- Email: [email protected]
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I. J. Radiation Oncology
● Biology ● Physics
Volume 66, Number 3, Supplement, 2006
starting consolidation, and 100 pts randomized to gefitinib maintenance and 109 pts randomized to placebo maintenance. Of all patients starting treatment on the study, 7% experienced ⱖ Gr 3 pneumonitis at some point during treatment. The incidence of ⱖ Gr 3 pneumonitis developing during concurrent chemoradiation, consolidation and maintenance (gefitinib or placebo) was ⬍1%, 7%, and ⬍1%,respectively. Of 444 patients whose RT details have been reviewed, V20 exceeded 35% in 18% of patients. V20 was not significantly associated with gender, age, stage (IIIA vs IIIB), or FEV1. There is strong evidence (p⫽0.005), of a relationship between V20 and the subsequent development of ⱖ Grade 3 pneumonitis. The risk of developing ⱖGr 3 pneumonitis increased by 5% for each percent increase in V20 (p⫽0.01). V20⬎35% was also significantly associated with the occurrence of ⱖ Grade 3 esophagitis (p⫽0.032). Median survival for patients with V20⬎35% was significantly worse than those with V20ⱕ35%, 12 vs 24 months, respectively (p⫽0.0006). Conclusions: The 7% incidence of significant pneumonitis observed in SWOG 0023 is within reasonable limits and is significantly correlated with V20 ⬎35%. It is not possible to say whether the poor survival observed in patients with V20⬎35% is related to tumor bulk or toxicity. Future SWOG lung studies in this group of patients will require V20 to be ⱕ 35%. Author Disclosure: L.E. Gaspar, Genentech, F. Consultant/Advisory Board; J. McCoy, None; K. Kelly, AstraZeneca, F. Consultant/Advisory Board; Sanofi-Aventis, F. Consultant/Advisory Board; K.S. Albain, Genentech, F. Consultant/Advisory Board; Sanofi-Aventis, F. Consultant/Advisory Board; AstraZeneca, F. Consultant/Advisory Board; J.J. Crowley, None; D.R. Gandara, None.
109
Sociodemographic Factors Are Significant Predictors of Toxicity in RTOG Non-Operative NSCLC Trials
B. Movsas1, S. Swann2, W. Curran3, J. Coyne4, A. Konski5, R. Komaki6, J. Bradley7, C. Langer5, H. Choy8, D. Watkins-Bruner4 1 Henry Ford Hospital, Detroit, MI, 2RTOG, Philadelphia, PA, 3Thomas Jefferson University, Philadelphia, PA, 4University of Pennsylvania, Philadelphia, PA, 5Fox Chase Cancer Center, Philadelphia, PA, 6MD Anderson Cancer Center, Houston, TX, 7Washington University, School of Medicine, St. Louis, MO, 8Southwestern University, Dallas, TX Purpose/Objective(s): Traditionally, treatment variables, but not sociodemographic factors, are closely analyzed to predict the risk of radiation toxicities. This analysis examines the association of sociodemographic factors with grade ⱖ 3 esophagitis and pneumonitis in Radiation Therapy Oncology Group (RTOG) non-operative non-small cell lung cancer (NSCLC) trials activated during the 1990’s. Materials/Methods: This secondary analysis is based on data from 1450 patients treated on 9 prospective RTOG non-operative NSCLC studies activated during the 1990’s. Studies included RTOG 9015, 9103, 9106, 9204, 9205, 9304 (RT arm only), 9311, 9410 & 9801. Six stratification levels based on the presence of chemotherapy (yes vs. no) and accrual year (1991-1994,19951998,1999-2002) were defined. Logistic regression models for toxicities tested the following variables controlling for strata: age, gender, race, KPS, weight (wt) loss, stage, histology, location of primary tumor, biological equivalent dose (BED) based on actual RT delivered, deviation from protocol dose (⬍95%vs ⱖ 95%), marital status, education level, number of persons in household, family/friends with cancer, employment status, and household income (adjusted to 2002 dollars). Results: There was a significant increase in gradeⱖ 3 esophagitis in the chemoRT strata (29%) compared to the RT strata (5%), but not in pneumonitis (15% for chemoRT vs. 18% for RT). In stratified multivariate analysis (MVA), the following factors were significantly associated with grade ⱖ 3 pneumonitis: lower lobe primaries (p⫽0.014), married/live-in relationship (p⫽0.0074), presence of family/friends with cancer (p⫽0.028) and the interaction of KPS & gender (p⫽0.015). In MVA, the following factors significantly predicted for gradeⱖ 3 esophagitis: White race (p⫽0.0084), deviation (⬍95%) of total dose (p⫽0.0004), and the interaction of KPS & wt loss (p⫽0.0002). Conclusions: It is revealing that sociodemographic factors, even more than treatment variables, have such strong associations with gradeⱖ 3 pneumonitis and esophagitis, suggesting that these factors may influence the degree of reporting or diagnosis of these toxicities. One could hypothesize that, rather than being truly more prevalent, severe pneumonitis is more readily reported/diagnosed in those patients who have a stronger ”voice“ (eg, married/live-in, have family/friends, not low-KPS/male). Similarly, White race predicted for higher rates of severe esophagitis. Pts with low KPS & ⬎wt loss, who may have less reserve, are at higher risk for severe esophagitis. The lower total RT dose suggests a reluctance to complete RT in the face of severe acute esophagitis. The increased pneumonitis observed with lower lobe primaries may be due to increased treatment volumes or other biologic factors. This analysis illustrates the need to include sociodemographic factors in risk models for RT toxicity for lung cancer and suggests increased vigilance is necessary to avoid under-reporting or under-diagnosis of pneumonitis and esophagitis. Author Disclosure: B. Movsas, None; S. Swann, None; W. Curran, None; J. Coyne, None; A. Konski, None; R. Komaki, None; J. Bradley, None; C. Langer, None; H. Choy, None; D. Watkins-Bruner, None.
