Clinical Research

NAPT supports and encourages cooperative research and innovation to advance the appropriate and cost-effective utilization of proton therapy

Compared with photon therapy, proton therapy can deliver less toxic treatments, which allows for more aggressive treatments and higher cure rates in some cancers. In other types of cancers, proton therapy reduces costly hospitalizations and long-term side effects compared with photon therapy. Less toxicity to healthy tissues is simply better for patients in the short and long term. There are over 800 published peer reviewed journal articles and numerous active clinical trials evaluating the benefits of proton therapy. The following is a small sample of recent research supporting the value of proton therapy. For a larger list of peer reviewed journal articles CLICK HERE.

Proton Therapy Preserves Quality of Life and Reduces Side Effects

Proton therapy has fewer side effects across all cancers than photon therapy, reducing costly side effects and hospitalizations during the course of treatment. Proton therapy better preserves quality of life across all cancers compared with photon therapy. Cancer survivors are living longer due to effective treatments developed in the last few years. It is more important than ever to preserve quality of life for long-term survivors.

1) Baumann BC, Mitra N, Harton JG, et al. Comparative Effectiveness of Proton vs Photon Therapy as Part of Concurrent Chemoradiotherapy for Locally Advanced Cancer. JAMA Oncol. 2019 Dec 26. Epub ahead of print] PubMed PMID: 31876914.

1) Verma V, Simone CB 2nd, Mishra MV. Quality of Life and Patient-Reported Outcomes Following Proton Radiation Therapy: A Systematic Review. J Natl Cancer Inst. 2018;110(4).
Head and neck cancers

Proton therapy improves overall survival and reduces high grade complications for head and neck cancers compared with photon therapy. Side effects of radiation for head and neck cancer can cause malnutrition, need for feeding tubes, dehydration, and other costly side effects that can require hospitalizations. Proton therapy delivers less radiation to healthy tissue and thus reduces the incidence of these costly side effects.

1) Patel SH, Wang Z, Wong WW, et al. Charged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis. Lancet Oncol. 2014;15(9):1027-38.

2) McDonald MW, Liu Y, Moore MG, et al. Acute toxicity in comprehensive head and neck radiation for nasopharynx and paranasal sinus cancers: cohort comparison of 3D conformal proton therapy and intensity modulated radiation therapy. Radiation Oncology. 2016;11:32.

3) Manzar GS, Lester SC, Routman DM, et al. Comparative analysis of acute toxicities and patient reported outcomes between intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) for the treatment of oropharyngeal cancer. Radiotherapy and Oncology. 2020;147:64-74.

4) Romesser PB, Cahlon O, Scher E, et al. Proton beam radiation therapy results in significantly reduced toxicity compared with intensity-modulated radiation therapy for head and neck tumors that require ipsilateral radiation. Radiotherapy and Oncology. 2016;118(2):286-92.

5) Blanchard P, Gunn GB, Lin A, et al. Proton Therapy for Head and Neck Cancers. Semin Radiat Oncol. 2018: 28(1): 53-63.

6) Holliday EB, Esmaeli B, Pinckard J, et al. A Multidisciplinary Orbit-sparing Treatment Approach That Includes Proton Therapy for Epithelial Tumors of the Orbit and Ocular Adnexa. Int J Radiat Oncol Biol Phys. 2016;95(1):344-352.

7) Wang L, Fossati P, Paganetti H, et al. The Biological Basis for Enhanced Effects of Proton Radiation Therapy Relative to Photon Radiation Therapy for Head and Neck Squamous Cell Carcinoma. Int J Part Ther. 2021;8(1):3-13.

8) Hanania AN, Zhang X, Gunn B, et al. Proton Therapy for Major Salivary Gland Cancer: Clinical Outcomes. Int J Part Ther. 2021;8(1):264-272.

9) Xingzhe L, Sarin K, Anna L, et al. Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Nasopharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy. JAMA Netw Open. 2021;4(6):e2113205.
Base of skull cancers and chordomas

Proton therapy is the treatment of choice for base of skull cancers and chordomas, where sensitive brain and ocular structures prevent safe treatment with conventional radiation. Proton therapy has been shown to improve tumor control and overall survival for these cancers compared with photon therapy.

1) Zhou J, Yang B, Wang X, et al. Comparison of the effectiveness of radiotherapy with photons and particles for chordoma after surgery: a meta-analysis. World Neurosurg. 2018;117:46-53.

