Development of Practical Proton Therapy System Based on Clinical Needs / 中国医疗器械杂志

In recent years, proton therapy technology has developed rapidly, and the number of patients treated with proton therapy has gradually increased. However, the application of proton therapy technology was far from practical needs. Because of the shortage of resources and the high cost, proton therapy systems are not accessible and affordable for most patients. In order to change this situation, it is necessary to develop a new truly practical proton therapy system based on clinical needs. Conceptual design of a practical proton therapy system was proposed. Compared with the existing system, one feature of the newly designed system is to reduce the maximum energy of the proton beam to 175~200 MeV; another feature is the configuration of deluxe and economical treatment rooms, the deluxe room is equipped with a rotating gantry and a six-dimensional treatment bed, and the economical room is equipped with a horizontal fixed beam and a patient vertical rotating setup device. This design can not only reduce the cost of proton therapy system and equipment room construction, but also facilitate the hospital to choose the appropriate configuration, which will ultimately benefit more patients.

Radiation-induced Myositis after Proton Beam Therapy to Huge Hepatocellular Carcinoma

Proton beam therapy (PBT) is one of the advances in radiotherapy techniques, which enables dose escalation with lower probability of radiation-induced liver or gastrointestinal injuries. However, the chest wall proximal to the tumor can be affected by high dose irradiation. Here, we report on a 58-year-old male patient who presented with huge hepatocellular carcinoma, received treatment with transarterial chemoembolization and PBT, and developed severe chest wall pain due to radiation-induced myositis. The patient's symptoms were controlled by oral steroids.

Application Status and Development Trends of Medical Proton and Heavy Ion Accelerators / 中国医疗器械杂志

Cancer therapy with accelerated proton or heavy ion beam is the most advanced radiotherapy technology, which is recognized by the international community at present. It is of great practical significance to study the medical proton and heavy ion accelerators and the radiotherapy technology, in order to promote the development of the advanced medical radiotherapy equipments and improve the quality of life of cancer patients in China. After a brief overview of cancer therapy with proton and heavy ion beam, this paper summarized and analyzed the application status of medical proton accelerators and medical heavy ion accelerators at home and abroad, and finally put forward the future development trends of medical proton and heavy ion accelerators and the radiotherapy technology, it can provide a reference for the progress and development strategies of the advanced radiotherapy equipments in China.

Development of the Extraction Reference Point Beam Diagnostic System for Proton Medical Accelerator / 中国医疗器械杂志

er to detect the beam quality of the SC200 superconducting cyclotron,measure the beam at the extraction reference and the acceptance of the accelerator is realized.This article mainly introduces the design that use the scintillation screen at the extraction reference to measure the beam profile,position and use the Faraday cup to measure the current intensity with 2.5 level accuracy.The remoted controlling of probes and the acquisition and processing of signal based on LabVIEW and PLC.

Current status of proton therapy techniques for lung cancer

Proton beams have been used for cancer treatment for more than 28 years, and several technological advancements have been made to achieve improved clinical outcomes by delivering more accurate and conformal doses to the target cancer cells while minimizing the dose to normal tissues. The state-of-the-art intensity modulated proton therapy is now prevailing as a major treatment technique in proton facilities worldwide, but still faces many challenges in being applied to the lung. Thus, in this article, the current status of proton therapy technique is reviewed and issues regarding the relevant uncertainty in proton therapy in the lung are summarized.

A Case of Hepatocellular Carcinoma Treated by Proton Beam Therapy as 1st Choice

Although first-line treatment option for single, small sized hepatocellular carcinoma in patients with preserved liver function and good performance status is resection or ablation, sometimes these modalities cannot be applied for variable reasons. For them, alternative options such as transarterial chemoeombolization, ethanol injection, and external radiation therapy can be considered, with variable success rates. Herein, we describe 45 year-old male who presented with a single small tumor located at caudate lobe. After multi-disciplinary discussion, the patient was treated with proton beam therapy, which resulted in favorable treatment outcome.

