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Is Proton Therapy Safer than Traditional Radiation? In this new study, researchers found that patients who received proton therapy instead of traditional radiation were less likely to experience side effects after receiving their cancer treatment. “These results support the whole rationale for proton therapy,” said the study’s lead investigator.
Foote R, et al. “The clinical case for proton beam therapy.” Radiation Oncology 2012; 7:174. This article is a great resource for clinicians who are learning about the benefits of proton beam therapy for the first time. It reviews the clinical indications for protons compared to other typical treatment modalities for disease sites ranging from ocular melanoma to prostate cancer.
Recommended Proton Therapy Indications. Updated April 2015, this document includes proton therapy indications from the National Association of Proton Therapy for Breast, Esophageal, Gastrointestinal, Hematologic, Prostate, and Thoracic Cancers. Indications include inclusion and exclusion criteria for various stages and diagnoses, and the scientific evidence supporting them.
Hammi. A. et al. "4D blood flow model for dose calculation to circulating blood and lymphocytes." Physics in Medicine & Biology. 2020; 65:5. Radiation is known to be damaging to the immune system, with recent studies linking radiation-induced lymphopenia (loss of lymphocytes, the white blood cells associated with immune response) with poor survival after radiotherapy. To better understand how radiation treatments affect circulating lymphocytes, researchers at MGH/Harvard Medical School developed a 4D computational blood flow model to calculate the blood dose during radiotherapy.
Please find further academic resources organized by cancer type below.
Dinh, Tru-Khang T. et al. "Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity Compared To Rectal Balloon Immobilization After Proton Beam Radiotherapy For Localized Prostate Cancer: A Retrospective Observational Study." International Journal of Radiation Oncology, Biology, and Physics 2020. The results of this study show that the use of rectal hydrogel spacer during proton therapy to treat prostate cancer had a significantly lower incidence of rectal bleeding compared with the use of a rectal balloon.
Mendenhall N, et al. “FiveYear Outcomes from 3 Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer.” International Journal of Radiation Oncology, Biology, and Physics 2014; 88(3): 596-602. Researchers determined that “proton therapy for low-, medium-, and high-risk prostate cancer patients is highly effective, minimally toxic, and associated with excellent patient-reported outcomes. Proton therapy compares favorably with other contemporary radiation modalities used in treating prostate cancer.”
Pugh T, et al. “Quality of Life and Toxicity from Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer.” International Journal of Radiation Oncology, Biology, and Physics 2013; 87(5): 946-53. A 24-month study of patients with non-metastatic prostate cancer was conducted, beginning before the patient began either passively scattered [PSPT] or spot-scanning proton beam therapy [SSPT] and continuing through follow-up appointments for a minimum of two years. The study found that both PSPT and SSPT resulted in an improved quality of life where sexual and urinary functions were concerned, compared to intensity-modulated radiation therapy.
Rana S, et al. “Proton therapy vs. VMAT for prostate cancer: a treatment planning study.” International Journal of Particle Therapy 2014; 1(1): 22-33. The treatment planning study found that, “for the same target coverage, in comparison to the VMAT [volumetric modulated arc therapy] technique,” Proton Therapy “is significantly better at sparing the rectum and the bladder [from radiation exposure], especially in the low- and medium-dose regions,” though it does result in a comparatively higher dose of radiation to the femoral heads.
Wang X, et al. “Accelerated partial-breast irradiation using intensity-modulated proton radiotherapy: do uncertainties outweigh potential benefits?” British Journal of Radiology 2013; 86:20130176. The Departments of Radiation Oncology and Radiation Physics at MD Anderson Cancer Center in Houston, Texas, found that passive-scatter pencil beam proton therapy for accelerated partial-breast irradiation provides as good or better dosimetry than intensity-modulated proton radiotherapy, with less uncertainty.
Weber D, et al. “Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview.” Radiation Oncology 2006; 1:22. Comparative analysis between proton and photon therapy found proton irradiation to improve the outcome for patients with both early and advanced breast cancer, with less radiation exposure for OAR like the heart and lungs.
Lin, S., et al. "Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer." Journal of Clinical Oncology. In a single-institution phase IIb trial reported in the Journal of Clinical Oncology, Steven H. Lin, MD, PhD, and colleagues found that proton beam therapy was associated with less toxicity and similar progression-free survival vs intensity-modulated radiation therapy in patients with locally advanced esophageal cancer.
Ling T, et al. “Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients.” Cancers 2014; 6:2356-2368. According to the Department of Radiation Medicine at Loma Linda University Medical Center, the radiation modality used to treat an esophageal cancer patient in conjunction with chemotherapy has a significant impact on whether the patient will have perioperative complications. Dr. Ling and his team’s comparative plans indicated that proton therapy delivered lower radiation doses to the heart than either IMRT or 3D-CRT, and lower lung doses in comparison to the IMRT plans.
