Recent advances in radiation oncology

Radiotherapy (RT) is very much a technology-driven treatment modality in the management of cancer. RT techniques have changed significantly over the past few decades, thanks to improvements in engineering and computing. We aim to highlight the recent developments in radiation oncology, focusing on the technological and biological advances. We will present state-of-the-art treatment techniques, employing photon beams, such as intensity-modulated RT, volumetric-modulated arc therapy, stereotactic body RT and adaptive RT, which make possible a highly tailored dose distribution with maximum normal tissue sparing. We will analyse all the steps involved in the treatment: imaging, delineation of the tumour and organs at risk, treatment planning and finally image-guidance for accurate tumour localisation before and during treatment delivery. Particular attention will be given to the crucial role that imaging plays throughout the entire process. In the case of adaptive RT, the precise identification of target volumes as well as the monitoring of tumour response/modification during the course of treatment is mainly based on multimodality imaging that integrates morphological, functional and metabolic information. Moreover, real-time imaging of the tumour is essential in breathing adaptive techniques to compensate for tumour motion due to respiration. Brief reference will be made to the recent spread of particle beam therapy, in particular to the use of protons, but also to the yet limited experience of using heavy particles such as carbon ions. Finally, we will analyse the latest biological advances in tumour targeting. Indeed, the effectiveness of RT has been improved not only by technological developments but also through the integration of radiobiological knowledge to produce more efficient and personalised treatment strategies.

[1]  K. Brock,et al.  Use of image registration and fusion algorithms and techniques in radiotherapy: Report of the AAPM Radiation Therapy Committee Task Group No. 132 , 2017, Medical physics.

[2]  N. Matsufuji Overview summary of clinical heavier-ion progress in Japan , 2017 .

[3]  Paolo Zaffino,et al.  Atlas-based segmentation in breast cancer radiotherapy: Evaluation of specific and generic-purpose atlases. , 2017, Breast.

[4]  Marco Durante,et al.  Charged-particle therapy in cancer: clinical uses and future perspectives , 2017, Nature Reviews Clinical Oncology.

[5]  B. Heijmen,et al.  The role of technology in clinical trials using stereotactic body radiotherapy , 2017, The British journal of radiology.

[6]  A. Rosenfeld,et al.  An Accurate Method to Quantify Breathing-induced Prostate Motion for Patients Implanted with Electromagnetic Transponders , 2017, Tumori.

[7]  Jacob G. Scott,et al.  A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. , 2017, The Lancet. Oncology.

[8]  R. Alonzi,et al.  Image-guided radiotherapy for prostate cancer in the United Kingdom: a national survey. , 2017, The British journal of radiology.

[9]  Ralph R. Weichselbaum,et al.  Radiotherapy and immunotherapy: a beneficial liaison? , 2017, Nature Reviews Clinical Oncology.

[10]  P. Lambin,et al.  Decision support systems for personalized and participative radiation oncology☆ , 2017, Advanced drug delivery reviews.

[11]  D. Jaffray,et al.  Radiotherapy for Cancer: Present and Future. , 2017, Advanced drug delivery reviews.

[12]  Radhe Mohan,et al.  Proton therapy - Present and future. , 2017, Advanced drug delivery reviews.

[13]  Steve B. Jiang,et al.  New concept on an integrated interior magnetic resonance imaging and medical linear accelerator system for radiation therapy , 2017, Journal of medical imaging.

[14]  M. Riboldi,et al.  Intra-fraction respiratory motion and baseline drift during breast Helical Tomotherapy. , 2017, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[15]  Laurentiu M. Pop,et al.  Rationale and evidence to combine radiation therapy and immunotherapy for cancer treatment , 2017, Cancer Immunology, Immunotherapy.

[16]  Benjamin Berkels,et al.  Survey of Non-Rigid Registration Tools in Medicine , 2017, Journal of Digital Imaging.

[17]  Guido Baroni,et al.  Commissioning of the 4-D treatment delivery system for organ motion management in synchrotron-based scanning ion beams. , 2016, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[18]  C. West,et al.  Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity? , 2016, Cancer letters.