Radiation Therapy against Pediatric Malignant Central Nervous System Tumors : Embryonal Tumors and Proton Beam Therapy

Radiation therapy is highly effective for the management of pediatric malignant central nervous system (CNS) tumors including embryonal tumors. With the increment of long-term survivors from malignant CNS tumors, the radiation-related toxicities have become a major concern and we need to improve the treatment strategies to reduce the late complications without compromising the treatment outcomes. One of such strategies is to reduce the radiation dose to craniospinal axis or radiation volume and to avoid or defer radiation therapy until after the age of three. Another strategy is using particle beam therapy such as proton beams instead of photon beams. Proton beams have distinct physiologic advantages over photon beams and greater precision in radiation delivery to the tumor while preserving the surrounding healthy tissues. In this review, I provide the treatment principles of pediatric CNS embryonal tumors and the strategic improvements of radiation therapy to reduce treatment-related late toxicities, and finally introduce the increasing availability of proton beam therapy for pediatric CNS embryonal tumors compared with photon beam therapy.

Radiation Therapy against Pediatric Malignant Central Nervous System Tumors : Embryonal Tumors and Proton Beam Therapy

Radiation therapy is highly effective for the management of pediatric malignant central nervous system (CNS) tumors including embryonal tumors. With the increment of long-term survivors from malignant CNS tumors, the radiation-related toxicities have become a major concern and we need to improve the treatment strategies to reduce the late complications without compromising the treatment outcomes. One of such strategies is to reduce the radiation dose to craniospinal axis or radiation volume and to avoid or defer radiation therapy until after the age of three. Another strategy is using particle beam therapy such as proton beams instead of photon beams. Proton beams have distinct physiologic advantages over photon beams and greater precision in radiation delivery to the tumor while preserving the surrounding healthy tissues. In this review, I provide the treatment principles of pediatric CNS embryonal tumors and the strategic improvements of radiation therapy to reduce treatment-related late toxicities, and finally introduce the increasing availability of proton beam therapy for pediatric CNS embryonal tumors compared with photon beam therapy.

Clinical Outcomes of Proton Beam Therapy for Choroidal Melanoma at a Single Institute in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study retrospectively evaluated the clinical outcomes and complications of proton beam therapy (PBT) in a single institution in Korea and quantitatively analyzed the change in tumor volume after PBT using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Twenty-four treatment-naïve patients who underwent PBT for choroidal melanoma between 2009 and 2015 were reviewed. Dose fractionation was 60-70 cobalt gray equivalents over 5 fractions. Orbital MRIs were taken at baseline and 3, 6, and 12 months after PBT and annually thereafter. The tumor volume was reconstructed and evaluated by stacking the tumor boundary in each thin-sliced axial T1-weighted image using MIM software. RESULTS: The median follow-up duration was 36.5 months (range, 9 to 82 months). One patient had suspicious local progression and two patients had distant metastasis. The 3-year local progression-free survival, distant metastasis-free survival, and overall survival rates were 95.8%, 95.8%, and 100%,respectively. Five Common Terminology Criteria for Adverse Event ver. 4.03 grade 3-4 toxicities were observed in four patients (16.7%), including one with neovascular glaucoma. The mean tumor volume at the baseline MRI was 0.565±0.084 mL (range, 0.074 to 1.610 mL), and the ratios of the mean volume at 3, 6, and 12 months to that at baseline were 81.8%, 67.3%, and 60.4%, respectively. CONCLUSION: The local controlrate and complication profile after PBT in patientswith choroidal melanoma in Korea were comparable with those reported in a previous PBT series. The change in tumor volume after PBT exhibited a gradual regression pattern on MRI.

Clinical outcome of proton therapy for patients with chordomas

PURPOSE: To investigate the clinical outcome of proton therapy (PT) in patients with chordoma. MATERIALS AND METHODS: Fifty-eight patients with chordoma treated with PT between June 2007 and December 2015 at the National Cancer Center, Korea, were retrospectively analyzed. The median total dose was 69.6 cobalt gray equivalent (CGE; range, 64.8 to 79.2 CGE). Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), overall survival (OS), and diseasespecific survival (DSS) rates were calculated by the Kaplan–Meier method. RESULTS: With the median follow-up of 42.8 months (range, 4 to 174 months), the 5-year LPFS, DMFS, OS, and DSS rates were 87.9%, 86.7%, 88.3%, and 92.9%, respectively. The tumor location was associated with the patterns of failure: the LPFS rates were lower for cervical tumors (57.1%) than for non-cervical tumors (93.1%) (p = 0.02), and the DMFS rates were lower for sacral tumors (53.5%) than for non-sacral tumors (100%) (p = 0.001). The total dose was associated with both the LPFS rate and DMFS rate. The initial tumor size was associated with the DMFS rate, but was not associated with the LPFS rate. Three patients had grade 3 late toxicity with none ≥grade 4. CONCLUSION: PT is an effective and safe treatment in patients with chordomas. The tumor location was associated with the patterns of failure: local failure was common in cervical tumors, and distant failure was common in sacral tumors. Further refinement of PT, such as the utilization of intensity modulated PT for cervical tumors, is warranted to improve the outcome.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma

