Role Of Proton Therapy Research Articles

Mitigating Radiotoxicity in the Central Nervous System: Role of Proton Therapy.

Central nervous system (CNS) radiotoxicity remains a challenge in neuro-oncology. Dose distribution advantages of protons over photons have prompted increased use of brain-directed proton therapy. While well-recognized among pediatric populations, the benefit of proton therapy among adults with CNS malignancies remains controversial. We herein discuss the role of protons in mitigating late CNS radiotoxicities in adult patients. Despite limited clinical trials, evidence suggests toxicity profile advantages of protons over conventional radiotherapy, including retention of neurocognitive function and brain volume. Modelling studies predict superior dose conformality of protons versus state-of-the-art photon techniques reduces late radiogenic vasculopathies, endocrinopathies, and malignancies. Conversely, potentially higher brain tissue necrosis rates following proton therapy highlight a need to resolve uncertainties surrounding the impact of variable biological effectiveness of protons on dose distribution. Clinical trials comparing best photon and particle-based therapy are underway to establish whether protons substantially improve long-term treatment-related outcomes in adults with CNS malignancies.

Proton Therapy in the Management of Luminal Gastrointestinal Cancers: Esophagus, Stomach, and Anorectum.

Simple SummaryRadiation treatment plays a major role in the management of luminal gastrointestinal cancers, mainly esophageal and anorectal cancers. There is a growing interest in the application of protons for gastrointestinal cancers, mainly owing to its dosimetric characteristics in decreasing dose to nearby organs at risk. We present here an up-to-date comprehensive review of the dosimetric and clinical literature on the use of proton therapy in the management of luminal gastrointestinal cancers.While the role of proton therapy in gastric cancer is marginal, its role in esophageal and anorectal cancers is expanding. In esophageal cancer, protons are superior in sparing the organs at risk, as shown by multiple dosimetric studies. Literature is conflicting regarding clinical significance, but the preponderance of evidence suggests that protons yield similar or improved oncologic outcomes to photons at a decreased toxicity cost. Similarly, protons have improved sparing of the organs at risk in anorectal cancers, but clinical data is much more limited to date, and toxicity benefits have not yet been shown clinically. Large, randomized trials are currently underway for both disease sites.

Successful treatment with proton beam therapy for a solitary sternal metastasis of breast cancer: a case report

BackgroundBreast cancer infrequently metastasizes to the sternum as solitary metastasis. We experienced successful treatment with proton beam therapy for a case of sternal metastasis of breast cancer. This case demonstrates for the first time the role of proton therapy in the treatment of oligometastatic sternal metastasis with limited tolerance of normal tissue due to previous photon irradiation.Case presentationA 40-year-old Japanese female presented with lumpiness in her left breast. The patient was diagnosed with breast cancer (cT1N0M0, cStage IA) and underwent partial mastectomy with axillary lymph node dissection. After the mastectomy, the patient received radiation therapy with 50 Gy in 25 fractions for initial irradiation of the left breast. After the initial irradiation of 50 Gy, the patient received 10 Gy in five fractions of a sequential boost for the tumor bed to a total dose of 60 Gy. Although the patient was administered tamoxifen after radiation therapy, solitary sternal metastasis occurred 6 months after radiation therapy. She refused chemotherapy and requested proton beam therapy for her sternal metastasis. The daily proton beam therapy fractions were 2.5 relative biological effectiveness, receiving a total dose of 70 Gy relative biological effectiveness. An acute side effect of grade 2 dermatitis according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. occurred during proton beam therapy, but there was no acute or late complication of more than grade 3. At 3 years after proton beam therapy, the patient remains in complete remission without surgery or chemotherapy.Discussion and conclusionProton beam therapy for solitary sternal metastasis of breast cancer is considered to be a therapeutic option.

SP-0683 The role of proton therapy in the treatment of esophageal cancer

SP-0683 The role of proton therapy in the treatment of esophageal cancer

Prostate bed irradiation with alternative radio-oncological approaches (PAROS) - a prospective, multicenter and randomized phase III trial

