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.
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.
Authors: Gilda G Hillman; Vinita Singh-Gupta; Lindsay Runyan; Christopher K Yunker; Joseph T Rakowski; Fazlul H Sarkar; Steven Miller; Shirish M Gadgeel; Seema Sethi; Michael C Joiner; Andre A Konski Journal: Radiother Oncol Date: 2011-11-11 Impact factor: 6.280
Authors: Gilda G Hillman; Vinita Singh-Gupta; David J Hoogstra; Lisa Abernathy; Joseph Rakowski; Christopher K Yunker; Shoshana E Rothstein; Fazlul H Sarkar; Shirish Gadgeel; Andre A Konski; Fulvio Lonardo; Michael C Joiner Journal: Radiother Oncol Date: 2013-09-07 Impact factor: 6.280
Authors: Søren M Bentzen; Louis S Constine; Joseph O Deasy; Avi Eisbruch; Andrew Jackson; Lawrence B Marks; Randall K Ten Haken; Ellen D Yorke Journal: Int J Radiat Oncol Biol Phys Date: 2010-03-01 Impact factor: 7.038
Authors: Andrew Jackson; Lawrence B Marks; Søren M Bentzen; Avraham Eisbruch; Ellen D Yorke; Randal K Ten Haken; Louis S Constine; Joseph O Deasy Journal: Int J Radiat Oncol Biol Phys Date: 2010-03-01 Impact factor: 7.038
Authors: Lawrence B Marks; Soren M Bentzen; Joseph O Deasy; Feng-Ming Spring Kong; Jeffrey D Bradley; Ivan S Vogelius; Issam El Naqa; Jessica L Hubbs; Joos V Lebesque; Robert D Timmerman; Mary K Martel; Andrew Jackson Journal: Int J Radiat Oncol Biol Phys Date: 2010-03-01 Impact factor: 7.038
Authors: Sarah L Kerns; Suman Kundu; Jung Hun Oh; Sandeep K Singhal; Michelle Janelsins; Lois B Travis; Joseph O Deasy; A Cecile J E Janssens; Harry Ostrer; Matthew Parliament; Nawaid Usmani; Barry S Rosenstein Journal: Semin Radiat Oncol Date: 2015-05-15 Impact factor: 5.934