Radiotherapy has been driven by constant technological advances since the discovery of X-rays in 1895. Radiotherapy aims to sculpt the optimal isodose on the tumour volume while sparing normal tissues. The benefits are threefold: patient cure, organ preservation and cost-efficiency. The efficacy and tolerance of radiotherapy were demonstrated by randomized trials in many different types of cancer (including breast, prostate and rectum) with a high level of scientific evidence. Such achievements, of major importance for the quality of life of patients, have been fostered during the past decade by linear accelerators with computer-assisted technology. More recently, these developments were augmented by proton and particle beam radiotherapy, usually combined with surgery and medical treatment in a multidisciplinary and personalized strategy against cancer. This article reviews the timeline of 100 years of radiotherapy with a focus on breakthroughs in the physics of radiotherapy and technology during the past two decades, and the associated clinical benefits.
Your institute does not have access to this article
Open Access articles citing this article.
Protein & Cell Open Access 23 April 2021
Effect of irradiation on the expression of E-cadherin and β-catenin in early and late radiation sequelae of the urinary bladder and its modulation by NF-κB inhibitor thalidomide
Strahlentherapie und Onkologie Open Access 10 March 2021
Signal Transduction and Targeted Therapy Open Access 01 May 2020
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Siegel, R., Naishadham, D. & Jemal, A. Cancer statistics, 2012. CA Cancer J. Clin. 62, 10–29 (2012).
Roentgen, W. C. On a new kind of ray (first report) [German]. Munch. Med. Wochenschr. 101, 1237–1239 (1959).
Paterson, J. R. The Treatment of Malignant Disease By Radium And X-Rays, Being a Practice of Radiotherapy (Williams & Wilkins, London, 1948).
Becquerel, J. & Crowther, J. A. Discovery of radioactivity. Nature 161, 609 (1948).
Curie, E. Marie and Pierre Curie and the discovery of radium. Br. J. Radiol. 23, 409–412 (1950).
Schäfer, W. & Witte, E. Über eine neue Körperhöhlenröntgenröhre zur Bestrahulung von Uterustumoren. Strahlentherapie 44, 283 (1932).
Grubbé, E. H. Priority in the use of X-rays. Radiology 21, 156–162 (1933).
Despeignes, V. Observation concernant un cas de cancer de l'estomac traité par les rayons Roentgen. Lyon Med. 82, 428–430 (1896).
Dubois, J. B. & Ash, D. in Radiation Oncology: A Century of Progress and Achievement: 1895–1995 (ed. Bernier, J.) 77–98 (ESTRO publication, Brussels, 1995).
Mould, R. F. A Century of X-rays and Radioactivity in Medicine (IOP Publishing, Bristol, 1993).
Thoraeus, R. A. A study of ionization method for measuring the intensity and absorption of roentgen rays and of the efficiency of different filters used in therapy. Acta Radiol. 15, 1–86 (1932).
Chaoul, H. Short-distance roentgenotherapy (contact roentgenotherapy). J. Radiol. Electrol. Arch. Electr. Medicale 31, 290–298 (1950).
Baclesse, F. Comparative study of results obtained with conventional radiotherapy (200 KV) and cobalt therapy in the treatment of cancer of the larynx. Clin. Radiol. 18, 292–300 (1967).
Pierquin, B., Chassagne, D. & Gasiorowski, M. Présentation technique et dosimétrique de curiepuncture par fils d'or-198. J. Radiol. Electrol. Med. Nucl. 40, 690–693 (1959).
Kramer, R. Radiation therapy in early laryngeal cancer. J. Mt Sinai Hosp. NY 14, 24–28 (1947).
Bergonié, J. & Tribondeau, L. L'interpretation de quelques resultats de la radiotherapie et essai de fixation d'une technique rationnelle. C. R. Seances. Acad. Sci. 143, 983–985 (1906).
Regaud, C. & Ferroux, R. Discordance entre les effects des rayons X sur les testicules et la peau, implications pour le fractionnement de la dose. Compt. Rend. Soc. Biol. 97, 431–434 (1927).
Coutard, H. Principles of X-ray therapy of malignant disease. Lancet 224, 1–8 (1934).
Taylor, L. S. History of the International Commission on Radiological Protection (ICRP). Health Phys. 1, 97–104 (1958).
