Clinical publication highlights

Clinical publication highlights

IBA - Clinical publication highlights

On this page, you find a comprehensive summary of the key outcome papers published on proton therapy.

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We hope you enjoy reading the abstracts, as well as the full text articles. 

Key papers April - June 2018


Risk of Radiation Vasculopathy and Stroke in Pediatric Patients Treated With Proton Therapy for Brain and Skull Base Tumors. To examine the rate of and identify risk factors for vasculopathy after proton therapy in pediatric patients with central nervous system and skull base tumors, the Jacksonville group analyzed 644 pediatric patients with central nervous system and skull base tumors were treated with proton therapy in their center. (publication accessible via )

Meta-analysis of the incidence and patterns of second neoplasms (SNs) after photon craniospinal irradiation (CSI) in children with medulloblastoma (MB). This meta-analysis reported that the 10-year cumulative incidence was 6.1% for all SNs, including 3.1% for SBNs (benign) and 3.7% for SMNs (malignant), with a majority in areas of exit RT dose. Studies are needed to determine whether the use of proton therapy, which has no exit RT dose, is associated with a lower incidence of SNs. (publication accessible via )

Proton therapy for central nervous system tumors in children. A systematic review conducted by John Hopkin and MGH.  It highlighted the capability of protons to decrease radiation exposure for children is regarded as an important advance in pediatric cancer care, particularly for central nervous system (CNS) tumors. Favorable clinical outcomes have been reported and justify the increased cost and burden of this therapy. (publication accessible via )

National Cancer Institute Workshop on Proton Therapy for Children: Considerations Regarding Brainstem Injury. Reports of brainstem necrosis after proton therapy have raised concerns over the potential biological differences among radiation modalities. A workshop was organized including twenty-seven physicians, physicists, and researchers from 17 institutions with expertise to discuss this issue. And the report of this workshop is published in the Red Journal. (publication accessible via )



Protons vs Photons for Brain and Skull Base Tumors. A systematic review summarizes the literature regarding the role of proton therapy compared to photon therapy in the treatment of adult brain and skull base tumors, including chordoma/chondrosarcoma, glioma, meningioma, pituitary tumor, acoustic neuroma, and craniopharyngioma.  (publication accessible via


Head and Neck

Proton Therapy for Head and Neck Cancer. A systematic review by MSKCC summarized the published clinical research, and the authors believe that widespread adoption of proton therapy will elucidate the true value of proton beam therapy and give a greater understanding of the full risks and benefits of proton therapy in head and neck cancer. (publication accessible via )



Does Proton Therapy Offer Demonstrable Clinical Advantages for Treating Thoracic Tumors? A review by the MD Anderson group examined the available data with regard to proton therapy for thoracic malignancies, and presented the unique challenges in translating the dosimetric advantages of proton therapy to clinical benefit for patients with thoracic tumors. Extensive improvements are needed in all aspects of the treatment process, from simulation, planning algorithms, and volumetric image guidance through to real-time tracking and treatment adaptation. (publication accessible via )



Potential Morbidity Reduction with Proton Radiation Therapy for Breast Cancer. A systematic review by MSKCC about the increasing emphasis on the mitigation of iatrogenic morbidity, with particular attention to heart and lung exposure in those receiving adjuvant chemoradiation. The paper summarized the dosimetric evidence and early clinical evidence that supports the efficacy and feasibility of proton radiation in breast cancer. (publication accessible via )



Finding Value for Protons: The Case of Prostate Cancer? A review by UPenn examined the dosimetric data and clinical outcome reports. Clinical studies largely suggest no difference in urinary side effects or erectile dysfunction. Regarding rectal toxicity, some studies found PBT was worse, others suggested PBT was better, and still others concluded there was no meaningful difference at all. A comparative trial has commenced the Prostate Advanced Radiation Technologies Investigating Quality of Life (PARTIQoL) trial. (publication accessible via )


Clinical trial

Clinical Trial Strategies to Compare Protons with Photons. Langendijk et al. the Groningen group on clinical trial strategies to compare protons and photons. The authors suggested that for the clinical validation of the added value of protons to improve local control, randomized controlled trials are required. However, for the added value of protons to prevent side effects, both model-based validation and randomized controlled trials can be used. (Publication accessible via )

Key papers January - March 2018


Proton Beam Therapy for Iris Melanomas in 107 Patients. A study reported outcomes of 107 iris melanoma patients treated with protons. Proton therapy showed efficacy and limited morbidity in iris melanomas. (publication accessible via )


