The evolution of proton beam therapy: Current and future status.

Proton beam therapy (PBT) has been increasingly used in a variety of cancers due to its excellent physical properties and superior dosimetric parameters. PBT may improve patient survival by improving the local tumor treatment rate while reducing injury to normal organs, which may result in fewer radiation-induced adverse effects. However, the significant cost of establishing and maintaining proton facilities cannot be overlooked. In addition, there has been significant controversy regarding routine application of this treatment in certain types of cancer. The challenges of PBT in the future mainly include the lack of basic clinical trials, unclear biological effects, immature imaging technology and miniaturization of imaging guidance. Overcoming these limitations may promote the rapid development of PBT. We herein provide an overview of the existing literature on the efficacy and toxicity of common oncological applications of proton beam therapy.

[1]  T. Björk-Eriksson,et al.  Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study , 2005, Acta oncologica.

[2]  K. Shirai,et al.  Dose-volume histogram parameters and clinical factors associated with pleural effusion after chemoradiotherapy in esophageal cancer patients. , 2011, International journal of radiation oncology, biology, physics.

[3]  J. Slater,et al.  Partial breast irradiation delivered with proton beam: results of a phase II trial. , 2011, Clinical breast cancer.

[4]  Barbara L. Smith,et al.  Accelerated partial-breast irradiation using proton beams: initial clinical experience. , 2006, International journal of radiation oncology, biology, physics.

[5]  R. Collins,et al.  Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials , 2005, The Lancet.

[6]  H. Sakurai,et al.  Clinical Results of Proton-Beam Therapy for Locoregionally Advanced Esophageal Cancer , 2010, Strahlentherapie und Onkologie.

[7]  H. Tsujii,et al.  Proton beam therapy with high-dose irradiation for superficial and advanced esophageal carcinomas. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[8]  H. Sandler,et al.  Comparative effectiveness study of patient‐reported outcomes after proton therapy or intensity‐modulated radiotherapy for prostate cancer , 2014, Cancer.

[9]  Joe Y. Chang,et al.  Early findings on toxicity of proton beam therapy with concurrent chemotherapy for nonsmall cell lung cancer , 2011, Cancer.

[10]  T. Sakae,et al.  Comparison of dose–volume histograms between proton beam and X-ray conformal radiotherapy for locally advanced non-small-cell lung cancer , 2014, Journal of radiation research.

[11]  K. Hoffman,et al.  National trends and determinants of proton therapy use for prostate cancer: A National Cancer Data Base study , 2016, Cancer.

[12]  Harald Paganetti,et al.  Relative biological effectiveness (RBE) values for proton beam therapy. , 2002, International journal of radiation oncology, biology, physics.

[13]  Daniel W. Miller,et al.  Proton radiation for treatment of cancer of the oropharynx: early experience at Loma Linda University Medical Center using a concomitant boost technique. , 2005, International journal of radiation oncology, biology, physics.

[14]  Tatsuya Nakamura,et al.  Clinical results of proton beam therapy for twenty older patients with esophageal cancer , 2015, Radiology and oncology.

[15]  Stanley J. Rosenthal,et al.  Neuroendocrine tumors of the sinonasal tract , 2002, Cancer.

[16]  Hisao Ito,et al.  Late toxicity after definitive concurrent chemoradiotherapy for thoracic esophageal carcinoma. , 2009, International journal of radiation oncology, biology, physics.

[17]  M. Socinski,et al.  High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial. , 2002, International journal of radiation oncology, biology, physics.

[18]  Uwe Schneider,et al.  Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors. , 2002, International journal of radiation oncology, biology, physics.

[19]  H. Ishikawa,et al.  High-dose concurrent chemo–proton therapy for Stage III NSCLC: preliminary results of a Phase II study , 2014, Journal of radiation research.

[20]  H. Paganetti,et al.  Comparison of second cancer risk due to out-of-field doses from 6-MV IMRT and proton therapy based on 6 pediatric patient treatment plans. , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[21]  H. Ishikawa,et al.  Proton beam therapy in Japan: current and future status. , 2016, Japanese journal of clinical oncology.

[22]  A. Taghian,et al.  Accelerated partial breast irradiation using proton beams: Initial dosimetric experience. , 2006, International journal of radiation oncology, biology, physics.

[23]  Joe Y. Chang,et al.  Phase 2 study of high‐dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer , 2011, Cancer.

[24]  R. Mulhern,et al.  Modeling radiation dosimetry to predict cognitive outcomes in pediatric patients with CNS embryonal tumors including medulloblastoma. , 2006, International journal of radiation oncology, biology, physics.

[25]  J. Cox,et al.  Are the results of RTOG 0617 mysterious? , 2012, International journal of radiation oncology, biology, physics.

[26]  J. Pulido,et al.  Cost-Effectiveness of Proton Beam Therapy for Intraocular Melanoma , 2015, PloS one.

[27]  C. Pepine,et al.  Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy. , 2003, JAMA.

[28]  A. Berman,et al.  Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions , 2015, Cancers.

[29]  J. Buchsbaum,et al.  Pediatric CSI: are protons the only ethical approach? , 2013, International journal of radiation oncology, biology, physics.

[30]  R. Reiazi,et al.  A Literature Survey on Cost-Effectiveness of Proton Beam Therapy in the Management of Breast Cancer Patients , 2015, Iranian journal of cancer prevention.

[31]  T. Hashimoto,et al.  Outcomes and prognostic factors for recurrence after high-dose proton beam therapy for centrally and peripherally located stage I non--small-cell lung cancer. , 2014, Clinical lung cancer.

[32]  U. Isacsson,et al.  Node-positive left-sided breast cancer patients after breast-conserving surgery: potential outcomes of radiotherapy modalities and techniques. , 2002, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[33]  T. Hashimoto,et al.  Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose–volume histogram analysis , 2015, Journal of radiation research.

