Development and Accuracy Evaluation of Augmented Reality-based Patient Positioning System in Radiotherapy: A Phantom Study.

BACKGROUND/AIM: To develop and evaluate the accuracy of augmented reality (AR)-based patient positioning systems in radiotherapy. MATERIALS AND METHODS: AR head-mounted displays (AR-HMDs), which virtually superimpose a three-dimensional (3D) image generated by the digital imaging and communications in medicine (DICOM) data, have been developed. The AR-based positioning feasibility was evaluated. Then, the setup errors of three translational axes directions and rotation angles between the AR and the conventional laser-based positioning were compared. RESULTS: The AR-based pelvic phantom positioning was feasible. The setup errors of AR-based positioning were comparable to laser-based positioning in all translational axis directions and rotation angles. The time necessary for AR-based positioning was significantly longer than that for laser-based positioning (171.0 s vs. 47.5 s, p<0.001). CONCLUSION: AR-based positioning for radiotherapy was feasible, and showed comparable positioning errors to those of conventional line-based positioning; however, a markedly longer setup time was necessary.

Improved error detection using a divided treatment plan in volume modulated arc therapy.

AIM: We sought to improve error detection ability during volume modulated arc therapy (VMAT) by dividing and evaluating the treatment plan. BACKGROUND: VMAT involves moving a beam source delivering radiation to tumor tissue through an arc, which significantly decreases treatment time. Treatment planning for VMAT involves many parameters. Quality assurance before treatment is a major focus of research. MATERIALS AND METHODS: We used an established VMAT prostate treatment plan and divided it into 12° × 30° sections. In all the sections, only image data that generated errors in one segment and those that were integrally acquired were evaluated by a gamma analysis. This was done with five different patient plans. RESULTS: The integrated image data resulting from errors in each section was 100% (tolerance 0.5 mm/0.5%) in the gamma analysis result in all image data. Division of the treatment plans produced a shift in the mean value of each gamma analysis in the cranial, left, and ventral directions of 94.59%, 98.83%, 96.58%, and the discrimination ability improved. CONCLUSION: The error discrimination ability was improved by dividing and verifying the portal imaging.

Relative biological effectiveness of therapeutic proton beams for HSG cells at Japanese proton therapy facilities.

We investigated the relative biological effectiveness (RBE) of therapeutic proton beams at six proton facilities in Japan with respect to cell lethality of HSG cells. The RBE of treatments could be determined from experimental data. For this purpose, we used a cell survival assay to compare the cell-killing efficiency of proton beams. Among the five linear accelerator (LINAC) X-ray machines at 4 or 6 MeV that were used as reference beams, there was only a small variation (coefficient of variation CV = 3.1% at D10) in biological effectiveness. The averaged value of D10 for the proton beams at the middle position of the spread-out Bragg peak (SOBP) was 4.98. These values showed good agreement, with a CV of 4.3% among the facilities. Thus, the average RBE10 (RBE at the D10 level) at the middle position of the SOBP beam for six facilities in Japan was 1.05 with a CV of 2.8%.

Curative-intent stereotactic body radiation therapy for residual breast cancer liver metastasis after systemic chemotherapy.

Liver metastases from breast cancer are generally treated with systemic therapy such as chemotherapy or hormonotherapy. However, local treatment options such as resection, radiofrequency ablation (RFA), and radiotherapy can also be considered to treat oligometastases. We report the case of a 45-year-old female treated with stereotactic body radiotherapy (SBRT) after chemotherapy against a solitary liver metastasis from primary breast cancer. A liver metastasis with diameter of 35 mm developed 3.5 years after surgery for primary breast cancer in 2004. Fourteen courses of triweekly docetaxel treatments considerably decreased the metastatic lesion, but there still remained a tiny lesion radiographically. Chemotherapy was stopped because of the side-effects of docetaxel, and then SBRT was selected for additional treatment, aiming at complete cure of metastasis. X-ray irradiation (52.8 Gy/4 fractions) was applied to the remaining metastatic lesion, and magnetic resonance imaging (MRI) showed no evidence of residual tumor 4 months after irradiation. Neither regrowth nor recurrences have been found until now, 24 months after SBRT. SBRT for oligometastases of breast cancer may be one of the possible curative-intent options, being less invasive than surgical resection or RFA.