PURPOSE: This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. MATERIALS AND METHODS: HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). RESULTS: A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62–92 GyE10. Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. CONCLUSION: PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

Radioprotective effects of delphinidin on normal human lung cells against proton beam exposure

BACKGROUND/OBJECTIVES: Exposure of the normal lung tissue around the cancerous tumor during radiotherapy causes serious side effects such as pneumonitis and pulmonary fibrosis. Radioprotectors used during cancer radiotherapy could protect the patient from side effects induced by radiation injury of the normal tissue. Delphinidin has strong antioxidant properties, and it works as the driving force of a radioprotective effect by scavenging radiation-induced reactive oxygen species (ROS). However, no studies have been conducted on the radioprotective effect of delphinidin against high linear energy transfer radiation. Therefore, this study was undertaken to evaluate the radioprotective effects of delphinidin on human lung cells against a proton beam. MATERIALS/METHODS: Normal human lung cells (HEL 299 cells) were used for in vitro experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay assessed the cytotoxicity of delphinidin and cell viability. The expression of radiation induced cellular ROS was measured by the 2′-7′-dicholordihydrofluorescein diacetate assay. Superoxide dismutase activity assay and catalase activity assay were used for evaluating the activity of corresponding enzymes. In addition, radioprotective effects on DNA damage-induced cellular apoptosis were evaluated by Western blot assay. RESULTS: Experimental analysis, including cell survival assay, MTT assay, and Western blot assay, revealed the radioprotective effects of delphinidin. These include restoring the activities of antioxidant enzymes of damaged cells, increase in the levels of pro-survival protein, and decrease of pro-apoptosis proteins. The results from different experiments were compatible with each to provide a substantial conclusion. CONCLUSION: Low concentration (2.5 µM/mL) of delphinidin administration prior to radiation exposure was radioprotective against a low dose of proton beam exposure. Hence, delphinidin is a promising shielding agent against radiation, protecting the normal tissues around a cancerous tumor, which are unintentionally exposed to low doses of radiation during proton therapy.

The Effect of Anti-reflux Therapy on Patients Diagnosed with Minor Disorders of Peristalsis in High-resolution Manometry / 대한소화기학회지

BACKGROUND/AIMS: Minor disorders of peristalsis are esophageal motility disorders categorized by the Chicago Classification (CC), version 3.0, which was announced in 2014. This study evaluated the efficacy of anti-reflux therapy in patients with minor peristaltic disorders. METHODS: Patients with minor peristaltic disorders in accordance with CC v3.0 were included. We reviewed the medical records of patients with esophageal high-resolution manometry findings, and investigated the demographic and clinical information as well as the medical therapy. Thereafter, the response to treatment was assessed after at least 4 weeks of treatment. RESULTS: A total of 24 patients were identified as having minor disorders of peristalsis from January 2010 to December 2015. The mean follow-up period was 497 days, and there were 17 patients (70.8%) patients with ineffective esophageal motility. In terms of anti-reflux therapy, proton pump inhibitors (PPIs) with prokinetic agents and PPIs alone were prescribed in 19 patients (79.2%) and 5 patients (20.8%), respectively. When the rate of response to the treatment was assessed, the responders rate (complete+satisfactory [≥50%] responses) was 54.2% and the non-responders rate (partial [<50%]+refractory responses) was 45.8%. Patients in the responder group were younger than those in the non-responder group (p=0.020). Among them, 13 patients underwent 24-hour multichannel intraluminal impedance-pH, and 10 patients (76.9%) were pathologic gastroesophageal reflux. CONCLUSIONS: The majority of esophageal minor peristaltic disorders were accompanied by gastroesophageal reflux, and therefore, they might respond to acid inhibitor. Further well-designed, prospective studies are necessary to confirm the effect of anti-reflux therapy in these patients.

