- Email: [email protected]
197PD: Identifying dosimetric predictors of toxicity in multiple lung tumors treated with stereotactic ablative radiotherapy (SABR)
Abstracts, ELCC 2016
Journal of Thoracic Oncology Vol. 11, Suppl. 4S (2016) S143–S146
Metastases to and from the lung 197PD Identifying dosimetric predictors of toxicity in multiple lung tumors treated with stereotactic ablative radiotherapy (SABR) H. Tekatli1 , S. Tetar1 , A. Warner2 , D. Palma2 , W. Verbakel1 , T. Nguyen2 , F. Spoelstra1 , S. Gaede2 , B. Slotman1 , S. Senan1 . 1 Radiation Oncology, Vrije University Medical Centre (VUMC), Amsterdam, Netherlands, 2 Radiation Oncology, London Regional Cancer Center, London Health Science Center, University of Western Ontario, London, ON, Canada Background: Stereotactic radiotherapy (SABR) is increasingly used for treating multiple synchronous lung lesions. Previous studies for solitary lesions revealed that contralateral lung doses predict the risk of radiation pneumonitis (RP). As dosimetric predictors for toxicity of SABR in patients with multiple lung lesions are unknown, we performed a multi-center retrospective study in this patient subgroup, and report on clinical outcomes and dosimetric parameters. Methods: Patients undergoing SABR using Volumetric Modulated Arc Therapy for 2 synchronous parenchymal lung lesions within 1 month between 2009 and 2014, were identified from the VU University Medical Center and London Health Sciences Centre. All lesions received a BED10 of 100 Gy. Patients with prior or subsequent non-SABR thoracic radiotherapy were excluded. A recursive partitioning analysis was performed on survival and toxicity outcomes (CTCAE v4.03) using the hazard function and binary function respectively, based on baseline patient factors and treatment characteristics, including lung doses (V5 Gy –V50 Gy in 5 Gy intervals). Results: 84 patients treated for 187 lesions were identified. 46% were treated for multiple lung metastases and 54% for multiple primary NSCLC lesions. Median age was 69.4 years, 97% of patients were treated for 2–3 lesions, and 56% had bilateral lesions. Most plan optimizations severely constrained the V5 Gy of contralateral lung. After a median follow-up time of 28 months, median OS was 35 months, and 5 year survival was 39%. Grade 2 toxicity was recorded in 20% of patients at 6 weeks after start of treatment: RP (n = 9), chest wall pain (n = 5), rib fracture (n = 2), and dyspnea (n = 1). A total of 33 deaths were observed, including 1 treatment-related death from RP, 17 due to progressive disease, and 15 due to other causes. Multivariable analysis showed that total lung minus PTV V35 Gy 6.5% (in 2 Gy/fraction equivalent) best predicted for grade 2 RP (p = 0.007). Conclusions: To the best of our knowledge, this is the first report on predictors of toxicity after SABR for multiple lung lesions. However, these findings should be further investigated in other patient populations, and using other delivery techniques for SABR. Legal entity responsible for the study: N/A Funding: N/A Disclosure: W. Verbakel, B. Slotman, S. Senan: The Department of Radiation Oncology of the VU University Medical Center has a
research agreement with Varian Medical Systems. Honoraria and travel support received from Varian Medical Systems. All other authors have declared no conflicts of interest. 198PD Nomogram for predicting overall survival after stereotactic body radiotherapy for pulmonary metastases: Development and external validation M. Guckenberger1 , S. Lang1 , M. Hoyer2 , M.M. Fode2 , J. Rieber3 , F. Sterzing3 . 1 Department for Radiation Oncology, ¨ ¨ Universitatsspital Zurich, Zurich, Switzerland , 2 Department of Oncology, Aarhus University Hospital, Aarhus C, Denmark, 3 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany Background: Radical treatment of pulmonary metastases is practiced with increasing frequency since the better recognition and understanding of oligo-metastatic disease. However, patient selection remains challenging with long-term overall survival (OS) in < 25% of the patients. This study aimed at generation of a nomogram predicting OS after stereotactic body radiotherapy (SBRT) for pulmonary metastases. Methods: A multi-institutional database (n = 23; DEGRO Working Group Stereotaxy) of 671 patients treated with SBRT for 964 pulmonary metastases was used as a training cohort. Cox regression analysis with backward selection of variables (Akaike information criteria) was performed to identify factors to be included in the model to predict 2-year OS after SBRT. Based on this model a nomogram was constructed, calibrated and validated using concordance-index statistics. The nomogram was externally validated using a monocentric database of 92 patients treated with SBRT for pulmonary metastases (University Hospital Aarhus). Results: The 2-year OS of the training cohort was 52.5%. Kanofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the treated metastasis and number metastases (1 versus > 1) were significant prognostic factors in the Cox model (all p < 0.05). The calculated concordance-index for the nomogram was 0.711. Based on the nomogram the training cohort was divided into 4 groups, predicted 2-year OS in these groups were 76.1%, 62.6%, 45.8% and 24.2%; 2-year OS using Kaplan–Meier analysis were 78.4%, 60.4%, 46.0% and 30.2%. The nomogram discriminated well between risk groups in the validation cohort: Kaplan–Meier based 2-year OS were 84%, 53%, and 40% for risks groups 1–3; there were insufficient patient numbers (n = 4) in risk group 4. Conclusions: We successfully generated and validated a nomogram predicting 2-years OS after SBRT for pulmonary metastases. Primary tumor histology was one of the most important factors influencing OS; however, future prognostic scores need to incorporate the genetic variability within different cancers types. Legal entity responsible for the study: University Hospital Heidelberg Funding: N/A Disclosure: All authors have declared no conflicts of interest.
