Dr. Liao's research activities aim to improve the therapeutic ratio of radiotherapy for thoracic malignancies through translational research. Specifically, her efforts focus on personalizing chemoradiotherapy for lung cancer by reducing treatment-related toxicity, and increasing cancer cure rates by using predictive biomarker strategies and advanced radiation delivery technology. She has continued her leadership role in conducting practice-changing clinical trials locally and nationally.

Dr. Liao's five most significant contributions in research include the following:

Successfully designed, led, and completed the first of the kind prospective randomized trial comparing IMRT and proton therapy for lung cancer. Dr. Liao is Principal Investigator of the first prospective randomized NCI PO1 funded multi-institutional trial “ A Bayesian Randomized trial of Image-Guided Adaptive Conformal Photon vs Proton Therapy, with Concurrent Chemotherapy, for Locally Advanced Non-Small Cell Lung Carcinoma: Treatment-Related Pneumonitis and Locoregional Recurrence ( NCT00915005)”. This clinical protocol compared proton and photon therapy for a “hard to treat” cancer. This protocol was critical in securing funding for her program project grant 2-P01CA021239, “Optimizing Proton Therapy,” PI Thomas Delaney; 9/25/2008−7/31/2013; $8,734,885 ($1,775,617/year). The hypothesis of this trial was based on the research findings from item 2 below, that the unique dosimetric characteristics of proton beams will reduce the dose and volume of the normal lung to radiation, hence further decreasing treatment-related lung toxicity. This protocol met the enrollment goal on 3/2014, and the first result was reported on 2016 ASCO meeting as a plenary presentation and included in the 2016 Best of ASCO. The manuscript was first submitted to the Lancet Journal with recommended transfer to the Lancet Respiratory Medicine, which she declined. The final version of the manuscript was resubmitted to JCO.

Translational research on secondary analyses on the data accumulated from protocol NCT00915005. This trial contributed greatly to the understanding of proton therapy and produced much valuable data. Dr. Liao worked with collaborators and was able to secure funding for a U19 ( 2U19CA021239-35, NIH/NCI, PI - Radhe Mohan, 9/25/2014-8/31/2018, $1,925,520 ($385,104/year) ), and a CPRIT ( RP160232, PI - Dragan Mirkovic/Pablo Yepes, 3/1/2016-2/28/2019, $835,395 ($275,114/year)) grant to perform secondary analyses on the data accumulated from this trial. Given the rapid proliferation of proton therapy facilities worldwide despite the lack of level I evidence of its effectiveness in lung cancer, Dr. Liao believes that the results are potentially practice-changing. She expects that results from ongoing analyses of secondary objectives including imaging, patient-reported outcomes, blood biomarkers, and cost effectiveness will considerably advance the state of the art in proton therapy, as will ongoing translational research to correlate biological and physical factors affecting response to protons vs. photons and radiation physics studies to assess the influence of uncertainties on proton therapy.

Established a bio-specimen repositories for biomarker research and facilitate translational research. This research effort is an expansion of the clinical trial as one of the secondary objectives and two protocols (Protocol Lab 2009-0307, PA13-0786). The aim is to identify predictive biomarkers for treatment outcome and to help select patients for the most effective treatment. The collected biospecimen including blood, plasma, serum, genome DNA, urine, and saliva are a rich resource for correlative studies to facilitate extramural funding. One example is that, using the blood samples from this study, combined with the clinical and radiation therapy dosimetric data, Dr. Liao is able to spearhead a research effort to study cardiac injury after chemoradiation for lung cancer. In the scope of the work, she has established research contract with ROCHE to use their high sensitive Cardiac Troponin kits to obtain preliminary data for extramural funding. Dr. Liao's R21 grant (1R21 CA222749-01) is entitled “Proton therapy to reduce heart damage for lung cancer patients”. Under the umbrellas of biomarker study and the infrastructure that she created, the thoracic service has accumulated a significant amount of biospecimen and clinical data on patients received concurrent chemoradiation treatment in the department of Radiation Oncology. The collaborative research effort has been expanded nationally and internationally with MGH, MAASTRO.

