Robust Intensity Modulated Proton Therapy (IMPT) Increases Estimated Clinical Benefit in Head and Neck Cancer Patients

Purpose To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors. Methods and Materials For 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm) and range error (±3%) combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT. Results The robustness criterion was met in the IMRT and minimax IMPT plans in all error scenarios, but this was only the case in 1 of 40 PTV-based IMPT plans. Seven (out of 10) patients had relatively large NTCP reductions in minimax IMPT plans compared to IMRT. For these patients, xerostomia and dysphagia NTCP values were reduced by 17.0% (95% CI; 13.0–21.1) and 8.1% (95% CI; 4.9–11.2) on average with minimax IMPT. Increasing the number of fields did not contribute to plan robustness, but improved organ sparing. Conclusions The estimated clinical benefit in terms of NTCP of robust optimized (minimax) IMPT is greater than that of IMRT and PTV-based IMPT in HNC patients. Furthermore, the target coverage of minimax IMPT plans in the presence of errors was comparable to IMRT plans.

[1]  Icru Prescribing, recording, and reporting photon beam therapy , 1993 .

[2]  A. Lomax,et al.  Intensity modulation methods for proton radiotherapy. , 1999, Physics in medicine and biology.

[3]  M. V. van Herk,et al.  The probability of correct target dosage: dose-population histograms for deriving treatment margins in radiotherapy. , 2000, International journal of radiation oncology, biology, physics.

[4]  L. Peters,et al.  Excellent disease control and survival in patients with advanced nasopharyngeal cancer treated with chemoradiation. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Hanne M Kooy,et al.  Target volume dose considerations in proton beam treatment planning for lung tumors. , 2005, Medical physics.

[6]  Uwe Schneider,et al.  Intensity modulated photon and proton therapy for the treatment of head and neck tumors. , 2006, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[7]  Timothy C Y Chan,et al.  Accounting for range uncertainties in the optimization of intensity modulated proton therapy , 2007, Physics in medicine and biology.

[8]  A. Lomax,et al.  Intensity modulated proton therapy and its sensitivity to treatment uncertainties 1: the potential effects of calculational uncertainties , 2008, Physics in medicine and biology.

[9]  U Oelfke,et al.  Worst case optimization: a method to account for uncertainties in the optimization of intensity modulated proton therapy , 2008, Physics in medicine and biology.

[10]  N. Aaronson,et al.  Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  Riccardo Calandrino,et al.  Intensity-modulated proton therapy versus helical tomotherapy in nasopharynx cancer: planning comparison and NTCP evaluation. , 2008, International journal of radiation oncology, biology, physics.

[12]  N. Tarbell,et al.  Radiation dose to the lens during craniospinal irradiation-an improvement in proton radiotherapy technique. , 2008, International journal of radiation oncology, biology, physics.

[13]  Thomas Bortfeld,et al.  Reducing the sensitivity of IMPT treatment plans to setup errors and range uncertainties via probabilistic treatment planning. , 2008, Medical physics.

[14]  T. Delaney,et al.  Prescribing, Recording, and Reporting Proton-Beam Therapy , 2009 .

[15]  Randall K Ten Haken,et al.  A comparison of dose-response models for the parotid gland in a large group of head-and-neck cancer patients. , 2010, International journal of radiation oncology, biology, physics.

[16]  Daniel W. Miller,et al.  Ion stopping powers and CT numbers. , 2010, Medical dosimetry : official journal of the American Association of Medical Dosimetrists.

[17]  Sandra Nuyts,et al.  Evidence-based organ-sparing radiotherapy in head and neck cancer. , 2010, The Lancet. Oncology.

[18]  A. Lomax,et al.  Is it necessary to plan with safety margins for actively scanned proton therapy? , 2011, Physics in medicine and biology.

[19]  Johannes A Langendijk,et al.  Potential benefits of scanned intensity-modulated proton therapy versus advanced photon therapy with regard to sparing of the salivary glands in oropharyngeal cancer. , 2011, International journal of radiation oncology, biology, physics.

[20]  Holly Ning,et al.  Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer. , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[21]  Anders Forsgren,et al.  Minimax optimization for handling range and setup uncertainties in proton therapy. , 2011, Medical physics.

[22]  Johannes A Langendijk,et al.  The potential benefit of radiotherapy with protons in head and neck cancer with respect to normal tissue sparing: a systematic review of literature. , 2011, The oncologist.

[23]  Johannes A Langendijk,et al.  Predictive modelling for swallowing dysfunction after primary (chemo)radiation: results of a prospective observational study. , 2012, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[24]  J. Langendijk,et al.  The potential benefit of swallowing sparing intensity modulated radiotherapy to reduce swallowing dysfunction: an in silico planning comparative study. , 2012, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[25]  Lei Dong,et al.  A beam-specific planning target volume (PTV) design for proton therapy to account for setup and range uncertainties. , 2012, International journal of radiation oncology, biology, physics.

[26]  A. Torresin,et al.  Set-up errors and planning target volume margins in head and neck cancer radiotherapy: a clinical study of image guidance with on-line cone-beam computed tomography , 2013, International Journal of Clinical Oncology.

[27]  Martin Stuschke,et al.  Multi-scenario based robust intensity-modulated proton therapy (IMPT) plans can account for set-up errors more effectively in terms of normal tissue sparing than planning target volume (PTV) based intensity-modulated photon plans in the head and neck region , 2013, Radiation oncology.

[28]  Hanne M Kooy,et al.  Dose uncertainties in IMPT for oropharyngeal cancer in the presence of anatomical, range, and setup errors. , 2013, International journal of radiation oncology, biology, physics.

[29]  Johannes A Langendijk,et al.  Selection of patients for radiotherapy with protons aiming at reduction of side effects: the model-based approach. , 2013, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[30]  Davide Fontanarosa,et al.  An in silico comparison between margin-based and probabilistic target-planning approaches in head and neck cancer patients. , 2013, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[31]  M. Stock,et al.  Robustness of IMPT treatment plans with respect to inter-fractional set-up uncertainties: Impact of various beam arrangements for cranial targets , 2013, Acta oncologica.

[32]  Rasmus Bokrantz,et al.  A critical evaluation of worst case optimization methods for robust intensity-modulated proton therapy planning. , 2014, Medical physics.

[33]  A J Lomax,et al.  Benchmarking of a treatment planning system for spot scanning proton therapy: comparison and analysis of robustness to setup errors of photon IMRT and proton SFUD treatment plans of base of skull meningioma. , 2014, Medical physics.

[34]  Frank Verhaegen,et al.  A simulation study on proton computed tomography (CT) stopping power accuracy using dual energy CT scans as benchmark , 2015, Acta oncologica.

[35]  Steffen Löck,et al.  Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis. , 2015, International journal of radiation oncology, biology, physics.

[36]  Bae 50 % , 2018, CME.