Copyright © 2016 by the European Lung Cancer Conference organisers, ESMO and IASLC. Published by Elsevier Inc. All rights reserved.
Journal of Thoracic Oncology Vol. 11, Suppl. 4S (2016) S143–S146
Metastases to and from the lung 197PD Identifying dosimetric predictors of toxicity in multiple lung tumors treated with stereotactic ablative radiotherapy (SABR) H. Tekatli1 , S. Tetar1 , A. Warner2 , D. Palma2 , W. Verbakel1 , T. Nguyen2 , F. Spoelstra1 , S. Gaede2 , B. Slotman1 , S. Senan1 . 1 Radiation Oncology, Vrije University Medical Centre (VUMC), Amsterdam, Netherlands, 2 Radiation Oncology, London Regional Cancer Center, London Health Science Center, University of Western Ontario, London, ON, Canada Background: Stereotactic radiotherapy (SABR) is increasingly used for treating multiple synchronous lung lesions. Previous studies for solitary lesions revealed that contralateral lung doses predict the risk of radiation pneumonitis (RP). As dosimetric predictors for toxicity of SABR in patients with multiple lung lesions are unknown, we performed a multi-center retrospective study in this patient subgroup, and report on clinical outcomes and dosimetric parameters. Methods: Patients undergoing SABR using Volumetric Modulated Arc Therapy for 2 synchronous parenchymal lung lesions within 1 month between 2009 and 2014, were identified from the VU University Medical Center and London Health Sciences Centre. All lesions received a BED10 of 100 Gy. Patients with prior or subsequent non-SABR thoracic radiotherapy were excluded. A recursive partitioning analysis was performed on survival and toxicity outcomes (CTCAE v4.03) using the hazard function and binary function respectively, based on baseline patient factors and treatment characteristics, including lung doses (V5 Gy –V50 Gy in 5 Gy intervals). Results: 84 patients treated for 187 lesions were identified. 46% were treated for multiple lung metastases and 54% for multiple primary NSCLC lesions. Median age was 69.4 years, 97% of patients were treated for 2–3 lesions, and 56% had bilateral lesions. Most plan optimizations severely constrained the V5 Gy of contralateral lung. After a median follow-up time of 28 months, median OS was 35 months, and 5 year survival was 39%. Grade 2 toxicity was recorded in 20% of patients at 6 weeks after start of treatment: RP (n = 9), chest wall pain (n = 5), rib fracture (n = 2), and dyspnea (n = 1). A total of 33 deaths were observed, including 1 treatment-related death from RP, 17 due to progressive disease, and 15 due to other causes. Multivariable analysis showed that total lung minus PTV V35 Gy 6.5% (in 2 Gy/fraction equivalent) best predicted for grade 2 RP (p = 0.007). Conclusions: To the best of our knowledge, this is the first report on predictors of toxicity after SABR for multiple lung lesions. However, these findings should be further investigated in other patient populations, and using other delivery techniques for SABR. Legal entity responsible for the study: N/A Funding: N/A Disclosure: W. Verbakel, B. Slotman, S. Senan: The Department of Radiation Oncology of the VU University Medical Center has a
research agreement with Varian Medical Systems. Honoraria and travel support received from Varian Medical Systems. All other authors have declared no conflicts of interest. 198PD Nomogram for predicting overall survival after stereotactic body radiotherapy for pulmonary metastases: Development and external validation M. Guckenberger1 , S. Lang1 , M. Hoyer2 , M.M. Fode2 , J. Rieber3 , F. Sterzing3 . 1 Department for Radiation Oncology, ¨ ¨ Universitatsspital Zurich, Zurich, Switzerland , 2 Department of Oncology, Aarhus University Hospital, Aarhus C, Denmark, 3 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany Background: Radical treatment of pulmonary metastases is practiced with increasing frequency since the better recognition and understanding of oligo-metastatic disease. However, patient selection remains challenging with long-term overall survival (OS) in < 25% of the patients. This study aimed at generation of a nomogram predicting OS after stereotactic body radiotherapy (SBRT) for pulmonary metastases. Methods: A multi-institutional database (n = 23; DEGRO Working Group Stereotaxy) of 671 patients treated with SBRT for 964 pulmonary metastases was used as a training cohort. Cox regression analysis with backward selection of variables (Akaike information criteria) was performed to identify factors to be included in the model to predict 2-year OS after SBRT. Based on this model a nomogram was constructed, calibrated and validated using concordance-index statistics. The nomogram was externally validated using a monocentric database of 92 patients treated with SBRT for pulmonary metastases (University Hospital Aarhus). Results: The 2-year OS of the training cohort was 52.5%. Kanofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the treated metastasis and number metastases (1 versus > 1) were significant prognostic factors in the Cox model (all p < 0.05). The calculated concordance-index for the nomogram was 0.711. Based on the nomogram the training cohort was divided into 4 groups, predicted 2-year OS in these groups were 76.1%, 62.6%, 45.8% and 24.2%; 2-year OS using Kaplan–Meier analysis were 78.4%, 60.4%, 46.0% and 30.2%. The nomogram discriminated well between risk groups in the validation cohort: Kaplan–Meier based 2-year OS were 84%, 53%, and 40% for risks groups 1–3; there were insufficient patient numbers (n = 4) in risk group 4. Conclusions: We successfully generated and validated a nomogram predicting 2-years OS after SBRT for pulmonary metastases. Primary tumor histology was one of the most important factors influencing OS; however, future prognostic scores need to incorporate the genetic variability within different cancers types. Legal entity responsible for the study: University Hospital Heidelberg Funding: N/A Disclosure: All authors have declared no conflicts of interest.
Copyright © 2016 by the European Lung Cancer Conference organisers, ESMO and IASLC. Published by Elsevier Inc. All rights reserved.