110
A Statistical Model of the Risk of Radiation Pneumonitis Based on Combined RTOG and Washington University Data
J. O. Deasy1, I. El Naqa1, A. H. Hope1, P. E. Lindsay1, W. T. Sause2, M. L. Graham3, W. R. Bosch1, J. W. Matthews1, J. D. Bradley1 1 Washington University School of Medicine, St. Louis, MO, 2LDS Hospital, Salt Lake City, UT, 3Phelps County Regional Hospital, Rolla, MO Purpose/Objective(s): To model of the risk of radiation pneumonitis (RP) by combining institutional and multi-institutional (RTOG) databases of patients treated with radiation therapy for lung cancer. Materials/Methods: Two datasets were combined: the WUSTL dataset (number of evaluable patients ⫽ 219) we have previously studied (Hope et al., IJROBP, in press), and image-based data from RTOG clinical trial 93-11 (number of evaluable patients ⫽ 129, 24 common with WUSTL). In the WUSTL dataset, all evaluable 3-D treatment plans for patients with registered
I. J. Radiation Oncology
● Biology ● Physics
Volume 66, Number 3, Supplement, 2006
starting consolidation, and 100 pts randomized to gefitinib maintenance and 109 pts randomized to placebo maintenance. Of all patients starting treatment on the study, 7% experienced ⱖ Gr 3 pneumonitis at some point during treatment. The incidence of ⱖ Gr 3 pneumonitis developing during concurrent chemoradiation, consolidation and maintenance (gefitinib or placebo) was ⬍1%, 7%, and ⬍1%,respectively. Of 444 patients whose RT details have been reviewed, V20 exceeded 35% in 18% of patients. V20 was not significantly associated with gender, age, stage (IIIA vs IIIB), or FEV1. There is strong evidence (p⫽0.005), of a relationship between V20 and the subsequent development of ⱖ Grade 3 pneumonitis. The risk of developing ⱖGr 3 pneumonitis increased by 5% for each percent increase in V20 (p⫽0.01). V20⬎35% was also significantly associated with the occurrence of ⱖ Grade 3 esophagitis (p⫽0.032). Median survival for patients with V20⬎35% was significantly worse than those with V20ⱕ35%, 12 vs 24 months, respectively (p⫽0.0006). Conclusions: The 7% incidence of significant pneumonitis observed in SWOG 0023 is within reasonable limits and is significantly correlated with V20 ⬎35%. It is not possible to say whether the poor survival observed in patients with V20⬎35% is related to tumor bulk or toxicity. Future SWOG lung studies in this group of patients will require V20 to be ⱕ 35%. Author Disclosure: L.E. Gaspar, Genentech, F. Consultant/Advisory Board; J. McCoy, None; K. Kelly, AstraZeneca, F. Consultant/Advisory Board; Sanofi-Aventis, F. Consultant/Advisory Board; K.S. Albain, Genentech, F. Consultant/Advisory Board; Sanofi-Aventis, F. Consultant/Advisory Board; AstraZeneca, F. Consultant/Advisory Board; J.J. Crowley, None; D.R. Gandara, None.
