INVITED REVIEW Proton therapy for lung cancer Romaine C. Nichols Jr. 1 , Randal H. Henderson 1 , Soon Huh 1 , Stella Flampouri 1 , Zuofeng Li 1 , Abubakr A. Bajwa 2 , Harry J. D’Agostino 3 , Dat C. Pham 4 , Nancy P. Mendenhall 1 & Bradford S. Hoppe 1 1 University of Florida Proton Therapy Institute, Jacksonville, FL, USA 2 Department of Medicine Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida College of Medicine, Jacksonville, FL, USA 3 Department of Surgery, University of Florida College of Medicine, Jacksonville, FL, USA 4 Department of Medical Oncology, University of Florida College of Medicine, Jacksonville, FL, USA Keywords literature review; lung cancer; proton therapy; radiation therapy; thoracic tumors. Correspondence Romaine C. Nichols Jr., University of Florida Proton Therapy Institute, 2015 North Jefferson Street, Jacksonville, FL 32206, USA. Tel: +1 904 588 1245 Fax: +1 904 588 1300 Email: rnichols@floridaproton.org Received: 11 October 2011; accepted 29 November 2011. doi: 10.1111/j.1759-7714.2011.00098.x Abstract Proton therapy is an emerging radiotherapy technology with the potential to improve the therapeutic index in the treatment of lung cancer patients. Since charged particles, such as protons, have a penetration length that can be modified by using different energies, protons offer the clinician the ability to modulate radiation dose deposition along the beam path. This facilitates an increase of the dose to the tumor target while minimizing the volume of normal tissue irradiation. Such precise delivery is particularly relevant in the setting of lung cancer where the targeted tissues are in close proximity to moderately radiation-sensitive organs like the spinal cord, heart, and esophagus, but are also effectively surrounded by the normal lung, which is extremely sensitive to radiation damage. Proton therapy has been investi- gated for the treatment of surgically curable yet medically inoperable patients as well as patients with regionally advanced disease. An overview of proton therapy Over the past 6 decades, radiotherapy technology has ad- vanced dramatically with significant improvements in clinical efficacy. These advancements have included the introduction of megavoltage beams,isocentric delivery techniques,custom- ized cerrobend blocking, computerized tomography (CT)- guided 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), image-guided radiotherapy (IGRT), and stereotactic radiosurgery. Radia- tion oncology teams can now fashion increasingly conformal radiotherapy dose distributions around targeted tissues. In conventional radiotherapy, X-rays deposit a high dose when entering tissues and a lower dose when exiting the tar- geted region, with most radiation dose deposition for any individual beam actually taking place outside of the target. Technologies that have improved the conformality of the radiation dose distribution deliver multiple beams from mul- tiple angles, which all intersect upon the tumor target. This dose delivery necessarily pushes a significant dose to the periphery of the field, which results in lower-dose radiation to areas of the body that are not involved with the malignancy. The “low-dose bath” offers no benefit to the patient and may, in fact, be associated with various degrees of toxicity, or even an increased risk of iatrogenic malignancy. In contrast to X-rays, charged particles such as protons deliver the dose within a defined region known as the Bragg Peak, which occurs at the end of the proton’s path in matter. The entry dose for a proton beam is consequently low relative to the dose at the end of the path, and there is no exit dose beyond the Bragg Peak (Fig 1). Protons can be rendered useful in the clinical setting through the creation of a “spread-out Bragg Peak”(SOBP), which is formed by deliver- ing an array of monoenergetic beams of different energies. The SOBP can be established at the depth of the tumor target with a much lower entry dose and no exit dose compared with X-ray radiotherapy (Fig 2). Because clinicians can control dose deposition along the beam path with protons, a con- formal dose distribution around the tumor target can be achieved with fewer beams. Figure 3 demonstrates typical dose distributions achieved with 3DCRT, IMRT and protons for a patient with stage III non-small cell lung cancer. Thoracic Cancer ISSN 1759-7706 Thoracic Cancer 3 (2012) 109–116 © 2011 Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd 109