Neurocognitive and Psychological Functioning of Children with an Intracranial Germ Cell Tumor / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to investigate the neurocognitive functioning of children with intracranial germ cell tumor (IGCT) prior to receiving proton beam therapy (PBT), and to identify differential characteristics of their neurocognitive functioning depending on tumor location. As a secondary object of this study, neurocognitive functions were followed up at 1-2 years after PBT to examine early post-treatment changes. MATERIALS AND METHODS: Between 2008 and 2014, 34 childrenwith IGCT treatedwho received PBT atNational Cancer Center, Korea were enrolled in this study. Standardized neurocognitive tests of intelligence, memory, and executive functioning were performed with baseline psychological assessments using the Child Behavior Checklist (CBCL). Follow-up assessments after PBT were conducted in 20 patients (T2). The results were analyzed based on the locations of tumors, which included the suprasellar, pineal gland, basal ganglia, and bifocal regions. RESULTS: The neurocognitive function of IGCT patients was significantly lower than that of the normal population in performance intelligence quotient (p=0.041), processing speed (p=0.007), memory (p < 0.001), and executive functioning (p=0.010). Patients with basal ganglia tumors had significantly lower scores for most domains of neurocognitive functioning and higher scores for CBCL than both the normal population and patients with IGCT in other locations. There was no significant change in neurocognitive function between T1 and T2 for all types of IGCT patients in first 1-2 years after PBT. CONCLUSION: Tumor location significantly affects the neuropsychological functioning in patients with IGCT. Neuropsychological functioning should be closely monitored from the time of diagnosis in IGCT patients.

Novel Therapeutic Strategies in the Management of Non-Variceal Upper Gastrointestinal Bleeding

Non-variceal upper gastrointestinal bleeding, the most common etiology of which is peptic ulcer disease, remains a persistent challenge despite a reduction in both its incidence and mortality. Both pharmacologic and endoscopic techniques have been developed to achieve hemostasis, with varying degrees of success. Among the pharmacologic therapies, proton pump inhibitors remain the mainstay of treatment, as they reduce the risk of rebleeding and requirement for recurrent endoscopic evaluation. Tranexamic acid, a derivative of the amino acid lysine, is an antifibrinolytic agent whose role requires further investigation before application. Endoscopically delivered pharmacotherapy, including Hemospray (Cook Medical), EndoClot (EndoClot Plus Inc.), and Ankaferd Blood Stopper (Ankaferd Health Products), in addition to standard epinephrine, show promise in this regard, although their mechanisms of action require further investigation. Non-pharmacologic endoscopic techniques use one of the following two methods to achieve hemostasis: ablation or mechanical tamponade, which may involve using endoscopic clips, cautery, argon plasma coagulation, over-the-scope clipping devices, radiofrequency ablation, and cryotherapy. This review aimed to highlight these novel and fundamental hemostatic strategies and the research supporting their efficacy.

Pharmacologic Management of Nonvariceal Upper Gastrointestinal Bleeding

Acute non-variceal upper gastrointestinal bleeding, the most common etiology of which is peptic ulcer disease, remains a persistent challenge despite a reduction in both its incidence and mortality. Both pharmacologic and endoscopic techniques have been developed to achieve hemostasis, with varying degrees of success. Among the pharmacologic therapies, proton pump inhibitor (PPI) remains the mainstay of treatment with potent acid suppression. Maintenance of the intragastric pH level above 6 by the administration of PPI prevents hemolysis caused by acid or pepsin and thereby promotes aggregation of platelets. Intragastric acid suppression can be achieved more effectively with continuous intravenous infusion of PPI after intravenous bolus injection. A high dose intravenous PPI is effective in reducing the risk of rebleeding, the need for surgery and repeated endoscopy. However, data regarding non-high dose intravenous PPIs are limited. In the future, novel PPIs and potassium-competitove acid blocker are in the area of interest. Combination therapy with the use of endoscopic hemostatic treatment and intravenous PPI administration is known to result in the best outcome for non-variceal upper gastrointestinal bleeding.

