Bibliography

Bibliography

Books

Proton Beam Therapy: How Protons Are Revolutionizing Cancer Treatment
(Yajnik S.,)

Here are discussed which conditions are suitable for treatment with proton therapy, how the treatment is delivered, and the current data supporting its use.

BREAST MALIGNANCIES

Axillary irradiation omitting axillary dissection in breast cancer: is there a role for shoulder-sparing proton therapy?
(Farace P. et al.)

Axillary radiation therapy and axillary lymph node dissection provide comparable local control and reduced lymphedema, but axillary irradiation could induce toxicity such as shoulder function impairment. proton therapy shows the potential to spare the shoulder without detrimental increase of the medium-to-low doses to the other normal tissues.

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Clinical Outcomes and Toxicity of Proton Radiotherapy for Breast Cancer.
(Verma V. et al. )

This study reviews the current state of proton therapy in the treatment of breast cancer and evaluates its role in the modern era of breast radiotherapy.

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Establishing Cost-Effective Allocation of Proton Therapy for Breast Irradiation.
(Mailhot Vega R.B. et al.)

Cardiac toxicity due to breast radiation therapy has been extensively reported and affects both life expectancy and QoL. proton therapy is able to limit the dose to the heart but is a costly treatment modality with limited access. This study uses a cost-effective analysis to help determine which patients may benefit the most from proton therapy referral.

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Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013.
(Taylor C.W. et al.)

Radiation therapy cures many women with breast cancer but can be toxic if the heart is exposed. This systematic review from 2003 to 2013 evaluates radiation doses to the heart from breast cancer radiation and shows that proton therapy delivers the lowest doses.

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New frontiers in proton therapy: applications in breast cancer.
(Orecchia R. et al.)

This paper reviews published data on proton therapy in the multimodality treatment of breast cancer so as to provide an overview of the advantages and critical issues relating to this irradiation modality. The authors show that proton therapy is able to optimize the dose to the target and reduce the irradiation of healthy tissues.

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Proton beam versus photon beam dose to the heart and left anterior descending artery for left-sided breast cancer.
(Lin L.L. et al.)

This study compared the dose to the heart, left anterior descending (LAD) artery and lung with proton and photon beam irradiation for left-sided early stage breast cancer. The dose to the heart was relatively low for both techniques, but proton therapy was associated with lower dose to the LAD, which is the critical structure for late radiation therapy effects.

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Can Proton Therapy Improve the Therapeutic Ratio in Breast Cancer Patients at Risk for Nodal Disease?
(Xu N. et al.)

Regional node irradiation in patients with invasive breast cancer often results in increased radiation exposure to organs at risk. This study shows that regional node target coverage is inferior with 3D conformal radiation therapy compared with either IMRT or 3D conformal RT+PT, with which OARs were exposed to less radiation. proton therapy offers both improved coverage of the regional lymph nodes and decreased dose to the heart, lung, and contralateral normal tissue.

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Early toxicity in patients treated with postoperative proton therapy for locally advanced breast cancer
(Cuaron J.J. et al.)

Postoperative proton therapy for patients with breast cancer is well tolerated, with acceptable rates of skin toxicity. proton therapy favorably spares normal tissue without compromising target coverage.

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Intensity modulated proton therapy for post mastectomy radiation of bilateral implant reconstructed breasts: a treatment planning study
(Jimenez R. et al.)

Delivery of post-mastectomy radiation (PMRT) in women with bilateral implants represents a technical challenge, particularly when attempting to cover regional lymph nodes. IMPT provides improved homogeneity to the chest wall and regional lymphatics with improved sparing of surrounding normal structures. It may also enable women with mastectomy to undergo radiation therapy without the need for delay in breast reconstruction.

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Partial breast radiation therapy with proton beam: 5-year results with cosmetic outcomes
(Bush D.A. et al.)

This paper is an update of a previous report of a phase 2 trial using proton therapy for partial breast irradiation in patients with early stage breast cancer. proton therapy produces excellent ipsilateral breast recurrence-free survival with minimal toxicity and excellent cosmetic results. The treatment proves to be adaptable to all breast sizes and lumpectomy cavity configurations.

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Phase II trial of proton beam accelerated partial breast irradiation in breast cancer
(Chang J. et al.)

Proton beam accelerated partial breast irradiation (PB-APBI) can be delivered with excellent disease control and tolerable skin toxicity to properly selected patients with early-stage breast cancer. Multiple-field PB-APBI may achieve a high rate of good-to-excellent cosmetic outcomes.

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Postoperative proton radiotherapy for localized and locoregional breast cancer: potential for clinically relevant improvements?
(Ares C. et al.)

When complex-target irradiation is needed, 3D conformal radiation therapy often compromises the target coverage and increases the dose to OARs, and IMRT increases the integral dose. On the other hand, IMPT improves target coverage and reduction of low doses to OARs, potentially reducing the risk of late-toxicity.

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Proton beam versus photon beam dose to the heart and left anterior descending artery for left-sided breast cancer
(Lin L.L. et al.)

The purpose of this study was to compare the dose to the heart, left anterior descending (LAD) artery and lung between proton therapy and radiation therapy for left-sided early stage breast cancer. proton therapy was associated with lower dose to the LAD, which is the critical structure for late radiation therapy effects, compared to even the most optimized photon beam plan with deep inspiration breath hold and IMRT.

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Proton radiotherapy for chest wall and regional lymphatic radiation; dose comparisons and treatment delivery
(MacDonald S.M. et al.)

The delivery of post-mastectomy radiation therapy can be challenging for patients with left-sided breast cancer that have undergone mastectomy. Proton radiation therapy enables delivery of radiation to the chest wall and regional lymphatics, including the internal mammary nodes, without compromise of coverage and with improved sparing of surrounding normal structures.

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Proton therapy for breast cancer after mastectomy: early outcomes of a prospective clinical trial
(MacDonald S.M. et al.)

Dosimetric planning studies have described potential benefits for the use of proton therapy for locally advanced breast cancer. This study shows that proton therapy for postmastectomy radiotherapy is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal radiotherapy delivery using standard methods.

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Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients
(Mast M.E. et al.)

IMPT could significantly decrease the dose to the heart and the region of the left anterior descending coronary artery compared to tangential IMRT with breath- hold, and could be particularly useful for patients at high risk for major coronary events.

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CENTRAL NERVOUS SYSTEM MALIGNANCIES

Differential dosimetric benefit of proton beam therapy over intensity modulated radiotherapy for a variety of targets in patients with intracranial germ cell tumors.
(Park J. et al.)

Dosimetric measures were performed to compare proton therapy and IMRT for intracranial germ cell tumors arising in various locations of the brain. Compared to IMRT, proton therapy provided superior target volume coverage and saved more normal tissue, with both passive scanning and spot scanning techniques.

