Early Prediction of Pathological Response of Chemoradiotherapy with FLT PET

Summary

Principal Investigator: KS CLIFFORD CHAO
Abstract: [unreadable] DESCRIPTION (provided by applicant): The overall goal of this pilot clincal imaging project is to determine the efficacy of 3'-deoxy-3'-18F- fluorothymidine (18F-FLT) PET to accurately predict pathological complete response (pathCR) early during treatment in patients with esophageal carcinoma undergoing preoperative chemoradiation. Approximately 600,000 new cases of esophageal cancer are diagnosed each year in the world, including approximately 13,900 new cases in the United States. Despite significant improvements in surgical management, long-term survival rates in patients with esophageal cancer have not changed dramatically. Achievement of pathCR after pre-operative chemoradiotherapy (CRT) is associated with improved patient outcomes; however, there is no effective method to predict pathological response before surgery. Thus, a patient with pathCR, for whom esophagectomy may be unnecessary, still undergoes surgery and faces the prohibitive side effects of this drastic surgical procedure. Additionally, CRT is associated with considerable morbidities and tools to predict and avoid ineffective therapy are lacking. Because deregulated proliferation is one of the hallmarks of cancer and its proliferation rate is associated with aggressive biologic behavior and response to therapy, imaging the proliferative state of cancer cells by non-invasive functional imaging is of great interest. Recently, 18F-FLT has been reported as a promising PET radiopharmaceutical for imaging cancer proliferation and has been validated in several in vitro and in vivo models. However, only a limited number of studies addressed its role in depicting changes in cancer proliferation and assessing response to CRT, and none of these studies have focused on esophageal cancer. We propose to conduct a clinical study to determine the optimal FLT PET imaging timepoint during the early course of CRT that has the highest predictive value for pathCR in patients with esophageal cancer. Esophgeal cancer was chosen for the reason that early prediction of pathCR could significantly impact clinical management decision, and, most importantly, it allows easy access for repeated biopsies to address the correlation between FLT PET signal and pathological changes in tumor proliferation. [unreadable] [unreadable] [unreadable]
Funding Period: 2006-09-25 - 2009-07-31
more information: NIH RePORT

Top Publications

  1. ncbi Additional value of PET/CT over PET in assessment of locoregional lymph nodes in thoracic esophageal squamous cell cancer
    Shuanghu Yuan
    Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China
    J Nucl Med 47:1255-9. 2006
  2. ncbi Hedgehog: an attribute to tumor regrowth after chemoradiotherapy and a target to improve radiation response
    Jennifer Sims-Mourtada
    Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 12:6565-72. 2006
  3. ncbi Functional imaging for early prediction of response to chemoradiotherapy: 3'-deoxy-3'-18F-fluorothymidine positron emission tomography--a clinical application model of esophageal cancer
    K S Clifford Chao
    Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Semin Oncol 33:S59-63. 2006
  4. ncbi Determining optimal clinical target volume margins on the basis of microscopic extracapsular extension of metastatic nodes in patients with non-small-cell lung cancer
    Shuanghu Yuan
    Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China
    Int J Radiat Oncol Biol Phys 67:727-34. 2007
  5. ncbi Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport
    J Sims-Mourtada
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 26:5674-9. 2007
  6. ncbi 3'-deoxy-3'-(18)F-fluorothymidine (FLT) positron emission tomography for early prediction of response to chemoradiotherapy--a clinical application model of esophageal cancer
    K S Clifford Chao
    Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Semin Oncol 34:S31-6. 2007
  7. ncbi Targeting hedgehog in cancer stem cells: how a paradigm shift can improve treatment response
    David C Y Tung
    The University of Texas, Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA
    Future Oncol 3:569-74. 2007

Scientific Experts

  • KS CLIFFORD CHAO
  • Shuanghu Yuan
  • David C Y Tung
  • J Sims-Mourtada
  • Guoren Yang
  • Jinming Yu
  • Yonghua Yu
  • Jennifer Sims-Mourtada
  • Xindong Sun
  • Dianbin Mu
  • J G Izzo
  • Weixia Zhong
  • Yongzheng Wang
  • Xue Meng
  • Jialin Wang
  • J Ajani
  • Jiandong Zhang
  • Yong Yin
  • Zheng Fu
  • Albert van der Kogel
  • Zhongxing Liao
  • Jaffer Ajani
  • Smith Apisarnthanarax
  • Tonghai Liu
  • Xinhua Yang
  • Tsung Teh Wu
  • Ritsuko Komaki
  • Shaoqing Chen
  • Rajyalashmi Luthra
  • Julie G Izzo
  • Usha Malhotra
  • Hongbo Guo

Detail Information

Publications7

  1. ncbi Additional value of PET/CT over PET in assessment of locoregional lymph nodes in thoracic esophageal squamous cell cancer
    Shuanghu Yuan
    Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China
    J Nucl Med 47:1255-9. 2006
    ....
  2. ncbi Hedgehog: an attribute to tumor regrowth after chemoradiotherapy and a target to improve radiation response
    Jennifer Sims-Mourtada
    Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 12:6565-72. 2006
    ..However, the relationship between Hh signaling and therapeutic response is unknown...
  3. ncbi Functional imaging for early prediction of response to chemoradiotherapy: 3'-deoxy-3'-18F-fluorothymidine positron emission tomography--a clinical application model of esophageal cancer
    K S Clifford Chao
    Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Semin Oncol 33:S59-63. 2006
    ..Clinical studies are needed to determine if FLT-PET can distinguish among degrees of response to neoadjuvant chemoradiation in patients with esophageal cancer...
  4. ncbi Determining optimal clinical target volume margins on the basis of microscopic extracapsular extension of metastatic nodes in patients with non-small-cell lung cancer
    Shuanghu Yuan
    Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China
    Int J Radiat Oncol Biol Phys 67:727-34. 2007
    ..To determine the optimal clinical target volume (CTV) margins around the nodal gross tumor volume (GTV) in non-small-cell lung cancer (NSCLC) patients by assessing microscopic tumor extension beyond regional lymph node capsules...
  5. ncbi Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport
    J Sims-Mourtada
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 26:5674-9. 2007
    ..These results suggest that the Hh pathway may be a target to overcome MDR and increase chemotherapeutic response...
  6. ncbi 3'-deoxy-3'-(18)F-fluorothymidine (FLT) positron emission tomography for early prediction of response to chemoradiotherapy--a clinical application model of esophageal cancer
    K S Clifford Chao
    Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Semin Oncol 34:S31-6. 2007
    ..The ability to visualize tumor cell proliferation may also contribute to the ability to improve precision delivery of radiation therapy...
  7. ncbi Targeting hedgehog in cancer stem cells: how a paradigm shift can improve treatment response
    David C Y Tung
    The University of Texas, Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA
    Future Oncol 3:569-74. 2007
    ..Future research focused on Hh and related signaling pathways involved in cancer might improve treatment response in malignancies resistant to traditional therapy...