BackgroundFor patients with treatment-naïve carcinoma of the prostate, hypofractionated irradiation becomes more and more popular. Due to the low α/β value of prostate cancer, increased single dose leading to a shortened treatment period seems to be safe and feasible. However, reliable data is lacking for post-prostatectomy patients so far. Further, the role of proton therapy is still under debate. Two prospective phase II trials with both, hypofractionated photon and proton therapy, provided promising results.Methods/ designThe PAROS trial is a prospective, multicenter and randomized phase III trial for men with localized prostate carcinoma after surgery. Post-prostatectomy patients will be randomized to either normofractionated radiotherapy (nRT) with photons (70.0/ 2.0 Gy), or hypofractionated radiotherapy (hRT) with photons (57.0/ 3.0 Gy) or hRT with protons (57.0/ 3.0 Gy relative biological effectiveness [RBE]). Block randomization is stratified by Gleason Score (≤ 7 vs. > 7) and treatment indication (adjuvant vs. salvage). The trial is planned to enroll 897 patients. The primary objective is to show an improvement in the bowel-score according to EORTC QLQ-PR25 after proton therapy compared to photon irradiation (week 12 vs. baseline). Secondary aims are non-inferiority of hRT compared to nRT with regard to biochemical progression-free survival (bPFS), overall survival (OS), quality of life and toxicity.DiscussionThe present study aims to evaluate the role of hypofractionated radiotherapy to the prostate bed with photons and protons leading to significant impact on future management of operated men with prostate cancer.Trial registrationDeutsches Register klinischer Studien: DRKS00015231; registered 27 September 2018.

36. Potential interest of protons comparing SRT and IMRT with photons for cases where prescribed dose is limited by OAR constraints

Introduction It is widely admitted that dose distributions obtained with protons are more conformal compared to photons. We investigate the role of protontherapy for those cases where it was not possible to fulfill OAR constraints with most advanced photon techniques and where the prescribed dose had to be decreased. This study investigates all cases where protontherapy provides a better OAR sparing compared to photons in general, but focuses only on the difficult cases as described above. Methods During 2015, all SRT/SBRT cases with CyberKnife and helical Tomotherapy where prescribed dose to target volumes had to be decreased to fulfill OAR dose constraints were listed. They were replanned with an IBA proton machine using the Pencil Beam Scanning technique on a RaySearch workstation, with the same PTV as photons. Range uncertainties were not taken into account, except while selecting the beam incidences. Results Among the 1310 SRT/SBRT and IMRT treatments, the plans that needed a decreased prescription dose can be classified in two categories: - When a serial organ is adjacent and limiting, as spinal cord for vertebra re-irradiation. - When a parallel organ received too much low doses when target volumes are too big, as for liver where 700 cm3 must receive less than a threshold. For the first category, proton plans didn’t allow delivering the initial prescribed dose either. The penumbra of Pencil Beam Scanning (3 mm spot) is not sharper compared to SRT/SBRT plans. For the second category, consisting of 11 liver lesions and 6 lung lesions with mediastinal nodes, initial prescribed dose can always be delivered when using the PBS technique. Conclusions Over one year, we counted 17 patients where it was necessary to decrease prescribed dose when applying photon treatments and where protons plans showed that the prescribed dose can be delivered. This is especially the case for large volumes in lung or liver.

Proton therapy for tumors of the base of the skull.

Relative to conventional photon irradiation, proton therapy has distinct advantages in its ability to more precisely target tumor while shielding adjacent normal tissues. In the setting of skull base tumors, proton therapy plays a critical role in the dose-escalation required for optimal tumor control of chordomas, chondrosarcomas, and malignancies of the paranasal sinuses and nasal cavity. For benign tumors such as craniopharyngiomas, pituitary adenomas and meningiomas, proton therapy can limit long-term adverse effects, such as secondary malignancies. This review summarizes published literature to date regarding the role of proton therapy in skull base tumors and introduces emerging proton therapy approaches such as pencil-beam scanning (PBS).

Context for Protons as Adjunctive Therapy in Neovascular Age-Related Macular Degeneration: A Review.

In the last few years we have witnessed increasing availability of proton therapy in the United States and worldwide. As a result, proton therapy is considered as either a primary or adjunctive approach for numerous indications where conventional radiation therapy shows promise but is accompanied by toxicities. Age-related macular degeneration (AMD) remains the leading cause of adult blindness in industrialized nations, and third worldwide, following cataract and glaucoma. Current standard therapy is intravitreal injection of anti-vascular endothelial growth factor agents. While this treatment shows improvement and stabilization in visual acuity for 40% of patients, 60% still experience disease progression. These injections are costly, necessitate repeated office visits, and carry the risk of endophthalmitis. The pathophysiology underlying neovascular AMD (nAMD) underscores the need to simultaneously target multiple pathways to retain useful vision. Radiation can be antiangiogenic, anti-inflammatory, and antiproliferative. Early photon therapy clinical trials were heterogeneous, and a Cochrane review of data demonstrated usefulness in treatment of nAMD but recommended further studies. Advantages of proton therapy over photon therapy include the ability to deliver a focal dose to the target while minimizing dose to normal structures, which is enhanced by unique treatment planning software that uses fluorescein angiography to verify target location and allows conformation of dose to the irregular shape and thickness characteristic of choroidal neovascular membranes, the pathognomonic finding in nAMD. Preliminary data suggest a potential role for proton therapy in the treatment of nAMD. In this article we review previous treatments for AMD, including those with both photon and proton radiation, and recommend future directions for clinical investigations to evaluate the role of proton therapy as an adjunct to antiangiogenic therapy, the current standard of care in this challenging setting.

