Lower Radiation Dose Improves Lung Cancer Survival

MIAMI BEACH – Less turned out to be better in a large clinical trial comparing radiation doses in patients treated with radiation and chemotherapy for stage III non–small cell lung cancer, investigators reported here.

The median overall survival rate at 1 year was 81% for patients treated with standard-dose (60 Gy) radiation, compared with 70.4% for those who received the high dose (74 Gy), according to preliminary findings from the radiation-dose arm of the ongoing phase III Radiation Therapy Oncology Group (RTOG) 0617 trial. The respective median survival rates were 21.7 months and 20.7 months (P = .02).

A planned interim analysis from the trial showed that the radiation comparison had crossed the prespecified boundary for futility, and the high-dose arm was stopped in June 2011, reported Dr. Jeffrey Bradley from Washington University in St. Louis.

"I think this changes practice: If [cancer centers] weren’t using 60 Gray before, perhaps they should go back to using 60 Gray, because it does not appear that a higher dose is better," Dr. Bradley commented at the annual meeting of the American Society of Radiation Oncology (ASTRO).

Dr. Tim R. Williams, from the Lynn Cancer Institute at Boca Raton (Fla.) Regional Hospital, the immediate-past chairman of ASTRO, noted that his center has used high-dose radiation in stage III non–small cell lung cancer (NSCLC) patients for about 5 years. Although practice patterns vary, it’s likely that many treatment centers currently use the higher dose, he said.

In RTOG 0617, a total of 500 patients with stage IIIA/IIIB NSCLC were scheduled for randomization to one of four arms in a 2 x 2 factorial design with patients assigned to receive either 74 Gy or 60 Gy radiation with or without cetuximab (Erbitux), on a background chemotherapy regimen of weekly paclitaxel (45 mg/m²) and carboplatin (titrated to an area-under-the-curve of 2).

The radiation was delivered in 2 Gy fractions over 30 to 37 fractions.

The analysis was performed on 426 patients who had been enrolled in the study before June 17, 2011.

Seeking to understand why the higher radiation dose was not better – the investigators had originally hypothesized that 74 Gy would result in a 7-month improvement in overall survival vs. 64 Gy.– they performed univariate analyses, and found that significant predictors for better outcomes included continuous therapy, nonsquamous histology, and, female gender. In multivariate analysis, radiation dose (60 Gy vs. 74 Gy) was associated with a hazard ratio for overall survival of 1.48 (P = .038),

nonsquamous histology versus squamous was associated with an HR of 1.52 (P = .025), and gross or internal tumor volume had a small but significant HR of 1.002 (P = .011).

Dr. Benjamin Movsas, chair of radiation oncology at the Henry Ford Health System in Detroit, the invited discussant, said that "as of 2011, level I evidence demonstrates no role for dose escalation in stage III non–small cell lung cancer."

He noted that although there were small differences between the radiation dose groups in terms of tumor histology, gross tumor volume, and other factors, they were not large enough to explain the differences in outcomes.

Citing the advice of his late father, also a physician, Dr. Movsas reminded the audience that "More is not always better."

The trial is continuing with patients assigned to 60 Gy radiation only, with the goal of evaluating the secondary study end point of overall survival of patients with or without cetuximab added to concurrent chemoradiotherapy.

The RTOG 0617 trial is supported by grants from the U.S. National Cancer Institute, with additional support from Bristol-Myers Squibb and ImClone.

Dr. Bradley and Dr. Williams had no disclosures. Dr. Movsas disclosed departmental research support from Varian and Philips. He also has served as a chair of an RTOG committee, but was not involved in the 0617 study.

MIAMI BEACH – Less turned out to be better in a large clinical trial comparing radiation doses in patients treated with radiation and chemotherapy for stage III non–small cell lung cancer, investigators reported here.

The median overall survival rate at 1 year was 81% for patients treated with standard-dose (60 Gy) radiation, compared with 70.4% for those who received the high dose (74 Gy), according to preliminary findings from the radiation-dose arm of the ongoing phase III Radiation Therapy Oncology Group (RTOG) 0617 trial. The respective median survival rates were 21.7 months and 20.7 months (P = .02).

A planned interim analysis from the trial showed that the radiation comparison had crossed the prespecified boundary for futility, and the high-dose arm was stopped in June 2011, reported Dr. Jeffrey Bradley from Washington University in St. Louis.

"I think this changes practice: If [cancer centers] weren’t using 60 Gray before, perhaps they should go back to using 60 Gray, because it does not appear that a higher dose is better," Dr. Bradley commented at the annual meeting of the American Society of Radiation Oncology (ASTRO).

Dr. Tim R. Williams, from the Lynn Cancer Institute at Boca Raton (Fla.) Regional Hospital, the immediate-past chairman of ASTRO, noted that his center has used high-dose radiation in stage III non–small cell lung cancer (NSCLC) patients for about 5 years. Although practice patterns vary, it’s likely that many treatment centers currently use the higher dose, he said.

In RTOG 0617, a total of 500 patients with stage IIIA/IIIB NSCLC were scheduled for randomization to one of four arms in a 2 x 2 factorial design with patients assigned to receive either 74 Gy or 60 Gy radiation with or without cetuximab (Erbitux), on a background chemotherapy regimen of weekly paclitaxel (45 mg/m²) and carboplatin (titrated to an area-under-the-curve of 2).

