Adaptive radiation therapy aids control of unresectable NSCLC

ATLANTA – Adjusting radiation therapy based on imaging results may improve control of locally advanced, unresectable non–small cell lung cancer, according to researchers.

When conformal radiation therapy was adapted midtreatment on the basis of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) results, patients had significantly better overall survival, progression-free survival, locoregional tumor control, and locoregional progression-free survival (LR-PFS) than did stage-matched controls treated with standard radiation doses in a phase II trial.

"We all know local failure remains a problem for locally advanced non–small cell lung cancer [NSCLC]," said Dr. Feng-Ming Kong, a pediatric radiation oncologist at Georgia Regents University Cancer Center in Augusta, Georgia. "We also know tumors change during treatment in terms of activity and volume, the change differs from patient to patient, and changes in volume are more evident on PET scans than on CTs," she said at the annual meeting of the American Society for Radiation Oncology.

In a previous study at the University of Michigan in Ann Arbor, Dr. Kong and her colleagues found that tumor response during treatment was prognostic for clinical response after radiation therapy (J. Clin. Oncol. 2007;25:3116-23 [doi: 10.1200/JCO.2006.10.3747]).

"We therefore hypothesized that PET scans obtained during treatment may be able to guide us for individualized, adaptive radiotherapy to deliver a more intensive dose to the active residual tumor, resulting in improved local tumor control," she said.

They enrolled 42 patients (median age 63, 67% male, 45% squamous histology). The patients received conformal radiation therapy in 30 daily fractions of 2.2-2.8 Gy up to 17.2% of normal tissue complication probability. The patients received concurrent weekly carboplatin and paclitaxel, as well as three cycles of consolidation therapy with the same drugs.

After patients had received 40-50 Gy, they had a CT-based resimulation, and underwent PET and CT imaging studies. When the patients had reached a total physical dose of 63-86 Gy (63.5 to 92 Gy to tumor, 64 to 102 Gy to lung), their treatment was replanned based on the midtreatment PET results, with dose escalation to FDG-avid regions.

Controls were stage-matched patients who were treated at the same time with standard 60 to 66 Gy radiation doses.

At a median follow-up of 25 months (minimum 10 months), the 2-year rate of locoregional tumor control, the primary endpoint, was 68% (P vs. controls = .02) and the rate of LR-PFS was 43% (P = .007). Overall survival at 2 years also was significantly better among patients treated with adaptive radiation therapy, at 51%, compared with 23% for controls (P = .02).

There were 19 deaths, 7 from disease progression, and 12 without progression. There were no grade 4 treatment toxicities and no treatment-related deaths. Four patients had grade 2 pneumonitis and three had grade 3 pneumonitis. Grade 2 esophagitis was seen in 14 patients, and grade 3 in 5 patients. Nine patients had grade 3 dyspnea, three had bleeding, and one had both dyspnea and bleeding.

"The most common site of failure for this group is distant after this kind of treatment, and the major causes of death actually seem to be non–cancer related," Dr. Kong said.

A randomized trial, RTOG 1106, is currently testing midtreatment adaptive radiation therapy.

The study was supported by grants from the National Institutes of Health and by an ASCO Young Investigator Award. Dr. Kong disclosed serving as principal investigator on a project funded by Varian Medical Systems.

ATLANTA – Adjusting radiation therapy based on imaging results may improve control of locally advanced, unresectable non–small cell lung cancer, according to researchers.

When conformal radiation therapy was adapted midtreatment on the basis of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) results, patients had significantly better overall survival, progression-free survival, locoregional tumor control, and locoregional progression-free survival (LR-PFS) than did stage-matched controls treated with standard radiation doses in a phase II trial.

"We all know local failure remains a problem for locally advanced non–small cell lung cancer [NSCLC]," said Dr. Feng-Ming Kong, a pediatric radiation oncologist at Georgia Regents University Cancer Center in Augusta, Georgia. "We also know tumors change during treatment in terms of activity and volume, the change differs from patient to patient, and changes in volume are more evident on PET scans than on CTs," she said at the annual meeting of the American Society for Radiation Oncology.

In a previous study at the University of Michigan in Ann Arbor, Dr. Kong and her colleagues found that tumor response during treatment was prognostic for clinical response after radiation therapy (J. Clin. Oncol. 2007;25:3116-23 [doi: 10.1200/JCO.2006.10.3747]).

"We therefore hypothesized that PET scans obtained during treatment may be able to guide us for individualized, adaptive radiotherapy to deliver a more intensive dose to the active residual tumor, resulting in improved local tumor control," she said.

They enrolled 42 patients (median age 63, 67% male, 45% squamous histology). The patients received conformal radiation therapy in 30 daily fractions of 2.2-2.8 Gy up to 17.2% of normal tissue complication probability. The patients received concurrent weekly carboplatin and paclitaxel, as well as three cycles of consolidation therapy with the same drugs.

