Thoracic -- Clinical Research Program

Our thoracic cancer clinical research team is developing new treatments for cancers that arise in the chest, especially lung cancer and mesothelioma. Our team's medical and radiation oncologists, pathologists, radiologists, and surgeons are at the forefront of developing many of the latest treatments for these cancers. We are also looking at new ways to improve lung function both during and after treatment for cancer.

Our researchers are investigating many leading-edge treatments, such as minimally invasive surgery for the removal of tumors and three-dimensional conformal radiation therapy. We have also pioneered the study of novel chemotherapy agents for thoracic cancers, including several of the latest targeted therapy agents.

Among our recent research accomplishments:

Molecular Pathology

  • We showed that DNA damage as measured by the comet assay is associated with the development of multiple primary tumors in individuals with non-small cell lung cancer (NSCLC). J Clin Oncol. 2008 Jul 20;26(21):3560-6. [PubMed Abstract]
  • We found that somatic mutations in MEK1 are present in lung adenocarcinomas and may provide a target for therapy in a subset of patients with lung adenocarcinoma. Cancer Res. 2008 Jul 15;68(14):5524-8. [PubMed Abstract]
  • We demonstrated that MET amplification is a mechanism of resistance in patients with clinical acquired resistance to erlotinib and gefitinib. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20932-7. [PubMed Abstract]
  • In drug-sensitive EGFR mutant lung cancer cells, we found that induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors. PLoS Med. 2007 Oct 9;4(10):e294. [PubMed Abstract]
  • As part of a large, NIH-funded collaboration, we defined multiple somatic alterations in lung adenocarcinoma. Nature. 2007 Dec 6;450(7171):893-8. [PubMed Abstract]
  • After analysis of EGFR and related signaling pathway genes in lung adenocarcinomas, we found that somatic mutation of FGFR4 may be important in the pathogenesis of a subset of lung adenocarcinomas. PLoS ONE. 2007 May 9;2(5):e426. [PubMed Abstract]
  • We demonstrated that KRAS mutations are not rare in patients with NSCLC who never smoked, occurring in about 15 percent of never smokers. Clin Cancer Res. 2008 Sep 15;14(18):5731-4. [PubMed Abstract]
  • As part of a large, NIH-funded collaboration, we carried out microarray analysis of a pathologically and clinically annotated series of lung adenocarcinomas. Nat Med. 2008 Aug; 14(8):822-7. [PubMed Abstract]

Imaging

  • We used positron emission tomography imaging of radiolabeled fluorodeoxyglucose (FDG-PET) and uni-dimensional, bi-dimensional, and three-dimensional measurements of lung tumors to prospectively assess the effects of stopping and restarting gefitinib or erlotinib in patients with acquired resistance to erlotinib or gefitinib. Clin Cancer Res. 2007 Sep 1;13(17):5150-5. [PubMed Abstract]
  • We showed that FDG-PET standardized uptake value (SUV) is an independent prognostic factor from clinical TNM (tumor, node, metastasis) stage, but SUV does not add to the prognostic significance of the pathologic TNM stage. J Thorac Cardiovasc Surg. 2007 Jun;133(6):1419-27. [PubMed Abstract]

Surgery

  • We demonstrated that patients with malignant pleural mesothelioma who underwent pleurectomy/decortication had a better survival rate than those who underwent extrapleural pneumonectomy. J Thorac Cardiovasc Surg. 2008 Mar;135(3):620-6, 626.e1-3. [PubMed Abstract]
  • We showed that a video-assisted thoracic surgery (VATS) approach to lobectomy for clinical stage I NSCLC in the elderly (patients 70 years of age and older) was associated with fewer complications and shorter hospital stays compared with thoracotomy. Ann Thorac Surg. 2008 Jan;85(1):231-5. [PubMed Abstract]
  • We showed that video-assisted thoracic surgery does not reduce the incidence of postoperative atrial fibrillation after pulmonary lobectomy. J Thorac Cardiovasc Surg. 2007 Mar;133(3):775-9. [PubMed Abstract]

