X-ray (also called photon) therapy has long been known to cause the development of potentially deadly new cancers in patients who undergo radiation therapy to treat their cancer. However, research shows that patients who choose proton therapy for cancer treatment have a significantly lower risk of developing a second cancer later in life.
In a comprehensive study published in Cancer, the prestigious, peer-reviewed journal of the American Cancer Society, researchers at Stanford University found that patients who were treated with x-ray therapy developed more than three times as many new cancers as patients treated with proton therapy.1
ABOUT THE STUDY
The study was conducted by Stanford University physicians Michael Xiang, MD, PhD; Daniel T. Chang, MD; and Erqi L. Pollom, MD, MS. Their research team conducted a retrospective cohort study using the National Cancer Database (NDCB), the most comprehensive cancer registry in the United States.
The study included over 450,000 patients of all ages with a variety of cancers, such as:
- Head and neck
- Lung (non-small cell)
- Bone/soft tissue
- Brain/central nervous system
Patients included in the study were treated with intensity-modulated radiation therapy (IMRT), 3-dimensional conformal radiation therapy (3DCRT), or proton therapy between 2004 and 2015. They were followed for a minimum of 2 years and an average of 5 years after receiving radiation therapy.
RESULTS HEAVILY FAVOR PROTON THERAPY
Compared to proton therapy, the incidence of second cancers was 3.5 times higher after IMRT and 3.6 times higher after 3DCRT, the two most common forms of x-ray radiation therapy. These differences were found to be highly significant. Proton therapy decreased the overall risk of developing a second cancer by over two-thirds (69%) compared to IMRT. In fact, proton therapy reduced the occurrence of second cancer for eight of the nine types of cancer most commonly treated with radiation therapy.
Compared to IMRT, proton therapy substantially reduced the risk of developing a second cancer for most disease sites, including:
- 82% reduction among prostate cancer patients
- 58% reduction among head and neck cancer patients
- 38% reduction among breast cancer patients with at least five years of follow-up
- 69% reduction among all cancer patients
These findings show the extraordinary benefits of proton therapy when it comes to reducing the risk of second cancers, confirming the results of prior modeling studies. The data powerfully bears out the theories regarding the benefits of proton therapy in terms of reducing the risk of second cancers.
The dramatic reduction in risk of second cancers is likely due to to the fact that protons concentrate their radiation delivery within the cancer much better than x-rays. Patients treated with x-rays absorb 2-3 times more radiation in their bodies than patients treated with protons.4-6 The excess radiation from x-rays can severely damage and mutate healthy cells, resulting in serious toxicities, including causing a new cancer.
STUDY CONFIRMS PRIOR RESEARCH
The Stanford study confirms the findings of a previously published study from Harvard using the other main American cancer registry, the Surveillance, Epidemiology, and End Results (SEER) Program. The Harvard study found the second cancer rate to be 48% lower after proton therapy, compared to x-ray treatment. The average follow-up period in the Harvard study was 6 years after radiation therapy. 18
The Harvard study noted that while proton therapy reduced second cancers in all age groups, protons may be particularly beneficial for young patients, who have decades to accumulate radiation-induced cancers. In children, for example, x-ray therapy is estimated to increase second cancers by 600-1,000%.19-21
As time passes and the follow-up period for these patients lengthens, the benefits of proton therapy could become even more pronounced. This is especially important for patients who expect to survive 10 years or more.
OTHER BENEFITS OF PROTON THERAPY FOR CANCER TREATMENT
The results of this study highlight yet another clinically-proven benefit of proton therapy for cancer treatment. Because proton therapy precisely targets the tumor and avoids unnecessary radiation to nearby healthy tissue and organs, patients have a lower risk of short-term and long-term side effects.
Depending on cancer type, other benefits of proton therapy include:
- 25% lower risk of erectile dysfunction7
- 35% less radiation to bladder8
- 59% less radiation to rectum8
- 27% reduction in overall risk of needing a feeding tube for oropharyngeal cancer9
- 45% reduction in overall risk of needing a feeding tube for nasopharyngeal cancer10
- Dramatic reduction of negative impact on taste, nausea and painful changes to the mouth in salivary gland treatment11
- 88% less radiation to the heart for left-sided breast cancer9,10
- 44% reduction in clinically significant radiation doses to the lung10
- 90% of partial breast irradiation cases result in good to excellent cosmetic outcomes at 5 years11
- 31% increase in disease control for aggressive tumors at base of skull (chordomas) at 5 years12
- 50% less likely to have secondary brain tumor from treatment13
- 55% reduction in average dose to the hippocampi (memory function) in treatment of meningioma14
- 26% reduction in lung toxicity compared with IMRT15
- 21% reduction in the risk of severe, treatment-related lymphopenia, particularly in lower esophagus16
- 3-4 day reduction in average hospital stay after surgery17
To learn about other cancers that can be treated with proton therapy, and to read about the benefits of proton therapy for those cancers, visit our Cancers We Treat page.