Geiger, H. & Müller, W. The electron counting tube [German]. Physikalische Zeitschrift 29, 839–841 (1928).
Curie, I. & Joliot, F. A new type of radioactivity [French]. Compt. Rend. Acad. Sci. (Fr.) 198, 254–256 (1934).
Johns, H., Bates, I. & Watson, T. 1000 Curie cobalt units for radiation therapy. I. The Saskatchewan cobalt 60 unit. Br. J. Radiol. 25, 296–302 (1952).
Laugier, A. The first century of radiotherapy in France [French]. Bull. Acad. Natl Med. 180, 143–160 (1996).
Courageot, E., Huet, C., Clairand, I., Bottollier-Depois, J. F. & Gourmelon, P. Numerical dosimetric reconstruction of a radiological accident in South America in April 2009. Radiat. Prot. Dosimetry 144, 540–542 (2011).
Pierquin, B. & Dutreix, A. For a new methodology in curietherapy: the system of Paris (endo- and plesioradiotherapy with non-radioactive preparation). A preliminary note [French]. Ann. Radiol. 9, 757–760 (1966).
Le Bourgeois, J.-P., Chavaudra, J. & Eschwege, F. Rádiotherapie Oncologique (Hermann, Paris, 1992).
Fry, D. W., Harvie, R. B., Mullett, L. B. & Walkinshaw, W. A travelling-wave linear accelerator for 4-MeV electrons. Nature 162, 859–861 (1948).
Emami, B. et al. Tolerance of normal tissue to therapeutic irradiation. Int. J. Radiat. Oncol. Biol. Phys. 21, 109–122 (1991).
Johns, H. E. & Cunningham, J. R. The Physics of Radiology 4th edn (Charles C. Thomas, Springfield, IL, 1983).
Tiemann, J. Practical irradiation planning using a “dedicated system” [German]. Strahlentherapie 148, 463–467 (1974).
Scientific Committee on Radiation Dosimetry (SCRAD) of the American Association of Physicists in Medicine. Protocol for the dosimetry of X-rays and gamma ray beams with maximum energies between 0.6 and 50 MeV. Phys. Med. Biol. 16, 379–396 (1971).
Horiot, J. C., van der Schueren, E., Johansson, K. A., Bernier, J. & Bartelink, H. The programme of quality assurance of the EORTC radiotherapy group. A historical overview. Radiother. Oncol. 29, 81–84 (1993).
Bernier, J., Hall, E. J. & Giaccia, A. Radiation oncology: a century of achievements. Nat. Rev. Cancer 4, 737–747 (2004).
Purdy, J. A. Current ICRU definitions of volumes: limitations and future directions. Semin. Radiat. Oncol. 14, 27–40 (2004).
Bonadonna, G. et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N. Engl. J. Med. 294, 405–410 (1976).
Veronesi, U. et al. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N. Engl. J. Med. 305, 6–11 (1981).
Veronesi, U. et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N. Engl. J. Med. 347, 1227–1232 (2002).
Gérard, J.-P. Guérir Le Cancer Sans Mutiler (Horvath, Lyon, 1995).
Krook, J. E. et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N. Engl. J. Med. 324, 709–715 (1991).
Påhlman, L. Initial report from a Swedish multicentre study examining the role of preoperative irradiation in the treatment of patients with resectable rectal carcinoma. Br. J. Surg. 80, 1333–1336 (1993).
Marsh, P. J., James, R. D. & Schofield, P. F. Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma. Dis. Colon Rectum 37, 1205–1214 (1994).
Kapiteijn, E. et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N. Engl. J. Med. 345, 638–646 (2001).
Gérard, J. P. et al. Improved sphincter preservation in low rectal cancer with high-dose preoperative radiotherapy : the Lyon R96-02 randomized trial. J. Clin. Oncol. 22, 2404–2409 (2004).
Sauer, R. et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N. Engl. J. Med. 351, 1731–1740 (2004).
Gérard, J. P. et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203. J. Clin. Oncol. 24, 4620–4625 (2006).
Sebag-Montefiore, D. et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 373, 811–820 (2009).
Gérard, J. P. et al. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J. Clin. Oncol. 28, 1638–1644 (2010).