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High-dose proton-based radiation therapy in the management of spine chordomas: outcomes and clinicopathological prognostic factors.
(Rotondo R.L. et al. )

Spinal chordomas can have high local recurrence rates after surgery with or without conventional dose RT. This paper shows that high-dose proton therapy can be an effective treatment: among patients undergoing surgery, those with primary chordomas undergoing preoperative RT, en bloc resection, and postoperative radiation therapy boost have the highest rate of local tumor control.

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Brainstem-sparing craniospinal irradiation delivered with pencil beam scanning proton therapy
(Hill-Kayser C. and Kirk M.)

Delivery of craniospinal irradiation (CSI) is a curative approach to recurrent ependymoma but is associated with risks from reirradiation particularly of the brainstem. PBS proton therapy allows delivery of CSI with sparing of normal tissue and compares favorably to previously described methods using X-rays.

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Definitive high-dose photon/proton radiotherapy for unresected mobile spine and sacral chordomas
(Chen Y.L. et al.)

The purpose of this study is to report the results of high-dose proton based definitive radiotherapy for unresected spinal chordomas. The results support the use of high-dose definitive radiotherapy for patients with medically inoperable or otherwise unresected, mobile spine or sacrococcygeal chordomas.

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Effectiveness and safety of spot scanning proton radiation therapy for chordomas and chondrosarcomas of the skull base: first long-term report
(Ares C. et al.)

Spot-scanning based proton therapy for skull-base chordomas and chondrosarcomas appears to be effective and safe. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering PT, complication-free, tumor control and survival rates are comparable.

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Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas and other sarcomas
(Delaney T.F.)

Negative surgical margins are uncommon for spine sarcomas, hence adjuvant radiotherapy may be recommended. However, the dose to the tumor may be constrained by the spinal cord, nerves, and visceral tolerance. This study shows that local control with high dose photon/proton radiation therapy is high in patients with primary tumors, and late morbidity appears to be acceptable.

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Outcomes of proton therapy for patients with functional pituitary adenomas
(Wattson D.A. et al.)

This study evaluates the efficacy and toxicity of proton therapy for functional pituitary adenomas (FPAs). Proton irradiation is an effective treatment for FPAs, with hypopituitarism remaining the primary adverse effect.

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Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas
(Delaney T.F. et al.)

Radiotherapy for spine sarcomas is constrained by spinal cord, nerve, and viscera tolerance. Negative surgical margins are uncommon hence low doses are recommended. A Phase II clinical trial evaluated high-dose photon/proton XRT for spine sarcomas: local control appears high in patients radiated at the time of primary presentation.

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Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma
(Brown A.P. et al.)

This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with proton CSI. Patients treated with proton therapy experienced less treatment-related morbidity than patients treated with conventional RT, including fewer acute gastrointestinal and hematologic toxicities.

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Proton therapy for atypical meningiomas
(McDonald M.W. et al.)

This paper reports clinical outcomes of proton therapy in patients with World Health Organization grade 2 (atypical) meningiomas. Fractionated proton therapy was associated with favorable tumor control rates.

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Proton therapy for low-grade gliomas: Results from a prospective trial
(Shih H.A. et al.)

This prospective study evaluates the potential treatment toxicity and progression-free survival in patients with low-grade glioma who received treatment with PT. Patients tolerate proton therapy well and only a subset develops neuroendocrine deficiencies.

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Proton therapy for skull base chordomas: an outcome study from the university of Florida proton therapy institute
(Deraniyagala R.L. et al.)

Skull base chordoma is a rare, locally aggressive tumor located adjacent to critical structures. Gross total resection is difficult to achieve, and proton therapy has the con- formal advantage of delivering a high postoperative dose to the tumor bed. The results obtained in this study are promising in terms of tumor control, and the toxicity profile is acceptable.

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Reirradiation for recurrent malignant brain tumor with radiotherapy or proton beam therapy. Technical considerations based on experience at a single institution
(Mizumoto M. et al.)

Radiotherapy for recurrent malignant brain tumors is usually limited because of the dose tolerance of the normal brain tissue. This study shows that reirradiation for recurrent malignant brain tumor using conventional RT, stereotactic radiation therapy or proton therapy was feasible and effective in selected cases.

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Spot scanning proton therapy for malignancies of the base of skull: treatment planning, acute toxicities and preliminary clinical outcomes
(Grosshans D.R. et al.)

This study describes treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, treatment was well tolerated and disease control rates and toxicity profiles were favorable.

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Spot-scanning based Proton Therapy for Intracranial Meningioma: Long-term Results from the Paul Scherrer Institute
(Weber D.C. et al.)

In this study about the long-term clinical results of spot scanning proton therapy for intracranial meningiomas, proton therapy was proved to be a safe and effective treatment modality for patients with untreated, recurrent, or incompletely resected tumors.

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Spot-scanning based Proton Therapy for Intracranial Meningioma: Long-term Results from the Paul Scherrer Institute
(Weber D.C. et al.)

In this study about the long-term clinical results of spot scanning proton therapy for intracranial meningiomas, proton therapy was proved to be a safe and effective treatment modality for patients with untreated, recurrent, or incompletely resected tumors.

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GASTROINTESTINAL MALIGNANCIES

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.
(Chuong M.D. et al. )

If radiation therapy is an essential part of the treatment for esophageal cancer, the dose must be focused on the tumor to reduce toxicities to the heart and lungs. Technological advancements like IMRT have decreased the risk of such toxicities, but a growing body of evidence indicates that further risk reductions are achieved with PT.

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Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis
(Makishima H. et al.)

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton therapy using clinical data and adaptive dose-volume histogram analysis. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons; hence proton therapy is a promising treatment modality for the management of esophageal cancer.

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Gastrointestinal cancer: non-liver proton therapy for gastrointestinal cancers
(Plastaras J.P., Dionisi F. and Wo J.Y.)

Multimodality therapy for gastrointestinal cancers carries considerable risk for toxicity, as they inherently occur amid visceral organs particularly sensitive to radiotherapy. In many sites, local recurrences after chemoradiation pose a particular challenge, and reirradiation in these sites may be done successfully with PT.

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Intensity modulated proton beam radiation for brachytherapy in patients with cervical carcinoma
(Clivio A. et al.)

In patients who are not eligible for brachytherapy, IMPT as a boost technique additionally to external beam radiation therapy provides good target coverage and conformity and superior dose-volume parameters, compared with recommendations to MRI-guided brachytherapy. For selected patients, IMPT might be a valid alternative to brachytherapy and also superior to reference VMAT plans.

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Pencil-beam scanning proton therapy for anal cancer: a dosimetric comparison with intensity-modulated radiotherapy
(Ojerholm E. et al.)

Concurrent chemoradiotherapy cures most patients with anal squamous cell carcinoma at the cost of significant treatment-related toxicities. If IMRT reduces side effects compared to older techniques, proton therapy offers additional advantages by reducing low dose radiation to important organs at risk.

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Protons offer reduced bone marrow, small bowel, and urinary bladder exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer
(Colaco R.J. et al.)