Radiation Therapy

  • We found that involved-field radiation therapy (IFRT) was not associated with a significant risk of failure in lymph node regions not included in the tumor volume and remains an acceptable method of treatment that allows for dose escalation while minimizing toxicity. J Clin Oncol. 2007 Dec 10;25(35):5557-61. [PubMed Abstract]
  • We demonstrated that treatment with doses of 80 Gy or more using three-dimensional conformal radiotherapy leads to a favorable five-year overall survival rate (36 percent) with an acceptable toxicity profile in patients with early-stage NSCLC. Cancer J. 2007 Jul-Aug;13(4):238-42. [PubMed Abstract]

New Agents

  • We showed that weekly treatment with 130 nm albumin-bound paclitaxel was well tolerated and demonstrated encouraging single-agent activity as initial treatment for patients with advanced NSCLC. J Clin Oncol. 2008 Feb 1;26(4):639-43. [PubMed Abstract]
  • We determined the efficacy of pralatrexate (PDX) in patients with mesothelioma.
  • We found that TZT-1027, as a single agent, had no activity in patients with previously untreated advanced NSCLC. Lung Cancer. 2007 Feb;55(2):181-5. [PubMed Abstract]
  • We showed that pralatrexate (120 mg/m2) plus docetaxel (35 mg/m2) plus vitamin supplementation is well tolerated with signs of efficacy against NSCLC and merits phase II testing. Clin Cancer Res. 2007 May 1;13(9):2692-8. [PubMed Abstract]
  • We demonstrated that pralatrexate as a single agent had no activity in malignant pleural mesothelioma. J Thorac Oncol. 2007 Apr;2(4):317-20. [PubMed Abstract]

Targeted Therapies

  • We showed that erlotinib is active in patients with bronchioloalveolar carcinoma (BAC) and adenocarcinoma with BAC features. We demonstrated that testing for EGFR and KRAS mutations can predict response rates and progression-free survival after treatment with erlotinib in this histologically enriched subset of patients with NSCLC. J Clin Oncol. 2008 Mar 20;26(9):1472-8. [PubMed Abstract]

Antibodies

  • We tested the targeting and pharmacokinetics of hu3S193, an antibody to Lewis Y antigen developed at Memorial Sloan Kettering, in patients with small cell lung cancer. J Thorac Oncol. 2007 Oct;2(10):947-52. [PubMed Abstract]

Combination Therapies

  • We determined the maximum tolerated dose of combined gefitinib and everolimus in patients with metastatic NSCLC. Cancer. 2007 Aug 1;110(3):599-605. [PubMed Abstract]
  • In patients with resected, early-stage NSCLC, we showed that the combination of cisplatin at 80 mg/m2 with docetaxel at 35 mg/m2 weekly or 75 mg/m2 every three weeks is no better tolerated than earlier generation chemotherapy regimens. J Thorac Oncol. 2007 Jul;2(7):638-44. [PubMed Abstract]
  • We showed that the American Joint Committee on Cancer staging system does not accurately predict survival in patients receiving multimodality therapy for esophageal adenocarcinoma. J Clin Oncol. 2007 Feb 10;25(5):507-12. [PubMed Abstract]
  • We demonstrated that combined-modality therapy with chemotherapy and radiation followed by surgery is feasible and associated with high rates of complete resection and pathologic complete response in superior sulcus NSCLC tumors. J Clin Oncol. 2007 Jan 20;25(3):313-8. [PubMed Abstract]
  • In patients with advanced solid tumors, we found that intermittent high-dose gefitinib (2,250 mg) can be administered on days one and two, followed by docetaxel (75 mg/m2) on day three. Cancer Chemother Pharmacol. 2007 Mar;59(4):467-75. [PubMed Abstract]

Integrative and Complementary Approaches

  • We have prepared American College of Chest Physicians (ACCP) evidence-based guidelines for the use of complementary therapies and integrative medicine in lung cancer patients. Our evaluation shows that complementary therapies have an increasingly important role in the control of symptoms associated with cancer and cancer treatment. Chest. 2007 Sep;132(3 Suppl):340S-354S. [PubMed Abstract]