Timeline


    2017 INFORMS Healthcare Conference. July 26, 2017

    Title: Impact Of False-Positives On The Cost-effectiveness of Lung Cancer Screening

    Presenting Author: Iakovos Toumazis, Postdoctoral Research Fellow, Department of Radiology, Stanford University, iakovos.toumazis[at]stanford.edu

    Co-Author(s):
    • Emily Tsai, University of California, Los Angeles, Los Angeles, CA
    • Ayca Erdogan, San Jose State University, San Jose, CA
    • Summer Han, Stanford University, Stanford, CA
    • Wenshuai Wan, University of Pennsylvania, Philadelphia, PA
    • Ann Leung, Stanford University, Stanford, CA
    • Sylvia K. Plevritis, Stanford University, Stanford, CA

    Abstract:We assess the benefits and costs of various screening strategies for lung cancer (LC) using a data driven microsimulation model. We simulate individuals’ LC progression in the presence and absence of screening strategies, which vary in terms of starting and stopping age, screening frequency, and smoking criteria. We identify the efficiency frontier and show that the cost-effectiveness of LC screening is significantly affected by the management of false-positive results. We examine the effect of the number of subsequent exams and disutility associated with false-positives and conduct univariate sensitivity analyses to test the robustness of our findings to changes in key input model parameters.


    New paper on lung cancer screening compliance July 12, 2017

    Title: Evaluating the impact of varied compliance to lung cancer screening recommendations using a microsimulation model

    Journal: Cancer Causes & Control

    Authors:

    • Summer Han, Stanford University, Stanford, CA
    • Ayca Erdogan, San Jose State University, San Jose, CA
    • Iakovos Toumazis, Stanford University, Stanford, CA
    • Ann Leung, Stanford University, Stanford, CA
    • Sylvia K. Plevritis, Stanford University, Stanford, CA

    Abstract:Background The US preventive services task force (USPSTF) recently recommended that individuals aged 55–80 with heavy smoking history be annually screened by low-dose computed tomography (LDCT), thereby extending the stopping age from 74 to 80 compared to the national lung screening trial (NLST) entry criterion. This decision was made partly with model-based analyses from cancer intervention and surveillance modeling network (CISNET), which assumed perfect compliance to screening. Methods As part of CISNET, we developed a microsimulation model for lung cancer (LC) screening and calibrated and validated it using data from NLST and the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO), respectively. We evaluated population-level outcomes of the lifetime screening program recommended by the USPSTF by varying screening compliance levels. Results Validation using PLCO shows that our model reproduces observed PLCO outcomes, predicting 884 LC cases [Expected(E)/Observed(O) = 0.99; CI 0.92–1.06] and 563 LC deaths (E/O = 0.94 CI 0.87–1.03) in the screening arm that has an average compliance rate of 87.9% over four annual screening rounds. We predict that perfect compliance to the USPSTF recommendation saves 501 LC deaths per 100,000 persons in the 1950 U.S. birth cohort; however, assuming that compliance behaviors extrapolated and varied from PLCO reduces the number of LC deaths avoided to 258, 230, and 175 as the average compliance rate over 26 annual screening rounds changes from 100 to 46, 39, and 29%, respectively. Conclusion The implementation of the USPSTF recommendation is expected to contribute to a reduction in LC deaths, but the magnitude of the reduction will likely be heavily influenced by screening compliance.

    Link: Han S.S., Erdogan S.A, Toumazis I., Leung A., Plevritis S.K., "Evaluating the impact of varied compliance to lung cancer screening recommendations using a microsimulation model", Cance Causes & Control, Online First


    Toumazis receives funding from NIH, June 29, 2017

    Title: Personalized, Dynamic Risk-based Lung Cancer Screening

    Principal Investigator: Iakovos Toumazis, Postdoctoral Research Fellow, Department of Radiology, Stanford University, iakovos.toumazis[at]stanford.edu

    Description: This project focuses on the problem of optimizing lung cancer screening for asymptomatic individuals at risk. The objective of this research is to develop stochastic, dynamic models incorporating past screening exams and the dynamic status of lung cancer risk factors to provide cost-effective, personalized, risk-based screening decisions. The anticipated findings of this proposal will improve the overall effectiveness of screening and enhance the shared decision making process between physicians and patients forming a basis for maximizing health benefit and reducing the harms associated with lung cancer screening.

