title: 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.
abstract: OBJECTIVE
  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
  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 (< or =45 cm(3)) vs. larger (>45 cm(3)) tumors.
  
  
  RESULTS
  The distribution of the GTV was as follows: < or =45 cm(3) in 79 (49%) and >45 cm(3) in 82 (51%) of 161 patients. The median GTV was 47.3 cm(3). N0 status and female gender were associated with better tumor responses. Patients with smaller (< or =45 cm(3)) tumors achieved a longer MST and better PFS than did patients with larger (>45 cm(3)) 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.
authors.affiliation: Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, PA, USA. maria.werner-wasik@jeffersonhospital.org
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.forename: R Suzanne
authors.initials: RS
authors.lastname: Swann
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bradley
authors.forename: Mary
authors.initials: M
authors.lastname: Graham
authors.forename: Bahman
authors.initials: B
authors.lastname: Emami
authors.forename: James
authors.initials: J
authors.lastname: Purdy
authors.forename: William
authors.initials: W
authors.lastname: Sause
mesh_terms: D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D012737:Sex Factors; D015996:Survival Rate; D047368:Tumor Burden