Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC)

Predictors for radiation pneumonitis and fibrosis

Feng Ming Kong, James A. Hayman, Kent A. Griffith, Gregory P. Kalemkerian, Douglas Arenberg, Susan Lyons, Andrew Turrisi, Allen Lichter, Benedick Fraass, Avraham Eisbruch, Theodore S. Lawrence, Randall K. Ten Haken

Research output: Contribution to journalArticle

227 Citations (Scopus)

Abstract

Purpose: We aimed to report the final toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non-small-cell lung cancer (NSCLC) by quantifying the dose-volume toxicity relationship of the lung. Methods and Materials: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-lung toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77%) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. Results: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15 (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 lung toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly (p < 0.001) associated with lung-dosimetric parameters such as the mean lung dose (MLD), volume of lung that received at least 20 Gy (V20), and the normal-tissue complication probability (NTCP) of the lung. If cutoffs are 30% for V20, 20 Gy for MLD, and 10% for NTCP, these factors have positive predictive values of 50% to 71% and negative predictive value of 85% to 89%. Conclusions: With long-term follow-up for toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative lung dose-volume toxicity-based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients.

Original languageEnglish (US)
Pages (from-to)1075-1086
Number of pages12
JournalInternational Journal of Radiation Oncology Biology Physics
Volume65
Issue number4
DOIs
StatePublished - Jul 15 2006

Fingerprint

Radiation Pneumonitis
fibrosis
Non-Small Cell Lung Carcinoma
toxicity
lungs
cancer
Radiation
dosage
Lung
radiation
predictions
grade
Pneumonia
Fibrosis
chemotherapy
Multivariate Analysis
Drug Therapy

Keywords

  • 3D conformal radiation
  • Dose escalation
  • Fibrosis
  • NSCLC
  • Pneumonitis

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC) : Predictors for radiation pneumonitis and fibrosis. / Kong, Feng Ming; Hayman, James A.; Griffith, Kent A.; Kalemkerian, Gregory P.; Arenberg, Douglas; Lyons, Susan; Turrisi, Andrew; Lichter, Allen; Fraass, Benedick; Eisbruch, Avraham; Lawrence, Theodore S.; Ten Haken, Randall K.

In: International Journal of Radiation Oncology Biology Physics, Vol. 65, No. 4, 15.07.2006, p. 1075-1086.

Research output: Contribution to journalArticle

Kong, FM, Hayman, JA, Griffith, KA, Kalemkerian, GP, Arenberg, D, Lyons, S, Turrisi, A, Lichter, A, Fraass, B, Eisbruch, A, Lawrence, TS & Ten Haken, RK 2006, 'Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): Predictors for radiation pneumonitis and fibrosis', International Journal of Radiation Oncology Biology Physics, vol. 65, no. 4, pp. 1075-1086. https://doi.org/10.1016/j.ijrobp.2006.01.051
Kong, Feng Ming ; Hayman, James A. ; Griffith, Kent A. ; Kalemkerian, Gregory P. ; Arenberg, Douglas ; Lyons, Susan ; Turrisi, Andrew ; Lichter, Allen ; Fraass, Benedick ; Eisbruch, Avraham ; Lawrence, Theodore S. ; Ten Haken, Randall K. / Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC) : Predictors for radiation pneumonitis and fibrosis. In: International Journal of Radiation Oncology Biology Physics. 2006 ; Vol. 65, No. 4. pp. 1075-1086.
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abstract = "Purpose: We aimed to report the final toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non-small-cell lung cancer (NSCLC) by quantifying the dose-volume toxicity relationship of the lung. Methods and Materials: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-lung toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77{\%}) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. Results: There were 17 (14.6{\%}) Grade 2 to 3 pneumonitis and 15 (13.8{\%}) Grade 2 to 3 fibrosis and no Grade 4 to 5 lung toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly (p < 0.001) associated with lung-dosimetric parameters such as the mean lung dose (MLD), volume of lung that received at least 20 Gy (V20), and the normal-tissue complication probability (NTCP) of the lung. If cutoffs are 30{\%} for V20, 20 Gy for MLD, and 10{\%} for NTCP, these factors have positive predictive values of 50{\%} to 71{\%} and negative predictive value of 85{\%} to 89{\%}. Conclusions: With long-term follow-up for toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative lung dose-volume toxicity-based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients.",
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AU - Griffith, Kent A.

AU - Kalemkerian, Gregory P.

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AU - Lyons, Susan

AU - Turrisi, Andrew

AU - Lichter, Allen

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KW - Pneumonitis

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