This study compares 3D conformal RT, IMRT and proton therapy plans in patients undergoing neoadjuvant chemoradiation for resectable rectal cancer. By reducing bone marrow exposure, proton therapy may reduce the acute hematologic toxicity of neoadjuvant chemoradiation.

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GENERAL ARTICLES

Assessment of radiation-induced second risks in proton therapy and IMRT for organs inside the primary radiation field
(Paganetti H. et al.)

Second malignancies in radiation therapy occur mainly within the beam path. Compared to traditional radiotherapy. proton therapy can significantly reduce the risk of developing an in-field second malignancy depending on treatment planning parameters.

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Comparative analysis of second malignancy risk in patients treated with Proton Therapy versus conventional Photon Therapy
(Chung C.S. et al.,)

Preliminary results here indicate that the use of proton therapy is associated with a significantly lower risk of secondary malignancies compared to RT, even if additional analyses are required given the prolonged latency period for the development of radiation-induced cancers.

Evaluation of potential proton therapy utilization in a market-based environment
(Dvorak T., Wazer D.E.,)

Existing utilization patterns of highly conformal radiation therapy were used to estimate that about 1/3 of a patients irradiated annually at the institution could be potentially treated with PT, with an incremental cost of 20% across the entire treated patient population.

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Radiation-induced cancers from modern radiotherapy techniques: intensity-modulated radiotherapy versus proton therapy
(Yoon M. et al.)

Comparisons of organ-specific equivalent dose were made to assess the risk of secondary cancer after IMRT and proton therapy in patients with prostate and head-and- neck cancer. The results showed the risk was either significantly lower with proton therapy or at least did not exceed the risk induced by conventional IMRT.

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When to wait for more evidence? Real options analysis in proton therapy
(Grutters J. et al.,)

As it is often unclear whether to adopt a new technology for cancer treatment or to wait for more evidence, a technique originating from financial economics called "real options analysis" can help make this trade-off. Regarding proton therapy, adopt and trial was found to be the preferred option.

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HEAD AND NECK MALIGNANCIES

Advances in radiation oncology for the management of oropharyngeal tumors
(Gunn G.B. and Frank S.J.)

The major benefits of modern radiation therapy in the treatment of oropharyngeal cancer are reduced xerostomia and better quality of life. Treatment-related toxicities must be kept in mind, particularly because most patients are expected to have a high probability of long-term survival after treatment. In this context, IMPT seems to provide additional advantages over IMRT by reducing radiation beam-path toxicities.

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Effectiveness of robust optimization in intensity-modulated proton therapy planning for head and neck cancers
(Liu W. et al.)

IMPT is highly sensitive to uncertainties in beam range and patient setup, which are conventionally addressed using geometrically expanded planning target volume (PTV). This paper evaluates IMPT for head & neck cancer and shows that robust optimization based on clinical target volume (CTV) provides significantly more robust dose distributions to targets and organs than PTV-based conventional optimization.

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Gastrostomy Tubes Decrease by Over 50% With Intensity Modulated Proton Therapy (IMPT) During the Treatment of Oropharyngeal Cancer Patients: A Case­Control Study
(Frank S.J. et al.,)

A potential advantage of IMPT over IMRT in the treatment of oropharyngeal carcinoma (OPC) is a decrease in toxicity. This study quantifies the incidence of gastrostomy tube use in OPC patients treated with IMPT and compares it to gastrostomy use in patients treated with IMRT. Preliminary data suggest that IMPT has a lower rate of grade 3 dysphagia.

High-dose proton beam therapy for sinonasal mucosal malignant melanoma
(Fuji H. et al.)

The significance of definitive radiotherapy for sinonasal mucosal melanoma (SMM) is still controversial. This study evaluates the role of high-dose proton therapy in patients with SMM. Findings suggest that high-dose proton therapy is an effective local treatment that is less invasive than surgery but with comparable outcomes.

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Proton radiation therapy for head and neck cancer
(Chan A. and Liebsch N.)

Conventional radiation therapy can be associated with significant acute and long-term treatment-related toxicities in the treatment of head & neck tumors. Superior dose localization properties of proton radiation therapy allow smaller volumes of normal tissue to be irradiated than is feasible with any photon technique and initial clinical experience with proton therapy appears promising.

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Proton radiation therapy for head and neck cancer: a review of the clinical experience to date
(Holliday E.B., Frank S.J.)

Proton therapy has been used for cancer treatment since the 1950s, and both the number of patients and the variety of tumors treated have increased since then. Great interest has been expressed in evaluating whether proton therapy can improve outcomes, especially early and late toxicity, when used in the treatment of head and neck malignancies. This review summarizes the progress made to date in addressing this question.

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Proton therapy for head and neck adenoid cystic carcinoma: initial clinical outcomes
(Linton O.R. et al.)

The purpose of this study is to report outcomes of proton therapy in head and neck adenoid cystic carcinoma. Initial outcomes are encouraging.

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Proton therapy for head and neck cancer
(Lukens J.N., Lin A. and Hahn S.M.)

Proton therapy for head and neck cancer is an area of active research, and the subject of heightened scrutiny due to the significant associated cost. This article highlights recent research into proton dosimetry, its clinical benefit relative to other advanced radiotherapy modalities, key safety and cost considerations.

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Protons in head-and-neck cancer: bridging the gap of evidence
(Ramaekers B.)

Cost-effectiveness analysis based on normal tissue complication probability models and planning studies proved feasible and informative and enables the analysis of individualized strategies. The increased effectiveness of IMPT does not seem to outweigh the higher costs for all head-and-neck cancer patients. However, when assuming equal survival among both modalities, there seems to be value in identifying those patients for whom IMPT is cost-effective.

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Systematic review and meta-analysis of radiotherapy in various head and neck cancers: comparing photons, carbon- ions and protons
(Ramaekers B. et al.)

This study synthesizes and compares available evidence considering the effectiveness of carbon-ion, proton and photon radiotherapy for head and neck cancer.

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The potential benefit of radiotherapy with protons in head and neck cancer with respect to normal tissue sparing: a systematic review of literature
(Van de Water T. et al.)

Protons have the potential for a significantly lower normal tissue dose, while keeping similar or better target coverage. Scanned IMPT probably offers the most advantage and will allow for a substantially lower probability of radiation-induced side effects.

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LIVER MALIGNANCIES

Clinical decision tool for optimal delivery of liver stereotactic body radiation therapy: Photons versus protons.
(Gandhi S.J. et al.)

Stereotactic body radiation therapy for liver tumors is often limited by liver dose constraints. When feasible, proton therapy should be considered as a treatment modality of choice to allow maximal liver sparing for dome and central tumors >3 cm and any tumor >5 cm if photon plans fail to achieve adequate coverage or exceed the mean liver threshold.

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Current and future treatments for hepatocellular carcinoma.
(Schlachterman A. et al. )

HCC has no definitively curative treatment: many treatment and management modalities exist with differing (dis-)advantages. This paper systematically discusses the current treatment modalities available for HCC, detailing relevant clinical data, risks and rewards and overall outcomes for each approach.