[19]  F. Alongi,et al.  Extreme hypofractionation for early prostate cancer: Biology meets technology. , 2016, Cancer treatment reviews.

[20]  L. Holloway,et al.  Uncertainties in volume delineation in radiation oncology: A systematic review and recommendations for future studies. , 2016, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[21]  M. Josipovic,et al.  Deep inspiration breath-hold radiotherapy for lung cancer: impact on image quality and registration uncertainty in cone beam CT image guidance. , 2016, The British journal of radiology.

[22]  R. Orecchia,et al.  From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer. , 2016, Breast.

[23]  R. Orecchia,et al.  VERO® radiotherapy for low burden cancer: 789 patients with 957 lesions , 2016, Ecancermedicalscience.

[24]  E. Cohen,et al.  Multidisciplinary Care of Laryngeal Cancer. , 2016, Journal of Oncology Practice.

[25]  Elisabetta Garibaldi,et al.  Image-guided radiation therapy (IGRT): practical recommendations of Italian Association of Radiation Oncology (AIRO) , 2016, La radiologia medica.

[26]  D. Pasquier,et al.  Surface imaging, laser positioning or volumetric imaging for breast cancer with nodal involvement treated by helical TomoTherapy , 2016, Journal of applied clinical medical physics.

[27]  Chiara Gianoli,et al.  MRI quantification of pancreas motion as a function of patient setup for particle therapy —a preliminary study , 2016, Journal of applied clinical medical physics.

[28]  R. Orecchia,et al.  Rationale and Protocol of AIRC IG-13218, Short-Term Radiotherapy for Early Prostate Cancer with Concomitant Boost to the Dominant Lesion , 2016, Tumori.

[29]  I. Daftari,et al.  Proton therapy for the management of uveal melanoma and other ocular tumors. , 2016, Chinese clinical oncology.

[30]  Tomasz Kubiak,et al.  Particle therapy of moving targets-the strategies for tumour motion monitoring and moving targets irradiation. , 2016, The British journal of radiology.

[31]  R. Orecchia,et al.  Bladder preservation in non-metastatic muscle-invasive bladder cancer (MIBC): a single-institution experience , 2016, Ecancermedicalscience.

[32]  R. Orecchia,et al.  Review of photon and proton radiotherapy for skull base tumours. , 2016, Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology.

[33]  R. Orecchia,et al.  Translational and rotational localization errors in cone-beam CT based image-guided lung stereotactic radiotherapy. , 2016, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[34]  M. Krasna,et al.  Stereotactic Body Radiotherapy and Ablative Therapies for Lung Cancer. , 2016, Surgical oncology clinics of North America.

[35]  M. Brambilla,et al.  Three-dimensional surface imaging for detection of intra-fraction setup variations during radiotherapy of pelvic tumors , 2016, La radiologia medica.

[36]  L. Licitra,et al.  Non-surgical organ preservation strategies for locally advanced laryngeal tumors: what is the Italian attitude? Results of a national survey on behalf of AIRO and AIOM , 2016, Medical Oncology.

[37]  D. Ebner,et al.  The Emerging Role of Carbon-Ion Radiotherapy , 2016, Front. Oncol..

[38]  M. Leech,et al.  Use of auto-segmentation in the delineation of target volumes and organs at risk in head and neck , 2016, Acta oncologica.

[39]  J. Wasiak,et al.  Impact of tumour bed boost integration on acute and late toxicity in patients with breast cancer: A systematic review. , 2016, Breast.

[40]  Michael G Jameson,et al.  A review of interventions to reduce inter‐observer variability in volume delineation in radiation oncology , 2016, Journal of medical imaging and radiation oncology.

[41]  D. Choi,et al.  Proton beam therapy in the management of skull base chordomas: systematic review of indications, outcomes, and implications for neurosurgeons , 2016, British journal of neurosurgery.

[42]  D. de Ruysscher,et al.  Proton Therapy in Children: A Systematic Review of Clinical Effectiveness in 15 Pediatric Cancers. , 2016, International journal of radiation oncology, biology, physics.

