Christian L Barney1, Nicholas Scoville1, Eric Allan1, Ahmet Ayan1, Dominic DiCostanzo1, Karl E Haglund1, John Grecula1, Terence Williams1, Meng Xu-Welliver1, Gregory A Otterson2, Jose G Bazan3. 1. Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio. 2. Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio. 3. Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio. Electronic address: jose.bazan2@osumc.edu.
Abstract
PURPOSE: To test the hypothesis that increasing radiation therapy (RT) dose to the thoracic vertebral bodies (TVBs) contributes to the development of hematologic toxicities (HTs) in patients with lung cancer. METHODS AND MATERIALS: Cases of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) treated with definitive chemoradiation with concurrent platinum-based doublet chemotherapy at our institution from 2007 to 2016 were identified. Mean TVB dose and the volume of TVBs receiving at least 5 to 60 Gy (V5-V60) were retrospectively recorded. Logistic regression was used to test associations between grade ≥3 HT (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability was evaluated using the Lyman-Kutcher-Burman (LKB) model for HT3+, and receiver operating characteristics analysis was used to determine dosimetric cut-points. RESULTS: We identified 201 patients, the majority having NSCLC (n=162, 81%) and stage III to IV disease (n=179, 89%). All patients received either cisplatin/etoposide (n=107, 53%) or carboplatin/paclitaxel (n=94, 47%). Median RT dose was 60 Gy (range, 60-70 Gy). The rate of HT3+ was 49% (n=99). Increasing mean TVB dose (per Gy) was associated with higher odds of developing HT3+ (odds ratio 1.041, 95% confidence interval 1.004-1.080, P=.032), as were increasing TVB V5 to V20. These dosimetric correlates to HT3+ persisted on multivariate analysis. Constrained optimization of the LKB model for HT3+ yielded the parameters: n=1, m=1.79, and TD50=21.4 Gy. Optimal cut-points identified were V5=65%, V10=60%, V20=50%, and mean dose=23.5 Gy. Patients with values above these cut-points had an approximately 2-fold increased risk of HT3+. CONCLUSIONS: We found that mean TVB dose and low-dose parameters (V5-V20) were associated with HT3+ in chemoradiation for lung cancer. Per the LKB model, bone marrow behaves like a parallel organ (n=1), implying that mean TVB dose is a useful predictor for toxicity. These data suggest that efforts to spare dose to the TVBs may reduce rates of severe HT.
PURPOSE: To test the hypothesis that increasing radiation therapy (RT) dose to the thoracic vertebral bodies (TVBs) contributes to the development of hematologic toxicities (HTs) in patients with lung cancer. METHODS AND MATERIALS: Cases of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) treated with definitive chemoradiation with concurrent platinum-based doublet chemotherapy at our institution from 2007 to 2016 were identified. Mean TVB dose and the volume of TVBs receiving at least 5 to 60 Gy (V5-V60) were retrospectively recorded. Logistic regression was used to test associations between grade ≥3 HT (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability was evaluated using the Lyman-Kutcher-Burman (LKB) model for HT3+, and receiver operating characteristics analysis was used to determine dosimetric cut-points. RESULTS: We identified 201 patients, the majority having NSCLC (n=162, 81%) and stage III to IV disease (n=179, 89%). All patients received either cisplatin/etoposide (n=107, 53%) or carboplatin/paclitaxel (n=94, 47%). Median RT dose was 60 Gy (range, 60-70 Gy). The rate of HT3+ was 49% (n=99). Increasing mean TVB dose (per Gy) was associated with higher odds of developing HT3+ (odds ratio 1.041, 95% confidence interval 1.004-1.080, P=.032), as were increasing TVB V5 to V20. These dosimetric correlates to HT3+ persisted on multivariate analysis. Constrained optimization of the LKB model for HT3+ yielded the parameters: n=1, m=1.79, and TD50=21.4 Gy. Optimal cut-points identified were V5=65%, V10=60%, V20=50%, and mean dose=23.5 Gy. Patients with values above these cut-points had an approximately 2-fold increased risk of HT3+. CONCLUSIONS: We found that mean TVB dose and low-dose parameters (V5-V20) were associated with HT3+ in chemoradiation for lung cancer. Per the LKB model, bone marrow behaves like a parallel organ (n=1), implying that mean TVB dose is a useful predictor for toxicity. These data suggest that efforts to spare dose to the TVBs may reduce rates of severe HT.
Authors: J P Pignon; R Arriagada; D C Ihde; D H Johnson; M C Perry; R L Souhami; O Brodin; R A Joss; M S Kies; B Lebeau Journal: N Engl J Med Date: 1992-12-03 Impact factor: 91.245
Authors: Kevin Albuquerque; David Giangreco; Courtney Morrison; Mohammed Siddiqui; Jim Sinacore; Ronald Potkul; John Roeske Journal: Int J Radiat Oncol Biol Phys Date: 2010-05-12 Impact factor: 7.038
Authors: Antonio Rossi; Massimo Di Maio; Paolo Chiodini; Robin Michael Rudd; Hiroaki Okamoto; Dimosthenis Vasilios Skarlos; Martin Früh; Wendi Qian; Tomohide Tamura; Epaminondas Samantas; Taro Shibata; Francesco Perrone; Ciro Gallo; Cesare Gridelli; Olga Martelli; Siow-Ming Lee Journal: J Clin Oncol Date: 2012-04-02 Impact factor: 44.544
Authors: Jose G Bazan; Gary Luxton; Edward C Mok; Albert C Koong; Daniel T Chang Journal: Int J Radiat Oncol Biol Phys Date: 2012-03-11 Impact factor: 7.038
Authors: Sarah M McGuire; Yusuf Menda; Laura L Boles Ponto; Brandie Gross; John Buatti; John E Bayouth Journal: Int J Radiat Oncol Biol Phys Date: 2011-02-06 Impact factor: 7.038
Authors: Ann H Klopp; Jennifer Moughan; Lorraine Portelance; Brigitte E Miller; Mohammad R Salehpour; Evangeline Hildebrandt; Jenny Nuanjing; David D'Souza; Luis Souhami; William Small; Rakesh Gaur; Anuja Jhingran Journal: Int J Radiat Oncol Biol Phys Date: 2013-05-01 Impact factor: 7.038
Authors: Nikhil T Sebastian; Rohit Raj; Rahul Prasad; Christian Barney; Jeremy Brownstein; John Grecula; Karl Haglund; Meng Xu-Welliver; Terence M Williams; Jose G Bazan Journal: Front Oncol Date: 2020-11-05 Impact factor: 6.244