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Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.
(Hong T.S. et al.)

To evaluate the efficacy and safety of high-dose hypofractionated proton therapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. High-dose hypofractionated proton therapy demonstrated high local control rates safely safely, supporting ongoing phase III trials of radiation in both types of tumors.

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Proton beam therapy for metastatic liver tumors.
(Fukumitsu N. et al.)

The purpose of this study was to investigate the safety and efficacy of proton therapy for the treatment of metastatic liver tumors. Proton therapy is a potentially safe and effective treatment for this clinical indication.

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Randomized Clinical Trial Comparing Proton Beam Radiation Therapy with Transarterial Chemoembolization for Hepatocellular Carcinoma: Results of an Interim Analysis.
(Bush D.A. et al. )

The authors report a trend toward improved local control and improved progression-free survival with proton therapy compared to transcatheter arterial chemoembolization (TACE), the ‘standard treatment’ for unresectable hepatoma.

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A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma
(Masato A.)

This study reports on a prospective phase I study of `in situ' tumor vaccination using CalTUMP, a newly developed immunoadjuvant, following local proton therapy for HCC to prevent the cancer recurrence. The treatment was feasible and safe in patients with heavily pre-treated HCC.

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Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis
(Lee S.U. et al.)

This study evaluates the clinical effectiveness and safety of proton therapy in advanced HCC patients with portal vein tumor thrombosis (PVTT). It suggests that proton therapy could improve local progression-free survival, relapse-free survival, and overall survival in advanced HCC patients with PVTT, and that it is feasible and safe for these patients.

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Is there a role for proton therapy in the treatment of hepatocellular carcinoma? A systematic review
(Dionisi F., Widesott L., Lorentini S., Amichetti M.)

This paper reviews the literature concerning the systematic use of proton therapy in the treatment of HCC, focusing on clinical results and technical issues. The literature search was conducted according to a specific protocol in the Medline and Scopus databases by two independent researchers covering the period of 1990-2012.

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Normal liver tissue sparing by intensity-modulated proton stereotactic body radiotherapy for solitary liver tumours
(Petersen J. et al.)

Stereotactic body radiotherapy (SBRT) is often the preferred treatment for advanced liver tumors that are out of range of surgical resection or radiofrequency ablation. However, only a minority of patients may be candidates because of the limited radiation tolerance of normal liver and intestine. Due to the favorable depth-dose characteristics of protons, a considerable sparing of normal tissue can be obtained using proton-based SBRT for solitary liver tumors.

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Phase I dose-escalation study of proton beam therapy for inoperable hepatocellular carcinoma
(Kim T.H. et al.)

The purpose of this study is to determine the optimal dose of proton therapy in hepatocellular carcinoma patients (HCC). proton therapy is safe and effective in patients with inoperable HCC, with at least 78 GyE10 of EQD2 needed to achieve sufficient local tumor control.

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Proton beam therapy for unresectable intrahepatic cholangiocarcinoma
(Ohkawa A. et al.)

Treatment for unresectable intrahepatic cholangiocarcinoma (ICC) has not been established. The aim of this study is to evaluate the outcomes of proton therapy for patients with unresectable ICC. The results suggest that long-term survival can be achieved for patients without distant metastasis.

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Proton therapy for hepatocellular carcinoma
(Ling T.C. et al.)

Proton therapy has seen an increasing role in the treatment of hepatocellular carcinoma (HCC). This review discusses the physical attributes and rationale for proton therapy in HCC. It also reviews recent literature regarding clinical outcomes of using proton therapy for the treatment of HCC.

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Proton-beam therapy for hepatocellular carcinoma associated with portal vein tumor thrombosis
(Sugahara S. et al.)

The prognosis of patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis is extremely poor, as effective treatment options are limited. This paper shows that proton therapy improves local control and significantly prolongs survival in these patients.

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Risk of second malignant neoplasm following proton versus intensity-modulated photon radiotherapies for hepatocellular carcinoma.
(Taddei P.J. et al.)

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world, but radiotherapy remains uncommon because of the likelihood of radiation-in- duced liver disease. This study suggests that proton therapy may reduce the risk of second malignant neoplasms compared to radiation therapy for some HCC patients.

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The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial
(Bush D.A. et al.)

Proton therapy may provide useful local-regional treatment for hepatocellular carcinoma (HCC). In this study, proton therapy was found to be a safe and effective local-regional therapy for inoperable HCC. A randomized controlled trial to compare its efficacy to a standard therapy has been initiated.

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The use of proton therapy in the treatment of gastrointestinal cancers: liver
(Dionisi F. and Ben-Josef E.)

This article reviews the role of proton therapy in the treatment of primary liver cancer focusing on hepatocellular carcinoma (HCC). The dose-sparing physical properties of protons are of great advantage in the treatment of HCC.

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LUNG CANCER AND THORACIC MALIGNANCIES

Ablative dose proton beam therapy for stage I and recurrent non-small cell lung carcinomas : Ablative dose PBT for NSCLC.
(Lee S.U. et al. )

Authors evaluate the efficacy and safety of ablative dose hypofractionated proton therapy for patients with stage I and recurrent non-small cell lung carcinoma. The studied treatment modality was safe and promising for stage I and recurrent NSCLC.

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Consensus Statement on Proton Therapy in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer.
(Chang J.Y. et al.)

This consensus report from the PTCOG Thoracic Subcommittee can be used to guide clinical practice and indications for PT, insurance approval, and clinical or translational research directions.

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Early experience with intensity modulated proton therapy for lung-intact mesothelioma: A case series.
(Pan H.Y. et al. )

IMPT produced lower mean doses to the contralateral lung, heart, esophagus, liver and ipsilateral kidney, and increased contralateral lung sparing when mediastinal boost was required for nodal disease. The authors conclude that IMPT is feasible for routine care of patients with lung-intact malignant pleural mesothelioma.

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Preoperative Proton Beam Therapy for Thymoma: A Case Report.
(Kojima H. et al. )

This paper assesses the case of a locally advanced thymoma treated with preoperative followed by complete surgical resection. The experience suggests that preoperative proton therapy may be an effective modality for reducing tumor size, facilitating complete resection, and preventing toxicity of radiation therapy.

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Prospective Study of Patient-Reported Symptom Burden in Patients With Non-Small-Cell Lung Cancer Undergoing Proton or Photon Chemoradiation Therapy.
(Wang X.S. et al.)

Most patients with advanced NSCLC develop radiation-induced symptoms despite careful treatment optimization. This study reports that patients receiving proton therapy have significantly less severe symptoms than those receiving IMRT or 3D conformal RT, even with a significantly higher radiation target dose.

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Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions.
(Berman A.T. et al.)

This extensive review presents the basic physics of proton therapy for lung cancer, and the existing data for early-stage and locally-advanced NSCLC as well as in special situations such as re-irradiation and post-operative RT. It also covers technical challenges such as anatomic changes and motion management, and future directions for proton therapy for lung cancer, including PBS.

