Pulmonary Toxicity Following Proton Therapy for Patients with Non-Small Cell Lung Cancer

Reporter: Lauren Hertan
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 4, 2013

Presenter: Lisa A. McGee
Presenter Affiliation: University of Florida Proton Therapy Institute, Jacksonville, FL


  • Chemoradiation is the standard of care for locally advanced, inoperable, non-small cell lung cancer (NSCLC).
  • Proton therapy (PT) has a logical benefit in the treatment of NSCLC given the close proximity to critical structures in the chest and the known toxicity with treatment. As such, there is ongoing research investigating the use of proton therapy.
  • The current study was designed to assess pulmonary toxicity, including pneumonitis, pulmonary fibrosis, pleural effusion, and bronchial stenosis, in patients with NSCLC treated with conventionally fractionated PT.


  • 47 patients with NSCLC were treated with curative intent with conventionally fractionated PT.
    • 41 patients were treated for primary disease.
    • 6 patients were treated for recurrent disease.
  • Most patients had locally advanced disease, 70.2% were stage III and 4.5% were stage IV.
  • Most patients (85%) had favorable baseline performance status (PS) 0-1; the remainder had a PS of 2.
  • The median PT dose was 74 CGE with 14 patients treated to a total dose >74 CGE.
  • 39 patients (83%) received chemotherapy.
  • Patients were followed every 3 months after PT with either CT or PET-CT.
  • Follow-up images were assessed by the author and re-evaluated by a body radiologist for radiographic toxicity. Medical records were also reviewed for clinical symptomatic toxicities.
  • Toxicity was graded per Common Terminology Criteria for Adverse Events version 4.0, and censored at the time of local failure.
    • Pneumonitis was recorded within the first 6 months after PT.
    • Pulmonary fibrosis was recorded after 6 months


  • The median follow-up time was 1.4 years for all patients and 2.3 years for living patients.
  • Survival:
    • 2-year overall survival (OS) rate in all patients: 41%.
    • 2-year OS in Stage III/IV patients, with PS 0-1: 49%.
  • Toxicity:
    • 19% (8 patients) experienced ? grade 2 pulmonary toxicity, with a median time of 0.6 years:
      • Pneumonitis:
        • Grade 2: 2 patients
      • Fibrosis:
        • Grade 1: 30 patients
        • Grade 2: 1 patient
        • Grade 3+: 1 patient
      • Pleural Effusion:
        • Grade 1: 14 patients
        • Grade 2: 1 patient
      • Bronchial Stenosis:
        • Grade 1: 3 patients
        • Grade 2: 2 patients
        • Grade 5: 1 patient
    • The patient with grade 5 bronchial stenosis had T1 N2 disease with a right lower-lobe primary and developed bronchial stenosis 12 months after PT, which led to pneumonia and death.
    • All 6 bronchial stenosis occurred in patients with right-sided tumors, which was found to be a significant predictor on univariate analysis (p = 0.0478). Right-sided primary tumor location also impacted grade 2+ pulmonary toxicity on univariate analysis (p = 0.0207).

Author's Conclusions

  • Two-year OS in stage III patients is promising.
  • Right-sided location of primary lung tumors predicts for grade 2+ pulmonary toxicity following PT, particularly bronchial stenosis.
  • Longer follow-up in a larger cohort is needed to confirm these results.

Clinical Implications

  • This was a small, single institution study evaluating pulmonary toxicity in patients treated with proton beam therapy.
  • There were some limitations to the study. No data was provided regarding dose to critical structures or association with development of toxicity. Specifically, there were 6 patients who developed bronchial stenosis, all of whom had right-sided primaries. However, no data was given as to the relationship between the tumor and the bronchus or the dose delivered to the bronchus.
  • Overall, the survival and toxicity data reported in the study is promising and further contributes to the growing body of literature suggesting dose escalation with proton therapy is both safe and effective.


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