High-dose RT 'clear detriment' to survival in patients with stage III lung cancer

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 - lung

In the setting of concurrent chemotherapy, high-dose radiotherapy did not improve survival of patients with stage III non-small-cell lung cancer (NSCLC) compared with treatment featuring standard-dose radiotherapy, according to the results of a randomized phase III clinical trial to be presented June 4 at the American Society of Clinical Oncology 2013 annual meeting in Chicago.

Median survival, 18-month overall survival and local failure rates at 18 months all favored standard-dose over high-dose radiotherapy, according to Jeffrey D. Bradley, MD, of Washington University School of Medicine in St. Louis, and colleagues.

The standard of care for locally advanced NSCLC is 60-Gy radiotherapy plus chemotherapy, though previous research has suggested that radiotherapy at 74-Gy could increase median survival time. To test the optimal radiotherapy dose, Bradley and colleagues randomized 464 patients with pathologically diagnosed unresectable stage IIIA or IIIB NSCLC to 60 Gy, 74 Gy and concurrent chemotherapy.

In addition to testing radiotherapy dose, the researchers also investigated the effect of cetuximab, which targets the epidermal growth factor receptor (EGFR) pathway and has radiation-sensitizing properties. All patient received chemotherapy of weekly paclitaxel and carboplatin, along with additional cycles of consolidation chemotherapy following the combined treatments.

A total of 419 patients were included in the final analysis, with a median follow-up time of 17.2 months. Median survival time was 28.7 months for the standard-dose and 19.5 months for the high-dose treatment, reported the researchers. Overall survival at 18-months was 66.9 percent and 53.9 percent for the 60 Gy and 74 Gy treatments, respectively.  The results indicated, “a clear detriment associated with the higher radiation dose," said Bradley in a release.

He also noted that use of 3D vs. intensity-modulated radiotherapy technique did not affect performance.

The findings indicate that targeted therapies, such as those that block EGFR, are the next phase of treatment, according to Bradley. He added that future research to improve radiotherapy will focus on adaptive radiotherapy, with radiation delivered being refocused on remaining tumor volume midway through treatment to increase dose per fraction.

The trial was conducted by the Radiation Therapy Oncology Group, a multi-institutional international group located in the American College of Radiology Center for Clinical Research in Philadelphia.