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Reducing Dose Uncertainty for Spot-Scanning Proton Beam Therapy of Moving Tumors by Optimizing the Spot Delivery Sequence.
(Li H. et al.)

The aim of this study was to develop and validate a new delivery strategy for reducing the respiratory motion-induced dose uncertainty of spot-scanning PT. The authors concluded that optimizing the delivery sequence can reduce the dose uncertainty, assuming the 4D-CT is a true representation of the patients' breathing patterns.

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Accelerated dose escalation with proton beam therapy for non-small cell lung cancer
(Gomez D.R., Chang J.Y.)

Local tumor control remains challenging in many cases of NSCLC, large or centrally located tumors. Concurrent chemotherapy and radiation can maximize tumor control and survival but a large proportion of patients cannot tolerate this therapy. The energy distribution of protons can be exploited to reduce involuntary irradiation of normal tissue and the resulting side effects.

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Adaptive/Nonadaptive Proton Radiation Planning and Outcomes in a Phase II Trial for Locally Advanced Non-small Cell Lung Cancer
(Koay E.J. et al.)

Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve same local, regional, and distant control and overall survival as non-adaptive plans, even in patients with larger tumors.

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Clinical implementation of intensity modulated proton therapy for thoracic malignancies
(Chang J.Y. et al.)

This paper reports early experience with IMPT for thoracic malignancies in terms of motion analysis and management, plan optimization and robustness, and quality assurance. IMPT using 4D CT-based planning, motion management, and optimization was implemented successfully and met quality assurance parameters for treating challenging thoracic cancers

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Comparison of dose-volume histograms between proton beam and X-ray conformal radiotherapy for locally advanced non- small-cell lung cancer
(Ohno T. et al.)

The purpose of this study was to compare the parameters of the dose-volume histogram between proton therapy and conformal radiation therapy for locally advanced NSCLC. The number of inadequate X-ray plans increased in cases with advanced nodal stage. This study indicated that some patients who cannot receive radiation therapy may be able to be treated using PT.

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Definitive reirradiation for locoregionally recurrent non-small cell lung cancer with proton beam therapy or intensity modulated radiation therapy: predictors of high-grade toxicity and survival outcomes
(McAvoy S.A. et al.)

Intrathoracic recurrence of NSCLC after initial treatment remains a dominant cause of death. IMRT and proton therapy are options for treating recurrent NSCLC, but rates of locoregional recurrence and distant metastasis are high, and patients should be selected carefully to maximize the benefit of additional aggressive local therapy while minimizing the risk of adverse side effects.

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Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer
(Colaco R.J. et al.)

Concurrent chemoradiotherapy is the standard of care in patients with limited-stage SCLC. While treatment with conventional radiation therapy is associated with high toxicity rates (particularly acute esophagitis and pneumonitis), this study shows that proton therapy with radical intent was well tolerated, with no cases of acute toxicities and better sparing of lung and esophagus.

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Early experience with intensity modulated proton therapy for lung-intact mesothelioma: A case series
(Pan H.Y. et al.)

The purpose of this study was to describe our experience implementing IMPT for lung-intact malignant pleural mesothelioma, including patient selection, treatment planning, dose verification, and process optimization. Results showed that IMPT is feasible.

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Early findings on toxicity of proton beam therapy with concurrent chemotherapy for nonsmall cell lung cancer
(Sejpal S.)

Concurrent chemoradiation therapy, the standard of care for locally advanced NSCLC, can cause life-threatening pneumonitis and esophagitis. Whereas radiation therapy often cannot be given at tumoricidal doses without toxicity to proximal normal tissue, higher doses of proton radiation can be delivered with a lower risk of esophagitis and pneumonitis.

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Feasibility of proton beam therapy for reirradiation of locoregionally recurrent non-small cell lung cancer
(McAvoy S.A. et al.)

Options are limited for patients with intrathoracic recurrence of NSCLC who previously received radiation. This paper reports 5-year experience with the toxicity and efficacy of proton therapy for reirradiation and shows that proton therapy is an option for treating recurrent NSCLC.

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High-dose concurrent chemo-proton therapy for Stage III NSCLC: preliminary results of a Phase II study
(Oshiro Y. et al.)

High-dose proton therapy with concurrent chemotherapy is safe to use in the treatment of unresectable stage III NSCLC.

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High-dose hypofractionated proton beam radiation therapy is safe and effective for central and peripheral early-stage non- small cell lung cancer: results of a 12-year experience at Loma Linda University Medical Center
(Bush D.A. et al. )

High-dose hypofractionated proton therapy achieves excellent outcomes for central or peripheral lung carcinomas. The 70-Gy regimen has been adopted as standard therapy for T1 tumors at Loma Linda. Larger T2 tumors show improved outcomes with higher doses, suggesting that better results could be seen with intensified treatment.

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High-dose proton beam therapy for stage I non-small cell lung cancer: Clinical outcomes and prognostic factors
(Makita C. et al.)

Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located NSCLC. The aim of this study was to evaluate the safety and efficacy of two proton therapy protocols for stage I NSCLC and to determine prognostic factors. Both high-dose proton therapy protocols achieved high local control rates with tolerable toxicities.

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Phase 2 study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer
(Chang J. et al.)

In this study, authors show that using proton therapy to escalate the radiation dose to the tumor could improve the toxicity of conventional concurrent chemoradiation therapy for stage III non-small cell lung cancer.

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Proton beam therapy for locally advanced lung cancer: A review
(Schild S.E. et al.)

This review examines proton therapy as a component of a combined modality program for locally advanced lung cancers. It is specifically written for non-radiation oncologists who desire greater understanding of this newer treatment modality, and shows that newer forms of radiotherapy such as proton therapy should positively impact the care of lung cancer patients.

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Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions
(Berman A.T., James S.S. and Rengan R.)

Lung cancer is the leading cancer cause of death in the US. Radiotherapy is an essential component of the definitive treatment of early-stage and locally- advanced lung cancer, and the palliative treatment of metastatic lung cancer. proton therapy has the potential to decrease the toxicity of radiotherapy and subsequently to improve the therapeutic ratio.

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Proton SBRT for medically inoperable stage I NSCLC
(Westover K.D. et al.)

The physical properties of proton beam radiation may offer advantages for treating patients with NSCLC. This study also shows its utility for the treatment of medically inoperable stage I NSCLC patients with stereotactic body radiation therapy (SBRT).

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Proton therapy with concurrent chemotherapy for non-small-cell lung cancer: technique and early results
(Hoppe B.S. et al.)

Proton therapy can deliver a more conformal dose distribution than radiation therapy and may allow safe dose escalation in stage III lung cancer. Early outcomes are presented here for patients who received mediastinal proton therapy with concurrent chemotherapy for NSCLC, which was associated with acceptable toxicity.

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Results of proton beam therapy without concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer
(Oshiro Y. et al.)

This study was performed retrospectively to evaluate the outcomes of patients with stage III NSCLC after proton therapy alone. The prognosis of patients with unresectable stage III NSCLC is poor without chemotherapy. Our data suggest that high-dose proton therapy is beneficial and tolerable for these patients.