[43]  Jan-Jakob Sonke,et al.  The first implementation of respiratory triggered 4DCBCT on a linear accelerator , 2016, Physics in medicine and biology.

[44]  Gregory C Sharp,et al.  Investigation of cone-beam CT image quality trade-off for image-guided radiation therapy , 2016, Physics in medicine and biology.

[45]  Mitsuhiro Nakamura,et al.  A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: A multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking , 2016, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[46]  Charles R. Thomas,et al.  Image Guided Radiation Therapy (IGRT) Practice Patterns and IGRT's Impact on Workflow and Treatment Planning: Results From a National Survey of American Society for Radiation Oncology Members. , 2016, International journal of radiation oncology, biology, physics.

[47]  Frederik Wenz,et al.  Deep Inspiration Breath Hold-Based Radiation Therapy: A Clinical Review. , 2016, International journal of radiation oncology, biology, physics.

[48]  Minsong Cao,et al.  Longitudinal diffusion MRI for treatment response assessment: Preliminary experience using an MRI-guided tri-cobalt 60 radiotherapy system. , 2016, Medical physics.

[49]  E. Yang,et al.  Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine , 2016, Prostate cancer.

[50]  J. Lagendijk,et al.  Quantification of intra-fraction motion in breast radiotherapy using supine magnetic resonance imaging , 2016, Physics in medicine and biology.

[51]  X. Liang,et al.  Radiobiological impact of dose calculation algorithms on biologically optimized IMRT lung stereotactic body radiation therapy plans , 2016, Radiation oncology.

[52]  G Baroni,et al.  Motion prediction in MRI-guided radiotherapy based on interleaved orthogonal cine-MRI , 2016, Physics in medicine and biology.

[53]  Niko Papanikolaou,et al.  Commissioning an Elekta Versa HD linear accelerator , 2016, Journal of applied clinical medical physics.

[54]  C. Matuschek,et al.  Hypofractionated Radiotherapy as Adjuvant Treatment in Early Breast Cancer. A Review and Meta-Analysis of Randomized Controlled Trials , 2015, Breast Care.

[55]  J. Antolak The Physics of Radiation Therapy , 2015 .

[56]  J. Adler,et al.  Is Equipment Development Stifling Innovation in Radiation Oncology? , 2015, International journal of radiation oncology, biology, physics.

[57]  U. Carl,et al.  Emerging Role of Hypofractionated Radiotherapy with Simultaneous Integrated Boost in Modern Radiotherapy of Breast Cancer , 2015, Breast Care.

[58]  Olivier Gevaert,et al.  Addition of MR imaging features and genetic biomarkers strengthens glioblastoma survival prediction in TCGA patients. , 2015, Journal of neuroradiology. Journal de neuroradiologie.

[59]  S. Demaria,et al.  Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. , 2015, The Lancet. Oncology.

[60]  A. Kiltie,et al.  Treatment of Breast and Prostate Cancer by Hypofractionated Radiotherapy: Potential Risks and Benefits , 2015, Clinical oncology (Royal College of Radiologists (Great Britain)).

[61]  A. Fassi,et al.  Geometric and dosimetric accuracy and imaging dose of the real-time tumour tracking system of a gimbal mounted linac. , 2015, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[62]  B. Beuthien-Baumann,et al.  Validation of functional imaging as a biomarker for radiation treatment response. , 2015, The British journal of radiology.

[63]  Sandro Rossi,et al.  The National Centre for Oncological Hadrontherapy (CNAO): Status and perspectives. , 2015, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[64]  R. Orecchia,et al.  Image-Guided Radiotherapy for Prostate Cancer using 3 Different Techniques: Localization Data of 186 Patients , 2015, Tumori.

[65]  David Sarrut,et al.  An image‐based method to synchronize cone‐beam CT and optical surface tracking , 2015, Journal of applied clinical medical physics.

[66]  R. Pötter,et al.  Carbon ion radiotherapy in Japan: an assessment of 20 years of clinical experience. , 2015, The Lancet. Oncology.