Aschele, C. et al. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J. Clin. Oncol. 29, 2773–2780 (2011).
Gérard, J.-P. et al. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J. Clin. Oncol. 28, 1638–1644 (2010).
Cummings, B. J., Harwood, A. R., Keane, T. J., Thomas, G. M. & Rider, W. D. Combined treatment of squamous cell carcinoma of the anal canal: radical radiation therapy with 5-fluorouracil and mitomycin-C, a preliminary report. Dis. Colon Rectum 23, 389–391 (1980).
Stallard, H. B. Radiotherapy for malignant melanoma of the choroid. Br. J. Ophthalmol. 50, 147–155 (1966).
Caujolle, J. P. et al. Proton beam radiotherapy for uveal melanomas at nice teaching hospital: 16 years' experience. Int. J. Radiat. Oncol. Biol. Phys. 78, 98–103 (2010).
Hounsfield, G. N. Nobel Award address. Computed medical imaging. Med. Phys. 7, 283–290 (1980).
Dutreix, A. The computer in radiotherapy [French]. Rev. Prat. 22, 1359–1360 (1972).
Mohan, R. Field shaping for three-dimensional conformal radiation therapy and multileaf collimation. Semin. Radiat. Oncol. 5, 86–99 (1995).
Dutreix, A. Prescription, precision, and decision in treatment planning. Int. J. Radiat. Oncol. Biol. Phys. 13, 1291–1296 (1987).
Oldham, M., Neal, A. & Webb, S. A comparison of conventional 'forward planning' with inverse planning for 3D conformal radiotherapy of the prostate. Radiother. Oncol. 35, 248–262 (1995).
Pollack, A. et al. Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J. Clin. Oncol. 18, 3904–3911 (2000).
Kuban, D. A. et al. Long-term results of the MD Anderson randomized dose-escalation trial for prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 70, 67–74 (2008).
Beckendorf, V. et al. 70 Gy versus 80 Gy in localized prostate cancer: 5-year results of GETUG 06 randomized trial. Int. J. Radiat. Oncol. Biol. Phys. 80, 1056–1063 (2011).
Peeters, S. T. et al. Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J. Clin. Oncol. 24, 1990–1996 (2006).
Dearnaley, D. P. et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol. 8, 475–487 (2007).
Zelefsky, M. J. et al. Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 70, 1124–1129 (2008).
Hoskin, P. J. et al. Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer. Radiother. Oncol. 103, 217–222 (2012).
Sathya, J. R. et al. Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. J. Clin. Oncol. 23, 1192–1199 (2005).
Brahme, A. Development of radiation therapy optimization. Acta Oncol. 39, 579–595 (2000).
Pow, E. H. et al. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int. J. Radiat. Oncol. Biol. Phys. 66, 981–991 (2006).
Nutting, C. M. et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol. 12, 127–136 (2011).
Glatstein, E. Intensity-modulated radiation therapy: the inverse, the converse, and the perverse. Semin. Radiat. Oncol. 12, 272–281 (2002).
Fenwick, J. D., Tomé, W. A., Soisson, E. T., Mehta, M. P. & Rock Mackie, T. Tomotherapy and other innovative IMRT delivery systems. Semin. Radiat. Oncol. 16, 199–208 (2006).
Leksell, L. The stereotaxic method and radiosurgery of the brain. Acta Chir. Scand. 102, 316–319 (1951).
Gérard, J. P. et al. Recommendation of the working group commissioned by the French Nuclear Safety Authority on stereotactic radiation therapy [French]. Cancer Radiother. 16 (Suppl.) S5–S9 (2012).
Salama, J. K., Kirkpatrick, J. P. & Yin, F. F. Stereotactic body radiotherapy treatment of extracranial metastases. Nat. Rev. Clin. Oncol. 9, 654–665 (2012).
Lagerwaard, F. J. et al. Outcomes of stereotactic ablative radiotherapy in patients with potentially operable stage I non-small cell lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 83, 348–353 (2012).
Milano, M. T., Katz, A. W., Zhang, H. & Okunieff, P. Oligometastases treated with stereotactic body radiotherapy: long-term follow-up of prospective study. Int. J. Radiat. Oncol. Biol. Phys. 83, 878–886 (2012).