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LYMPHOMAS

Proton therapy for Hodgkin lymphoma
(Rutenberg M.S., Flampouri S., Hoppe B.S.)

This paper reviews the outcomes of Hodgkin lymphoma treated with proton therapy and discusses the ability of protons to reduce radiation dose to OARs and the impact on the most significant late complications related to the treatment.

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Proton therapy in the management of non-Hodgkin lymphoma
(Sachsman S. et al.)

This study reviews a single institution's experience managing patients with non-Hodgkin lymphoma (NHL) treated with PT. proton therapy proved to be a feasible and effective treatment for NHL with favorable early outcomes.

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OCULAR MALIGNANCIES AND BENIGN CONDITIONS

Neoadjuvant proton beam irradiation followed by transscleral resection of uveal melanoma in 106 cases.
(Willerding G.D. et al.)

This study evaluates the clinical results after neoadjuvant proton therapy followed by transscleral resection of large uveal melanoma. Neoadjuvant proton therapy may help to prevent local recurrence after transscleral resection: additional vitreoretinal surgery was frequently needed in but the majority of patients avoided enucleation and functional blindness.

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Outcomes of treatment with stereotactic radiosurgery or proton beam therapy for choroidal melanoma.
(Sikuade M.J. et al. )

This study shows that the use of stereotactic radiosurgery and proton therapy has proven to be effective to treat large choroidal melanoma of tumors unsuitable for plaque radiotherapy. Over a 10-year period, patients treated with proton therapy retain better vision post-operatively.

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Treatment of Retinoblastoma: The Role of External Beam Radiotherapy.
(Kim J.Y. et al. )

Due to the risk of RT-related secondary cancers in children, EBRT is avoided as much as possible in the treatment of constitutional retinoblastoma. When EBRT is required, proton therapy is one method that can reduce the radiation dose to the adjacent orbital bone while maintaining an adequate dose to the tumor.

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Charged particle radiation therapy for uveal melanoma: a systematic review and meta-analysis
(Wang Z. et al.)

The present analysis evaluates the efficacy and adverse effects of charged particle therapy (protons, helium ions, or carbon ions) for uveal melanoma. CPT was associated with lower retinopathy and cataract formation rates. Better outcomes may also be possible in terms of local recurrence, retinopathy, and cataract formation rates.

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Local recurrence after primary proton beam therapy in uveal melanoma: Risk factors, retreatment approaches and outcome
(Seibel I. et al.)

This study evaluates the risk factors, recurrence rates, re-treatments, and long-term patient outcomes following proton therapy for uveal melanoma. It is shown that each globe retaining re-treatment approach can result in satisfying local tumor control. In case of early detection of local recurrence preservation of the globe can be warranted.

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Outcomes of proton therapy for the treatment of uveal metastases
(Kamran S.C. et al.)

Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. proton therapy is an effective and efficient means of treating uveal metastases, with minor acute adverse effects.

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Proton beam therapy for presumed and confirmed iris melanomas: a review of 36 cases
(Rahmi A. et al.)

This paper reports the clinical features and outcomes of iris melanomas treated by PT. proton therapy appears to be the treatment of choice for the conservative treatment of iris melanomas with excellent tumor control and an acceptable complication rate.

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Proton beam therapy leads to excellent local control rates in choroidal melanoma in the intermediate fundus zone
(Schönfeld S. et al.)

This study evaluates long-term outcomes of proton therapy in the treatment of choroidal melanoma of the intermediate zone of the fundus and demonstrates the effectiveness of proton therapy in tumor control and preservation of the globe in the analyzed patients.

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Proton radiation therapy for the treatment of retinoblastoma
(Mouw K.W. et al.)

This study investigates long-term disease and toxicity outcomes for pediatric retinoblastoma patients treated with PT. Long-term follow-up of retinoblastoma patients treated with proton therapy demonstrates that it can achieve high local control rates, even in advanced cases, with many patients retaining useful vision in the treated eye.

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PANCREATIC MALIGNANCIES

Proton therapy for pancreatic cancer.
(Nichols R.C. et al.)

RT is commonly used to treat pancreatic malignancies although its ultimate utility is compromised by the exquisitely radiosensitive normal tissues surrounding the pancreas. That is why protons appear to be a superior modality for radiation therapy delivery to patients with unresectable tumors or for postoperative RT.

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Spot-scanned pancreatic stereotactic body proton therapy: A dosimetric feasibility and robustness study.
(Sio T.T. et al. )

This paper explores the dosimetric potential of spot-scanned stereotactic body proton therapy (SBPT) for pancreatic cancer, and provides a critical basis for clinical translation of spot size, optimization technique, and OTV expansion for pancreatic SBPT.

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A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas
(Thompson R.F. et al.)

Uncontrolled local growth is the cause of death in ~ 30% of patients with unresectable pancreatic cancers. In this study, the authors investigate the potential use of double scattering and PBS proton therapy in limiting dose to critical OARs. If proton therapy does not appear to reduce OAR volumes receiving high dose, it is however able to reduce the treated volume receiving low-intermediate doses.

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Phase I study of preoperative short-course chemoradiation with proton beam therapy and capecitabine for resectable pancreatic ductal adenocarcinoma of the head
(Hong T.S. et al.)

This study shows the safety and feasibility of 1 week of chemoradiation with proton therapy and capecitabine followed by early surgery.

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Proton therapy with concomitant capecitabine for pancreatic and ampullary cancers is associated with a low incidence of gastrointestinal toxicity
(Nichols R.C. Jr. et al.)

Proton therapy may allow for significant sparing of the small bowel and stomach and is associated with a low rate of gastrointestinal toxicity. The favorable toxicity profile associated with proton therapy may allow for radiotherapy dose escalation, chemotherapy intensification, and possibly increased acceptance of preoperative radiotherapy.

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Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer
(Nichols R.C. Jr et al.)

The potential role for adjuvant proton therapy for resected pancreatic head cancer was assessed in this study. By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation.

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PEDIATRIC MALIGNANCIES

Comparing Intelligence Quotient Change After Treatment With Proton Versus Photon Radiation Therapy for Pediatric Brain Tumors.
(Kahalley L.S. et al.)

This paper compares long term IQ change in pediatric patients with brain tumors treated with proton therapy or RT. It remains unclear if proton therapy results in clinically meaningful cognitive sparing that significantly exceeds that of modern radiation therapy protocols. Additional long-term data are needed.

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Cost effectiveness of proton versus photon radiation therapy with respect to the risk of growth hormone deficiency in children.
(Mailhot Vega R. et al.)

Proton therapy may prove to be cost effective if chronic medical complications can be avoided. This paper is the first evidence-based guide for identifying children with brain tumors who may benefit the most from proton therapy with respect to endocrine dysfunction: proton therapy proves to be more cost effective when the hypothalamus can be spared.

