Brachytherapy; Dose-Response Relationship, Radiation; Electrons; Gamma Rays; Radiotherapy; Radiotherapy Planning, Computer-Assisted; X-Rays; Photons; Radiotherapy, Intensity-Modulated
Public Health Interests
Cancer; Medical technology; Modeling; Nanotechnology; Prostate cancer; Radiation
Therapeutic Radiology: Radiological Physics
Radiation oncology is a technology-driven medical specialty. It utilizes high-energy photons and charged particles to destroy cancer cells inside human body. The goal of radiation therapy is to maximize radiation dose deliverable to the tumor while minimizing collateral damages to the nearby healthy tissues and critical organs. A successful administration of radiation therapy requires good understanding of the dose-deposition properties of ionizing radiation as well as the technical pitfalls involved in the planning, delivery and evaluation of radiation treatments, in addition to making a correct diagnosis and understanding the basic cancer biology. My research has focused on the following three main areas: 1) Developing radiation dosimetry and quality assurance tools to improve the accuracy and efficacy of radiation radiation; 2) Developing image-guidance strategies and tools for effective implementation of invidualized adaptive radiotherapy; and 3) Radiobiological modeling of human tissue dose-response for designing new and improved radiation therapy treatment strategies.
Extensive Research Description
An example of my research in basic radiation dosimetry involved the determination of dose rate constant (DRC) for radioactive sources used in interstitial brachytherapy. The DRC is a fundamental quantity that links the intrinsic dosimetry properties of a radioactive source to the proper fulfillment of prescription dose in patient dosimetry. An accurate determination of DRC has been regarded as one of the most important tasks in characterizing the basic properties of radioactive sources. However, accurate determination of DRC for the sources emitting photons of less than 50 keV has remained a challenge in radiation dosimetry because of the lack of a suitable absolute dosimeter for accurate measurement of doses near the source. Existing experimental techniques have large overall uncertainties on the order of 8-10% at one standard deviation and 15% at the 95% confidence level.
We have developed a general formalism for DRC that permitted detailed elucidation of the general properties underlying the determination of DRC. Based on this theoretical finding, we have subsequently developed a new photon spectrometry technique for accurate determination of the DRC of low-energy interstitial brachytherapy sources. This new technique eliminated many of the difficulties associated with the existing experimental techniques and has provided new and independent determinations of DRC for over twenty low-energy brachytherapy source models. Its application has led to the discovery of a 15% discrepancy in the DRC reported for a newly marketed cesium-131 source and has helped resolve a large discrepancy in the DRCs reported in literature for a novel polymer-encapsulated palladium-103 source. The photon spectrometry technique is efficient and robust. We are developing it into a national resource for DRC determination and for periodic quality assurance check of DRC.
An example of my research work in treatment plan optimization and evaluation involved the derivation of a new radiobiological formalism for biologically effective dose (BED) of permanent interstitial brachytherapy (PIB) using sources of different decay half-lives. In PIB, the cancer cells are subjected to continuous photon irradiation. Because tumor cell repopulation and sub-lethal damage repair occur simultaneously during dose delivery, the net cell kill and therefore the clinical efficacy of PIB depend not only on the delivered dose but also on the interplay between the temporal patterns of dose delivery and cellular kinetics.
The BED formula captures this interplay and has enabled systematic evaluation of the potential clinical impacts of using mixed sources on cancers presenting different biological properties. This formalism has also enabled us to systematically examine the radiobiological effects of prostate edema in PIB for early stage prostate cancer and many of the theoretical issues related to the design of an effective dose compensation approach for edema-induced dose deficits.
This latter application has provided some of the preliminary data for a R01 research project currently funded by NIH since September 2008 (R01CA134627-01 Prostate Edema in Permanent Interstitial Brachytherapy, PI: Zhe Chen, Ph.D). The R01 project aims to quantitatively characterize the dosimetric and radiobiologic effects of prostate edema and to develop effective therapeutic interventions so that the efficacy of PIB can be optimized for each individual prostate cancer patient.
Other examples of my research work have dealt with clinical dosimetry and quality assurance for radiation therapy techniques ranging from intensity-modulated radiation therapy (IMRT), total-skin electron therapy (TSET) for cultaneous T-cell lymphoma, total-body irradiation (TBI) for bone marrow transplant and image guidance in the planning, delivery and evaluation of radiation therapy.
- Optically stimulated luminescence dosimetry for in vivo verification of total-body irradiation (TBI) for bone marrow transplant
- Intervention strategies for effective management of edema-induced dose variations in permanent interstitial brachytherapy for prostate cancer
- Photon spectrometry for dosimetric characterization of low energy photon-emitting radioactive sources in interstitial brachytherapy
- Quantifying and managing the dosimetric effects of respiratory motion on image-guided stereotactic body radiosurgery for inoperable lung tumors
- Image-guided adaptive radiotherapy for prostate cancer
- Harder EM, Chen ZJ, Park HS, Mancini BR, Decker RH. Dose-Volume Predictors of Esophagitis After Thoracic Stereotactic Body Radiation Therapy. Am J Clin Oncol. 2015 May 15. [Epub ahead of print]
- Liu H, Ye J, Kim JJ, Deng J, Kaur MS, Chen Z. Dosimetric comparison of two arc-based stereotactic body radiotherapy techniques for early-stage lung cancer. Med. Dosimetry, 2015, 40, 76-81.
