Clinical Indications

Proton therapy is an effective treatment choice for certain cancer and tumor types. It can be precisely targeted to the tumor, causes less damage to healthy tissue compared to other radiation alternatives and has fewer short- and long-term side effects. The primary tumors treated with protons are listed below. Research continues to report promising results in other tumors.

Key criteria used in evaluating patients for proton therapy include:

  • Solid, localized tumors
  • Proximity to critical structures or vital organs
  • Inability to tolerate standard X-ray therapy
  • Recurrent malignancy
  • Potential for secondary malignancies

Brain Tumors

Brain tumors refer to tumors which originate in the brain as well as to those tumors which arise from the meninges (the protective covering of the brain underneath the skull), ependymal cells (the cells which form the fluid which bathes the central nervous system), nerve sheaths and pituitary gland (tumors of the pituitary are technically endocrine tumors, but are managed as brain cancers).  In addition to these tumors, other types of tumors can appear in the brain, including lymphomas.

The proper management of brain tumors varies by the type and the location of the cancer. The management can involve any of the following: surgery, chemotherapy and radiation therapy. It is not unusual to use more than one type of approach to brain tumors, and some tumors, such as "high grade gliomas," are often treated with all three approaches.

The fixed anatomy of the brain makes it an ideal site for treatment using proton therapy. Some of the earliest uses of protons in the treatment of cancer were for brain cancers. Doses to non-target brain (defined as the normal brain minus the tumor area) are decreased by more than 80% in some cases when using protons versus X-ray radiation, including IMRT. This decreased dose to normal brain tissues may result in better overall function in future years.1

The brain tumors most appropriate for proton therapy include, but are not limited to:

  • Low grade gliomas
  • Grade III gliomas (also called anaplastic astrocytomas)
  • Meningiomas
  • Arterio-venous malformations (AVM)
  • Ependymomas
  • Medulloblastomas (a common pediatric brain cancer)
  • Pineoblastomas
  • Supratentorial PNET
  • Germ cell tumors

Head and Neck Tumors

Tumors of the head and neck are treated with surgery, chemotherapy and radiation therapy. In some instances, a combination of any or all of these treatments is used.

Head and neck tumors treated with proton therapy include:

  • Nasopharynx
  • Nasal cavity and paranasal sinuses
  • Tonsil, base of tongue and other parts of the oropharynx

Depending on the site of treatment, protons may offer substantial reduction in dose-delivery to non-target structures, such as the eyes, optic nerves and salivary glands. Reducing dose to these structures may result in a lower risk of significant side effects, such as blindness, dry eye and dry mouth.2 The risk for secondary malignancies is also significantly reduced.1

Base-of-skull Tumors

Although often slow-growing, chordomas and chondrosarcomas present complex challenges in clinical management. They often impinge upon the brain stem or spinal cord and can invade central nervous system tissue. It is generally not possible to completely resect the tumor with adequate margins. The location also often limits the dose of standard X-ray radiation that can be delivered, and the results of conventional treatment are suboptimal. The relative ease of patient immobilization and shallow tumor depths make base-of-skull tumors amenable to treatment with proton therapy because protons can deliver a high dose while avoiding damage to healthy brain or spinal cord tissues. Control rates with protons have been reported to be much higher than for X-ray radiotherapy in these regions.3

Prostate Cancer

Proton therapy offers an alternative to conformal X-ray therapy, surgery and other treatments, and has the potential to be at least as effective with fewer and less severe side effects.4 The ability of any radiation treatment to control prostate cancer depends on the dose of radiation delivered. The potential for significant damage to nearby critical structures, such as the bladder and rectum, often limits the dose that can be delivered to the prostate. With proton therapy, higher doses of radiation can be delivered to the tumor while still largely sparing the bladder and rectum.5 Studies on proton treatment of the prostate have reported a reduction in radiation of 35% to the bladder and 59% to the rectum when compared to IMRT.6

For many types of prostate cancer proton therapy is the preferred treatment.4

Pediatric tumors

The use of proton therapy for pediatric applications is one of the most compelling. Pediatric tumors are often treated with radiation therapy as a part of the multi-modality approach to eradicating the tumor. Pediatric patients, because of their young age and increased susceptibility to developing additional cancers, pose a dilemma when prescribing radiation therapy: "Is the short-term benefit of the radiation therapy going to create significant problems in the long term?"