    For more information click here.


    2016 INFORMS International Conference. June 14, 2016

    Title: Evaluating The Impact Of Diagnostic Biomarkers On The Cost-effective Efficiency Frontier Of Alternative Lung Cancer Screening Strategies

    Presenting Author: Iakovos Toumazis, Postdoctoral Research Fellow, Department of Radiology, Stanford University, iakovost[at]stanford.edu

    Co-Author(s):
    • Ayca Erdogan, San Jose State University, San Jose, CA, ayca.erdogan[at]sjsu.edu
    • Sylvia K. Plevritis, Stanford University, Stanford, CA, sylvia.plevritis[at]stanford.edu

    Abstract: We investigate the benefits and costs of various screening strategies for lung cancer when computerized tomography is combined with a hypothetical diagnostic biomarker test using a data driven microsimulation model. The model simulates individuals’ lung cancer progression in the presence and absence of a biomarker test under different screening strategies, which vary in terms of start age, stop age and frequency of screening. We identify the cost-effective frontier and show that adding a biomarker test may potentially increase the health benefit and decrease the total cost of screening under specific screening strategies. A sensitivity analysis is conducted on the test’s accuracy and cost.


    2016 INFORMS International Conference. June 12, 2016

    Title: Personalized Treatment Decisions For Metastatic Colorectal Cancer Patients

    Presenting Author: Iakovos Toumazis, Postdoctoral Research Fellow, Department of Radiology, Stanford University, iakovost[at]stanford.edu

    Co-Author(s):
    • Murat Kurt, Merck Research Labs, murat.kurt7[at]gmail.com
    • Toumazi Artemis, French National Institute of Health and Medical Research (INSERM), Paris, France, artemis.toumazi[at]gmail.com
    • Loukia G. Karacosta, Postdoctoral Research Fellow, Department of Radiology, Stanford University, loukia[at]stanford.edu
    • Changhyun Kwon, Associate Professor, University of South Florida, chkwon[at]usf.edu

    Abstract: Colorectal cancer (CRC) is the third most lethal cancer in the US affecting both genders. Metastatic CRC (mCRC) is inoperable and rarely curable. Chemotherapy is the only treatment option for mCRC patients. Treatments' toxicity and tumor's drug resistance are identified as main reasons for treatment's failure. We formulated the chemotherapy scheduling problem as a finite-horizon, discrete-time Markov decision process that jointly optimize the duration and sequence of the available drugs. We calibrated our model using a clinical database developed from published clinical trials. The resulting optimal policy improves survival without compromising quality of life.


    CISNET Semi-Annual Meeting. May 11-12, 2016

    As a member of the CISNET Lung group, Iakovos Toumazis attended the Semi-Annual meeting at the Massachusetts General Hospital (MGH) in Boston, MA.


    CISNET Annual Meeting. November 17-18, 2015

    As a member of the CISNET Lung group, Iakovos Toumazis attended the Annual meeting at the NCI in Rockville, MD.