Badiyan S, et al. "Outcomes of patients with stage II-III non-small cell lung cancer treated with proton therapy: The Proton Collaborative Group Prospective Registry Trial.&" Abstract presented at PTCOG 2016. In this multi-site registry trial, patients diagnosed with non-small cell lung cancer, staged IIa to IIIb, were treated with proton therapy. Outcomes varied across the registry sample, but the researchers were able to conclude that Proton Beam Therapy resulted in limited toxicity for all registered patients.
Chang J, et al. "Phase II Study of High-Dose Proton Therapy with Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer.&" Cancer 2011; 117(20):4707-4713. Forty-four patients with Stage III non-small cell lung cancer were treated with passive scatter proton therapy, along with weekly carboplatin and paclitaxel. This treatment regimen was well-tolerated. Dr. Chang and his team reported the median overall survival time of 29.4 months to be "encouraging."
Lee, A., et al. "Long-Term Update of Proton Beam Re-Irradiation for Recurrent Head and Neck Cancer." International Journal of Radiation Oncology 2020; 11(5): 1181. In this recent scholarly article, an update is given on a past clinical trial of using proton beam re-irradiation for treating recurrent head and neck cancer. The update confirms that using this treatment type for recurrent head and neck cancer is effective against tumor control while also providing acceptable acute and late toxicity profiles.
Ausat, N., et al. "Outcomes following Proton Therapy for Squamous Cell Carcinoma of the Larynx." International Journal of Radiation Oncology 2020; 106(5): 1213. In this study, researchers concluded that proton therapy for SCC of the larynx demonstrates a high rate of overall survival, local-regional control, and disease-free survival with a low toxicity profile.
Manzar, G., 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. IMPT is associated with improved PROs, reduced PEG-tube placement, hospitalization, and narcotic requirements. Mucositis, dysphagia, and pain were decreased with IMPT. Benefits were predominantly seen in patients treated definitively or with CRT.
Lee, A., et al. "Proton Therapy for Non-Skull Base Head and Neck Adenoid Cystic Carcinoma." International Journal of Radiation Oncology 2020; 106(5): 1196. Proton therapy is a feasible option for ACC of the non-skull base head and neck in the definitive and postoperative setting offering low rates of acute and late toxicity. Patients with metastatic disease also had acceptable outcomes and local treatment was well tolerated.
Amichetti M, et al. "Radiosurgery with photons or protons for benign and malignant tumours of the skull base: a review." Radiation Oncology 2012; 7: 210. Proton stereotactic radiosurgery has been advocated as the preferred treatment of larger and/or more complex skull base tumors due to its success in minimizing normal tissue toxicity.
Holliday E, et al. "Proton Therapy Reduces Treatment-Related Toxicities for Patients with Nasopharyngeal Cancer: A Case-Match Control Study of Intensity-Modulated Proton Therapy and Intensity-Modulated Photon Therapy." International Journal of Particle Therapy 2015; 2(1): 19-28. Researchers compared cases of nasopharyngeal cancer patients treated with proton therapy to those treated with photon therapy in a 2:1 ratio, based on T stage, N stage, WHO classification, and other factors. They found that patients treated with proton therapy had less need for gastrostomy tubes as a result of treatment, largely because proton therapy led to better dose sparing in the oral cavity. Proton therapy also meant significantly lower radiation dose to the brainstem, whole brain, and mandible.
Jakobi A, et al. "NTCP reduction for advanced head and neck cancer patients using proton therapy for complete or sequential boost treatment versus photon therapy." (Abstract Only.) Acta Oncologica 2015; 54(9): 1658-64. Dr. Jakobi and her team determined that a radiation treatment plan comprised purely of the proton therapy modality is more beneficial than IMRT with a sequential proton boost in that it "reduces the expected toxicity risk while maintaining good tumor coverage" in head and neck squamous cell carcinoma patients.
Patel S, et al. "Charged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis." Lancet Oncology 2014. Published online. "Compared with photon therapy, charged particle therapy [like proton beam therapy] could be associated with better outcomes for patients with malignant diseases of the nasal cavity and paranasal sinuses." In fact, researchers found that proton therapy demonstrated significantly higher disease-free survival at 5 years and locoregional control at longest follow-up.
Divya Yerramilli, et al. "Proton Beam Therapy (For CNS Tumors)." Adult CNS Radiation Oncology, 2018. "For patients with intracranial tumors, there are a variety of pathologies, ranging from incurable malignancies to benign tumors. Malignancies may require high doses for tumor control that far exceed certain normal tissue tolerance, and protons may allow dose escalation where it was previously unachievable with standard photon options."
James O. Galle, MD, et al. "Reirradiation with Proton Therapy for Recurrent Gliomas." International Journal of Particle Therapy, July 2015. For recurrent gliomas, reirradiation with proton therapy is an effective treatment option. Large treatment volumes are able to be irradiated to high doses with rates of toxicity similar to fractionated stereotactic radiation therapy.