One major concern is the development of secondary malignant neoplasms (SMN) in addition to site-specific radiation complications. This second-malignancy potential, along with many of the other late onset-effects, is related to both the dose and the volume of irradiation used initially. With secondary-tumor rates for pituitary tumors published in the 3% range and now reported as high as 10% over a 20-year follow-up, pediatric radiation oncologists are now becoming especially mindful of unwanted integral doses.

Proton therapy can offer significant sparing to critical structures which are outside the treatment field. For example, in a child receiving radiation therapy to the brain and spine, protons can decrease the dose (versus conventional X-Ray treatment) by as much as 99%. Proton therapy achieves its conformal dose delivery through the use of only a few (often one or two) beams. The simplicity of proton beam design translates into both reproducibility of delivery (important for critical delivery plans) and decrease of integral dose to non-intended targets. This is critically important in the treatment of pediatric brain cancers. The radiation of healthy and still-developing brain tissue surrounding the tumor can have serious consequences. Protons patients are 10% less likely to experience a marked drop in IQ than those treated with photons.1

Juxtaspinal Cord Tumors

A complete surgical resection of juxtaspinal cord tumors is generally impossible because of tumor invasion and/or adherence to the vertebrae, spinal cord or peripheral nerve roots. The spinal cord serves as the main dose limiting organ for standard X-ray radiotherapy. Proton therapy literally "wraps" the isodose distribution around the spinal cord using abutting, patched fields and keeping dose to the spinal cord within tolerance levels, while treating the target tissue to a considerably higher dose. Chordomas and Blastomas are usually treated using multiple fields to get the dose wrapped around the spine.

Ocular (Uveal) Melanoma

Uveal melanomas are malignant tumors of the eye and are the most common eye tumor. These tumors historically have been treated by complete removal of the eye. However, precise forms of radiation treatment have been used to minimize the need for removal, while sparing the critical structures of the globe (cornea, lens, retina, fovea, optic nerve). Protons have been used since the mid-1970s. Clinical study results reveal control rates greater than 95%,7 with long-term survival consistent with survival rates for patients who have had their diseased eyes removed.8 Most patients treated with proton therapy have retained useful vision in their treated eyes.9 Results indicate that proton therapy is particularly useful for medium and large tumors, as well as smaller lesions. The overall data certainly indicates that proton therapy is a highly effective treatment for uveal melanoma, especially in cases where tumor thickness precludes adequate treatment with radioactive plaques.10

Paranasal Sinus Tumors

As a result of a relatively sparse lymphatic drainage system, tumors arising in the paranasal sinus are not as prone to distant metastases as tumors arising in other head and neck sites. Therefore, local control may be more closely coupled with survival.11 The depth-dose precision and high radiation dosage control of proton therapy have a high success rate for tumors in close approximation to the visual system (optic nerves and chiasm).12 Current analyses indicate local control rates are in excess of 82% and result in minimal visual complications.13

Non-small-cell Lung Cancer

When lung cancer is caught at an early stage, it is curable with surgical resection in more than 50% of cases by removal of the tumor and possibly of the entire lung. Some patients who are unable to undergo surgery, are prescribed radiotherapy, with published results being inferior to those of surgical resection.14 Several proton centers are studying using proton therapy for such patients in an effort to increase the dose delivered to the tumor while minimizing the damage to the surrounding normal heart and lung. Preliminary clinical results suggest that this treatment yields good rates of local tumor control while minimizing lung injury.15

Arteriovenous Malformations (AVM)

Arteriovenous malformations (AVMs) of the brain were among the first lesions to be treated in single dose proton therapy. Results and complications are size and dose dependent. While the Gamma Knife and stereotactic irradiation X-ray radiation using a linear accelerator are highly effective for smaller lesions, irregularly shaped and larger AVMs typically can be better treated with stereotactic proton radiosurgery. Multi-modality treatment, including embolization and/or microsurgery, can yield cure rates of 75%, even for some very large AVMs.

