to radiation therapy (RT) improves survival in patients with intermediate- and high-risk prostate cancer (PCa), but it is not known whether combined androgen blockade (CAB) with a gonadotropin-releasing hormone agonist (GnRH-A) and a nonsteroidal antiandrogen improves survival over GnRH-A monotherapy.This study evaluated patients with intermediate- and high-risk PCa diagnosed in 2001 through 2015 who underwent RT with either GnRH-A alone or CAB using the Veterans Affairs Informatics and Computing Infrastructure. Associations between CAB and prostate cancer-specific mortality (PCSM) and overall survival (OS) were determined using multivariable regression with Fine-Gray and multivariable Cox proportional hazards models, respectively. For a positive control, the effect of long-term versus short-term GnRH-A therapy was tested.The cohort included 8,423 men (GnRH-A, 4,529; CAB, 3,894) with a median follow-up of 5.9 years. There were 1,861 deaths, including 349 resulting from PCa. The unadjusted cumulative incidences of PCSM at 10 years were 5.9% and 6.9% for those receiving GnRH-A and CAB, respectively (P=.16). Compared with GnRH-A alone, CAB was not associated with a significant difference in covariate-adjusted PCSM (subdistribution hazard ratio [SHR], 1.05; 95% CI, 0.85-1.30) or OS (hazard ratio, 1.02; 95% CI, 0.93-1.12). For high-risk patients, long-term versus short-term GnRH-A therapy was associated with improved PCSM (SHR, 0.74; 95% CI, 0.57-0.95) and OS (SHR, 0.82; 95% CI, 0.73-0.93).In men receiving definitive RT for intermediate- or high-risk PCa, CAB was not associated with improved PCSM or OS compared with GnRH alone.

    View details for DOI 10.6004/jnccn.2019.7335

    View details for Web of Science ID 000500944300010

    View details for PubMedID 31805534

  • Nomogram to Predict the Benefit of Intensive Treatment for Locoregionally Advanced Head and Neck Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research Mell, L. K., Shen, H., Nguyen-Tan, P. F., Rosenthal, D. I., Zakeri, K., Vitzthum, L. K., Frank, S. J., Schiff, P. B., Trotti, A., Bonner, J. A., Jones, C. U., Yom, S. S., Thorstad, W. L., Wong, S., Shenouda, G., Ridge, J. A., Zhang, Q. E., Le, Q. 2019

    Abstract

    PURPOSE: Previous studies indicate the benefit of therapy depends on patients' risk for cancer recurrence relative to non-cancer mortality (omega ratio). We sought to test the hypothesis that head and neck cancer (HNC) patients with a higher omega ratio selectively benefit from intensive therapy.EXPERIMENTAL DESIGN: We analyzed 2688 patients with stage III-IVB HNC undergoing primary radiation therapy (RT) with or without systemic therapy on three phase III trials (RTOG 9003, RTOG 0129, and RTOG 0522). We used generalized competing event regression to stratify patients according to omega ratio, and compared the effectiveness of intensive therapy as a function of predicted omega ratio (i.e., omega score). Intensive therapy was defined as treatment on an experimental arm with altered fractionation (AFX) and/or multiagent concurrent systemic therapy. A nomogram was developed to predict patients' omega score based on tumor, demographic, and health factors. Analysis was by intention-to-treat.RESULTS: Decreasing age, improved performance status, higher body mass index, node positive status, P16 negative status, and oral cavity primary predicted a higher omega ratio. Patients with omega score ≥ 0.80 were more likely to benefit from intensive treatment (5-year OS, 70.0% vs. 56.6%; HR 0.73, 95% CI 0.57-0.94; P=0.016) than those with a omega score < 0.80 (5-year OS, 46.7% vs. 45.3%; HR 1.02, 95% CI 0.92-1.14; P=0.69;P=0.019 for interaction). In contrast, the effectiveness of intensive therapy did not depend on risk of progression.CONCLUSION: HNC patients with a higher omega score selectively benefit from intensive treatment. A nomogram was developed to help select patients for intensive therapy.