109
Sociodemographic Factors Are Significant Predictors of Toxicity in RTOG Non-Operative NSCLC Trials
B. Movsas1, S. Swann2, W. Curran3, J. Coyne4, A. Konski5, R. Komaki6, J. Bradley7, C. Langer5, H. Choy8, D. Watkins-Bruner4 1 Henry Ford Hospital, Detroit, MI, 2RTOG, Philadelphia, PA, 3Thomas Jefferson University, Philadelphia, PA, 4University of Pennsylvania, Philadelphia, PA, 5Fox Chase Cancer Center, Philadelphia, PA, 6MD Anderson Cancer Center, Houston, TX, 7Washington University, School of Medicine, St. Louis, MO, 8Southwestern University, Dallas, TX Purpose/Objective(s): Traditionally, treatment variables, but not sociodemographic factors, are closely analyzed to predict the risk of radiation toxicities. This analysis examines the association of sociodemographic factors with grade ⱖ 3 esophagitis and pneumonitis in Radiation Therapy Oncology Group (RTOG) non-operative non-small cell lung cancer (NSCLC) trials activated during the 1990’s. Materials/Methods: This secondary analysis is based on data from 1450 patients treated on 9 prospective RTOG non-operative NSCLC studies activated during the 1990’s. Studies included RTOG 9015, 9103, 9106, 9204, 9205, 9304 (RT arm only), 9311, 9410 & 9801. Six stratification levels based on the presence of chemotherapy (yes vs. no) and accrual year (1991-1994,19951998,1999-2002) were defined. Logistic regression models for toxicities tested the following variables controlling for strata: age, gender, race, KPS, weight (wt) loss, stage, histology, location of primary tumor, biological equivalent dose (BED) based on actual RT delivered, deviation from protocol dose (⬍95%vs ⱖ 95%), marital status, education level, number of persons in household, family/friends with cancer, employment status, and household income (adjusted to 2002 dollars). Results: There was a significant increase in gradeⱖ 3 esophagitis in the chemoRT strata (29%) compared to the RT strata (5%), but not in pneumonitis (15% for chemoRT vs. 18% for RT). In stratified multivariate analysis (MVA), the following factors were significantly associated with grade ⱖ 3 pneumonitis: lower lobe primaries (p⫽0.014), married/live-in relationship (p⫽0.0074), presence of family/friends with cancer (p⫽0.028) and the interaction of KPS & gender (p⫽0.015). In MVA, the following factors significantly predicted for gradeⱖ 3 esophagitis: White race (p⫽0.0084), deviation (⬍95%) of total dose (p⫽0.0004), and the interaction of KPS & wt loss (p⫽0.0002). Conclusions: It is revealing that sociodemographic factors, even more than treatment variables, have such strong associations with gradeⱖ 3 pneumonitis and esophagitis, suggesting that these factors may influence the degree of reporting or diagnosis of these toxicities. One could hypothesize that, rather than being truly more prevalent, severe pneumonitis is more readily reported/diagnosed in those patients who have a stronger ”voice“ (eg, married/live-in, have family/friends, not low-KPS/male). Similarly, White race predicted for higher rates of severe esophagitis. Pts with low KPS & ⬎wt loss, who may have less reserve, are at higher risk for severe esophagitis. The lower total RT dose suggests a reluctance to complete RT in the face of severe acute esophagitis. The increased pneumonitis observed with lower lobe primaries may be due to increased treatment volumes or other biologic factors. This analysis illustrates the need to include sociodemographic factors in risk models for RT toxicity for lung cancer and suggests increased vigilance is necessary to avoid under-reporting or under-diagnosis of pneumonitis and esophagitis. Author Disclosure: B. Movsas, None; S. Swann, None; W. Curran, None; J. Coyne, None; A. Konski, None; R. Komaki, None; J. Bradley, None; C. Langer, None; H. Choy, None; D. Watkins-Bruner, None.
110
A Statistical Model of the Risk of Radiation Pneumonitis Based on Combined RTOG and Washington University Data
J. O. Deasy1, I. El Naqa1, A. H. Hope1, P. E. Lindsay1, W. T. Sause2, M. L. Graham3, W. R. Bosch1, J. W. Matthews1, J. D. Bradley1 1 Washington University School of Medicine, St. Louis, MO, 2LDS Hospital, Salt Lake City, UT, 3Phelps County Regional Hospital, Rolla, MO Purpose/Objective(s): To model of the risk of radiation pneumonitis (RP) by combining institutional and multi-institutional (RTOG) databases of patients treated with radiation therapy for lung cancer. Materials/Methods: Two datasets were combined: the WUSTL dataset (number of evaluable patients ⫽ 219) we have previously studied (Hope et al., IJROBP, in press), and image-based data from RTOG clinical trial 93-11 (number of evaluable patients ⫽ 129, 24 common with WUSTL). In the WUSTL dataset, all evaluable 3-D treatment plans for patients with registered