Preliminary Results of a Radiation Therapy Oncology Group Trial (RTOG 9311), A Dose Escalation Study Using 3D Conformal Radiation Therapy in Patients with Inoperable Non-small Cell Lung Cancer

William Levin, MD
University of Pennsylvania Cancer Center
Last Modified: November 4, 2001

Presenter: M.V. Graham
Affiliation: Radiation Oncology, Phelps County Regional Medical Center, Rolla, MO


  • Some investigators and clinicians are now questioning the utility of elective nodal irradiation in the treatment of lung cancer.
  • Theoretically, if the volume of tissue to be irradiated were to exclude clinically uninvolved lymph nodes, then radiation dose could be escalated without a significant increase in treatment-related toxicity.
  • For many types of cancer, increased total radiation dose has been correlated with better local control of disease.

Materials and Methods

  • One-hundred and sixty-three patients were entered in a Phase I/II 3-dimensional radiation therapy dose escalation trial.
  • Patients were stratified for different radiation treatment levels depending on their V20 (the percentage of their total lung volume that would receive in excess of 20 Gy with the treatment plan).
  • Patients with a V20<25% (Group 1) received 70.9 Gy/33 fractions, 77.4Gy/36 fractions, 83.8 Gy/39 fractions and 90.3 Gy/42 fractions successively.
  • Patients with a V20 of 25-37% (Group 2) received 70.9 Gy and 77.4 Gy successively.
  • The treatment arm for patients with a V20>37% (Group 3) closed early secondary to poor accrual(2 patients) and the perception of excessive risk for the development of pneumonitis.
  • Patients were allowed to receive neoadjuvant chemotherapy before radiation therapy only, but not concurrently.


  • The following acute grade 3 toxicities were observed: one weight loss (Group 1,70.9 Gy; one nausea and vomiting(Group 1, 77.4 Gy); one esophagitis (Group 1, 90.3 Gy); and one pneumonitis (Group 2, 77.4Gy). One acute grade 4 lymphopenia was observed (Group 1, 83.8 Gy).
  • The following late grade 3 toxicities were observed (greater than 90 days from the completion of therapy): one cardiac (Group 1, 70.9 Gy); four esophageal (two Group 1, 70.9 Gy, one Group 1, 83.8 Gy and one Group 2, 77.4 Gy) and seventeen grade 3 lung toxicities (seven Group 1, 70.9 Gy, six Group 1, 77.4 Gy, three Group 2, 70.9 Gy and one Group 2, 77.4 Gy).
  • There were no grade 4 or 5 esophageal or pulmonary late toxicities.

Author's Conclusions

  • To date, the maximal tolerable radiation dose has not been reached.
  • Since grade 3 acute nonhematologic toxicity has been seen in both the Group 1 at 90.3 Gy and Group 2 at 77.4 Gy, additional patients are being accrued.
  • The development of late pulmonary toxicity is of concern and will need to be followed.

Clinical/Scientific Implications

  • Patients did not receive concurrent chemoirradiation, which is rapidly becoming the standard of care in patients not undergoing surgical resection.
  • The relationship between volume of tissue irradiated and toxicity is not a simple one, and further investigations must be done to elucidate these other contributing factors.
  • As with any dose escalation study, long-term follow-up is necessary to truly address the issue of safety.
  • Exclusion of elective nodal irradiation is not a widely excepted practice at this time.