Becoming a national leader in clinical trials on proton therapy. Proton therapy is more costly than even the best currently available photon technology, and evidence demonstrating clinical benefit is increasingly demanded to justify the financial burden on the healthcare system. However, randomized trials comparing outcomes between different treatment technologies are practically non-existent, and trials of protons vs. photons are no exception. To establish level 1 evidence for proton therapy, we worked with the leadership of Corporate group RTOG (now NRG) and institutions and hospitals with proton facilities (total 15 now and the number continues to increase) and developed RTOG 1308, a “Phase III Randomized Trial Comparing Overall Survival after Photon versus Proton Radiochemotherapy for Inoperable Stage II-IIIB NSCLC”. This protocol was funded through CTEP. She serves as the Principle Investigator for this historical protocol in the history of particle therapy for thoracic malignancies. This trial has been active since 2014, and a total of 99 patients have been recruited to this trial. This phase III trial is probably the only opportunity for radiation oncology community to compare the survival after photons and protons chemoradiation for lung cancer patients.

Continuing her efforts in research of technological advancement including proton, Dr. Liao is leading another Randomized Phase I/II trial of image-guided, intensity-modulated photon (IMRT) or scanning beam proton therapy (IMPT) both with simultaneous integrated boost (SIB) dose escalation to the gross tumor volume (GTV) with concurrent chemotherapy for stage II/III non-small cell lung cancer (NSCLC) (MDA protocol: 2011-1058). This protocol use a novel radiation therapy technique called simultaneous integrated boost, which will delivery differential higher doses to tumor and lower dose to normal structure. This trial is significant because it is the only protocol that assess the impact of intensity modulated radiation therapy using either photon or protons, whereas the all the previous trials compared 3D Conformal proton with intensity modulated photons. She has completed the phase I portion and currently on phase II portion of this trial.

Expanded research collaborations with imaging, symptom research, and behavior science.

Dr. Liao has continued a long term collaboration with the symptom research department in the institution and was a Co-Principal Investigator on an R21 grant that investigated correlation of inflammatory cytokines and symptom burden in lung cancer patients who underwent chemoradiation. The final result has been published in the Journal of Clinical Oncology. The institution was awarded an RO1 grant entitled “ Reducing the symptom burden produced by aggressive cancer therapies", 5 R01 CA026582-31, NIH/NCI, PI - Charles Cleeland, 5/1/2013-4/30/2015”. $424,012 ($84,800/year). We are the first group reporting decreased symptom burden in patients treated with proton radiation compared with those treated with IMRT or 3D CRT.

- Dr. Liao has always been interested in imaging biomarker. She has received sister institution network finding for a project “Diffusion-weighted magnetic resonance imaging for early response assessment of neoadjuvant chemoradiation for squamouse cell carcinoma of the esophagus, Sister Institution Network Fund Application, UTMDACC, 1/1/2015-12/31/2016, $99,998 ($49,999/year)”. This project is a collaborative effort with 3 institutions in China and MD Anderson Cancer Center, and this project is ongoing.

- Dr. Liao is the institutional PI for another innovative project “A Randomized Trial of Incentives for Research Participation, (1R01CA197332-01, NIH/NCI, PI - Scott D. Halpern, 7/1/2015-6/30/2020, $288,642, ($67,841/year)). This clinical trial is built upon the population of RTOG 1308m to address the question if financial incentives impacts on patient participation of clinical trial. This project is currently ongoing as well.

Dr. Liao's translational and clinical research activities have been highly productive, as evidenced in her CV by publications in highly respected peer-reviewed scientific journals, by invitations to write review articles, and by invitations to national and international meetings as keynote or panel speakers. She has accumulated rich experience and knowledge, developed leadership skills and effectiveness to conduct critical research projects and corporate trials. Dr. Liao anticipates that her research will continue its success as many completed projects mature with results presented to and accepted by the international scientific community, and ongoing projects progress smoothly.