[34]  A. Lomax,et al.  Radiation Oncology BioMed Central Review Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview , 2006 .

[35]  Andrew K. Lee,et al.  Proton Beam Therapy for the Treatment of Prostate Cancer , 2014, Cancer journal.

[36]  Alfred R. Smith,et al.  Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques? , 2005, International journal of radiation oncology, biology, physics.

[37]  M. Kasami,et al.  High-dose proton beam therapy for sinonasal mucosal malignant melanoma , 2014, Radiation oncology.

[38]  P. Johnstone,et al.  Clinical Benefits of Proton Beam Therapy for Tumors of the Skull Base. , 2016, Cancer control : journal of the Moffitt Cancer Center.

[39]  Ulf Isacsson,et al.  Economic evaluation of proton radiation therapy in the treatment of breast cancer. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[40]  H. Shih,et al.  Second nonocular tumors among survivors of retinoblastoma treated with contemporary photon and proton radiotherapy , 2014, Cancer.

[41]  J. Slater,et al.  A Technique of Partial Breast Irradiation Utilizing Proton Beam Radiotherapy: Comparison with Conformal X-Ray Therapy , 2007, Cancer journal.

[42]  M. Socinski,et al.  Randomized phase II trial of induction chemotherapy followed by concurrent chemotherapy and dose-escalated thoracic conformal radiotherapy (74 Gy) in stage III non-small-cell lung cancer: CALGB 30105. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  J. Loeffler,et al.  Proton radiation therapy for primary sphenoid sinus malignancies: Treatment outcome and prognostic factors , 2009, Head & neck.

[44]  J. Fowler,et al.  Primary analysis of the phase II component of a phase I/II dose intensification study using three-dimensional conformal radiation therapy and concurrent chemotherapy for patients with inoperable non-small-cell lung cancer: RTOG 0117. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  J H LAWRENCE,et al.  Pituitary irradiation with high-energy proton beams: a preliminary report. , 1958, Cancer research.

[46]  A. Taghian,et al.  Dosimetric comparison of proton and photon three-dimensional, conformal, external beam accelerated partial breast irradiation techniques. , 2006, International journal of radiation oncology, biology, physics.

[47]  K. Sheng,et al.  Size matters: a comparison of T1 and T2 peripheral non-small-cell lung cancers treated with stereotactic body radiation therapy (SBRT). , 2010, The Journal of thoracic and cardiovascular surgery.

[48]  Yoshihiro Takai,et al.  A phase II study on stereotactic body radiotherapy for stage I non-small cell lung cancer. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[49]  R. Wilson Radiological use of fast protons. , 1946, Radiology.

[50]  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.

[51]  Ronald C. Chen,et al.  Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer. , 2012, JAMA.

[52]  Steven H. Lin,et al.  Improving Outcomes for Esophageal Cancer using Proton Beam Therapy. , 2016, International journal of radiation oncology, biology, physics.

[53]  K. Muro,et al.  Phase II study of chemoradiotherapy with 5-fluorouracil and cisplatin for Stage II-III esophageal squamous cell carcinoma: JCOG trial (JCOG 9906). , 2011, International journal of radiation oncology, biology, physics.

[54]  J. Ashman,et al.  Proton beam therapy for locally advanced lung cancer: A review. , 2014, World journal of clinical oncology.

[55]  A. Lomax,et al.  Potential role of intensity-modulated photons and protons in the treatment of the breast and regional nodes. , 2003, International journal of radiation oncology, biology, physics.

[56]  Alfred R. Smith,et al.  The more important heavy charged particle radiotherapy of the future is more likely to be with heavy ions rather than protons. , 2013, Medical physics.

[57]  B. Fullerton,et al.  Proton radiotherapy for orbital rhabdomyosarcoma: clinical outcome and a dosimetric comparison with photons. , 2005, International journal of radiation oncology, biology, physics.

[58]  Gary A Ezzell,et al.  The clinical case for proton beam therapy , 2012, Radiation oncology.

[59]  Steven H. Lin,et al.  Proton beam therapy for the treatment of esophageal cancer. , 2016, Chinese clinical oncology.

[60]  W. H. Bragg,et al.  XXXIX. On the α particles of radium, and their loss of range in passing through various atoms and molecules , 1905 .

[61]  T. Sakae,et al.  Designed-seamless irradiation technique for extended whole mediastinal proton-beam irradiation for esophageal cancer , 2012, Radiation oncology.

[62]  K. Goto,et al.  Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced non-small cell lung cancer. , 2016, Japanese Journal of Clinical Oncology.

[63]  Nicholas G Zaorsky,et al.  Evolution of advanced technologies in prostate cancer radiotherapy , 2013, Nature Reviews Urology.

[64]  Steven L. Chang,et al.  Survival Analyses of Patients With Metastatic Renal Cancer Treated With Targeted Therapy With or Without Cytoreductive Nephrectomy: A National Cancer Data Base Study. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[65]  Tatsuya Nakamura,et al.  Preliminary treatment results of proton beam therapy with chemoradiotherapy for stage I–III esophageal cancer , 2016, Cancer medicine.

[66]  S. Hancock,et al.  Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[67]  K. Kagei,et al.  Clinical results of proton beam therapy for cancer of the esophagus. , 2005, International journal of radiation oncology, biology, physics.

[68]  W. Curran,et al.  Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. , 2015, The Lancet. Oncology.

[69]  Radhe Mohan,et al.  Stray radiation dose and second cancer risk for a pediatric patient receiving craniospinal irradiation with proton beams , 2009, Physics in medicine and biology.

[70]  Narikazu Boku,et al.  Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.