    INFORMS 2015 Presentation. November 04, 2015

    Title: Sequencing Chemotherapy Agents for Metastatic Colorectal Cancer Patients

    Presenting Author: Iakovos Toumazis, Postdoctoral Research Fellow, Department of Radiology, Stanford University, iakovost[at]stanford.edu

    Co-Author(s):
    • Murat Kurt, Merck Research Labs, murat.kurt7[at]gmail.com
    • Toumazi Artemis, Claude Bernard University Lyon 1, Department of Mathematics, artemis.toumazi[at]gmail.com
    • Loukia G. Karacosta, Postdoctoral Research Fellow, Department of Radiology, Stanford University, loukia[at]stanford.edu
    • Changhyun Kwon, Associate Professor, University of South Florida, chkwon[at]usf.edu
    • Daniel A. Goldstein,Fellow, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, daniel.alexander.goldstein[at]emory.edu

    Abstract: Colorectal cancer is the third most lethal cancer in the US affecting both genders. Despite advancements in chemotherapy treatment, long-term survival for the advanced stage of the disease remains poor. With the goal of improving the effectiveness of chemotherapy treatment for metastatic colorectal cancer patients we developed a Markov decision process model that jointly optimize the duration and sequence of the available drugs. The obtained optimal policy improves survival by at least 6 months.


    2015 MDM Annual Presentation. October 19, 2015

    Title: Sequencing Chemotherapy Agents for Metastatic Colorectal Cancer Patients

    Presenting Author: Iakovos Toumazis, Postdoctoral Research Fellow, Department of Radiology, Stanford University, iakovost[at]stanford.edu

    Co-Author(s):
    • Murat Kurt, Merck Research Labs, murat.kurt7[at]gmail.com
    • Toumazi Artemis, Claude Bernard University Lyon 1, Department of Mathematics, Claude Bernard University Lyon 1, France, artemis.toumazi[at]gmail.com
    • Loukia G. Karacosta, Postdoctoral Research Fellow, Department of Radiology, Stanford University, loukia[at]stanford.edu
    • Changhyun Kwon, Associate Professor, University of South Florida, Tampa FL, chkwon[at]usf.edu
    • Daniel A. Goldstein, Fellow, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta GA, daniel.alexander.goldstein[at]emory.edu

    Abstract:
    Purpose: Advancements in chemotherapy treatment have improved long term survival for metastatic colorectal cancer (mCRC) while raising financial concerns. We analyze the cost-effectiveness of clinically accepted combinations of up to three lines of therapies from 8 chemotherapy regimens to evaluate the progress made in colorectal cancer treatment and examine how treatment sequencing affects the effectiveness of treatment plans.
    Methods: We considered the process of administering chemotherapy treatments for mCRC patients where treatments are discontinued when they lead to disease progression or 2 adverse events (AE). Upon an AE, treatment in use is paused for 2 weeks to clean the adverse effects from the event. We calibrated probability distributions for survival, disease progression, and the occurrence of AEs using published data from over 500 clinical trials and evaluated the effectiveness of treatment sequences with respect to quality-adjusted life-years (QALYs) and costs. All outcomes were discounted at a 3% annual rate. We analyzed the sensitivity of the incremental cost effectiveness ratios (ICERs) to costs and various parameters. We assessed the probabilistic efficiency behavior of the sequences, and calculated the number of AEs and occurrences of disease progressions under each of them through simulations.
    Results: We tested 178 different sequences including single and two-lines of chemotherapy regimens and 8 of them formed the efficient frontier. The mean cost/QALY ranged from $5,963 to $87,430 for the efficient sequences. Under none of the efficient treatment plans, the mean number of AEs was more than 2.5 and the events were spaced more than 30 weeks apart on average. The ICER of the treatment plan consisting of FOLFOX+Bevacizumab, FOLFIRI+Bevacizumab and CapeOx was $153,820/QALY over LV5FU alone, and it was most sensitive to treatment disutility, drug cost, and the AE likelihood. While all treatment plans were efficient with at least 50% chance, those on the frontier were more robust in that all of them were efficient with at least 87% chance with more than half of them being efficient with at least 97% chance.
    Conclusions: Improvements in health outcomes may come at a high incremental cost for mCRC patients and be highly dependent on sequencing of treatments. While single and two lines of therapies can be efficient based on cost/QALY, majority of the efficient sequences consist of three-lines of therapies.