Proton therapy for pediatric head and neck malignancies
. A study conducted by the UPenn group reported acute toxicities and early outcomes following PBT for pediatric head and neck malignancies. The study demonstrated low rates of acute toxicity and local control rates similar to historical reports. (publication accessible via )

Esophageal cancer

Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma (EC). 19 patients with EC treated with IMPT concurrently with chemotherapy. Clinical complete response was achieved in 84%. The most common grade 3 acute toxicities were esophagitis and fatigue. IMPT is an effective treatment for EC, with high tumor response, good local control, and acceptable acute toxicity.  (publication accessible via )

Key papers November - December 2017


Proton Beam Therapy for Iris Melanomas in 107 Patients. A study reported outcomes of 107 iris melanoma patients treated with protons. Proton therapy showed efficacy and limited morbidity in iris melanomas. (publication accessible via )


Proton therapy for pediatric head and neck malignancies. A study conducted by the UPenn group reported acute toxicities and early outcomes following PBT for pediatric head and neck malignancies. The study demonstrated low rates of acute toxicity and local control rates similar to historical reports. (publication accessible via )

Esophageal cancer

Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma (EC). 19 patients with EC treated with IMPT concurrently with chemotherapy. Clinical complete response was achieved in 84%. The most common grade 3 acute toxicities were esophagitis and fatigue. IMPT is an effective treatment for EC, with high tumor response, good local control, and acceptable acute toxicity.  (publication accessible via )

Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy.Compared the relative risk of radiation-induced lymphopenia between IMRT and PBT in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT), PBT was significantly associated with a reduction in grade 4 lymphopenia risk. (publication accessible via )


Acute toxicity of image-guided hypofractionated proton therapy for localized prostate cancer. A study reported toxicity of 526 localized prostate cancer patients treated with proton therapy and demonstrated the safety of HFPT for localized PCa patients in terms of acute toxicity.  (publication accessible via )

Minimal toxicity after proton beam therapy for prostate and pelvic nodal irradiationresults from the proton collaborative group REG001-09 trial. This PCG study evaluated toxicity outcomes for non-metastatic prostate cancer patients who received pelvic radiation therapy. The study demonstrated PBT significantly less acute GI toxicity than is expected using IMXT which may be related to small bowel sparing from PBT. (publication accessible via )


Proton therapy for locally advanced breast cancer: A systematic review of the literature.This systematic review reported that protons offered a better target coverage than photons, even compared with intensity modulation radiation therapy (including static or rotational IMRT or tomotherapy). Protons decreased mean heart dose by a factor of 2 or 3, i.e. 1 Gy with proton therapy versus 3 Gy with conventional 3D, and 6 Gy for IMRT. (publication accessible via )


Key papers May - October 2017

Head and Neck

Proton therapy for head and neck cancer: expanding the therapeutic window. Published in the Lancet Oncology, this review article summarized the recent published outcomes of proton therapy head and neck cancer. In reviewing PT for different subsites including unilateral irradiation, oropharyngeal carcinoma, nasopharyngeal carcinoma, sinonasal cancer, tumors of the skull base and reirradiation, the authors pointed out that the clinical benefits of PT in terms of toxicity sparing are becoming increasingly apparent ranging from incremental to substantial in the selected patient groups. (Publication accessible via )


Consensus Guidelines for Implementing Pencil-Beam Scanning Proton Therapy for Thoracic Malignancies on Behalf of the PTCOG Thoracic and Lymphoma Subcommittee. This consensus provides guidance for implementing PBS for thoracic treatments. IMPT represents the latest advanced PT technology, however motion uncertainty, tissue density heterogeneity of chest organs can have a significant impact on dose distribution. This consensus guidelines list strategies and steps for PBS IMPT. (Publication accessible via )

Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small-Cell Lung Cancer: Final Results of a Phase 2 Study. Published in JAMA Oncology, this MD Anderson study reported the final (5-year) results of a prospective study of 64 patients unresectable stage III NSCLC treated with concurrent chemotherapy and passively scattered PBT (74-Gy relative biological effectiveness). The authors concluded that concurrent chemotherapy and PBT to treat unresectable NSCLC afford promising clinical outcomes and rates of toxic effects compared with historical photon therapy data. (Publication accessible via )