Sources & Studies
- Xiang M, Chang DT, Pollom EL. Second cancer risk after primary cancer treatment with three-dimensional conformal, intensity-modulated, or proton beam radiation therapy. Cancer. 2020;0:1-9.
- Journy NM, Morton LM< Kleinerman RA, Bekelman JE, Berrington de Gonzalez A. Second primary cancers after intensity-modulated vs 3-dimensional conformal radiation therapy for prostate cancer. JAMA Oncol. 2016;2:1368-1370.
- Diallo I, Haddy N, Adjadj E, et al. Frequency distribution of second solid cancer locations in relation to the irradiated volume among 115 patients treated for childhood cancer. Int J Radiat Oncol Biol Phys. 2009;74:876-883.
- Eaton BR, MacDonald SM, Yock TI, Tarbell NJ. Secondary malignancy risk following proton radiation therapy. Front Oncol. 2015;5:261.
- Chargari C, Goodman KA, Diallo I, et al. Risk of second cancers in the era of modern radiation therapy: does the risk/benefit analysis overcome theoretical models? Cancer Metastasis Rev. 2016;35:277-288.
- Hoppe BS, Flampouri S, Su Z, et al. Consolidative involved-node proton therapy for stage IA-IIIB mediastinal Hodgkin lymphoma: preliminary dosimetric outcomes from a phase II study. Int J Radiat Oncol Biol Phys. 2012;83:260-267.
- Comparative toxicity and cost of Intensity-Modulated Radiotherapy, Proton Radiation, and Stereotactic Body Radiotherapy Among Younger Men With Prostate Cancer. Read More
- Dose–Volume Comparison of Proton Therapy and Intensity-Modulated Radiotherapy for Prostate Cancer. Read More
- Gastrostomy Tubes Decrease by Over 50% With Intensity Modulated Proton Therapy (IMPT) During the Treatment of Oropharyngeal Cancer Patients. Read More
- Proton therapy reduces treatment-related toxicities for patients with nasopharyngeal cancer: a case-match control study of IMPT and IMRT. Read More
- Proton beam radiation therapy results in significantly reduced toxicity compared with intensity-modulated radiation therapy for head and neck tumors that require ipsilateral radiation. Read More
- Effectiveness and Safety of Spot Scanning Proton Radiation Therapy for Chordomas and Chondrosarcomas of the Skull Base: First Long-Term Report. Read More
- A comparison of critical structure dose and toxicity risks in patients with low grade gliomas treated with IMRT versus proton radiation therapy. Read More
- Projected second tumor risk and dose to neurocognitive structures after proton versus photon radiotherapy for benign meningioma. Read More
- A Multi-Institutional Analysis of Trimodality Therapy for Esophageal Cancer in Elderly Patients. Read More
- Lymphocyte-sparing Effect of proton therapy in patients with esophageal cancer treated with definitive chemoradiation. Read More
- Multi-institutional analysis of radiation modality use and postoperative outcomes of neoadjuvant chemoradiation for esophageal cancer. Read More
- Chung CS, Yock TI, Nelson K, Xu Y, Keating NL, Tarbell NJ. Incidence of second malignancies among patients treated with proton versus photon radiation. Int J Radiat Oncol Biol Phys. 2013 Sep 1;87(1):46-52. doin: 10.1016/j.ijrobp.2013.04.030. Pub 2013 Jun 15.
- Curtis RE, Freedman DM, Roe E, et al. eds. New malignancies among cancer survivors: SEER Cancer Registries, 1973-2000. NIH Publ. No. 05-5302. National Cancer Institute; 2006.
- Yock TI, Caruso PA. Risk of second cancers after photon and proton radiotherapy: a review of the data. Health Phys. 2012;103:577.
- Taylor C, Correa C, Duane FK, et al. Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials. J Clin Oncol. 2017;35:1641-1649.