    Colorectal chemotherapy scheduling project is accepted to the 2015 Healthcare Special Interest Group meeting at MSOM conference. April 2, 2015

    Toumazis will present the project titled "A Dynamic Programming Approach to Palliative Chemotherapy Scheduling for Metastic Colorectal Cancer Patient," during the 2015 Healthcare Special Interest Group meeting at MSOM conference. The workshop will be held on Sunday June 28, 2015 at the Rotman School of Management, University of Toronto, Ontario, Canada.
    The program will consist of 35-minute presentations of papers followed by 10 minutes of discussion. The selection criteria of the papers favor cutting-edge collaborative work between academics and clinicians/healthcare administrators with important methodological and practical impact.


    Colorectal chemotherapy scheduling paper wins 2015 SHS Graduate Student Paper Competition. January 13, 2015

    Toumazis will present the winning paper, "Scheduling Palliative Chemotherapy Treatments for Metastatic Colorectal Cancer Patients," during the Healthcare Systems Process Improvement Conference in Orlando, Florida (February 18-20, 2015).
    The paper was evaluated based on different criteria, depending on the type of submission, including: potential impact on the field or significance of the work; originality; technical quality (e.g., design, measurement, and analysis methods); presentation quality (writing, data presentation, graphics); length; integration with existing evidence; and any ethical concerns.

    Some of the highlights of the paper are:
    • We model the treatment decision making process for metastatic colorectal cancer patients.
    • Sequence of treatments and their respective duration are jointly optimized.
    • Risk of increasing toxicity levels and developing drug resistance are incorporated in the model.
    • Real clinical data were used to calibrate the model.
    • The proposed optimal treatment schedule prolongs the expected survival of patients.
    • The optimal treatment plan maintains quality of life at high levels.

    Credit should be given to the co-authors of the paper: Murat Kurt, Artemis Toumazi, Loukia G. Karacosta, and Changhyun Kwon.

    Authors of the paper - From left to right: Dr. Murat Kurt, Dr. Loukia G. Karacosta, Mr. Iakovos Toumazis, Dr. Changhyun Kwon (Miss Artemis Toumazi is not present in this photo).
    Iakovos Toumazis (center) receiving the award at the 2015 Healthcare Systems Process Improvement Conference.

    Iakovos Toumazis successfully defends his dissertation proposal. November 24, 2014

    Dissertation Title: "Dynamic Programming approaches to the palliative chemotherapy scheduling problem for metastatic colorectal cancer patients"

    When the student has identified a research topic, has become thoroughly acquainted with previous work in that area, and explored the topic well enough to have developed a credible research plan, the student then writes a dissertation proposal.
    A copy of the proposal must be submitted to each member of the Ph.D. Committee, and is defended approximately two weeks later in an oral examination that lasts approximately two hours.
    The student should schedule the defense after the major professor is satisfied that the topic is significant, research plans are sound, and the student’s qualifications are adequate to address the problem. The student should not hesitate to discuss the proposal with members of the Committee in advance.


    INFORMS 2014 Presentation. November 12, 2014

    Title: Eliciting Cholesterol Management Guidelines' Valuation of Future Life

    Presenting Author: Iakovos Toumazis, Universtiy at Buffalo (SUNY), Buffalo, NY

    Co-Author(s):
    • Brian Denton, Associate Professor, University of Michigan, btdenton[at]umich.edu
    • Murat Kurt, Assistant Professor, University at Buffalo (SUNY), muratkur[at]buffalo.edu
    • Osman Ozaltin, Assistant Professor, North Carolina State University, oyozalti[at]ncsu.edu
    • Nilay Shah, Mayo Clinic, Division of Health Care Policy and Resea, Shah.Nilay[at]mayo.edu

    Abstract: Lipid abnormalities increase the risk of heart attack and stroke. Treatment guidelines are developed to deal with the complexity of treating these abnormalities. We consider the trade-off between the benefits and side effects of statins, and develop an inverse stochastic dynamic program to elicit time valuation of current guidelines. We use clinical data to illustrate the outcomes on Type 2 diabetes patients.


