Promise and Pitfalls of Heavy-Particle Therapy

SUMMARY: Radiation Therapy involves the use of X-Rays, gamma rays and charged particles for cancer treatment. External-beam radiation therapy is most often delivered using a linear accelerator in the form of Photon beams (either x-rays or gamma rays). Photons have no mass and are packets of energy of an electromagnetic wave. Electrons and Protons are charged particles and Electrons are considered light particles whereas Protons are considered heavy particles. Electron beams are used to irradiate skin and superficial tumors, as they are unable to penetrate deep into the tissues. The different types of external beam radiation treatments include 3-Dimensional Conformal Radiation Therapy (3D-CRT) meant to deliver radiation to very precisely shaped target areas, IMRT or Intensity Modulated Radiation Therapy which allows different areas of a tumor or nearby tissues to receive different doses of radiation, Image Guided Radiation Therapy (IGRT) which allows reduction in the planned volume of tissue to be treated as changes in a tumor size are noted during treatment, Stereotactic RadioSurgery (SRS) which can deliver one or more high doses of radiation to a small tumor, Stereotactic Body Radiation Therapy (SBRT) or CYBERKNIFE® which is similar to SRS but also takes the normal motion of the body into account while treating malignancies involving the lung and liver and Proton Beam therapy. Proton beams unlike Photons, enter the skin and travel through the tissues and deposit much of their energy at the end of their path (known as the Bragg peak) and deposit less energy along the way. This is unlike Photons which deposit energy all along the path through the tissues and the deposited dose decreases with increasing depth. As a result, with Proton beam therapy, normal tissues are exposed to less radiation compared with Photons. Despite this advantage, tissue heterogeneity such as organ motion, tumor volume changes during treatment can have a significant negative impact on target coverage for Proton beam therapy and can result in damage to the surrounding tissues and potential complications. The authors in this review discussed the clinical applications of Proton therapy in Adult and Pediatric malignancies. Pediatric patients with malignancies have greater benefit with Proton beam therapy, with a statistically significant lower risk of secondary malignancies and less damage to the developing tissues and organs, compared to Photon therapy (External Beam Radiation Therapy). This clinical benefit may be less so in adult malignancies in spite of superior dosimetry, compared to external beam radiation, as adults are less prone to secondary malignancies compared to children.


Prostate Cancer: Majority of the patients receiving Proton beam treatment in the United States have prostate cancer. Several randomized trials have concluded that higher radiation dose to the prostate gland leads to better tumor control. Proton beam therapy may deliver this promise, but with associated toxicities, in particular rectal bleeding. This is by virtue of the anatomy of the prostate gland which is deep in the pelvis. Outcomes and patient reported side effects were similar when men with prostate cancer were treated with similar doses of radiation using either Proton beam therapy or External beam radiation therapy. The American Society of Therapeutic Radiology and Oncology (ASTRO) has recommended that Proton beam therapy for patients with prostate cancer should be offered in the context of a clinical trial or registry, as there is not enough evidence suggesting clinical benefit in this patient population.

Breast Cancer: Proton beam therapy may be of value in select situations, such as patients with bilateral implants after mastectomy and in clinical scenarios where cardiac or pulmonary risks with Photon therapy are not acceptable. This is because of a significant reduction in the radiation doses to the heart, lung and contralateral breast with Proton therapy compared to Photon therapy.

Lung Cancer: Proton beam therapy for NSCLC (Non Small Cell Lung Cancer) is in the early stages of evaluation and has the advantage of reduced radiation to the normal lung and heart. This may be relevant in patients with inoperable early stage NSCLC with poor lung function, prior chest irradiation or in those with multifocal lung cancers requiring more than one treatment course. Proton therapy can be of significant value in patients with Stage IIIA NSCLC who in addition to chemoradiation may be candidates for pneumonectomy, thus sparing the contralateral lung from radiation related toxicities.

Head and Neck Cancers: Proton therapy may be of value in nasopharyngeal carcinoma and malignancies involving the oropharynx and paranasal sinuses. Proton therapy limits the radiation dose to the brain stem, optic structures, mandible and salivary glands, decreasing the risk of xerostomia and osteoradionecrosis of the mandible.

GI Malignancies: Proton beam therapy is the preferable treatment for hepatocellular carcinoma in patients with Child-Pugh class B and class C cirrhosis, as it is able to spare more liver tissue from radiation.

Brain Tumors: Meningiomas are ideal tumors for Proton beam therapy, with less cerebral adverse events and therefore has a positive impact on quality of life of patients. Clinical trials are underway to test this hypothesis.


Medulloblastoma- CranioSpinal Irradiation: There is a significant long term advantage with Proton CranioSpinal Irradiation compared to conventional or IMRT photon CSI. There is a 6-12 times lower risk of secondary malignancies due to lower radiation doses to normal tissues. This is more relevant because craniospinal axis irradiation results in the most exposure of a childs tissue to radiation.

Rhabdomyosarcoma: This is the most common soft tissue sarcoma in children arising in the head and neck region and Proton therapy can significantly reduce the mean doses to the retina, optic nerve, parotid and cochlea.

Ependymoma, Craniopharyngioma, Retinoblastoma and Glioma: Proton therapy for these tumors has been associated with lower acute and long term toxicities as well lower risk of secondary malignancies.

The authors concluded that the most benefit for Proton beam therapy is in pediatric malignancies, no significant benefit in skin cancer and marginal benefit in adult lung and prostate cancer. With ongoing advances in the delivery of Proton therapy such as Intensity Modulated Proton Therapy (IMPT) and other expensive therapeutic interventions, economics will take precedence, until and unless a clear clinical benefit is proven. Mitin T and Zietman AL. J Clin Oncol 2014;32:2855-2863