Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis.

PURPOSE The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. METHODS AND MATERIALS For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. RESULTS Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. CONCLUSIONS Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.

[1]  B. Zackrisson,et al.  Radiation-induced trismus in the ARTSCAN head and neck trial , 2014, Acta oncologica.

[2]  G. Cosnard,et al.  Selection and Delineation of Lymph Node Target Volumes in Head and Neck Conformal and Intensity-Modulated Radiation Therapy , 2004 .

[3]  Robert Jeraj,et al.  Intensity-modulated x-ray (IMXT) versus proton (IMPT) therapy for theragnostic hypoxia-based dose painting. , 2008, Physics in medicine and biology.

[4]  Lei Xing,et al.  Evaluation of patterns of failure and subjective salivary function in patients treated with intensity modulated radiotherapy for head and neck squamous cell carcinoma , 2007, Head & neck.

[5]  M K Martel,et al.  Patterns of local-regional recurrence following parotid-sparing conformal and segmental intensity-modulated radiotherapy for head and neck cancer. , 2000, International journal of radiation oncology, biology, physics.

[6]  Radhe Mohan,et al.  Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas: II--clinical results. , 2004, International journal of radiation oncology, biology, physics.

[7]  Johannes A Langendijk,et al.  Delineation of organs at risk involved in swallowing for radiotherapy treatment planning. , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[8]  Uwe Oelfke,et al.  Radiation Oncology Intensity-modulated Radiotherapy of Nasopharyngeal Carcinoma: a Comparative Treatment Planning Study of Photons and Protons , 2022 .

[9]  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.

[10]  F Hofheinz,et al.  Automatic volume delineation in oncological PET , 2011, Nuklearmedizin.

[11]  Arjen van der Schaaf,et al.  The potential of intensity-modulated proton radiotherapy to reduce swallowing dysfunction in the treatment of head and neck cancer: A planning comparative study , 2013, Acta oncologica.

[12]  M. Baumann,et al.  Place of proton radiotherapy in future radiotherapy practice. , 2013, Seminars in radiation oncology.

[13]  Ulrike Schick,et al.  Dose-response analysis of acute oral mucositis and pharyngeal dysphagia in patients receiving induction chemotherapy followed by concomitant chemo-IMRT for head and neck cancer. , 2012, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  Randall K Ten Haken,et al.  Chemo-IMRT of oropharyngeal cancer aiming to reduce dysphagia: swallowing organs late complication probabilities and dosimetric correlates. , 2011, International journal of radiation oncology, biology, physics.

[15]  Daniela Thorwarth,et al.  Dose painting with IMPT, helical tomotherapy and IMXT: a dosimetric comparison. , 2008, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[16]  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.

[17]  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.

[18]  Steven J Frank,et al.  Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: a treatment planning comparison. , 2013, Medical dosimetry : official journal of the American Association of Medical Dosimetrists.

[19]  J. Purdy,et al.  Dose‐response analysis for nasopharyngeal carcinoma. An historical perspective , 1982, Cancer.

[20]  Jan-Jakob Sonke,et al.  Setup uncertainties of anatomical sub-regions in head-and-neck cancer patients after offline CBCT guidance. , 2009, International journal of radiation oncology, biology, physics.

[21]  V. Grégoire,et al.  A dose escalation study with intensity modulated radiation therapy (IMRT) in T2N0, T2N1, T3N0 squamous cell carcinomas (SCC) of the oropharynx, larynx and hypopharynx using a simultaneous integrated boost (SIB) approach. , 2013, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[22]  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.

[23]  Johannes A Langendijk,et al.  Delineation guidelines for organs at risk involved in radiation-induced salivary dysfunction and xerostomia. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[24]  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.

[25]  V. Budach,et al.  HPV in , 2014 .

[26]  Ulf Isacsson,et al.  Potential outcomes of modalities and techniques in radiotherapy for patients with hypopharyngeal carcinoma. , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[27]  M. Baumann,et al.  Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[28]  M. Truong,et al.  Brachial plexus contouring with CT and MR imaging in radiation therapy planning for head and neck cancer. , 2010, Radiographics : a review publication of the Radiological Society of North America, Inc.

[29]  Johannes A Langendijk,et al.  Protons in head-and-neck cancer: bridging the gap of evidence. , 2013, International journal of radiation oncology, biology, physics.

[30]  Sadek Nehmeh,et al.  Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study. , 2008, International journal of radiation oncology, biology, physics.

[31]  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.

[32]  J. Petera,et al.  IMRT with the use of simultaneous integrated boost in treatment of head and neck cancer: acute toxicity evaluation. , 2006, Acta medica.

[33]  Claudio Fiorino,et al.  NTCP modeling of subacute/late laryngeal edema scored by fiberoptic examination. , 2009, International journal of radiation oncology, biology, physics.

[34]  Radhe Mohan,et al.  Multiple regions-of-interest analysis of setup uncertainties for head-and-neck cancer radiotherapy. , 2006, International journal of radiation oncology, biology, physics.

[35]  E. B. Butler,et al.  Smart (simultaneous modulated accelerated radiation therapy) boost: a new accelerated fractionation schedule for the treatment of head and neck cancer with intensity modulated radiotherapy. , 1999, International journal of radiation oncology, biology, physics.

[36]  Srinivasan Vijayakumar,et al.  Development and validation of a standardized method for contouring the brachial plexus: preliminary dosimetric analysis among patients treated with IMRT for head-and-neck cancer. , 2008, International journal of radiation oncology, biology, physics.

[37]  T. Vercauteren,et al.  Three-phase adaptive dose-painting-by-numbers for head-and-neck cancer: initial results of the phase I clinical trial. , 2013, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[38]  Liane Oehme,et al.  Automatische Volumenabgrenzung in der onkologischen PET – Bewertung eines entsprechenden Software-Werkzeugs und Vergleich mit manueller Abgrenzung anhand klinischer Datensätze , 2012 .

[39]  A Fogliata,et al.  A treatment planning comparison of 3D conformal therapy, intensity modulated photon therapy and proton therapy for treatment of advanced head and neck tumours. , 2001, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[40]  Michael Baumann,et al.  Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced head-and-neck cancer. , 2012, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[41]  Michael Goitein,et al.  Intensity modulation in radiotherapy: photons versus protons in the paranasal sinus. , 2003, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[42]  Daniela Thorwarth,et al.  Hypoxia dose painting by numbers: a planning study. , 2007, International journal of radiation oncology, biology, physics.

[43]  J. Steinbach,et al.  Effect of [(18)F]FMISO stratified dose-escalation on local control in FaDu hSCC in nude mice. , 2014, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[44]  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.

[45]  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.