Proton therapy in craniospinal irradiation: a systematic review

AbstractAimCraniospinal irradiation is a technique indicated when a patient has a malignancy that has either disseminated, or is at risk of disseminating, throughout the subarachnoid space. While the craniospinal axis is treatable with conventional radiotherapy, the high doses to organs at risk carry an increased risk of acute and late side effects. Proton craniospinal irradiation is an expensive technique that shows great theoretical promise arising from reduced exit doses. The purpose of this systematic review is to determine the potential role of proton therapy as a standard modality for craniospinal irradiation.Materials and methodsA literature review was performed to determine the efficacy and cost of proton craniospinal irradiation. The Cochrane Library and the Inspec, Medline (via Pubmed) and Scopus databases were searched. After exclusion criteria were applied, the remaining papers were systematically appraised utilising the Scottish Intercollegiate Guidelines Network critical appraisal checklists.ResultsA total of 14 articles remained following the application of the screening and critical appraisal processes. In total, five of the articles concluded that the risk of secondary malignancy was lower with proton therapy, while ten of the articles included data showing that toxicity rates and organs at risk doses were lower with proton therapy. Doses to most thoracic and abdominal organs at risk analysed in the literature were reduced when proton therapy was used, with the sole exception of the oesophagus, the dose to which depended on whether or not the entire vertebral body was treated. Proton therapy also delivered optimal doses to organs at risk in the head and neck compared with conformal radiation therapy. However, in one study that compared tomotherapy to proton therapy, tomotherapy outperformed proton therapy by delivering lower doses to organs at risk in the head and neck, as well as the kidneys. The two cost-effectiveness studies did not indicate proton therapy as an optimal modality for all treatment sites; however, one of the studies found that for medulloblastoma, protons were more cost effective than conventional radiation therapy.FindingsProton therapy is a superior treatment option for craniospinal irradiation. The reduction in risk of toxicity and radiocarcinogenesis offered by proton craniospinal irradiation appear to outweigh the increased costs.

SP-0305: Role of proton therapy in the treatment of paediatric malignancies

SP-0305: Role of proton therapy in the treatment of paediatric malignancies

TH‐A‐19A‐03: Impact of Proton Dose Calculation Method On Delivered Dose to Lung Tumors: Experiments in Thorax Phantom and Planning Study in Patient Cohort

Purpose:Evaluate Monte Carlo (MC) dose calculation and the prediction of the treatment planning system (TPS) in a lung phantom and compare them in a cohort of 20 lung patients treated with protons.Methods:A 2‐dimensional array of ionization chambers was used to evaluate the dose across the target in a lung phantom. 20 lung cancer patients on clinical trials were re‐simulated using a validated Monte Carlo toolkit (TOPAS) and compared to the TPS.Results:MC increases dose calculation accuracy in lung compared to the clinical TPS significantly and predicts the dose to the target in the phantom within ±2%: the average difference between measured and predicted dose in a plane through the center of the target is 5.6% for the TPS and 1.6% for MC. MC recalculations in patients show a mean dose to the clinical target volume on average 3.4% lower than the TPS, exceeding 5% for small fields. The lower dose correlates significantly with aperture size and the distance of the tumor to the chest wall (Spearman's p=0.0002/0.004). For large tumors MC also predicts consistently higher V5 and V10 to the normal lung, due to a wider lateral penumbra, which was also observed experimentally. Critical structures located distal to the target can show large deviations, though this effect is very patient‐specific.Conclusion:Advanced dose calculation techniques, such as MC, would improve treatment quality in proton therapy for lung cancer by avoiding systematic overestimation of target dose and underestimation of dose to normal lung. This would increase the accuracy of the relationships between dose and effect, concerning tumor control as well as normal tissue toxicity. As the role of proton therapy in the treatment of lung cancer continues to be evaluated in clinical trials, this is of ever‐increasing importance.This work was supported by National Cancer Institute Grant R01CA111590.