- Nath SK, Chen Z, Rowe B, Blitzblau R, Aneja S, Grube BJ, Horowitz NR, Weidhass JB. A phase II trial of balloon-catheter partial breast brachytherapy optimization in the treatment of stage 0, I, and IIA breast carcinoma. J. Radiat Oncol, 2014, 3, 371-378.
- Abbas H, Chang B, Chen Z. Motion management in gastrointestinal cancers. J. Gastrointest Oncol, 2014, 5, 223-235.
- Klein EE, Dogan N, Chen Z, Fiorino C, Oncology Scan – The vision of medical physics. Int J Radiat Oncol Biol Phys, 2014, 88, 251-253.
- Abolfath RM, Carlson DJ, Chen ZJ, Nath R. A molecular dynamics simulation of DNA damage induction by ionizing radiation. Phys Med Biol. 2013 Oct 21;58(20):7143-57. doi: 10.1088/0031-9155/58/20/7143. Epub 2013 Sep 20.
- Lloyd S, Chen Z, Foss FM, Girardi M, Wilson LD. Acute toxicity and risk of infection during total skin electron beam therapy for mycosis fungoides. J Am Acad Dermatol. 2013 Oct;69(4):537-43. doi: 10.1016/j.jaad.2013.04.063. Epub 2013 Jul 9.
- Chen Z, Bongiorni P, Nath R, Experimental characterization of the dosimetric properties of a newly designed I-Seed model AgX100 125I interstitial brachytherapy source. Brachytherapy, 2012, 11:476-482.
- Chen Z, Roberts KB, Decker R, Pathare P, Rockwell S, Nath R, The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers. Phys Med Biol, 2011, 56: 4895-4912.
- Carlson DJ, Keall PJ, Loo BW Jr, Chen ZJ, Brown JM. Hypofractionation results in reduced tumor cell kill compared to conventional fractionation for tumors with regions of hypoxia. Int J Radiat Oncol Biol Phys. 2011 Mar 15;79(4):1188-95. doi: 10.1016/j.ijrobp.2010.10.007. Epub 2010 Dec 22.
- Chen ZJ, Nath R. A systematic evaluation of the dose-rate constant determined by photon spectrometry for 21 different models of low-energy photon-emitting brachytherapy sources. Phys Med Biol. 2010 Oct 21;55(20):6089-104.
- Chen Z, Bongiorni P, Nath R. Impact of source-production revision on the dose-rate constant of 131Cs interstitial brachytherapy sources. Med Phys. 2010 Jul;37(7):3607-10.
- Nath R, Bice WS, Butler WM, Chen Z, Meigooni AS, Narayana V, Rivard MJ, Yu Y; AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: report of Task Group 137. Med Phys. 2009 Nov;36(11):5310-22.
- Chen ZJ, Deng J, Roberts K, Nath R. On the need to compensate for edema-induced dose reductions in preplanned (131)Cs prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2008 Jan 170(1):303-10. Epub 2007 Nov 5.
- Chen ZJ, Nath R. Photon spectrometry for the determination of the dose-rate constant of low-energy photon-emitting brachytherapy sources. Med Phys. 2007 Apr34(4):1412-30.
- Nath R, Chen ZJ. Silver fluorescent x-ray yield and its influence on the dose rate constant for nine low-energy brachytherapy source models. Med Phys. 2007 Oct34(10):3785-93.
- Chen Z, Deng J, Roberts K, Nath R. Potential impact of prostate edema on the dosimetry of permanent seed implants using the new 131Cs (model CS-1) seeds. Med. Phys. 2006 33:968-75.
- Nath R, Bongiorni P, Chen Z, Gragnano J, Rockwell S. Dose rate dependence of the relative biological effectiveness of 103Pd for continuous low dose rate irradiation of BA1112 rhabdomyosarcoma cells in vitro relative to acute exposures. Int J Radiat Biol. 2005 Sep;81(9):689-99.
- Nath R, Bongiorni P, Chen Z, Gragnano J, Rockwell S. Relative biological effectiveness of 103Pd and 125I photons for continuous low-dose-rate irradiation of Chinese hamster cells. Radiat Res. 2005 May;163(5):501-9.
- Nath R, Bongiorni P, Chen Z, Gragnano J, Rockwell S. Development of a rat solid tumor model for continuous low-dose-rate irradiation studies using 125I and 103Pd sources. Brachytherapy. 2004;3(3):159-72.
- Chen Z, Agostinelli AG, Wilson LD, Nath R. Matching the dosimetry characteristics of a dual-field Stanford technique to a customized single-field Stanford technique for total skin electron therapy. Int J Radiat Oncol Biol Phys. 2004 Jul 1;59(3):872-85.
- Chen Z, Nath R. Biologically effective dose (BED) for interstitial seed implants containing a mixture of radionuclides with different half-lives. Int J Radiat Oncol Biol Phys. 2003 Mar 1;55(3):825-34.
- Chen Z, Xing L, Nath R. Independent monitor unit calculation for intensity modulated radiotherapy using the MIMiC multileaf collimator. Med Phys. 2002 Sep;29(9):2041-51.