Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.
To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC).



Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans.



The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively.



In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters.
Department of Radiology, Juntendo University Urayasu Hospital, Chiba, Japan.
Tatsuya
T
Inoue
Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Joachim
J
Widder
Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Lisanne V
LV
van Dijk
Department of Radiation Oncology, Kansai Medical University Hirakata Hospital, Osaka, Japan.
Hideki
H
Takegawa
Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Osaka, Japan.
Masahiko
M
Koizumi
Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Osaka, Japan.
Masaaki
M
Takashina
Department of Radiation Oncology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Keisuke
K
Usui
Department of Radiation Oncology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Chie
C
Kurokawa
Department of Radiation Oncology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Satoru
S
Sugimoto
Department of Radiology, Juntendo University Urayasu Hospital, Chiba, Japan; Department of Radiation Oncology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Anneyuko I
AI
Saito
Department of Radiation Oncology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Keisuke
K
Sasai
Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Aart A
AA
Van't Veld
Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Johannes A
JA
Langendijk
Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: e.w.korevaar@umcg.nl.
Erik W
EW
Korevaar
D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D009038:Motion; D009367:Neoplasm Staging; D058958:Organs at Risk / Q000528:radiation effects*; D056888:Patient Positioning / Q000379:methods; D061766:Proton Therapy / Q000379:methods*; D000069079:Radiation Exposure / Q000032:analysis; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D061106:Radiotherapy Setup Errors / Q000517:prevention & control*; D020266:Radiotherapy, Conformal / Q000379:methods; D015203:Reproducibility of Results; D015656:Respiratory Mechanics; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D047368:Tumor Burden / Q000528:radiation effects