title: Long-term outcome of phase I/II prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer.
abstract: The aim of this phase I/II study was to assess the long-term clinical benefits and toxicities of proton beam therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC).
  
  
  
  From June 2006 to September 2011, 35 patients with medically inoperable T1N0M0 (central or superior location, 12 patients) or T2-3N0M0 (any location, 23 patients) NSCLC were treated with 87.5Gy at 2.5Gy/fraction of proton therapy. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 4.0.
  
  
  
  The median follow-up time was 83.1months (95% CI: 69.2-97.1months). For all 35 patients, the 1, 3, and 5-year overall survival rates were 85.7%, 42.9%, and 28.1%, respectively. The 5-year local recurrence-free, regional recurrence-free, and distant metastasis-free survival rates were 85.0%, 89.2%, and 54.4%, respectively. Different T stages had no effect on local and regional recurrence (p=0.499, p=1.00). However, with the increase in T stages, the distant metastasis rate increased significantly (p=0.006). The most common adverse effects were dermatitis (grade 2, 51.4%; grade 3, 2.9%) and radiation pneumonitis (grade 2, 11.4%; grade 3, 2.9%). Other grade 2 toxicities included esophagitis (2.9%), rib fracture (2.9%), heart toxicities (5.7%), and chest wall pain (2.9%).
  
  
  
  According to our long-term follow-up data, proton therapy with ablative doses is well tolerated and effective in medically inoperable early-stage NSCLC. Systemic therapy should be considered to reduce the rate of distant metastasis in cases of T2 and T3 lesions.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. Electronic address: jychang@mdanderson.org.
authors.forename: Joe Y
authors.initials: JY
authors.lastname: Chang
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.affiliation: Department of Radiation Oncology, MGH, Harvard Medical School, United States.
authors.forename: Noah C
authors.initials: NC
authors.lastname: Choi
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Shen
authors.initials: S
authors.lastname: Chan
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gomez
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: O'Reilly
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Melenda
authors.initials: M
authors.lastname: Jeter
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Gillin
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Radhe
authors.initials: R
authors.lastname: Mohan
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Swisher
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hahn
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D009367:Neoplasm Staging; D000072078:Positron Emission Tomography Computed Tomography; D011446:Prospective Studies; D061766:Proton Therapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D015996:Survival Rate
keywords: Early stage; Non-small cell lung cancer; Phase I/II study; Proton therapy; Survival; Toxicity