[Effects of stereotactic radiotherapy targeting for recurrent gastric cancer].

We report the effects of stereotactic radiotherapy (SRT) targeting for distant solitary metastases from gastric cancer that were uncontrollable with chemotherapy. SRT(52.8 Gy per 4 fractions) was performed in 3 patients with liver metastasis and 1 patient with lung metastasis. Although SRT showed no effect in the patient with lung metastasis, complete remission from liver metastasis with cystic change was observed in all 3 patients. One patient died due to multiple liver metastasis, and the other 2 patients are alive 27 and 41 months after SRT without liver metastasis. Although pneumothorax and pleural effusion were recognized in 1 case, grade 3 or 4 adverse events were not recognized in all 4 cases. SRT showed excellent local therapeutic effects without serious complications, suggesting that this is an effective treatment for localized metastasis from gastric cancer.

[A case of paraaortic lymph node metastasis of gastric cancer resistant to chemotherapy successfully treated with chemoradiation therapy].

We report a case of recurrent gastric cancer with paraaortic lymph nodes (No.16LNs) that was effectively controlled with chemoradiation therapy. A 63-year-old man underwent distal gastrectomy, cholecystectomy, and D2 dissection in July 2004 for advanced gastric cancer in the lower third area that was diagnosed as moderately differentiated stage II adenocarcinoma [T1(SM), N2, H0, P0, CY0, M0]. He suffered from No.16LNs metastasis with serum CEA elevation in October 2007, and therefore, 4 courses of S-1, followed by 3 courses of CPT-11 as second-line treatment, 14 courses of docetaxel as third-line treatment, and 15 courses of paclitaxel+cisplatin as fourth-line chemotherapy, were administrated. Enlargement of No.16LNs with serum CEA elevation was observed in October 2010. Other metastases were not observed, and hence, chemoradiotherapy (CRT; S-1: 80 mg/body+total of 65 Gy per 26 Fr) for No.16LNs was performed. A partial response and reduction of serum CEA level were noted, and the patient is alive with no sign of progression 18 months after CRT. Grade 1 adverse events including anemia, fatigue, and anorexia were recognized. It is thought that chemoradiation therapy is an effective treatment for localized LN metastasis originating from gastric cancer resistant to chemotherapy.

[Complete remission of liver metastasis from gall bladder carcinoma after stereotactic radiotherapy-a case report].

A 75-year-old man was diagnosed as gall bladder carcinoma by postoperative histological examination following laparoscopic cholecystectomy. He underwent the second surgery of resection of liver bed and port sites with lymph node dissection. Isolated hepatic metastasis of 20 mm in diameter was found in S4/8 by MRI 18 months postoperatively, and stereotactic radiotherapy (52.8 Gy/4 Fr) was done for the metastatic lesion. The lesion could not be detected by CT 7 months after the radiotherapy, and thereafter no local recurrence has been observed for 24 months. However, lymph node metastasis of #9 was diagnosed 31 months postoperatively. Liniac radiotherapy (60 Gy/20 Fr)was performed and stable disease has been obtained for 9 months. The patient is alive at present of 43 months after surgery without any other site of the disease, and his quality of life is well maintained. Stereotactic radiotherapy showed an excellent local therapeutic effect without any serious complications, suggesting that this is a potent modality for isolated liver metastasis of gall bladder carcinoma.

[A case of recurrent gastric cancer successfully treated with radiation therapy].

We report a case of recurrent gastric cancer that was effectively controlled with radiation therapy. A 63-year-old man underwent total gastrectomy, cholecystectomy and D2 dissection in February 2006 for early gastric cancer in the upper third area that was diagnosed with papillary adenocarcinoma and Stage IA (T1 (SM), N0, H0, P0, CY0, M0). He underwent lateral segmentectomy of the liver for liver metastasis of S2/3. He suffered from No. 12 lymph node(LN)metastasis in February 2009, so CPT-11, next to S-1, was administered. Portal tumor thrombosis (PTT) and liver S8 metastasis were observed in September 2009. First, chemoradiotherapy (CRT) ( S-1 80 mg/body+total of 65 Gy per 26 Fr) for #12 LN and PTT was performed and, in turn, stereotactic radiation therapy (SRT: total of 52.8 Gy per 4 Fr) was performed. A complete response in all of tumors was noted and he was presently alive with no sign of recurrence after 19 months after CRT and SRT. Grade 3 or 4 adverse events were not recognized. It is thought that radiation therapy is one of effective treatments for localized metastasis from gastric cancer.