    SMDM Presentation. October 21, 2014

    Title: Eliciting Lipid Management Guidelines' Valuation of Future Life

    Presenting Author: Iakovos Toumazis, Universtiy at Buffalo (SUNY), Buffalo, NY

    Co-Author(s):
    • Osman Ozaltin, Assistant Professor, North Carolina State University, oyozalti[at]ncsu.edu
    • Murat Kurt, Assistant Professor, University at Buffalo (SUNY), muratkur[at]buffalo.edu
    • Brian Denton, Associate Professor, University of Michigan, btdenton[at]umich.edu

    Abstract:
    Purpose: Discount factors are critical in assessing the cost effectiveness of treatments as they reflect the time value of costs and benefits. We considered the trade-off between the benefits and side effects of statins to elicit the discounted present value of each future life year for current lipid management guidelines.
    Method: We formulated the statin initiation problem for Type 2 diabetes patients as a Markov decision process where the state of the process is defined as the patient's total cholesterol and high density lipoprotein (HDL) levels, and the statin initiation decision is revisited annually. We considered six guidelines: Adult Treatment Panel (ATP) III, Canadian, British, European Union, Australian and New Zealand. For each guideline, we used inverse optimization to find the discounted present value of each future life year that makes the guideline non-dominated with respect to total expected QALYs prior to a first major cardiovascular event and the risk of a first major cardiovascular event. For patients diagnosed with Type 2 diabetes at age 40, we used Mayo Clinic electronic medical records to model the progression of their total cholesterol, HDL, triglycerides, systolic blood pressure, and HbA1c. We incorporated the adverse effects of statins into the model using a constant disutility factor.
    Result: Among all guidelines we considered, the underlying present values of future life years for males were never more than those of females. The present value of a life year for males varied from 20% to 70% of that for females between ages 45 and 65. All guidelines were consistent in discounting future with time-varying annual discount factors. Guidelines which initiate statins at earlier ages, such as ATP III, valued the far future more than those which initiate statins relatively later. For males, all guidelines exhibited a sharp decrease in discounting life years after age 45; for females this threshold was at age 55. While no guideline discounted the value of a life year immediately following the diagnosis of Type 2 diabetes, all guidelines were consistent with a present value of < 0.001 years beyond age 80.
    Conclusion: Our analyses show that guidelines discount future life years with time-variant annual discount factors and show a substantial difference between the implied present value of life years for males and females.


    Iakovos Toumazis is now a U.S. permanent resident. June 30, 2014

    Iakovos Toumazis passes A-exam. March 17, 2014

    The Ph.D. Advanced Examination, sometimes called the "Prelim” or “A-exam”, is taken near the end of formal course work, before substantial dissertation research has begun.
    The format of the exam consists of questions from the individual committee members to which written responses are required. Although questions do not necessarily have to pertain to the student's intended dissertation research, one of the exam’s purposes is to gauge the student's capability for pursuing research in his or her area of interest.


    Toumazis' Dissertation Committee formed. February 2, 2014
    Co-chairs:
    • Changhyun Kwon, Assistant Professor, University at Buffalo, chkwon[at]buffalo.edu
    • Murat Kurt, Assistant Professor, University at Buffalo, muratkur[at]buffalo.edu

    Member:


    INFORMS 2013 presentation. October 8, 2013

    Title: Advanced Risk Measures Applied in Hazardous Materials Routing

    Presenting Author: Iakovos Toumazis, PhD Student, University at Buffalo, iakovost[at]buffalo.edu

    Co-Author: Changhyun Kwon, Assistant Professor, University at Buffalo, chkwon[at]buffalo.edu

    Abstract: New classes of risk measures are introduced and analyzed for local route planning in hazardous materials transportation. In particular, value-at-risk, conditional value-at-risk, and a general class of spectral risk measures are considered for risk-averse and flexible routing methods. Tractable computational methods are suggested.