Grimm, J. et al. Dose tolerance limits and dose volume histogram evaluation for stereotactic body radiotherapy. J. Appl. Clin. Med. Phys. 12, 3368 (2011).
Thariat, J. et al. Cyberknife robotic stereotactic radiotherapy: technical aspects and recent developments [French]. Bull. Cancer 97, 807–818 (2010).
Bucci, M. K., Bevan, A. & Roach, M. 3rd. Advances in radiation therapy: conventional to 3D, to IMRT, to 4D, and beyond. CA Cancer J. Clin. 55, 117–134 (2005).
Ling, C. C., Yorke, E. & Fuks, Z. From IMRT to IGRT: frontierland or neverland? Radiother. Oncol. 78, 119–122 (2006).
Thariat, J. et al. Image-guided radiation therapy for muscle-invasive bladder cancer. Nat. Rev. Urol. 9, 23–29 (2012).
Schwartz, D. L. Current progress in adaptive radiation therapy for head and neck cancer. Curr. Oncol. Rep. 14, 139–147 (2012).
Schwartz, D. L. et al. Adaptive radiotherapy for head-and-neck cancer: initial clinical outcomes from a prospective trial. Int. J. Radiat. Oncol. Biol. Phys. 83, 986–993 (2012).
Mazeron, J. J. et al. GEC-ESTRO recommendations for brachytherapy for head andneck squamous cell carcinomas. Radiother. Oncol. 91, 150–156 (2009).
Speight, J. L. & Roach, M. 3rd. Radiotherapy in the management of clinically localized prostate cancer: evolving standards, consensus, controversies and new directions. J. Clin. Oncol. 23, 8176–8185 (2005).
Hannoun-Levi, J.-M., Chand-Fouche, M.-E., Dejean, C. & Courdi, A. Dose gradient impact on equivalent dose at 2 Gy for high dose rate interstitial brachytherapy. J. Contemp. Brachyther. 4, 14–20 (2012).
Crook, J. M. et al. Comparison of health-related quality of life 5 years after SPIRIT: surgical prostatectomy versus interstitial radiation intervention trial. J. Clin. Oncol. 29, 362–368 (2011).
Caccialanza, M., Piccinno, R., Beretta, M. & Gnecchi, L. Results and side effects of dermatologic radiotherapy: a retrospective study of irradiated cutaneous epithelial neoplasms. J. Am. Acad. Dermatol. 41, 589–594 (1999).
Gérard, J. P. et al. Renaissance of contact X-ray therapy for treating rectal cancer. Exp. Rev. Med. Devices 8, 483–492 (2011).
Vaidya, J. S. et al. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet 376, 91–102 (2010).
Veronesi, U. et al. A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated. Eur. J. Cancer 37, 2178–2183 (2001).
Bartelink, H. et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N. Engl. J. Med. 345, 1378–1387 (2001).
Whelan, T. J. et al. Long-term results of hypofractionated radiation therapy for breast cancer. N. Engl. J. Med. 362, 513–520 (2010).
Polgár, C. et al. Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: recommendations of the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009). Radiother. Oncol. 94, 264–273 (2010).
Offersen, B. V., Overgaard, M., Kroman, N. & Overgaard, J. Accelerated partial breast irradiation as part of breast conserving therapy of early breast carcinoma: a systematic review. Radiother. Oncol. 90, 1–13 (2009).
Thwaites, D. I. & Malicki, J. Physics and technology in ESTRO and in radiotherapy and oncology: past, present and into the 4th dimension. Radiother. Oncol. 100, 327–332 (2011).
Maingon, P. et al. Radiotherapy of advanced mycosis fungoides: indications and results of total skin electron beam and photon beam irradiation. Radiother. Oncol. 54, 73–78 (2000).
Flickinger, J. et al. Acoustic neuroma radiosurgery with marginal tumor doses of 12 to 13 Gy. Int. J. Radiat. Oncol. Biol. Phys. 60, 225–230 (2004).
Haie-Meder, C., Siebert, F. A. & Pötter, R. Image guided, adaptive, accelerated, high dose brachytherapy as model for advanced small volume radiotherapy. Radiother. Oncol. 100, 333–343 (2011).