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Paediatric brain tumours: A review of radiotherapy, state of the art and challenges for the future regarding protontherapy and carbontherapy.
(Laprie A. et al. )

Brain tumors are the most frequent radiation therapy indications in paediatrics, with frequent late toxic effects on cognitive, osseous, visual, auditory and hormonal systems. Both proton therapy and carbon ion therapy show promising results, with the benefit of decreasing late effects without altering global survival.

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Pencil beam scanning proton therapy for pediatric intracranial ependymoma.
(Ares C. et al.)

Data indicate the safety and effectiveness of proton therapy in this study assessing the clinical outcomes and late side effects of pencil beam scanning proton therapy delivered to children with intracranial ependymoma.

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Proton Therapy for Pediatric Hodgkin Lymphoma.
(Wray J. et al. )

Compared to photon RT, proton therapy reduces the radiation dose to OAR, which is expected to translate into less long-term morbidity. proton therapy for pediatric Hodgkin lymphoma shows no short-term severe toxicity and yields similar short-term control to recently published large multi-institutional clinical trials.

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Proton versus conventional radiotherapy for pediatric salivary gland tumors: Acute toxicity and dosimetric characteristics.
(Grant S.R. et al. )

This retrospective study evaluates acute toxicity profiles and dosimetric data for children with salivary gland tumors treated with adjuvant photon/electron-based radiation therapy or proton therapy. proton therapy was associated with a more favorable acute toxicity and dosimetric profile. Continued follow-up is needed to identify long-term toxicity and survival data.

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Tumour control and Quality of Life in children with rhabdomyosarcoma treated with pencil beam scanning proton therapy.
(Leiser D. et al.)

This paper assesses the clinical outcomes in children with rhabdomyosarcoma (RMS) treated with pencil beam scanning PT. PBS proton therapy led to excellent outcomes, with minimal late non-ocular toxicity and good QoL.

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Use of proton therapy for re-irradiation in pediatric intracranial ependymoma.
(Eaton B.R. et al. )

This paper reports disease control, survival and treatment-associated toxicity with the use of proton therapy for re-irradiation of intracranial ependymoma. proton therapy appears safe and efficacious for this specific indication of treatment.

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Clinical outcomes and late endocrine, neurocognitive, and visual profiles of proton radiation for pediatric low-grade gliomas
(Greenberger B.A. et al.)

Primary low-grade gliomas are common brain tumors of childhood, and many of them require radiation therapy as definitive treatment. Increased conformality could decrease the incidence and severity of late effects. proton therapy appears to be associated with good clinical outcomes, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis.

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Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient
(Zhang R. et al.,)

Pediatric patients who received radiation therapy are at risk of developing side effects such as radiogenic second cancer. proton therapy confers lower predicted risk of second cancer than radiation therapy for pediatric medulloblastoma patients receiving craniospinal irradiation.

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Cost effectiveness of proton versus photon radiation therapy with respect to the risk of growth hormone deficiency in children
(Mailhot Vega R. et al.)

This study provides the first evidence-based guide for identifying children with brain tumors who may benefit the most from proton therapy with respect to endocrine dysfunction. Indeed, proton therapy may be more cost effective when the radiation dose to the hypothalamus can be spared, but not when tumors are involving or directly adjacent to the hypothalamus.

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Incidence and dosimetric parameters of pediatric brainstem toxicity following proton therapy
(Indelicato D.J. et al.)

Proton therapy offers superior low and intermediate radiation dose distribution compared with photon radiation therapy for brain and skull base tumors. This article investigates the tolerance of the pediatric brainstem to proton therapy and shows that the utilization of current national brainstem dose guidelines is associated with a low risk of brainstem toxicity in pediatric patients.

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Involved-node proton therapy in combined modality therapy for hodgkin lymphoma: results of a phase 2 study
(Hoppe B.S.)

This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma with mediastinal involvement.

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Outcomes and acute toxicities of proton therapy for pediatric atypical teratoid/rhabdoid tumor of the central nervous system
(McGovern S.L. et al.)

Atypical teratoid/rhabdoid tumor (AT/RT) of the CNS is a rare cancer primarily affecting children younger than 5 years old. This paper is the largest report of children with AT/RT treated with PT, and preliminary survival outcomes in this young pediatric population are encouraging compared to historic results.

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Proton beam therapy reduces the incidence of acute haematological and gastrointestinal toxicities associated with craniospinal irradiation in pediatric brain tumors
(Song S.,)

This study shows that the acute toxicity of proton beam craniospinal irradiation (CSI) was lower compared to that of conventional photon beam CSI in children with brain tumors.

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Proton beam therapy versus conformal photon radiation therapy for childhood craniopharyngioma: multi-institutional analysis of outcomes, cyst dynamics, and toxicity
(Bishop A.J. et al)

This paper compares proton therapy with IMRT for pediatric craniopharyngioma in terms of disease control, cyst dynamics and toxicity.

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Proton radiation therapy for pediatric medulloblastoma and supratentorial primitive neuroectodermal tumors: outcomes for very young children treated with upfront chemotherapy
(Jimenez R. et al.)

Upfront chemotherapy followed by 3D proton therapy presents good disease early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor.

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Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons
(MacDonald S.M. et al.)

This study reports on clinical outcomes for pediatric patients treated with proton therapy for intracranial ependymoma and compares the dose distributions of IMRT, 3D conformal proton therapy and IMPT.

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Proton radiotherapy for pediatric bladder/prostate rhabdomyosarcoma: clinical outcomes and dosimetry compared to intensity modulated radiation therapy
(Cotter S.E. et al.)

This paper reports the clinical outcomes of 7 children with bladder/prostate rhabdomyosarcoma treated with proton therapy and compares proton therapy plans with matched IMRT plans, with an emphasis on dose savings to reproductive and skeletal structures. proton therapy provides significant dose savings to normal structures compared to IMRT and is well tolerated in this patient population.

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Proton radiotherapy for pediatric central nervous system ependymoma: clinical outcomes for 70 patients
(MacDonald S.M., et al.)

Ependymoma is treated with maximal surgical resection and localized radiotherapy. Minimizing unnecessary exposure to radiation is of paramount importance for young children. proton therapy spares healthy tissue outside the target region, and outcomes for children treated with proton therapy compare favorably with the literature.

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Proton radiotherapy for pediatric central nervous system germ call tumors: early clinical outcomes
(MacDonald S.M. et al.)

This paper reports early clinical outcomes for children with CNS germ cell tumors treated with proton therapy and compares dose distributions for IMRT, 3D-CPT and IMPT with PBS for whole-ventricular irradiation with and without an involved-field boost. Preliminary disease control with proton therapy compares favorably to the literature and dosimetric comparisons demonstrate the advantage of proton therapy over IMRT for whole-ventricle radiation, with superior dose distributions and fewer beam angles.

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Proton radiotherapy for pediatric Ewing's sarcoma: initial clinical outcomes
(Rombi B. et al.)

This study presents preliminary clinical outcomes including late effects on pediatric Ewing’s sarcoma patients treated with PT. This treatment modality was well tolerated with few adverse events.