[67]  Mert R. Sabuncu,et al.  Multi-atlas segmentation of biomedical images: A survey , 2014, Medical Image Anal..

[68]  William Small,et al.  Contouring Guidelines for the Axillary Lymph Nodes for the Delivery of Radiation Therapy in Breast Cancer: Evaluation of the RTOG Breast Cancer Atlas. , 2013, International journal of radiation oncology, biology, physics.

[69]  Mechthild Krause,et al.  ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer. , 2015, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[70]  Colin G Orton,et al.  Point/Counterpoint: Within the next ten years treatment planning will become fully automated without the need for human intervention. , 2014, Medical physics.

[71]  Timothy P Hanna,et al.  Estimating the demand for radiotherapy from the evidence: a review of changes from 2003 to 2012. , 2014, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[72]  P. Lambin,et al.  Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach , 2014, Nature Communications.

[73]  Chuxiong Ding,et al.  Commissioning and initial stereotactic ablative radiotherapy experience with Vero , 2014, Journal of applied clinical medical physics.

[74]  C. Branch,et al.  Mechanisms of Injury to Normal Tissue after Radiotherapy: A Review , 2014, Plastic and reconstructive surgery.

[75]  L. Livi,et al.  Simultaneous integrated boost–intensity‐modulated radiotherapy in head and neck cancer , 2013, The Laryngoscope.

[76]  Hiroki Shirato,et al.  Use of dMLC for implementation of dynamic respiratory-gated radiation therapy. , 2013, Medical physics.

[77]  M. Barton,et al.  The Potential for an Enhanced Role for MRI in Radiation-therapy Treatment Planning , 2013, Technology in cancer research & treatment.

[78]  Young-Taek Oh,et al.  Can initial diagnostic PET-CT aid to localize tumor bed in breast cancer radiotherapy: feasibility study using deformable image registration , 2013, Radiation oncology.

[79]  M. Riboldi,et al.  Deep inspiration breath‐hold technique guided by an opto‐electronic system for extracranial stereotactic treatments , 2013, Journal of applied clinical medical physics.

[80]  Jean-François Daisne,et al.  Atlas-based automatic segmentation of head and neck organs at risk and nodal target volumes: a clinical validation , 2013, Radiation oncology.

[81]  M. S. Thomsen,et al.  Delineation of target volumes and organs at risk in adjuvant radiotherapy of early breast cancer: National guidelines and contouring atlas by the Danish Breast Cancer Cooperative Group , 2013, Acta oncologica.

[82]  T Solberg,et al.  Commissioning of the Varian TrueBeam linear accelerator: a multi-institutional study. , 2013, Medical physics.

[83]  Christian P Karger,et al.  Clinical evaluation of a laser surface scanning system in 120 patients for improving daily setup accuracy in fractionated radiation therapy. , 2013, International journal of radiation oncology, biology, physics.

[84]  D. Jaffray Image-guided radiotherapy: from current concept to future perspectives , 2012, Nature Reviews Clinical Oncology.

[85]  Alan Effraim Nahum,et al.  (Radio)Biological Optimization of External-Beam Radiotherapy , 2012, Comput. Math. Methods Medicine.

[86]  J. Torres-Roca,et al.  A molecular assay of tumor radiosensitivity: a roadmap towards biology-based personalized radiation therapy. , 2012, Personalized medicine.

[87]  Jan-Jakob Sonke,et al.  Quality assurance for image-guided radiation therapy utilizing CT-based technologies: a report of the AAPM TG-179. , 2012, Medical physics.

[88]  Lakshmi Santanam,et al.  Quality assurance for nonradiographic radiotherapy localization and positioning systems: report of Task Group 147. , 2012, Medical physics.

[89]  L. Zeng,et al.  Update on the systematic review of palliative radiotherapy trials for bone metastases. , 2012, Clinical oncology (Royal College of Radiologists (Great Britain)).

[90]  Moyed Miften,et al.  Biological-based optimization and volumetric modulated arc therapy delivery for stereotactic body radiation therapy. , 2011, Medical physics.

