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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.
Please find further academic resources organized by cancer type below.
Mendenhall N, et al. “Five-Year 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.
Marnitz S, et al. “Which technique for radiation is most beneficial for patients with locally advanced cervical cancer? Intensity modulated proton therapy versus intensity modulated photon treatment, helical tomotherapy and volumetric arc therapy for primary radiation – an intraindividual comparison.” Radiation Oncology 2015; 10:91. In this comparative study, intensity modulated proton therapy (IMPT) “offered the best sparing of [the patient’s] small bowel and rectum and therefore could contribute to a significant reduction of acute and late toxicity in cervical cancer treatment.”
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.&"
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.