Photo of Noah C. Choi,  MD, DMRT

Noah C. Choi, MD, DMRT

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-5184
Fax: (617) 726-3603

Noah C. Choi, MD, DMRT

Massachusetts General Hospital


  • Professor, Radiation Oncology, Harvard Medical School
  • Director, Thoracic Radiation Oncology, Radiation Oncology , Massachusetts General Hospital


Research Abstract

I have searched for means to improve clinical outcome of patients with lung cancer. For this goal, I have divided my effort into two parts:

(A). Bioimaging in Radiotherapy for Lung Cancer: I have searched for molecular biomarkers that are surrogates for tumor response to radiotherapy (RT) or chemo-radiotherapy (CRT) in lung cancer. Fluoro-2-deoxyglucose (FDG) is glucose analog. Thus, 18F-FDG PET can measure FDG uptake representing glucose metabolism in vivo noninvasively.

To determine molecular bioimaging biomarkers that are capable for identifying patients with residual cancer after standard dose of RT or CRT and for guiding supplementary dose of RT or salvage surgery, I have conducted a prospective study, Bioimaging in Radiotherapy for Lung Cancer (Partners Protocol 03-282) to measure metabolic response parameters (MRPs) with which novel strategy, individualized RT can be developed. This was supported by NIH/NIBIB grant R01 EB002907. Specific aims of this study were:

(1). Investigate the time-course of metabolic response, measured with 18F-FDG PET, to RT or CRT in lung cancer and determine the earliest time point where the nadir of FDG uptake representing the maximum metabolic response (MRglc-MMR) is attainable.

(2). Determine correlation between the nadir value of residual FDG uptake representing MMR (MRglc-MMR) after RT or CRT and subsequent complete tumor control at 12 months.

(3). Determine the values of MRglc-MMR that correspond to tumor control probability (TCP) ≥95%, 90%, 75% and 50% at 12 months.

(4). Determine the optimum cutoff value of MRglc-MMR based on its predicted TCP, sensitivity (having residual cancer) and specificity (having no residual cancer).

The update of this study showed the following: (1). MRglc-MMR is attainable 10 days (S2) after completion of standard dose of RT or CRT, (2). Residual MRglc at S2 is strongly correlated with tumor control probability (TCP) at 12 months (m). Their values corresponding to TCP 95%, 90% and 50% are 0.70, 0.91, and 1.95 of maximum standard uptake value (SUVmax) and 0.036, 0.050 and 0.134 μmol/min/gm of simplified kinetic method (SKM), respectively, and (3). The optimum cutoff value at S2 is SUVmax ≤1.45 or MRglc ≤0.071 μmol/min/gm (SKM) with corresponding predicted TCP 80%, sensitivity 100% and specificity 63%. This means that this cutoff value will identify all patients with residual cancer for supplementary therapy while it still includes 37% of patients who already attained complete tumor control for additional therapy. To minimize the magnitude of false positive group, we tested 3’-deoxy-3’-[18F]-fluorothymidine (18FFLT) PET in a cohort of patients with increased MRglc at 10 days through 6 m months after RT suggesting either local recurrence or inflammation, and 18F-FLT PET was able to distinguish local recurrence from inflammation correctly with a sensitivity of 83% and a specificity of 89%. Therefore, 18F-FLT PET might be useful in supplementing 18F-FDG PET in this subgroup of patients. We will continue to refine MRPs including the cutoff values.

(B). Proton Therapy for Lung Cancer: I have collaborated with MD Anderson Cancer Center as MGH principal investigator for two proton protocols in lung cancer. They are: (1): Partners Protocol 09-247 (Phase II Bayesian randomized trial of image-guided adaptive conformal photon vs proton therapy, with concurrent chemotherapy, for locally advanced non-small cell lung carcinoma with study endpoints of treatment related pneumonitis and locoregional recurrence; (2) Partners Protocol 09-266 (Phase II escalated/accelerated proton radiotherapy for inoperable stage I (T1-T2, N0, M0) and selected stage II (T3N0M0) non-small cell lung cancer. I am also co-study chair for RTOG (NRG) protocol 1308 (Partners protocol 14-268), a phase III randomized trial comparing overall survival after photon versus proton radiotherapy and concurrent chemotherapy for inoperable stage II-IIIB NSCLC.