[91]  J. Hendry,et al.  Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: α/β = 1.4 (0.9-2.2) Gy. , 2012, International journal of radiation oncology, biology, physics.

[92]  E. Kouwenhoven,et al.  Magnetic resonance imaging- versus computed tomography-based target volume delineation of the glandular breast tissue (clinical target volume breast) in breast-conserving therapy: an exploratory study. , 2011, International journal of radiation oncology, biology, physics.

[93]  C Bert,et al.  Motion in radiotherapy: particle therapy , 2011, Physics in medicine and biology.

[94]  I. Chetty,et al.  Advances in Treatment Techniques: Arc-Based and Other Intensity Modulated Therapies , 2011, Cancer journal.

[95]  S. Tyldesley,et al.  Estimating the need for radiotherapy for patients with prostate, breast, and lung cancers: verification of model estimates of need with radiotherapy utilization data from British Columbia. , 2011, International journal of radiation oncology, biology, physics.

[96]  Stephanie Lamart,et al.  Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. , 2011, The Lancet. Oncology.

[97]  Jürgen Hesser,et al.  Breath-hold target localization with simultaneous kilovoltage/megavoltage cone-beam computed tomography and fast reconstruction. , 2010, International journal of radiation oncology, biology, physics.

[98]  Deric M. Park,et al.  Improving the radiosensitivity of radioresistant and hypoxic glioblastoma. , 2010, Future oncology.

[99]  Matthias Guckenberger,et al.  Feasibility study for markerless tracking of lung tumors in stereotactic body radiotherapy. , 2010, International journal of radiation oncology, biology, physics.

[100]  T. Gevaert,et al.  Gating and tracking, 4D in thoracic tumours. , 2010, Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique.

[101]  Dirk De Ruysscher,et al.  PET scans in radiotherapy planning of lung cancer. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[102]  Joshua D. Lawson,et al.  Evaluation of automatic atlas-based lymph node segmentation for head-and-neck cancer. , 2010, International journal of radiation oncology, biology, physics.

[103]  E. Pignoli,et al.  Radiobiological basis and clinical results of the simultaneous integrated boost (SIB) in intensity modulated radiotherapy (IMRT) for head and neck cancer: A review. , 2010, Critical reviews in oncology/hematology.

[104]  Issam El Naqa,et al.  Development of RTOG consensus guidelines for the definition of the clinical target volume for postoperative conformal radiation therapy for prostate cancer. , 2010, International journal of radiation oncology, biology, physics.

[105]  Samuel Ryu,et al.  American Society for Therapeutic Radiology and Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the performance of stereotactic body radiation therapy. , 2004, International journal of radiation oncology, biology, physics.

[106]  J. Bartek,et al.  The DNA-damage response in human biology and disease , 2009, Nature.

[107]  Shiva K. Das,et al.  A role for biological optimization within the current treatment planning paradigm. , 2009, Medical physics.

[108]  M. Martel,et al.  Calculation and prediction of the effect of respiratory motion on whole breast radiation therapy dose distributions. , 2009, Medical dosimetry : official journal of the American Association of Medical Dosimetrists.

[109]  M. Hoogeman,et al.  Clinical accuracy of the respiratory tumor tracking system of the cyberknife: assessment by analysis of log files. , 2009, International journal of radiation oncology, biology, physics.

[110]  X Allen Li,et al.  Improved critical structure sparing with biologically based IMRT optimization. , 2009, Medical physics.

[111]  J. F. De Los Santos,et al.  Automatic segmentation of whole breast using atlas approach and deformable image registration , 2009 .

[112]  Bruno Speleers,et al.  Intensity-modulated radiotherapy as primary therapy for prostate cancer: report on acute toxicity after dose escalation with simultaneous integrated boost to intraprostatic lesion. , 2008, International journal of radiation oncology, biology, physics.

[113]  R. Mak,et al.  Bladder preservation: optimizing radiotherapy and integrated treatment strategies , 2008, BJU international.

[114]  Do-Hoon Kim,et al.  Clinical experience using hypofractionated radiation schedules in breast cancer. , 2008, Seminars in radiation oncology.