WE‐A‐WAB‐01: New Technologies Addressing the Range Uncertainty of Proton Therapy

The role of proton therapy in radiation therapy is currently expanding. In the U.S., there are at present 11 clinical proton treatment facilities, with 10 centers operating proton gantries and 6 additional facilities under construction. One of the main challenges in proton therapy is the uncertainty in predicting proton range. Range uncertainties in proton therapy are related to ambiguity in converting x‐ray CT attenuation data to proton relative stopping power and are further compounded by organ deformation and internal motion as well as increasing relative biological effectiveness in the distal part of proton beams. Closely related to this issue is the continued development of image guidance technology in the treatment room that ideally will provide feedback for in‐room treatment plan modifications (adaptive proton therapy). Proton therapy treatment planning applies quite substantial range uncertainty margins, negating, in part, some of the advantages of the finite range. The problem of range uncertainty in proton therapy has been addressed in many ways, the ultimate goal being to reduce this uncertainty to ∼1 mm. Approaches to address this problem include Monte Carlo simulations to study the effects of different sources on proton range uncertainty, studies showing the amount of range uncertainties in patients, robust planning techniques, and various technological and calibration methods that attempt to improve the accuracy of relative proton stopping power and to detect and minimize range errors at the time of treatment, e.g., dual energy CT scanners, proton CT and radiography, prompt gamma registration and monitoring of proton radiation therapy with PET imaging. This symposium will present a broad overview of the current status of modern computational and imaging approaches to addressing the range‐uncertainty problem of proton beams in radiation therapy.Learning Objectives:1. Understand the prevailing range uncertainties in proton therapy and how they can affect clinical practice.2. Learn how the magnitude of range uncertainties has been studied with Monte Carlo simulations and in patients.3. Get an overview of new technologies addressing the range uncertainty problem in proton therapy.4. Learn about principles of proton computed tomography and radiography and how these techniques may be used for better range definition and pre‐treatment quality assurance.5. Learn about the use of prompt gamma emission for proton therapy range verification.6. Learn about the different implementations and initial clinical experience of PET verification of treatment delivery in proton and ion therapy.

Role of proton therapy in the treatment of cancer

Conventional radiation therapy directs photons (X-rays) and electrons at tumours with the intent of eradicating the neoplastic tissue while preserving adjacent normal tissue. Radiationinduced damage to healthy tissue and second malignancies are always a concern. Proton beam radiotherapy, one form of charged particle therapy, allows for excellent dose distributions, with the added benefit of no exit dose. These character istics make this form of radiotherapy an excellent choice for the treatment of tumours located next to critical structures. Although proton therapy is clearly capable of providing superior dose distributions as compared with photons, there are still some questions remain unanswered. Current evidence provides a limited indication for PBT. Actual clinical studies are needed to validate the virtual clinical data. This review focuses specifically on the clinical outcomes and adverse events with charged particle radiation therapy compared with other treatments in patients with cancer. Standart foton radyoterapisi ile cevre normal dokular korunur

The role of proton therapy in the treatment of large irradiation volumes: a comparative planning study of pancreatic and biliary tumors

Purpose: The purpose of this study was to examine the potential benefit of proton therapy for abdominal tumors. Extensive comparative planning was conducted investigating the most up-to-date photon and proton irradiation technologies. Methods and Materials: A number of rival plans were generated for four patients: two inoperable pancreatic tumors, one inoperable and one postoperative biliary duct tumor. The dose prescription goal for these large targets was 50 Gy, followed by a boost dose up to 20 Gy to a smaller planning target volume (PTV). Photon plans were developed using “forward” planning of coplanar and noncoplanar conformal fields and “inverse” planning of intensity-modulated (IM) fields. Proton planning was simulated as administered using the so called spot-scanning technique. Plans were evaluated on the basis of normal tissues’ dose–volume constraints (Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1990;21:109–122) and coverage of treatment volumes with prescribed doses. Results: For all cases, none of the forward calculated photon plans was able to deliver 50 Gy to large PTVs at the same time respecting the dose–volume constraints on all critical organs. Nine evenly spaced IM fields achieved or nearly achieved all maximum dose constraints to critical structures for two out of three inoperable patients. IM plans also obtained good results for the postoperative patient, even though the dose to the liver was very close to the maximum allowed. In all cases, photon irradiation of large PTV1s to 50 Gy followed by a 20 Gy boost entailed a risk very close to or higher than 5% for serious complications to the kidneys, liver, or bowel. Simple arrangements of 2, 3, and 4 proton fields obtained better dose conformation to the target, allowing the delivery of planned doses including the boost to all patients, without excessive risk of morbidity. Dose homogeneity inside the targets was also superior with protons. Conclusion: For the irradiation of large PTVs located in the abdominal cavity, where multiple, parallel structured organs surround the target volumes, proton therapy, delivered with a sophisticated isocentric technique, has the potential to achieve superior dose distributions compared with state-of-the-art photon irradiation techniques. IM photon plans obtain better results in the postoperative case, because the reduced volume lessens the effect of the unavoidable increase of integral dose to surrounding tissues.