Understanding the Treatment Strategies of Intracranial Germ Cell Tumors: Focusing on Radiotherapy

Intracranial germ cell tumors (ICGCT) occur in 2-11% of children with brain tumors between 0-19 years of age. For treatment of germinoma, relatively low radiation doses with or without chemotherapy show excellent 10 year survival rate of 80-100%. Past studies showed that neoadjuvant chemotherapy combined with focal radiotherapy resulted in unacceptably high rates of periventricular tumor recurrence. The use of generous radiation volume which covers the whole ventricular space with later boost treatment to primary site is considered as standard treatment of intracranial germinomas. For non-germinomatous germ cell tumors (NGGCT), 10-year overall survival rate is still much inferior than that of intracranial germinoma despite intensive chemotherapy and high-dose radiotherapy. Craniospinal radiotherapy combined with cisplatin-based chemotherapy provides the best treatment outcome for NGGCT; 60-70% of overall survival rate. There is a debate on the surgical role whether surgery can contribute to improved treatment outcome of NGGCT when added to combined chemoradiotherapy. Because higher dose of radiotherapy is required for treatment of NGGCT than for germinoma, it is tested whether whole ventricular irradiation can replace craniospinal irradiation in intermediate risk group of NGGCT to minimize radiation-related late toxicity in the recent studies. To minimize the treatment-related neural deficit and late sequelae while maintaining long-term survival rate of ICGCT patients, optimized administration of chemotherapy and radiotherapy should be selected. Use of technically upgraded radiotherapy modalities such as intensity-modulated radiotherapy or proton beam therapy is expected to bring an improved neurocognitive outcome with longitudinal assessment of the patients.

Phase I Dose-Escalation Study of Proton Beam Therapy for Inoperable Hepatocellular Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to determine the optimal dose of proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: Inoperable HCC patients who had naive, recurrent, or residual tumor to treatment were considered eligible for PBT. Patients received PBT with 60 GyE in 20 fractions (dose level 1; equivalent dose in 2 Gy fractions [EQD2], 65 GyE10); 66 GyE in 22 fractions (dose level 2; EQD2, 71.5 GyE10); or 72 GyE in 24 fractions (dose level 3; EQD2, 78 GyE10). Dose-limiting toxicity was determined by grade > or = 3 acute toxicity. RESULTS: Twenty-seven patients were enrolled; eight, seven, and 12 patients were treated with dose levels 1, 2, and 3, respectively. Overall, treatment was well tolerated, with no dose-limiting toxicities. The complete response (CR) rates of primary tumors after PBT for dose levels 1, 2, and 3 were 62.5% (5/8), 57.1% (4/7), and 100% (12/12), respectively (p=0.039). The 3-and 5-year local progression-free survival (LPFS) rates among 26 patients, excluding one patient who underwent liver transplantation after PBT due to its probable significant effect on disease control, were 79.9% and 63.9%, respectively, and the 3-and 5-year overall survival rates were 56.4% and 42.3%, respectively. The 3-year LPFS rate was significantly higher in patients who achieved CR than in those who did not (90% vs. 40%, p=0.003). CONCLUSION: PBT is safe and effective and an EQD2 > or = 78 GyE10 should be delivered for achievement of local tumor control.

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center

PURPOSE: The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. MATERIALS AND METHODS: The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. RESULTS: The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. CONCLUSION: The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.

Radiotherapy for prostate cancer

Radiotherapy has an important role in the management of prostate cancer patients. It can be used as definitive treatment in place of surgery, postoperative adjuvant radiotherapy, or salvage treatment when recurrences develop after surgery. During definitive radiotherapy treatment, dose escalation can improve biochemical control but has not led to improved survival to date. Hypofractionated radiotherapy is applied for prostate cancer treatment, since prostate cancer has a low alpha/beta ratio. Contrary to theoretical expectations, hypofractionated treatment does not show improved therapeutic results and decreased toxicity, but it can reduce overall treatment time. Ongoing non-inferiority trials may assist in determining optimal hypofractionated treatment regimens. Adjuvant radiotherapy in patients with pathological T3 or positive resection margins can improve biochemical control and might increase overall survival. However, there is debate regarding the superiority of adjuvant radiotherapy over early salvage radiotherapy in high-risk patients after surgery. To address this issue, it will be necessary to wait for the results of current randomized trials.