Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non–Small-Cell Lung Cancer

Werner-Wasik, Maria; Swann, R. Suzanne; Bradley, Jeffrey; Graham, Mary; Emami, Bahman; Purdy, James; Sause, William

doi:10.1016/j.ijrobp.2007.06.034

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Volume 70, Issue 2 , Pages 385-390, 1 February 2008

Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non–Small-Cell Lung Cancer

Maria Werner-Wasik, M.D.
- Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, PA
- Reprint requests to: Maria Werner-Wasik, M.D., Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, 111 S. 11th St., Philadelphia, PA 19107. Tel: (215) 955-6705; Fax: (215) 955-0412
R. Suzanne Swann, Ph.D.
- Radiation Therapy Oncology Group Headquarters, Philadelphia, PA
Jeffrey Bradley, M.D.
- Washington University, St. Louis, MO
Mary Graham, M.D.
- Phelps County Regional Medical Center, Rolla, MO
Bahman Emami, M.D.
- Loyola University Medical Center, Maywood, IL
James Purdy, Ph.D.
- University of California, Davis, Medical Center, Sacramento, CA
William Sause, M.D.
- LDS Hospital, Salt Lake City, UT

Received 5 February 2007; received in revised form 24 May 2007; accepted 20 June 2007. published online 14 September 2007.

Purpose

Patients with non–small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels. We investigated the effect of the gross tumor volume (GTV) on the outcome.

Methods and Materials

The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller (≤45 cm³) vs. larger (>45 cm³) tumors.

Results

The distribution of the GTV was as follows: ≤45 cm³ in 79 (49%) and >45 cm³ in 82 (51%) of 161 patients. The median GTV was 47.3 cm³. N0 status and female gender were associated with better tumor responses. Patients with smaller (≤45 cm³) tumors achieved a longer MST and better PFS than did patients with larger (>45 cm³) tumors (29.7 vs. 13.3 months, p < 0.0001; and 15.8 vs. 8.3 months, p < 0.0001, respectively). Increasing the radiation dose had no effect on the MST or PFS. On multivariate analysis, only a smaller GTV was a significant prognostic factor for improved MST and PFS (hazard ratio [HR], 2.12, p = 0.0002; and HR, 2.0, p = 0.0002, respectively). The GTV as a continuous variable was also significantly associated with the MST and PFS (HR, 1.59, p < 0.0001; and HR, 1.39, p < 0.0001, respectively).

Conclusions

Radiation dose escalation up to 90.3 Gy did not result in improved MST or PFS. The tumor responses were greater in node-negative patients and women. An increasing GTV was strongly associated with decreased MST and PFS. Future radiotherapy trials patients might need to use stratification by tumor volume.

Tumor volume, Lung cancer, Radiotherapy dose escalation