2) Amichetti M, Cianchetti M, Amelio D, et al. Proton therapy in chordoma of the base of the skull: a systematic review. Neurosurg Rev. 2009;32(4):403-16.

3) Holtzman A, Rotondo, R Rutenberg, M et al. Clinical Outcomes Following Dose-Escalated Proton Therapy for Skull-Base Chordoma. Int J Part Ther. 2021;8(1):179–188.
Brain tumors

Proton therapy can improve outcomes when used to treat brain tumors, offering reduced side effects and treatment options where no safe options exist in the treatment of recurrent brain tumors. Proton therapy can also decrease injury to normal brain tissues in primary brain tumor treatment.

1) Hug EB, DeVries A, Thornton AF, et al. Management of atypical and malignant meningiomas: Role of high-dose, 3D-conformal radiation therapy. J Neurooncol. 2000;48(2):151-160.

2) Combs SE, Debus J, Schulz-Ertner D. Radiotherapeutic alternatives for previously irradiated recurrent gliomas. BMC Cancer. 2007;7:167.

3) Brown PD, Chung C, Liu DD, et al. A prospective phase II randomized trial of proton radiotherapy vs. intensity modulated radiotherapy for patients with newly diagnosed glioblastoma. Neuro-Oncology. 2021;
Breast Cancer

Proton therapy reduces radiation dose to the heart and lungs, preventing long term cardiac toxicity for patients with breast cancer.

1) Hug EB. Proton Therapy for Primary Breast Cancer. Breast Care (Basel). 2018 Jul;13(3):168-172. doi: 10.1159/000489893. Epub 2018 Jun 15. PMID: 30069176; PMCID: PMC6062734.

2) Laugaard Lorenzen E, Christian Rehammar J, Jensen MB, Ewertz M, Brink C. Radiation-induced risk of ischemic heart disease following breast cancer radiotherapy in Denmark, 1977-2005. Radiother Oncol. 2020 Nov;152:103-110. doi: 10.1016/j.radonc.2020.08.007. Epub 2020 Aug 25. PMID: 32858067.

3) Braunstein LZ, Cahlon O. Potential Morbidity Reduction With Proton Radiation Therapy for Breast Cancer. Semin Radiat Oncol. 2018 Apr;28(2):138-149. doi: 10.1016/j.semradonc.2017.11.009. PMID: 29735190.

4) Lin LL, Vennarini S, Dimofte A, Ravanelli D, Shillington K, Batra S, Tochner Z, Both S, Freedman G. Proton beam versus photon beam dose to the heart and left anterior descending artery for left-sided breast cancer. Acta Oncol. 2015 Jul;54(7):1032-9. doi: 10.3109/0284186X.2015.1011756. Epub 2015 Mar 19. PMID: 25789715.

5) Mutter R, Choi I, Jimenez R, et al. Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee. Int J Radiat Oncol Biol Phys. 2021 Oct;11(2):337-359. doi: 10.1016/j.ijrobp.2021.05.110
Locally advanced stage non-small cell lung cancer

Proton therapy improves survival for locally advanced stage non-small cell lung cancer compared with photon therapy.

1) Higgins KA, O’Connell K, Liu Y, et al. National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2017;97(1):128-137.
Early stage non-small cell lung cancer

Proton therapy improves survival for early stage non-small cell lung cancer compared with photon therapy.

1) Nantavithya C, Gomez DR, Wei X, et al. Phase 2 Study of Stereotactic Body Radiation Therapy and Stereotactic Body Proton Therapy for High-Risk, Medically Inoperable, Early-Stage Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2018;101(3):558-563.

2) Chi A, Chen H, Wen S, et al. Comparison of particle beam therapy and stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer: A systematic review and hypothesis-generating meta-analysis. Radiother Oncol. 2017;123(3):346-354.
Esophageal cancer

Proton therapy improves overall survival and reduces high grade complications and resulting costly hospitalizations for esophageal cancer compared with photon therapy.

1) : Lin SH, Hobbs BP, Verma V, et al. Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer. J Clin Oncol. 2020;38(14):1569‐1579.

2) Xi M, Xu C, Liao Z, et al. Comparative Outcomes After Definitive Chemoradiotherapy Using Proton Beam Therapy Versus Intensity Modulated Radiation Therapy for Esophageal Cancer: A Retrospective, Single-Institutional Analysis. Int J Radiat Oncol Biol Phys. 2017;99(3):667-676.