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  • Chang JY, Zhang W, Komaki R, Choi NC, Chan S, Gomez D, O'Reilly M, Jeter M, Gillin M, Zhu X, Zhang X, Mohan R, Swisher S, Hahn S, Cox JD. Long-term outcome of phase I/II prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer. Radiother Oncol 2017. PubMed
  • Choi NC, Gainor J, Ackman J, Lim R, Sharp GC, El Fakhri G, Niemierko A. ORAL02.03: Robust Correlation Between Metabolic Response Measured with (18)F-FDG PET Soon After Therapy and Clinical Outcome in Lung Cancer: Topic: Radiation Oncology. J Thorac Oncol 2016; 11:S253-S254. PubMed
  • Mak KS, Gainor JF, Niemierko A, Oh KS, Willers H, Choi NC, Loeffler JS, Sequist LV, Shaw AT, Shih HA. Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases. 2015. PubMed
  • Mumenthaler SM, Foo J, Choi NC, Heise N, Leder K, Agus DB, Pao W, Michor F, Mallick P. The Impact of Microenvironmental Heterogeneity on the Evolution of Drug Resistance in Cancer Cells. Cancer Inform 2015; 14:19-31. PubMed
  • Shusharina N, Cho J, Sharp GC, Choi NC. Correlation of (18)F-FDG avid volumes on pre-radiation therapy and post-radiation therapy FDG PET scans in recurrent lung cancer. Int J Radiat Oncol Biol Phys 2014; 89:137-44. PubMed
  • Choi NC, Chun TT, Niemierko A, Ancukiewicz M, Fidias PM, Kradin RL, Mathisen DJ, Lynch TJ, Fischman AJ. Potential of 18F-FDG PET toward personalized radiotherapy or chemoradiotherapy in lung cancer. Eur J Nucl Med Mol Imaging 2013. PubMed
  • Lee MS, Mamon HJ, Hong TS, Choi NC, Fidias PM, Kwak EL, Meyerhardt JA, Ryan DP, Bueno R, Donahue DM, Jaklitsch MT, Lanuti M, Rattner DW, Fuchs CS, Enzinger PC. Preoperative cetuximab, irinotecan, cisplatin, and radiation therapy for patients with locally advanced esophageal cancer. Oncologist 2013; 18:281-7. PubMed
  • Mak RH, Alexander BM, Asomaning K, Heist RS, Liu CY, Su L, Zhai R, Ancukiewicz M, Napolitano B, Niemierko A, Willers H, Choi NC, Christiani DC. A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy. Cancer 2012. PubMed
  • Westover KD, Seco J, Adams JA, Lanuti M, Choi NC, Engelsman M, Willers H. Proton SBRT for medically inoperable stage I NSCLC. J Thorac Oncol 2012; 7:1021-5. PubMed
  • Alexander BM, Wang XZ, Niemierko A, Weaver DT, Mak RH, Roof KS, Fidias P, Wain J, Choi NC. DNA repair biomarkers predict response to neoadjuvant chemoradiotherapy in esophageal cancer. Int J Radiat Oncol Biol Phys 2012. PubMed
  • Mak RH, Doran E, Muzikansky A, Kang J, Neal JW, Baldini EH, Choi NC, Willers H, Jackman DM, Sequist LV. Outcomes after combined modality therapy for EGFR-mutant and wild-type locally advanced NSCLC. Oncologist 2011; 16:886-95. PubMed
  • Mak RH, Digumarthy SR, Muzikansky A, Engelman JA, Shepard JA, Choi NC, Sequist LV. Role of 18F-fluorodeoxyglucose positron emission tomography in predicting epidermal growth factor receptor mutations in non-small cell lung cancer. Oncologist 2011; 16:319-26. PubMed
  • Mak RH, Mamon HJ, Ryan DP, Miyamoto DT, Ancukiewicz M, Kobayashi WK, Willett CG, Choi NC, Blaszkowsky LS, Hong TS. Toxicity and outcomes after chemoradiation for esophageal cancer in patients age 75 or older. 2010; 23:316-23. PubMed
  • Mori S, Lu HM, Wolfgang JA, Choi NC, Chen GT. Effects of interfractional anatomical changes on water-equivalent pathlength in charged-particle radiotherapy of lung cancer. J. Radiat. Res. 2009; 50:513-9. PubMed
  • Gaissert HA, Keum DY, Wright CD, Ancukiewicz M, Monroe E, Donahue DM, Wain JC, Lanuti M, Allan JS, Choi NC, Mathisen DJ. POINT: Operative risk of pneumonectomy--influence of preoperative induction therapy. J Thorac Cardiovasc Surg 2009; 138:289-94. PubMed
  • Patel AA,Wolfgang JA,Niemierko A,Hong TS,Yock T,Choi NC. Implications of respiratory motion as measured by four-dimensional computed tomography for radiation treatment planning of esophageal cancer. Int J Radiat Oncol Biol Phys 2009; 74:290-6. PubMed
  • Roedl JB,Colen RR,Holalkere NS,Fischman AJ,Choi NC,Blake MA. Adenocarcinomas of the esophagus: response to chemoradiotherapy is associated with decrease of metabolic tumor volume as measured on PET-CT. Comparison to histopathologic and clinical response evaluation. Radiother Oncol 2008; 89:278-86. PubMed
