Phase 1 study of dose escalation in hypofractionated proton beam therapy for non-small cell lung cancer

Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):665-70. doi: 10.1016/j.ijrobp.2013.03.035. Epub 2013 May 18.

Abstract

Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control.

Methods and materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment.

Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT.

Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Cetuximab
  • Dose Fractionation, Radiation
  • Esophagitis / etiology
  • Esophagitis / pathology
  • Esophagus / radiation effects
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Lymphatic Irradiation / methods
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Organs at Risk / radiation effects
  • Prospective Studies
  • Proton Therapy / adverse effects
  • Proton Therapy / methods*
  • Radiation Pneumonitis / etiology
  • Relative Biological Effectiveness

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Cetuximab