麻豆传媒

SAN ANTONIO -- Patients with unresectable non-small cell lung cancer (NSCLC) had less treatment-related pneumonitis with no decrement in survival when treated with intensity-modulated radiation therapy (IMRT) instead of 3D conformal RT, investigators reported here.

Severe pneumonitis occurred half as often with IMRT compared with 3D-CRT (3.8% versus 8.0%), and patients treated with IMRT were significantly more likely to complete consolidation chemotherapy.

Two-year overall survival (OS) was 53.2% with IMRT and 49.4% with 3D-CRT. Progression-free survival (PFS), disease control, and distant metastasis-free survival (DMFS) were similar between groups, reported , of the University of Texas MD Anderson Cancer Center in Houston, and colleagues at the American Society for Radiation Oncology meeting.

"Survival was similar despite the fact that the 'deck was stacked' against IMRT," Chun said. "Patients in the IMRT group had more advanced disease and greater planning target volume (PTV). Treating physicians could choose either 3D conformal or IMRT, and we suspect that IMRT often was selected for treatment of more difficult tumors."

The analysis provides insight into the surprising primary results of the trial, which tested two doses of radiation therapy and showed that a higher dose not only did not improve survival, but was associated with inferior survival as compared with the standard dose, said , of Emory University Winship Cancer Institute in Atlanta.

"What we learned in this analysis is that there was less toxicity with IMRT -- less pneumonitis and less heart toxicity," Curran told 麻豆传媒. "It starts to help us understand that if we are going to higher doses, or even if we use standard doses, at least as reported in this study, the patients receiving IMRT appeared to tolerate the treatment better.

"It starts to help us realize that some of the concerns we had about IMRT -- a low dose that spreads through both lungs and might lead to a higher rate of lung inflammation -- might not be a concern. In fact, the rate of pneumonitis was lower, at least in this study. We also learned that IMRT is a way to control the radiation dose to the heart."

Secondary Analysis

The standard of care for locally advanced NSCLC is concurrent chemoradiation therapy, most often with IMRT or 3D-CRT. Radiation-associated pneumonitis is a potential adverse effect of treatment and is related to the extent of lung tissue exposure to radiation. IMRT can spare tissue exposure, but the impact on survival relative to 3D-CRT had not been examined in a large prospective trial, Chun said.

The randomized trial compared two strategies of systemic therapy and concurrent radiation therapy in patients with locally advanced NSCLC. Investigators in the trial could choose the radiation technique use for each patient, and radiation technique was one of the prespecified stratification factors.

The primary objective of RTOG-0617 was to compare two doses of radiation (60 and 74 Gy) in combination with platinum-based chemotherapy with or without cetuximab (Erbitux), followed by platinum-based consolidation therapy. Chun reported findings from a secondary analysis of outcomes by type of radiation therapy technique.

The analysis involved 482 patients, 53% treated with 3D-CRT and 47% with IMRT. Endpoints evaluated in the trial included 2-year OS, PFS, local control, DMFS, severe (grade 3+) toxicity, and amount of chemotherapy administered. The trial had a median follow-up of 22.9 months.

In saying that the "deck was stacked" against IMRT, Chun pointed out that the IMRT group had more stage IIIB disease (39% versus 30%, P=0.056), larger PTV (486 versus 427 mL, P=0.005), and higher PTV:lung radio (0.15 versus 0.13, P=0.013).

The difference in 2-year survival in the IMRT group did not achieve statistical significance (P=0.597). Other 2-year outcomes also did not differ significantly: PFS (25.2% with IMRT, 27% with 3D-CRT, P=0.595), local control (30.8% versus 37.1%, P=0.50), and DMFS (45.9% versus 49.6%, P=0.66).

Better Tolerated

Severe pneumonitis occurred significantly more often with 3D-CRT (P=0.046). Chun reported that more lung tissue was exposed to low-dose radiation with IMRT (lung V5, 55% with 3D-CRT versus 62% with IMRT, P<0.0001), but lung V5 was not significantly associated with the severe pneumonitis (P=0.14) or with grade 3+ hematologic toxicity (P=0.57). Mean lung dose was slightly higher with 3D-CRT (18.1 versus 17.7 Gy for IMRT), but was not associated with severe pneumonitis (P=0.09).

In a multivariate analysis that included all patients and tumor sizes, higher-dose radiation exposure (lung V20) was significantly associated with severe pneumonitis (P=0.009), as was more advanced disease stage (IIIA versus IIIB, P=0.0385), but not radiation therapy technique (3D-CRT versus IMRT, OR 0.44, P=0.0621).

A multivariate analysis limited to PTV >460 mL, a surrogate for larger tumors, showed that the chosen radiation therapy technique did significantly affect the likelihood of severe pneumonitis (3D-CRT versus IMRT, OR 0.22, 95% CI 0.06-0.82, P=0.02). A trend toward a significant association was observed for lung V20 (P=0.051).

Radiation exposure to the heart proved to be a key factor in survival, said Chun. Across the board, IMRT was associated with less heart exposure to radiation compared with 3D-CRT:

• V20: 19.3% versus 23.5% (P=0.049)
• V40: 6.8% versus 11.4% (P=0.003)
• V60: 1.4% versus 2.4% (P=0.045)

In a univariate analysis, heart V20 was significant with 2-year OS (HR 1.008, 95% CI 1.004-1.013, P=0.0005), as was heart V40 (HR 1.013, 95% CI 1.006-1.021, P=0.0005).

Patients treated with IMRT were more likely to receive planned chemotherapy, including full concurrent chemotherapy (55.7% versus 52.0%, P=0.31) and full consolidation therapy (37.3% versus 29.1%, P=0.05).

The results suggest that IMRT may offer an opportunity for reasonable outcomes in patients with larger tumors, Curran said.

"What these results say is that there should never be a stage III lung cancer trial that does not allow IMRT," he said. "If people have trouble meeting the radiation dose constraints with 3D-CRT, they should look at IMRT."

The results also could have implications for payers, who have balked at covering higher-cost IMRT without justification in the form tangible benefits, Curran added.

Comment