    View details for DOI 10.1158/1078-0432.CCR-19-1832

    View details for PubMedID 31420360

  • Reducing prolonged chemoradiation treatment times for cervical cancer. BMJ open quality Vitzthum, L., Yuan, J., Jones, D., Boldt, A., Dusenbery, K. 2019; 8 (3): e000516

    Abstract

    Prolonged total treatment times (TTTs) beyond 56 days are associated with worse outcomes for cervical cancer treated with radiation therapy. We reviewed treatment times in a cohort of 24 consecutive patients treated with definitive chemoradiation (CRT) at our institution and found that only 14 patients (58.3%) completed treatment in less than or equal to 56 days. The primary objectives of this institutional quality improvement initiative were to identify sources for delays in treatment completion and to implement effective measures in an effort to minimise prolonged TTT. Pareto plot and process mapping were used to identify and resolve root causes of prolonged treatment. The Plan-Do-Study-Act method was then implemented to reduce treatment duration. Post-intervention treatment times were prospectively evaluated in 81 subsequent patients treated with definitive CRT. Process mapping identified inefficiencies with scheduling, staggered treatments and inadequate patient and staff education. Institutional changes were implemented, heavily utilising oncology nurses' skill set in staff re-education and care coordination. Our workflow was redesigned to reduce/eliminate treatment delays. These interventions led to a significant improvement in the percentage of patients meeting the goal TTT compared with the pre-intervention cohort (85.2% vs 58.3%, p<0.01), and results were sustainable in additional 47 patients prospectively followed subsequently, potentially making a positive impact on their treatment outcomes.

    View details for DOI 10.1136/bmjoq-2018-000516

    View details for PubMedID 31637317

  • Prognostic Role of p16 in Nonoropharyngeal Head and Neck Cancer JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Bryant, A. K., Sojourner, E. J., Vitzthum, L. K., Zakeri, K., Shen, H., Nguyen, C., Murphy, J. D., Califano, J. A., Cohen, E. W., Mell, L. K. 2018; 110 (12): 1393–99

    Abstract

    Previous studies have reported conflicting information regarding the prognostic role of p16 in nonoropharyngeal head and neck squamous cell carcinoma (HNSCC).Using the US Veterans Affairs database, we analyzed 1448 patients with locoregionally advanced HNSCC and known p16 status diagnosed between 2005 and 2015 and treated with surgery, radiotherapy, or chemoradiotherapy. Tumor p16 status was determined through manual review of pathology reports of primary tumor specimens. Oropharyngeal (n = 1061) or nonoropharyngeal (n = 387; hypopharyngeal, laryngeal, or oral cavity) tumor site was determined from tumor registry data and manually reviewed for accuracy. We used multivariable Cox regression to analyze the effect of p16 status on overall survival (OS), cancer-specific survival (CSS), and competing mortality (CM) for oropharyngeal or nonoropharyngeal tumor sites. All statistical tests were two-sided.In multivariable models adjusting for treatment, stage, age, comorbidity, and body mass index, patients with p16-positive tumors had improved OS, CSS, and CM compared with patients with p16-negative tumors in both oropharyngeal (OS: hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.40 to 0.71, P < .001; CSS: HR = 0.50, 95% CI = 0.35 to 0.73, P < .001; CM: HR = 0.59, 95% CI = 0.38 to 0.93, P = .02) and nonoropharyngeal primary sites (OS: HR = 0.41, 95% CI = 0.25 to 0.69, P < .001; CSS: HR = 0.37, 95% CI = 0.18 to 0.77, P = .008; CM: HR = 0.46, 95% CI = 0.23 to 0.95, P = .04). The prognostic impact of p16 status did not statistically significantly differ by primary tumor site for OS, CSS, or CM (Pinteraction > .05).Our findings support the hypothesis that p16 has a similar prognostic role in both nonoropharyngeal and oropharyngeal cancer. Consideration should be given to increased testing for p16 in laryngeal, hypopharyngeal, and oral cavity primaries.

    View details for DOI 10.1093/jnci/djy072

    View details for Web of Science ID 000455209700014

    View details for PubMedID 29878161

    View details for PubMedCentralID PMC6292787

  • Comparison of Comorbidity and Frailty Indices in Patients With Head and Neck Cancer Using an Online Tool JCO CLINICAL CANCER INFORMATICS Vitzthum, L. K., Feng, C. H., Noticewala, S., Hines, P. J., Nguyen, C., Zakeri, K., Sojourner, E. J., Shen, H., Mell, L. K. 2018; 2: 1–9