After patients had received 40-50 Gy, they had a CT-based resimulation, and underwent PET and CT imaging studies. When the patients had reached a total physical dose of 63-86 Gy (63.5 to 92 Gy to tumor, 64 to 102 Gy to lung), their treatment was replanned based on the midtreatment PET results, with dose escalation to FDG-avid regions.

Controls were stage-matched patients who were treated at the same time with standard 60 to 66 Gy radiation doses.

At a median follow-up of 25 months (minimum 10 months), the 2-year rate of locoregional tumor control, the primary endpoint, was 68% (P vs. controls = .02) and the rate of LR-PFS was 43% (P = .007). Overall survival at 2 years also was significantly better among patients treated with adaptive radiation therapy, at 51%, compared with 23% for controls (P = .02).

There were 19 deaths, 7 from disease progression, and 12 without progression. There were no grade 4 treatment toxicities and no treatment-related deaths. Four patients had grade 2 pneumonitis and three had grade 3 pneumonitis. Grade 2 esophagitis was seen in 14 patients, and grade 3 in 5 patients. Nine patients had grade 3 dyspnea, three had bleeding, and one had both dyspnea and bleeding.

"The most common site of failure for this group is distant after this kind of treatment, and the major causes of death actually seem to be non–cancer related," Dr. Kong said.

A randomized trial, RTOG 1106, is currently testing midtreatment adaptive radiation therapy.

The study was supported by grants from the National Institutes of Health and by an ASCO Young Investigator Award. Dr. Kong disclosed serving as principal investigator on a project funded by Varian Medical Systems.

ATLANTA – Adjusting radiation therapy based on imaging results may improve control of locally advanced, unresectable non–small cell lung cancer, according to researchers.

When conformal radiation therapy was adapted midtreatment on the basis of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) results, patients had significantly better overall survival, progression-free survival, locoregional tumor control, and locoregional progression-free survival (LR-PFS) than did stage-matched controls treated with standard radiation doses in a phase II trial.

"We all know local failure remains a problem for locally advanced non–small cell lung cancer [NSCLC]," said Dr. Feng-Ming Kong, a pediatric radiation oncologist at Georgia Regents University Cancer Center in Augusta, Georgia. "We also know tumors change during treatment in terms of activity and volume, the change differs from patient to patient, and changes in volume are more evident on PET scans than on CTs," she said at the annual meeting of the American Society for Radiation Oncology.

In a previous study at the University of Michigan in Ann Arbor, Dr. Kong and her colleagues found that tumor response during treatment was prognostic for clinical response after radiation therapy (J. Clin. Oncol. 2007;25:3116-23 [doi: 10.1200/JCO.2006.10.3747]).

"We therefore hypothesized that PET scans obtained during treatment may be able to guide us for individualized, adaptive radiotherapy to deliver a more intensive dose to the active residual tumor, resulting in improved local tumor control," she said.

They enrolled 42 patients (median age 63, 67% male, 45% squamous histology). The patients received conformal radiation therapy in 30 daily fractions of 2.2-2.8 Gy up to 17.2% of normal tissue complication probability. The patients received concurrent weekly carboplatin and paclitaxel, as well as three cycles of consolidation therapy with the same drugs.

After patients had received 40-50 Gy, they had a CT-based resimulation, and underwent PET and CT imaging studies. When the patients had reached a total physical dose of 63-86 Gy (63.5 to 92 Gy to tumor, 64 to 102 Gy to lung), their treatment was replanned based on the midtreatment PET results, with dose escalation to FDG-avid regions.

Controls were stage-matched patients who were treated at the same time with standard 60 to 66 Gy radiation doses.

At a median follow-up of 25 months (minimum 10 months), the 2-year rate of locoregional tumor control, the primary endpoint, was 68% (P vs. controls = .02) and the rate of LR-PFS was 43% (P = .007). Overall survival at 2 years also was significantly better among patients treated with adaptive radiation therapy, at 51%, compared with 23% for controls (P = .02).

There were 19 deaths, 7 from disease progression, and 12 without progression. There were no grade 4 treatment toxicities and no treatment-related deaths. Four patients had grade 2 pneumonitis and three had grade 3 pneumonitis. Grade 2 esophagitis was seen in 14 patients, and grade 3 in 5 patients. Nine patients had grade 3 dyspnea, three had bleeding, and one had both dyspnea and bleeding.

"The most common site of failure for this group is distant after this kind of treatment, and the major causes of death actually seem to be non–cancer related," Dr. Kong said.

A randomized trial, RTOG 1106, is currently testing midtreatment adaptive radiation therapy.

The study was supported by grants from the National Institutes of Health and by an ASCO Young Investigator Award. Dr. Kong disclosed serving as principal investigator on a project funded by Varian Medical Systems.