Radiation therapy for gastric wall metastasis from esophageal carcinoma.

An 86-year-old man with dysphagia underwent gastrointestinal fiberscopy (GIF) and was found to have a circumferential type 3 advanced carcinoma in the upper thoracic esophagus and a type 2 tumor in the posterior wall of the gastric body. Microscopic examination of biopsy specimens of both tumors demonstrated moderately differentiated squamous cell carcinoma. He was diagnosed as having stage IVb (T3N0M1b) esophageal carcinoma with gastric wall metastasis. A total of 60 Gy in 30 fractions of three-dimensional conformal radiation therapy (3D-CRT) was first administered to the esophageal carcinoma, next to the gastric wall metastasis. Concurrent chemotherapy was not given because of the patient's refusal. No subjective morbidity was observed during the treatment. In the GIF study immediately after 3D-CRT, both esophageal and gastric wall tumors had attained a complete response. The dysphagia dissolved as the esophageal tumor shrunk. The patient has been doing well for 17 months after the start of 3D-CRT. No local recurrence was observed in either the esophagus or the stomach during follow-up GIF. Considering the dismal prognosis of esophageal carcinoma patients with intramural metastasis to the stomach, a watchful follow-up is needed.

[A case of advanced gastric cancer successfully treated with chemoradiotherapy targeting for recurrent lymph node metastasis].

The patient was a 75-year-old male, who was diagnosed with type 3 advanced gastric cancer and bulky lymph node metastasis. Two courses of neoadjuvant chemotherapy (S-1, CDDP) which showed a partial remission and distal gastrectomy were performed. Although he received S-1 medication as adjuvant chemotherapy, lymph node recurrence appeared 6 months after the operation. Radiation therapy at a total dose of 65 Gy (10MV X ray, 2.5 Gy/day × 26 Fr) selectively targeting for recurrent lymph node metastasis with S-1 medication were applied. There were no adverse effects during chemoradiation therapy and the metastatic node showed regression (30 mm to 15 mm). Sixteen months passed from chemoradiation, and the patient remains alive with no signs of relapse without any treatment after the chemoradiation. Therefore, our case suggests that chemoradiation therapy could be an effective treatment for recurrent lymph nodes metastasis in gastric cancer.

[A case of liver metastasis from gastric cancer treated with stereotactic radiation therapy].

We report a case of liver metastasis from gastric cancer that was effectively controlled with stereotactic radiation therapy (SRT). A 77-year-old man underwent total gastrectomy, splenectomy, cholecystectomy and D2 dissection in February 2007 for type 3 gastric cancer in the upper third area that was diagnosed well to moderately differentiated adenocarcinoma and Stage II (T3 (SE) N0 H0 P0 CY0 M0). He suffered from the liver and peritoneal metastases with ascites in December 2007, so S-1 was administered. Ascites was disappeared, but liver metastasis was enlarged. Therefore, SRT (total of 52.8 Gy per 4 fractions) was performed for the liver metastasis. A clear reduction in tumor size was noted and he was presently alive with no sign of recurrence after 2 years. Immediately after SRT, grade 3 neutropenia and grade 2 AST/ALT elevation were occurred. Grade 2 pneumothorax and pleural effusion were recognized in August 2009 as tardive adverse event. It is thought that SRT is one of effective treatments for liver metastasis from gastric cancer.

External-beam radiotherapy for clinically localized prostate cancer in Osaka, Japan, 1995-2006: time trends, outcome, and risk stratification.