    Abstract

    Comorbidity is an independent predictor of mortality and treatment tolerance in head and neck cancer and should be considered with regard to treatment intensification. Multiple previously validated models can be used to evaluate comorbidity and propensity to benefit from intensive treatment, but they have not been directly compared.An online tool was developed and used to calculate the Charlson Comorbidity Index (CCI), Adult Comorbidity Evaluation-27 (ACE-27), Cumulative Illness Rating Scale for Geriatrics (CIRS-G), Geriatric 8 (G8), Cancer and Aging Research Group (CARG), and Generalized Competing Event (GCE) scores. To assess interrater variability, five evaluators independently calculated scores on a retrospective cohort of 20 patients. Correlation between models as well as age and performance status were calculated from a cohort of 40 patients.The GCE and G8 models had an excellent (intraclass correlation coefficient and Fleiss' kappa ≥ 0.75) degree of interrater agreement. The CCI, ACE-27, CIRS-G, and CARG had a good (intraclass correlation coefficient and Fleiss' kappa 0.6-0.74) degree of interrater agreement. There was statistically significant correlation between models, especially with the CCI, ACE-27, and CIRS-G indices. Increased age was correlated with an increased CCI score and having moderate to severe comorbidity was correlated with the ACE-27 model. Except for the G8 model, the comorbidity indices were not associated with Eastern Cooperative Oncology Group performance status.We developed an online tool to calculate indices of comorbidity in patients with head and neck cancer with a high degree of reproducibility. Comorbidity is not strongly correlated with performance status and should be independently evaluated in patients.

    View details for DOI 10.1200/CCI.18.00082

    View details for Web of Science ID 000462336800001

    View details for PubMedID 30652602

  • Optimism bias' in contemporary national clinical trial network phase III trials: are we improving? ANNALS OF ONCOLOGY Zakeri, K., Noticewala, S. S., Vitzthum, L. K., Sojourner, E., Shen, H., Mell, L. K. 2018; 29 (10): 2135–39

    Abstract

    Previous studies have found that overestimating treatment effects (i.e. 'optimism bias') leads to underpowered clinical trials. The prevalence of 'optimism bias' in contemporary National Clinical Trials Network (NCTN) cancer clinical trials is unknown.We conducted a systematic review of NCTN phase III randomized trials published from January 2007 to January 2017. We compared the hypothesized versus observed treatment effects in each trial, and examined whether trial-related factors were correlated with the study results. We also reviewed the methods of each protocol to assess whether a rationale for the hypothesized effect size was provided.We identified 161 clinical trials, of which 130 were eligible for analysis. Original protocols could not be located for 8 trials (5.0%). Twenty-eight trials (21.5%) observed a statistically significant difference in the primary end point favoring the experimental treatment. The median ratio of observed-to-expected hazard ratios among trials that observed a statistically significant effect on the primary end point was 1.07 (range: 0.33-1.28) versus 1.32 (range: 0.86-2.02) for trials that did not, compared with 1.34 and 1.86, respectively, for National Cancer Institute (NCI) trials published between 1955 and 2006. An effect size at least as large as the one projected in the protocol trials was observed in 9.8% of trials, compared with 17% of NCI trials published from 1955 to 2006. Most trials (64.6%) provided no rationale to support the magnitude of the proposed treatment effect in the protocol.Despite a reduction in 'optimism bias' compared with previous eras, most contemporary NCTN phase III trials failed to establish statistically significant benefits of new cancer therapies. Better rationalization of proposed effect sizes in research protocols is needed.

    View details for DOI 10.1093/annonc/mdy340

    View details for Web of Science ID 000455165100018

    View details for PubMedID 30412223

    View details for PubMedCentralID PMC6454418

  • The role of p16 as a biomarker in nonoropharyngeal head and neck cancer. Oncotarget Vitzthum, L. K., Mell, L. K. 2018; 9 (70): 33247–48

    View details for DOI 10.18632/oncotarget.26053

    View details for PubMedID 30279955

  • Generalized Competing Event Models Can Reduce Cost and Duration of Cancer Clinical Trials JCO CLINICAL CANCER INFORMATICS Zakeri, K., Panjwani, N., Carmona, R., Shen, H., Vitzthum, L. K., Zhang, Q. E., Murphy, J. D., Mell, L. K. 2018; 2: 1–12

    Abstract

    Generalized competing event (GCE) models improve stratification of patients according to their risk of cancer events relative to competing causes of mortality. The potential impact of such methods on clinical trial power and cost, however, is uncertain. We sought to test the hypothesis that GCE models can reduce estimated clinical trial cost in elderly patients with cancer.Patients with nonmetastatic head and neck (n = 9,677), breast (n = 22,929), or prostate cancer (n = 51,713) were sampled from the SEER-Medicare database. Using multivariable Cox proportional hazards models, we compared risk scores for all-cause mortality (ACM) and cancer-specific mortality (CSM) with GCE-based risk scores for each disease. We applied a cost function to estimate the cost and duration of clinical trials with a primary end point of overall survival in each population and in high-risk subpopulations. We conducted sensitivity analyses to examine model uncertainty.For the purpose of enriching subpopulations, GCE models reduced estimated clinical trial cost compared with Cox models of ACM and CSM in all disease sites. The relative cost reductions with GCE models compared with ACM and CSM models, respectively, were -68.4% and -14.4% in prostate cancer, -38.8% and -18.3% in breast cancer, and -17.1% and -4.1% in head and neck cancer. Cost savings in breast and prostate cancers were on the order of millions of dollars. The GCE model also reduced relative clinical trial duration compared with CSM and ACM models for all disease sites. The optimal risk score cutoff for clinical trial enrollment occurred near the top tertile for all disease sites.GCE models have significant potential to improve clinical trial efficiency and reduce cost, with a potentially large impact in prostate and breast cancers.