Evidence-based Review on the Use of Proton Therapy in Lymphoma from the Particle Therapy Cooperative Group (PTCOG) Lymphoma Subcommittee. In an effort to draw attention to the use of proton therapy in lymphoma, and as a resource for future consideration of proton therapy coverage for lymphoma by other expert panels and insurance agencies, the PTCOG lymphoma subcommittee has developed an evidence-based review on the use of proton therapy in lymphoma. The committee recommended that proton therapy should be reasonably considered in appropriately selected lymphoma patients when it can significantly decrease the dose to critical structures. (publication accessible via )


Systematic assessment of clinical outcomes and toxicities of proton radiotherapy for reirradiation. This review assessed clinical outcomes and toxicity profiles by evaluating available evidence regarding PBT reRT. The authors posit that PBT may be the safest option to reirradiate patients with locoregional recurrences, and thus PBT may be the best approach for offering select patients a new chance of cure. (publication accessible via )


Quality of Life and Patient-Reported Outcomes Following Proton Radiation Therapy: A Systematic Review. Evaluating quality of life (QOL) and patient-reported outcomes (PROs) is essential to establishing PBT's "value" in oncologic therapy. This systematic review reported that PBT provides favorable QOL/PRO profiles for select brain, head/neck, lung, and pediatric cancers; measures for prostate and breast cancers were more modest. These results have implications for cost-effective cancer care and prudently designed QOL evaluation in ongoing trials. (publication accessible via )


Key papers March - April 2017

Liver cancer

Analysis of repeated proton beam therapy for patients with hepatocellular carcinoma.  Published in the Green Journal, the researchers in Japan reported outcomes of 83 patients treated with definitive repeated PBT. Patients received a median doses for the 1st, 2nd, 3rd and 4th treatments were 71.0, 70.0, 70.0, and 69.3 GyE, and there was no severe acute toxicity, and no radiation-induced liver dysfunction (RILD) was observed. The 2- and 5-year OS rates were 87.5% and 49.4%. (Publication accessible via )

Breast cancer

Joint Estimation of Cardiac Toxicity and Recurrence Risks after Comprehensive Nodal Photon versus Proton Therapy for Breast Cancer. Published in the Red Journal, this study generated proton plans for 41 left-side breast cancer patients who underwent postlumpectomy comprehensive nodal photon irradiation, then evaluated the risks of cardiotoxicity and breast cancer recurrence. It is reported that proton therapy can reduce the predicted risk of cardiac toxicity by up to 2.9% and risk of recurrence of breast cancer by 0.9%, compared to modern photon techniques. (Publication accessible via )

Pediatric cancer

Supine craniospinal irradiation in pediatric patients by proton pencil beam scanning. Published in the Green Journal by the Trento group in Italy, this paper reported methods and techniques for performing PBS CSI effectively. Special methods included 1) supine patient position 2) field-junctions via the ancillary-beam technique 3) lens-sparing by three beam whole brain irradiation 4) applied a movable snout and beam splitting technique to reduce the lateral penumbra for dose reduction to kidney. (Publication accessible via )

Patient selection

Using a knowledge-based planning solution to select patients for proton therapy. Published in the Green Journal, a knowledge-based-planning solution developed by the Dutch group for proton therapy patient selection is reported to provide efficient, patient-specific selection for protons by using plan-libraries to model and predict organ-at-risk (OAR) dose-volume-histograms (DVH). (Publication accessible via )

Key papers October 2016 - March 2017


Patterns of care in proton therapy for children. Published in the Red Journal, this paper examined patterns of treatments received for pediatric patients with primary CNS malignancies. The authors pointed out that as we continue to demonstrate the potential benefits of PBT in children, efforts are needed to expand the accessibility of PBT for children of all socioeconomic background and regions of the country. (Publication accessible

Lifetime attributable risk of radiation-induced secondary cancer. A group of Japanese researchers compared the lifetime attributable risk of secondary cancer (LAR) induced by proton therapy and IMRT in pediatric patients. The paper reported that for categories of brain, head and neck, thoracic, abdominal and whole craniospinal irradiation, the LAR of PBT was significantly lower than IMRT. (Publication accessible )


PRONTOX – a randomized control trial. Although radiochemotherapy with photons is the standard treatment for now for locally advanced NSCLC, but acute radiation-induced toxicity such as esophagitis and pneumonitis can be potentially life-threatening. The Dresden group has commenced this randomized control trial that aims to show a decrease of 39% to 12% of early and intermediate radiation-induced toxicity using proton therapy. (Publication accessible )