PURPOSE: To establish an initial database of external-beam radiotherapy (EBRT) for clinically localized prostate cancer used in Osaka, Japan, and, by analyzing the results of the Osaka multicenter cooperative study, to determine time trends, outcome, and applicability of existing and the authors' original risk stratification methods. PATIENTS AND METHODS: Data of 652 patients with clinically localized prostate cancer (T1-4 N0 M0) were accrued from July to December 2007. These patients had been treated from 1995 through 2006 with consecutive definitive EBRT of > or = 60 Gy at eleven institutions, mainly in Osaka. Altogether, 436 patients were eligible for analysis using several risk stratification methods, namely, those of D'Amico et al., the National Comprehensive Cancer Network (NCCN), and Seattle, as well as the authors' original Prostate Cancer Risk Index (PRIX). RESULTS: The number of patients showed a tenfold increase over 10 years, together with a rapid spread of the use of Gleason Score from 0% to > 90% of cases. The dominant RT dose fractionation was 70 Gy/35 fractions (87%). Hormone therapy had been administered to 95% of the patients and the higher PRIX corresponded to the higher rate of hormone usage. 3- and 5-year biochemical relapse-free survival (bRFS) rates were 85% and 70%, respectively. The D'Amico (p = 0.132), NCCN (p = 0.138), Seattle (p = 0.041) and PRIX (p = 0.044) classifications showed weak or no correlation with bRFS, while the own modified three-class PRIX (PRIX 0, 1-5, 6) showed a strong correlation (p = 0.002). CONCLUSION: The use of prostate EBRT in Japan is still in its infancy, but is rapidly expanding. The short-term outcomes have been satisfactory considering the moderate RT dose. A very high rate of hormone usage may affect the outcome favorably, but also may compromise the usefulness of current risk stratification.

Acute morbidity of proton therapy for prostate cancer: the Hyogo Ion Beam Medical Center experience.

PURPOSE: To investigate the incidence and influencing factors of acute genitourinary (GU) and gastrointestinal morbidities in patients with prostate cancer treated with proton therapy. METHODS AND MATERIALS: A total of 287 patients with histologically proven Stage cT1-T4N0M0 prostate cancer were treated with proton therapy between 2003 and 2004. Of these, 204 (71%) received neoadjuvant androgen suppression therapy. The patients were treated with 190-230-MeV protons using lateral-opposed techniques to a dose of 74 GyE. Dose-volume histogram analyses were performed. The incidence of acute morbidity was evaluated using the National Cancer Institute Common Toxicity Criteria, version 2.0. Clinical factors, including age, clinical target volume, initial prostate-specific antigen level, T stage, presence of diabetes mellitus, and the use of androgen suppression therapy, were investigated to determine whether those affected the incidence of acute GU morbidity. RESULTS: None developed Grade 2 or higher acute gastrointestinal morbidity. In contrast, 111 (39%) and 4 (1%) patients experienced acute Grade 2 and Grade 3 GU morbidities, respectively. However, 87% of the patients were successfully relieved by the administration of a selective alpha-1 blocker. Multivariate analysis showed that a larger clinical target volume (p = 0.001) and the use of androgen suppression therapy (p = 0.017) were significant factors for the prediction of acute Grade 2-3 GU morbidity. CONCLUSION: In our experience with proton therapy, a low incidence of acute gastrointestinal morbidity was observed. In contrast, the incidence of acute GU morbidity was similar to that in other reports of photon radiotherapy. Additional follow-up is warranted to elucidate the long-term safety and efficacy of proton therapy for prostate cancer.

Particle irradiation suppresses metastatic potential of cancer cells.

Particle radiotherapy such as proton and carbon ion has been producing promising clinical results worldwide. The purpose of this study was to compare metastatic capabilities of malignant tumor cells after irradiation with photon, proton, and carbon ion beams to clarify their ion beam-specific biological effects. We examined the biological properties of highly aggressive HT1080 human fibrosarcoma cells to assess their metastatic processes in terms of cell adhesion capability to extracellular matrix, expression of integrins, cell migration, cell invasive capability, and matrix metalloproteinase-2 activity in vitro. We then assessed the metastatic capabilities of LM8 mouse osteosarcoma irradiated with carbon ion or photon beam in the syngeneic mice. Both proton and carbon ion irradiation decreased cell migration and invasion in a dose-dependent manner and strongly inhibited matrix metalloproteinase-2 activity. On the other hand, lower X-ray irradiation promoted cell migration and invasion concomitant with up-regulation of alphaVbeta3 integrin. For cancer cells treated with carbon ion irradiation, the number of pulmonary metastasis was decreased significantly in vivo. These findings suggest that particle irradiation suppresses metastatic potential even at lower dose, whereas photon irradiation promotes cell migration and invasive capabilities at lower dose level, and provide preclinical evidence that ion beam radiotherapy may be superior to conventional photon beam therapy in possible preventive effects on metastases of irradiated malignant tumor cells.