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Proton radiotherapy for pediatric sarcoma
(Ladra M.M. and Yock T.I.)

Radiotherapy plays an integral role in the local control of pediatric sarcomas, which often arise adjacent to critical structures and growing organs. proton therapy shows either equivalent or improved outcomes, and lower toxicity for soft tissue sarcoma compared to RT. For bone and cartilaginous sarcomas, a clearer advantage exists for proton therapy due to its ability to increase total dose while respecting adjacent structures.

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Proton radiotherapy for pediatric tumors: review of first clinical results
(Rombi B. et al.,)

Proton therapy has been used safely and effectively for medulloblastoma, primitive neuro-ectodermal tumors, craniopharyngioma, ependymoma, germ cell intracranial tumors, low-grade glioma, retinoblastoma, rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma and other bone sarcomas. Other possible applications are emerging. The main advantage of proton therapy is the sparing of intermediate-to-low-dose to healthy tissue.

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Proton radiotherapy for solid tumors of childhood
(Cotter S.E. et al.)

The increasing efficacy of pediatric cancer therapy has produced many long-term survivors who now struggle with serious morbidities mostly related to radiation therapy. proton therapy holds great promise to drastically reduce these treatment-related late effects in long term survivors by reducing dose to normal tissue.

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Proton therapy for pediatric and adolescent esthesioneuroblastoma
(Lucas J.T. Jr. et al.)

Esthesioneuroblastoma of the paranasal sinus comprises less than 3% of tumors in pediatric and adolescent patients. The collective adult literature indicates a critical role for radiotherapy in attaining cure, yet pediatric outcome data is limited. This study shows that proton therapy provides excellent locoregional disease control even in patients with locally advanced disease and intracranial extension.

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Proton therapy for spinal ependymomas: planning, acute toxicities, and preliminary outcomes
(Amsbaugh M.J. et al.)

Proton therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. This study reports acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton therapy at the MD Anderson Cancer Center.

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Proton therapy for uveal melanoma in 43 juvenile patients: long-term results
(Petrovic A. et al.)

This study examines the metastatic and survival rates, eye retention probability and visual outcomes of juvenile patients after proton therapy for uveal melanoma. It is shown that metastatic and survival rates are significantly better for juvenile than for adult patients.

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Proton therapy in pediatric skull base and cervical canal low-grade bone malignancies
(Habrand J.L. et al.)

This paper evaluates outcomes and tolerance of high-dose radiation therapy and proton therapy in the management of skull base and cervical canal primary bony malignancies in children. High-dose combined fractionated photon-proton therapy is well tolerated in children and allows excellent local control with minimal long-term toxicity.

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Proton-Beam Radiation Therapy and Health-Related Quality of Life in Children With CNS Tumors
(Armstrong F.D., Holtz Children's Hospital,)

Children treated for CNS tumors with conventional radiation therapy or cranial radiation therapy (CRT) are at high risk of neurocognitive impairment or dysfunction. Delaying or reducing CRT and using chemotherapy as primary therapy have improved survival and the neurocognitive trajectory. Similarly, the use of proton therapy may now offer the next step with respect to both survival and long-term neurocognitive functioning.

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Spot-scanning proton radiation therapy for pediatric chordoma and chondrosarcoma: clinical outcome of 26 patients treated at paul scherrer institute
(Rombi B. et al.)

Spot-scanning proton therapy shows excellent clinical outcomes with acceptable rates of late toxicity in pediatric patients with chordoma or chondrosarcoma of the skull base or axial skeleton.

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The risk of radiation-induced second cancers in the high to medium dose region: a comparison between passive and scanned proton therapy, IMRT and VMAT for pediatric patients with brain tumors
(Moteabbed M. et al.)

The incidence of second malignant tumors is a clinically observed adverse late effect of radiation therapy. This study aims to evaluate the risk of second cancer incidence for pediatric patients with brain/head and neck tumors and compare passive scattering and pencil beam scanning PT, IMRT and VMAT.

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Tumor control and QoL outcomes of very young children with atypical teratoid/rhabdoid tumor treated with focal only chemo- radiation therapy using pencil beam scanning proton therapy
(Weber D.C. et al.,)

The aim of this analysis is to assess the early clinical results of PBS proton therapy in the treatment of young children with non-metastatic atypical teratoid/rhabdoid tumor of the central nervous system. PBS proton therapy is proven to be an effective treatment for those patients, with manageable acute toxicity.

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PROSTATE MALIGNANCIES

Early outcomes from three prospective trials of image-guided proton therapy for prostate cancer
(Mendenhall N.P. et al.)

Early outcomes with image-guided proton therapy for prostate cancer suggest high efficacy and minimal toxicity, with only 1.9% grade III genito-urinary symptoms and less than 0.5% grade III gastro-intestinal toxicities.

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Erectile function, incontinence, and other quality of life outcomes following proton therapy for prostate cancer in men 60 years old and younger
(Hoppe B.S. et al.)

Young men (60 years old) undergoing proton therapy for treatment of prostate cancer have excellent outcomes with respect to erectile dysfunction, urinary incontinence, and other health-related quality of life parameters during the first 2 years after treatment.

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Five-year outcomes from 3 prospective trials of image-guided proton therapy for prostate cancer
(Mendenhall N.P.)

Five-year clinical outcomes with image-guided proton therapy for prostate cancer included extremely high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes.

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Multi-institutional Phase II study of proton beam therapy for organ-confined prostate cancer focusing on the incidence of late rectal toxicities
(Nihei K. et al.)

Proton therapy is theoretically an excellent modality for external beam radiotherapy, providing an ideal dose distribution. However, it is not clear whether proton therapy for prostate cancer can clinically control toxicities. This prospective study has revealed that proton therapy for localized prostate cancer can achieve a low incidence of late grade II or greater rectal toxicities.

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Proton beam therapy for localized prostate cancer 101: basics, controversies, and facts
(Wisenbaugh E.S. et al.)

Proton therapy for prostate cancer has become a source of controversy in the urologic community, and the rapid dissemination and marketing of this technology has led to many patients inquiring about this therapy. This article reviews the basic science of the proton beam and examines the literature so that every urologist is able to comfortably discuss this option with inquiring patients.

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Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from proton radiation oncology group/American College of Radiology 95-09
(Zietman A.L. et al.)

This randomized controlled trial aimed at testing the hypothesis that increasing radiation dose delivered to men with early-stage prostate cancer improves clinical outcomes. The results showed superior long-term cancer control compared to conventional-dose radiation. This was achieved without an increase in grade III late urinary or rectal morbidity.

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SARCOMAS

Proton-based radiotherapy for unresectable or incompletely resected osteosarcoma
(Ciernik I.F. et al.)

A study was undertaken to assess clinical outcomes and the role of proton therapy for local control of osteosarcoma. It was shown that proton therapy to deliver high radiotherapy doses allows locally curative treatment for some patients with unresectable or incompletely resected osteosarcoma.

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