[115]  Indira Madani,et al.  Evidence behind use of intensity-modulated radiotherapy: a systematic review of comparative clinical studies. , 2008, The Lancet. Oncology.

[116]  C. Grau,et al.  Image-guided adaptive radiotherapy – integration of biology and technology to improve clinical outcome , 2008, Acta oncologica.

[117]  Karl Otto,et al.  Volumetric modulated arc therapy: IMRT in a single gantry arc. , 2007, Medical physics.

[118]  Jan J W Lagendijk,et al.  MRI/linac integration. , 2008, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[119]  Dirk Verellen,et al.  Innovations in image-guided radiotherapy , 2008, Nature Reviews Cancer.

[120]  K. Ang,et al.  Strategic plans to promote head and neck cancer translational research within the radiation therapy oncology group: a report from the translational research program. , 2007, International journal of radiation oncology, biology, physics.

[121]  Timothy Solberg,et al.  Multi-institutional clinical experience with the Calypso System in localization and continuous, real-time monitoring of the prostate gland during external radiotherapy. , 2007, International journal of radiation oncology, biology, physics.

[122]  James M Galvin,et al.  Intensity modulating and other radiation therapy devices for dose painting. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[123]  Ke Sheng,et al.  A motion phantom study on helical tomotherapy: the dosimetric impacts of delivery technique and motion , 2006, Physics in medicine and biology.

[124]  T. Lawrence,et al.  Antimetabolite radiosensitizers. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[125]  Masahiro Hiraoka,et al.  Development of a four-dimensional image-guided radiotherapy system with a gimbaled X-ray head. , 2006, International journal of radiation oncology, biology, physics.

[126]  M. Frommer,et al.  Role of radiotherapy in cancer control in low-income and middle-income countries. , 2006, The Lancet. Oncology.

[127]  John R Yarnold,et al.  Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: long-term results of a randomised trial. , 2006, The Lancet. Oncology.

[128]  T. Lawrence,et al.  New and Emerging Radiosensitizers and Radioprotectors , 2006, Cancer investigation.

[129]  S. Rafla,et al.  The contribution of integrated PET/CT to the evolving definition of treatment volumes in radiation treatment planning in lung cancer. , 2005, International journal of radiation oncology, biology, physics.

[130]  Cedric X. Yu,et al.  Real-time intra-fraction-motion tracking using the treatment couch: a feasibility study , 2005, Physics in medicine and biology.

[131]  Michael Baumann,et al.  TCP and NTCP: a basic introduction. , 2005, Rays.

[132]  R. Jeraj,et al.  Confirmation, refinement, and extension of a study in intrafraction motion interplay with sliding jaw motion. , 2005, Medical physics.

[133]  D. Hill,et al.  Non-rigid image registration: theory and practice. , 2004, The British journal of radiology.

[134]  E. Hall,et al.  Radiation-induced second cancers: the impact of 3D-CRT and IMRT. , 2003, International journal of radiation oncology, biology, physics.

[135]  Anders Brahme,et al.  Biological Response to Radiation Therapy , 2003, Acta oncologica.

[136]  Carmel Mothersill,et al.  Radiation-Induced Bystander Effects: Past History and Future Directions , 2001, Radiation research.

[137]  Ronin,et al.  Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. , 1995, The New England journal of medicine.

[138]  P. Harari,et al.  Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. , 1999, Cancer research.

[139]  D J Brenner,et al.  Fractionation and protraction for radiotherapy of prostate carcinoma. , 1999, International journal of radiation oncology, biology, physics.

[140]  S. Hellman Stopping metastases at their source. , 1997, The New England journal of medicine.

[141]  M J Murphy,et al.  The Cyberknife: a frameless robotic system for radiosurgery. , 1997, Stereotactic and functional neurosurgery.

[142]  J O Deasy,et al.  Tomotherapy: a new concept for the delivery of dynamic conformal radiotherapy. , 1993, Medical physics.

[143]  T. McMillan,et al.  The 5Rs of radiobiology. , 1989, International journal of radiation biology.

[144]  H. Withers,et al.  Four R's of radiotherapy , 1975 .