Footnotes: 
  1. Metz J. Reduced normal tissue toxicity with proton therapy. OncoLink 4.28.2002. Available at : http://www.oncolink.com/treatment/article.cfm?c=9&s=70&id=211. Accessed May 1, 2009.
  2. Steneker M.; Lomax A.; Schneider U.; Intensity modulated photon and proton therapy for the treatment of head and neck tumors. Ratiotherapy and Oncology 2006, (80) 263-267.
  3. Rutz H.P.; Weber D.; et al. Extracranial chordoma: Outcome in patients treated with function-preserving surgery followed by spot-scanning proton beam irradiation. Int.J. Radiat. Oncol. Biol. Phys 2007 (67), 512-520.
  4. Slater, J.D.; Rossi, C.J. Jr.; Yonemoto, L.T.; et al. Proton therapy for prostate cancer: The initial Loma Linda University experience. Int. J. Radiat. Oncol. Biol. Phys. 2004, 59 (2), 348-352.
  5. Fowler J. What can we expect from dose escalation using proton beams. Clinical Oncology 2003,15: S10-S15.
  6. Vargas C.; Fryer A.; Mahajan C.; et al. Dose-volume comparison of proton therapy and intensity-modulated radiotherapy for prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 2008, 70 (3), 744-51.
  7. Gragoudas, E.S.; Li, W.; Goitein, M.; et al. Evidence-based estimates of outcome in patients irradiated for intraocular melanoma. Arch Opthalmol. 2002, 120 (12), 1665-1671.
  8. Munzenrider J.E.; Gragoudas E.S.; Seddon J.M.; et al. Conservative treatment of uveal melanoma: probability of eye retention after proton treatment. Int. J. Radiat. Oncol. Biol. Phys 1988, 15 (3), 553-8.
  9. Egan, K.M.; Gragoudis, E.S.; Seddon, J.M.; et al. The risk of enucleation after proton beam irradiation of uveal melanoma. Ophthalmology. 1989, 96 (9), 1377-1382.
  10. Henderson, M.A.; Sherazi H.; Mendonca M.S.; et al. Stereotactic radiosurgery and fractionated stereotactic radiotherapy in the treatment of uveal melanoma. Technol Cancer Res Treat. 2006, 5(4), 411-9.
  11. Snyers A.; Janssens G.O.; Wickler M.B.; et al. Malignant tumors of the nasal cavity and paranasal sinuses: Long-term outcome and morbidity with emphasis on hypothalamic-pituitary deficiency. Int. J. Radiat. Oncol. Biol. Phys. 2008, 10/08 (Epub ahead of print).
  12. MacDonald S.; DeLaney T.; and Loeffler J. Proton beam radiation therapy. Cancer Invest. 2006, (24):199-208.
  13. Weber D.C.; Chan A.W.; Lessell S.; McIntyre J.F.; et al. Visual outcome of accelerated fractionated radiation for advanced sionasal malignancies employing photons/protons. Radiother Oncol. 2006, 81(3), 243-9.
  14. Ghosh S.; Sujendran V.; Alexiou C. Long-term results of surgery versus continuous hyperfractionated accelerated radiotherapy (CHART) in patients aged >70 years with stage 1 non-small cell lung cancer. Eur J Cardiothorac Surg. 2003, 24(6), 1002-7.
  15. Cox et al. Proton therapy with concurrent chemotherapy can reduce toxicity and allow higher radiation doses in advanced non-small cell lung cancer. ASCO annual meeting 2008.