Long-term outcome of a prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer. This MD Anderson study published in the Green Journal reported proton therapy for early stage NSCLC patients who were not suitable for SBRT due to lesion size and location. The study reported encouraging 5-year overall survival rate and recurrence-free rate. The authors concluded that this long-term follow-up data demonstrated proton therapy with ablative doses is well tolerated and effective in medically inoperable early-stage NSCLC. (Publication accessible )


Long-term outcomes of proton therapy for previously untreated hepatocellular carcinoma (HCC). The Japanese group in University of Tsukuba conducted this retrospective study of 129 patients with stage 0 to C disease (BCLC) treated with proton therapy. The study reported favourable long-term efficacies with mild adverse effect in BCLC stage 0 to C patients. (Publication accessible )


Evidence-based medicine

Establishing evidence-based indications for proton therapy. An overview of current clinical trials of proton therapy published in the Red Journal. A total 122 ongoing trials with target enrolment of over 42,000 patients. The most common PBT clinical trials are about gastrointestinal tract tumors, tumors of the central nervous system and prostate cancer. There are 5 randomized studies between proton and photon are on lung, esophagus, head and neck, prostate and breast. The paper demonstrated that PBT clinical trials are rapidly expanding. (Publication accessible )

Patient estimates for proton therapy

Published in the Green Journal, this ESTRO-HERO (Health Economics in Radiation Oncology) analysis reported about 4 million new cancer patients are predicted in 2025 in Europe, a 15.9% increase compared to the number of 2012, and about 2 million cancer patients would have an indication for radiotherapy in 2025, a 16.1% increase from year 2012. New radiotherapy techniques enable delivery precision and less toxic effects combined with new chemotherapy could also influence the number of candidates for radiotherapy treatments. This paper is to raise awareness for resource planning and placing investments to adequately manage demands of cancer patients. (Publication accessible:

Key papers January - October 2016

Head and neck cancer

A retrospective study reported that proton therapy significantly reduced toxicity compared with IMRT for head and neck tumors. The toxicity outcome confirm the dosimetry advantages of proton which resulted in significantly lower rates of grade 2 or above acute dysgeusia, mucositis and nausea. (Publication accessible via )

A matched analysis compared PBRT and IMRT for nasopharynx and paranasal sinus cancers with concurrent chemotherapy, reported that PBRT was associated with a lower opioid pain requirement and a lower rate of gastrostomy tube dependence. (Publication accessible via )

Proton therapy can be a safe and effective curative reirradiation strategy for head and neck cancer, with acceptable rates of toxicity and durable disease control. A study reported encouraging 2-year rates of local regional control, overall survival and late toxicity. (Publication accessible via )

Hodgkin lymphoma

A registry study of collective proton centres reported a 2-year relapse-free survival of 85% with no grade 3 toxicity occurred. Hodgkin lymphoma young survivors are at great risk of developing chronic morbidities and secondary cancer, these patients may derive considerable benefit with proton therapy. (Article accessible via )

Gastrointestinal malignancy

A randomized trial comparing proton therapy with transarterial chemoembolization (TACE) for hepatocellular carcinoma, reported a trend toward improved local tumour control, progression-free survival, and significantly fewer hospitalization days after proton treatment. (Publication accessible via )


A systematic review examined clinical outcomes and toxicities of proton therapy for gastrointestinal neoplasms. The findings include that proton therapy was associated with reduced toxicity for esophageal cancer and pancreatic cancer while achieving similar disease control and survival compared to photon techniques. For hepatocellular carcinoma, proton therapy demonstrated a trend towards improved local control and progression-free survival. (Publication accessible via )


A systematic review reported findings on clinical outcomes and toxicity of proton therapy for breast cancer. Toxicity was comparable or improved to published photon data. Proton offers excellent potential to minimize the risk of cardiac events, keeping the mean heart dose at ≤1Gy. (Publication accessible via )



A large series of 1327 localized prostate cancer patients reported 5-year biochemical control rate, toxicity and patient-reported quality of life after proton therapy. The study concluded that image guided proton therapy provided excellent biochemical control rates and the actuarial rates of high-grade toxicity were low.  Publication accessible via )

Cost effectiveness

A systematic review of the cost-effectiveness of proton therapy found that proton therapy was a cost-effective option for several pediatric brain tumors, selected left-sided breast cancer, selected head and neck cancer and locoregionally advanced non-small cell lung cancer. (Publication accessible via )

Clinical Decision

A clinical decision support system (PRODECIS) for choosing proton or photon modality for head and neck patients. Based on evaluation and comparison of dosimetry, toxicity, and cost-effectiveness, the system successfully quantified patients for proton or photon treatment choice. Publication accessible via )




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