The radiation was delivered in 2 Gy fractions over 30 to 37 fractions.

The analysis was performed on 426 patients who had been enrolled in the study before June 17, 2011.

Seeking to understand why the higher radiation dose was not better – the investigators had originally hypothesized that 74 Gy would result in a 7-month improvement in overall survival vs. 64 Gy.– they performed univariate analyses, and found that significant predictors for better outcomes included continuous therapy, nonsquamous histology, and, female gender. In multivariate analysis, radiation dose (60 Gy vs. 74 Gy) was associated with a hazard ratio for overall survival of 1.48 (P = .038),

nonsquamous histology versus squamous was associated with an HR of 1.52 (P = .025), and gross or internal tumor volume had a small but significant HR of 1.002 (P = .011).

Dr. Benjamin Movsas, chair of radiation oncology at the Henry Ford Health System in Detroit, the invited discussant, said that "as of 2011, level I evidence demonstrates no role for dose escalation in stage III non–small cell lung cancer."

He noted that although there were small differences between the radiation dose groups in terms of tumor histology, gross tumor volume, and other factors, they were not large enough to explain the differences in outcomes.

Citing the advice of his late father, also a physician, Dr. Movsas reminded the audience that "More is not always better."

The trial is continuing with patients assigned to 60 Gy radiation only, with the goal of evaluating the secondary study end point of overall survival of patients with or without cetuximab added to concurrent chemoradiotherapy.

The RTOG 0617 trial is supported by grants from the U.S. National Cancer Institute, with additional support from Bristol-Myers Squibb and ImClone.

Dr. Bradley and Dr. Williams had no disclosures. Dr. Movsas disclosed departmental research support from Varian and Philips. He also has served as a chair of an RTOG committee, but was not involved in the 0617 study.

MIAMI BEACH – Less turned out to be better in a large clinical trial comparing radiation doses in patients treated with radiation and chemotherapy for stage III non–small cell lung cancer, investigators reported here.

The median overall survival rate at 1 year was 81% for patients treated with standard-dose (60 Gy) radiation, compared with 70.4% for those who received the high dose (74 Gy), according to preliminary findings from the radiation-dose arm of the ongoing phase III Radiation Therapy Oncology Group (RTOG) 0617 trial. The respective median survival rates were 21.7 months and 20.7 months (P = .02).

A planned interim analysis from the trial showed that the radiation comparison had crossed the prespecified boundary for futility, and the high-dose arm was stopped in June 2011, reported Dr. Jeffrey Bradley from Washington University in St. Louis.

"I think this changes practice: If [cancer centers] weren’t using 60 Gray before, perhaps they should go back to using 60 Gray, because it does not appear that a higher dose is better," Dr. Bradley commented at the annual meeting of the American Society of Radiation Oncology (ASTRO).

Dr. Tim R. Williams, from the Lynn Cancer Institute at Boca Raton (Fla.) Regional Hospital, the immediate-past chairman of ASTRO, noted that his center has used high-dose radiation in stage III non–small cell lung cancer (NSCLC) patients for about 5 years. Although practice patterns vary, it’s likely that many treatment centers currently use the higher dose, he said.

In RTOG 0617, a total of 500 patients with stage IIIA/IIIB NSCLC were scheduled for randomization to one of four arms in a 2 x 2 factorial design with patients assigned to receive either 74 Gy or 60 Gy radiation with or without cetuximab (Erbitux), on a background chemotherapy regimen of weekly paclitaxel (45 mg/m²) and carboplatin (titrated to an area-under-the-curve of 2).

The radiation was delivered in 2 Gy fractions over 30 to 37 fractions.

The analysis was performed on 426 patients who had been enrolled in the study before June 17, 2011.

Seeking to understand why the higher radiation dose was not better – the investigators had originally hypothesized that 74 Gy would result in a 7-month improvement in overall survival vs. 64 Gy.– they performed univariate analyses, and found that significant predictors for better outcomes included continuous therapy, nonsquamous histology, and, female gender. In multivariate analysis, radiation dose (60 Gy vs. 74 Gy) was associated with a hazard ratio for overall survival of 1.48 (P = .038),

nonsquamous histology versus squamous was associated with an HR of 1.52 (P = .025), and gross or internal tumor volume had a small but significant HR of 1.002 (P = .011).

Dr. Benjamin Movsas, chair of radiation oncology at the Henry Ford Health System in Detroit, the invited discussant, said that "as of 2011, level I evidence demonstrates no role for dose escalation in stage III non–small cell lung cancer."

He noted that although there were small differences between the radiation dose groups in terms of tumor histology, gross tumor volume, and other factors, they were not large enough to explain the differences in outcomes.

Citing the advice of his late father, also a physician, Dr. Movsas reminded the audience that "More is not always better."

The trial is continuing with patients assigned to 60 Gy radiation only, with the goal of evaluating the secondary study end point of overall survival of patients with or without cetuximab added to concurrent chemoradiotherapy.

The RTOG 0617 trial is supported by grants from the U.S. National Cancer Institute, with additional support from Bristol-Myers Squibb and ImClone.

Dr. Bradley and Dr. Williams had no disclosures. Dr. Movsas disclosed departmental research support from Varian and Philips. He also has served as a chair of an RTOG committee, but was not involved in the 0617 study.