3) Lin SH, Merrell KW, Shen J, et al. Multi-institutional analysis of radiation modality use and postoperative outcomes of neoadjuvant chemoradiation for esophageal cancer. Radiother Oncol. 2017;123(3):376-381.

4) Wang J, Wei C, Tucker SL, et al. Predictors of postoperative complications after trimodality therapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2013;86(5):885-91.

5) Lin SH, Hobbs B, Thall P, et al. Results of a Phase II Randomized Trial of Proton Beam Therapy vs Intensity Modulated Radiation Therapy in Esophageal Cancer. Int J Radiat Oncol Biol Phys. 2019;105(3):680-681.
Hepatocellular carcinoma

Proton therapy improves survival for hepatocellular carcinoma compared with photon therapy and stereotactic body radiation therapy.

1) Sanford NN, Pursley J, Noe B, et al. Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival. Int J Radiat Oncol Biol Phys. 2019;105(1):64-72.

2) Hasan S, Abel S, Verma V, et al. Proton beam therapy versus stereotactic body radiotherapy for hepatocellular carcinoma: practice patterns, outcomes, and the effect of biologically effective dose escalation. J Gastrointest Oncol. 2019;10(5):999-1009.

3) Cheng JY, Liu CM, Wang YM, et al. Proton versus photon radiotherapy for primary hepatocellular carcinoma: a propensity-matched analysis. Radiat Oncol. 2020;15(1):159.
Pancreatic and gastrointestinal tumors

Proton reduces side effects for pancreatic and gastrointestinal tumors compared with photon therapy.

1) Verma V, Lin SH, Simone CB, et al. Clinical outcomes and toxicities of proton radiotherapy (PT) for gastrointestinal neoplasms: a systematic review. J Gastrointest Oncol. 2016;7(4):644-664.
Recurrent tumors

Proton therapy offers a curative option not available with photon therapy for recurrent tumors. When cancers recur, traditional radiation is often not a safe treatment option, leaving cancer patients with limited treatment options and prognosis. Proton therapy gives patients with cancer recurrence a treatment option they would not have with conventional radiation and can lead to cures in select patients.

1) Verma V, Rwigema JM, Malyapa RS, et al. Systematic assessment of clinical outcomes and toxicities of proton radiotherapy for reirradiation. Radiother Oncol. 2017;125(1):21-30.

2) Chao HH, Berman AT, Simone CB 2nd, et al. Multi-Institutional Prospective Study of Reirradiation with Proton Beam Radiotherapy for Locoregionally Recurrent Non-Small Cell Lung Cancer. J Thorac Oncol. 2017;12(2):281-292.
Prostate cancer

Proton beam therapy is effective for treating prostate cancer, with excellent long-term outcomes and fewer long-term, costly side effects such as bowel toxicities.

1) Hoppe BS, Michalski JM, Mendenhall NP, et al. Comparative effectiveness study of patient-reported outcomes after proton therapy or intensity-modulated radiotherapy for prostate cancer. Cancer. 2014; 120:1076-1082.

2) Mendenhall NP, Hoppe BS, Nichols RC, et al. Five-year outcomes from 3 prospective trials of image-guided proton therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2014; 88:596-602.

3) Grewal AS, Schoenewolf C, Jeong Min E, et al. Four-Year Outcomes from a Prospective Phase II Clinical Trial of Moderately Hypofractionated Proton Therapy for Localized Prostate Cancer. Int J Radiat Oncol Biol Phys. 2019;105: 713-722
Pediatric Cancer

Proton therapy is the preferred treatment for pediatric patients needing curative radiotherapy. Proton radiotherapy decreases the risks for cancers caused by radiotherapy, decreases brain injury and improves neurocognitive function after treatment, and significantly reduces overall acute and acute and chronic life-long side effects.

1) Kahalley LS, Peterson R, Ris MD, et al. Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma. J Clin Oncol. 2020;38(5):454-461. doi:10.1200/JCO.19.01706

2) Chung CS, Yock TI, Nelson K, et al. Incidence of second malignancies among patients treated with proton versus photon radiation. Int J Radiat Oncol Biol Phys. 2013;87(1):46-52.

3) Yock TI, Yeap BY, Ebb DH, et al. Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: A phase 2 single-arm study. Lancet Oncol. 2016;17(3):287-298.
Secondary Malignancies

Proton therapy leads to fewer secondary radiation-induced cancer across all cancer than photon therapy.

1) 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;126(15):3560-3568.

2) 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;87(1):46-52.