Tsujii, H. et al. Clinical results of carbon ion radiotherapy at NIRS. Radiat. Res. 48 (Suppl. A), A1–A13 (2007).
Suit, H. D. et al. Increased efficacy of radiation therapy by use of proton beam. Strahlenther. Onkol. 166, 40–44 (1990).
Catterall, M. Neutron therapy at Hammersmith Hospital 1970 to 1985. A re-examination of results. Strahlenther. Onkol. 165, 298–301 (1989).
De Ruysscher, D. et al. Charged particles in radiotherapy: a 5-year update of a systematic review. Radiother. Oncol. 103, 5–7 (2012).
Dendale, R. et al. Proton beam radiotherapy for uveal melanoma: results of Curie Institut-Orsay proton therapy center. Int. J. Radiat. Oncol. Biol. Phys. 65, 780–787 (2006).
Feuvret, L. et al. A treatment planning comparison of combined photon-proton beams versus proton beams-only for the treatment of skull base tumors. Int. J. Radiat. Oncol. Biol. Phys. 69, 944–954 (2007).
Tubiana, M. Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother. Oncol. 91, 4–15 (2009).
Shirai, T. et al. Recent progress of new cancer therapy facility at HIMAC. Proc. IPAC2011, 3604–3606 (2011).
Suit, H. et al. Proton vs carbon ion beams in the definitive radiation treatment of cancer patients. Radiother. Oncol. 95, 3–22 (2010).
Kraft, G. The radiobiological and physical basis for radiotherapy with protons and heavier ions. Strahlenther. Onkol. 166, 10–13 (1990).
Kamada, T. Clinical evidence of particle beam therapy (carbon). Int. J. Clin. Oncol. 17, 85–88 (2012).
Ohno, T. et al. Carbon ion radiotherapy at the Gunma University Heavy Ion Medical Center: new facility set-up. Cancers 3, 4046–4060 (2011).
Rieken, S. et al. Proton and carbon ion radiotherapy for primary brain tumors delivered with active raster scanning at the Heidelberg Ion Therapy Center (HIT): early treatment results and study concepts. Radiat. Oncol. 7, 41 (2012).
Castro, J. R. et al. Experience in charged particle irradiation of tumors of the skull base: 1977–1992. Int. J. Radiat. Oncol. Biol. Phys. 29, 647–655 (1994).
Perez, C. A., Brady, L. W. & Roti, J. L. in Principles and Practice of Radiation Oncology (eds Perez, C. A. & Brady, L. W.) 1–78 (Lippincott-Raven, Philadelphia, 1998).
Borella, L. et al. Volume and costs of the hospital management of cancer in France in 1999 [French]. Bull. Cancer 89, 809–821 (2002).
Kulthau, K. A. et al. Prospective sudy of health-related quality of life for children with brain tumors treated with proton radiotherapy. J. Clin. Oncol. 30, 2079–2086 (2012).
Pisani, P., Parkin, D. M., Bray, F. & Ferlay, J. Estimates of the worldwide mortality from 25 cancers in 1990. Int. J. Cancer 83, 18–29 (1999).
Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N. Engl. J. Med. 324, 1685–1690 (1991).
The authors acknowledge Pascale Martino, Adrian Plesu, Bastien Chanoux, Vincent Corvasce, Jerome Mandrillon and Karen Benezery for their help in making figures.
J. P. Gérard acts as a consultant for Ariane Medical Systems. The other authors declare no competing interests.
About this article
Cite this article
Thariat, J., Hannoun-Levi, JM., Sun Myint, A. et al. Past, present, and future of radiotherapy for the benefit of patients. Nat Rev Clin Oncol 10, 52–60 (2013). https://doi.org/10.1038/nrclinonc.2012.203
Nature Reviews Physics (2021)
Protein & Cell (2021)
Effect of irradiation on the expression of E-cadherin and β-catenin in early and late radiation sequelae of the urinary bladder and its modulation by NF-κB inhibitor thalidomide
Strahlentherapie und Onkologie (2021)
Dying tumor cell-derived exosomal miR-194-5p potentiates survival and repopulation of tumor repopulating cells upon radiotherapy in pancreatic cancer
Molecular Cancer (2020)
Signal Transduction and Targeted Therapy (2020)