  • Kozak KR, Hong TS, Sluss PM, Lewandrowski EL, Aleryani SL, Macdonald SM, Choi NC, Yock TI. Cardiac blood biomarkers in patients receiving thoracic (chemo)radiation. Lung Cancer 2008; 62:351-5. PubMed
  • Rietzel E, Liu AK, Chen GT, Choi NC. Maximum-Intensity Volumes for Fast Contouring of Lung Tumors Including Respiratory Motion IN 4DCT Planning. Int J Radiat Oncol Biol Phys 2008; 71:1245-52. PubMed
  • Halasz LM, Choi NC. Does prophylactic cranial irradiation reduce the incidence of brain metastases in extensive small-cell lung cancer? Nat Clin Pract Oncol 2008; 5:308-9. PubMed
  • Wright CD, Choi NC, Wain JC, Mathisen DJ, Lynch TJ, Fidias P. Induction chemoradiotherapy followed by resection for locally advanced Masaoka stage III and IVA thymic tumors. Ann Thorac Surg 2008; 85:385-9. PubMed
  • Mori S, Wolfgang J, Lu HM, Schneider R, Choi NC, Chen GT. Quantitative assessment of range fluctuations in charged particle lung irradiation. Int J Radiat Oncol Biol Phys 2007; 70:253-61. PubMed
  • Sher DJ, Wolfgang JA, Niemierko A, Choi NC. Quantification of mediastinal and hilar lymph node movement using four-dimensional computed tomography scan: implications for radiation treatment planning. Int J Radiat Oncol Biol Phys 2007; 69:1402-8. PubMed
  • Wright CD, Fidias P, Choi NC, Shepard JA, Hasserjian RP. Case records of the Massachusetts General Hospital. Case 16-2007. A 61-year-old man with a mediastinal mass. N Engl J Med 2007; 356:2185-93. PubMed
  • Rietzel E, Liu AK, Doppke KP, Wolfgang JA, Chen AB, Chen GT, Choi NC. Design of 4D treatment planning target volumes. Int J Radiat Oncol Biol Phys 2006; 66:287-95. PubMed
  • Roof KS, Coen J, Lynch TJ, Wright C, Fidias P, Willett CG, Choi NC. Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer. Int J Radiat Oncol Biol Phys 2006; 65:1120-8. PubMed
  • Flampouri S, Jiang SB, Sharp GC, Wolfgang J, Patel AA, Choi NC. Estimation of the delivered patient dose in lung IMRT treatment based on deformable registration of 4D-CT data and Monte Carlo simulations. Phys Med Biol 2006; 51:2763-79. PubMed
  • Mohiuddin MM, Choi NC. The role of radiation therapy in non-small cell lung cancer. Semin Respir Crit Care Med 2005; 26:278-88. PubMed
  • Rietzel E, Chen GT, Choi NC, Willet CG. Four-dimensional image-based treatment planning: Target volume segmentation and dose calculation in the presence of respiratory motion. Int J Radiat Oncol Biol Phys 2005; 61:1535-50. PubMed
  • Shih HA, Jiang SB, Aljarrah KM, Doppke KP, Choi NC. Internal target volume determined with expansion margins beyond composite gross tumor volume in three-dimensional conformal radiotherapy for lung cancer. Int J Radiat Oncol Biol Phys 2004; 60:613-22. PubMed
  • Lynch TJ, Wright CD, Choi NC, Aquino SL, Mark EJ. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 26-2004. A 56-year-old woman with cough and a lung nodule. N Engl J Med 2004; 351:809-17. PubMed
  • Choi NC. Radioprotective effect of amifostine in radiation pneumonitis. Semin Oncol 2004; 30:10-7. PubMed
  • Roof KS, Fidias P, Lynch TJ, Ancukiewicz M, Choi NC. Radiation dose escalation in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 2003; 57:701-8. PubMed
  • Wirth LJ, Lucca J, Ostler P, Fidias P, Lynch C, J. Induction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: a Phase I study. Clin Cancer Res 2003; 9:1698-704. PubMed
  • Roof KS, Fidias P, Lynch TJ, Choi NC. Radiation dose intensification in limited-stage small-cell lung cancer. Clin Lung Cancer 2003; 4:339-46. PubMed
  • Choi NC, Fischman AJ, Niemierko A, Ryu JS, Lynch T, Wain J, Wright C, Fidias P, Mathisen D. Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2002; 54:1024-35. PubMed
  • Padera TP, Kadambi A, di Tomaso E, Carreira CM, Brown EB, Boucher Y, Choi NC, Mathisen D, Wain J, Mark EJ, Munn LL, Jain RK. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 2002; 296:1883-6. PubMed
  • Wright CD, Menard MT, Wain JC, Donahue DM, Grillo HC, Lynch TJ, Choi NC, Mathisen DJ. Induction chemoradiation compared with induction radiation for lung cancer involving the superior sulcus. Ann Thorac Surg 2002; 73:1541-4. PubMed
  • Ryu JS, Choi NC, Fischman AJ, Lynch TJ, Mathisen DJ. FDG-PET in staging and restaging non-small cell lung cancer after neoadjuvant chemoradiotherapy: correlation with histopathology. Lung Cancer 2002; 35:179-87. PubMed