    View details for DOI 10.1200/CCI.17.00124

    View details for Web of Science ID 000461551600001

    View details for PubMedID 30652559

  • Head and Neck Soft Tissue Sarcomas Treated with Radiation Therapy. Rare tumors Vitzthum, L. K., Brown, L. C., Rooney, J. W., Foote, R. L. 2016; 8 (2): 6165

    Abstract

    Head and neck soft tissue sarcomas (HNSTSs) are rare and heterogeneous cancers in which radiation therapy (RT) has an important role in local tumor control (LC). The purpose of this study was to evaluate outcomes and patterns of treatment failure in patients with HNSTS treated with RT. A retrospective review was performed of adult patients with HNSTS treated with RT from January 1, 1998, to December 31, 2012. LC, locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and predictors thereof were assessed. Forty-eight patients with HNSTS were evaluated. Five-year Kaplan-Meier estimates of LC, LRC, DFS, and OS were 87, 73, 63, and 83%, respectively. Angiosarcomas were found to be associated with worse LC, LRC, DFS, and OS. Patients over the age of 60 had lower rates of DFS. HNSTSs comprise a diverse group of tumors that can be managed with various treatment regimens involving RT. Angiosarcomas have higher recurrence and mortality rates.

    View details for DOI 10.4081/rt.2016.6165

    View details for PubMedID 27441072

    View details for PubMedCentralID PMC4935821

  • Study of Na+/H+ exchange-mediated pHi regulations in neuronal soma and neurites in compartmentalized microfluidic devices. Integrative biology : quantitative biosciences from nano to macro Vitzthum, L., Chen, X., Kintner, D. B., Huang, Y., Chiu, S. Y., Williams, J., Sun, D. 2010; 2 (1): 58–64

    Abstract

    Regulation of intracellular pH (pH(i)) in neurons is crucial to maintain their physiological function. In the current study, newly-developed polydimethylsiloxane (PDMS) microfluidic devices were used to independently investigate pH(i) regulation in neuronal soma and neurites. Embryonic cortical neurons were cultured in PDMS microfluidic devices with soma growing in one chamber (seeded) and neurites extending through a set of perpendicular microchannels into the opposite parallel chamber (non-seeded). Neurons in the microchambers were characterized by the vital dye calcein-red, polarized mitochondria, and expression of neuronal specific beta-tubulin (type-III), axonal Tau-1 protein, dendritic microtubule associated protein (MAP-2), and Na(+)/H(+) exchanger isoform 1 (NHE-1). Neurites exhibited higher resting pH(i) than soma (7.16 +/- 0.09 vs. 6.90 +/- 0.15). The neurites had a proton extrusion rate 3.7-fold faster than in soma following NH(4)Cl prepulse-mediated acidification (p < 0.05). The difference in the pH(i) regulation rates between neurites and soma can be accounted for by the larger surface area to volume ratio in the neurites. Interestingly, pharmacological inhibition of NHE-1 activity blocked the pH(i) regulation in soma and in neurites by approximately 70% (p < 0.05). Taken together, our study demonstrated that the microfluidic devices provide a useful tool to study neuronal pH(i) regulation in soma and their neurites. We conclude that NHE-1 plays an important role in regulation of pH(i) in both compartments.

    View details for DOI 10.1039/b918440f

    View details for PubMedID 20473413

    View details for PubMedCentralID PMC2875691

  • Global engineering education initiative through student organization. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference Sagstetter, A. M., Vitzthum, L. K., Meyer, J. R., Nimunkar, A. J., Webster, J. G. 2009; 2009: 2022–24

    Abstract

    Engineering is becoming a more globally aware discipline that is revolutionizing the way individuals interact internationally. Engineering World Health (EWH) - Madison Chapter is a student-initiated organization that has developed opportunities to facilitate both local and global engineering education. Through EWH - Madison Chapter student-initiated activities, this organization has developed an interface between Traditional, Technical, and Translational education mediums. This study attests to the development of global engineering programs in the context of biomedical applications.

    View details for DOI 10.1109/IEMBS.2009.5334420

    View details for PubMedID 19964768

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