A case of hepatocellular carcinoma initially treated by carbon ions, followed by protons for marginal recurrence with portal thrombus.

We report a case of hepatocellular carcinoma (HCC), initially treated by carbon ions, then subsequently by protons for marginal recurrence. A 52-year-old man with stage II HCC was enrolled in the clinical study for carbon ion therapy. A total dose of 52.5 GyE in 8 fractions was delivered through a right lateral port for 13 days. Dynamic CT performed 7 months after the initiation of carbon ion therapy showed a decrease in the size of the tumor. Dynamic CT performed 12 months after the therapy revealed marginal recurrence of HCC accompanied with portal vein tumor thrombus (PVTT). Proton therapy of 66 GyE in 22 fractions was delivered through posterior and right lateral ports for 33 days. Dynamic CT performed 3 months after the initiation of proton therapy showed a regression of the recurrent tumor and disappearance of the PVTT. No serious adverse effects were observed during or after these two treatments. He was free from further recurrence 27 months after the initiation of the first carbon ion therapy. Both carbon ions and protons were effective with minimal side effects.

Experience with conformal proton therapy for early prostate cancer.

A study was conducted to evaluate the use of proton beam therapy for the treatment of organ-confined prostate cancer. This is a preliminary assessment of treatment-related morbidity and tumor response. Sixteen patients with T1-T2b prostate cancer underwent proton beam therapy. Acute and late toxicity was scored according to the National Cancer Institute Common Toxicity Criteria Grading System (version 2.0, April 1999) and to the Radiation Therapy Oncology Group grading system, respectively. Local control was assessed using magnetic resonance imaging (MRI) and prostate-specific antigen (PSA) values. Although skin toxicity and bladder irritability were commonly observed, none of the patients developed grade III or IV toxicity. Of 9 patients in whom the primary lesion was detected by MRI, partial response and no change (NC) was observed in 6 (66.7%) and 3 (33.3%) patients, respectively. Four patients presented normal PSA value before treatment due to the previous endocrine therapy. However, the other 12 patients with elevated PSA value before treatment showed complete response. No patients showed PSA failure within the median follow-up period of 11.9 months. Although longer follow-up is necessary, minimum toxicity and good short-term clinical responses were observed following proton beam therapy in T1-T2 prostate cancer patients.

Cell biological basis for combination radiotherapy using heavy-ion beams and high-energy X-rays.

We investigated the biological effect of combining carbon-beam and X-ray in vitro. The results showed that when we employed Gray equivalent as the indication of therapeutic dose, the effects could be explained with simple additive way in the treatment plan. This fact provides important information about the combined therapy of carbon-beam and X-ray.

Status of the clinical work at Hyogo.

On April 1, 2001, the Hyogo Ion Beam Medical Center (HIBMC) was opened as the first facility in the world to provide ion beam therapy using 2 types of beams, protons and carbon-ions. We will introduce the HIBMC, and report the results of the clinical study and general practice.

Preclinical biological assessment of proton and carbon ion beams at Hyogo Ion Beam Medical Center.

PURPOSE: To assess the biologic effects of proton and carbon ion beams before clinical use. METHODS AND MATERIALS: Cultured cells from human salivary gland cancer (HSG cells) were irradiated at 5 points along a 190 MeV per nucleon proton and a 320 MeV per nucleon carbon ion beam, with Bragg peaks modulated to 6 cm widths. A linac 4 MV X-ray was used as a reference. Relative biologic effectiveness (RBE) values at each point were calculated from survival curves. Cells were also irradiated in a cell-stack phantom to identify that localized cell deaths were observed at predefined depth. Total body irradiation of C3H/He mice was performed, and the number of regenerating crypts per jejunal section was compared to calculate intestinal RBE values. For carbon ion and referential 4 MV X-ray beams, mouse right legs were irradiated by four-fractional treatment and followed up for skin reaction scoring. RESULTS: RBE values calculated from cell survival curves at the dose that would reduce cell survival to 10% (D10) ranged from 1.01 to 1.05 for protons and from 1.23 to 2.56 for carbon ions. The cell-stack phantom irradiation revealed localized cell deaths at predefined depth. The intestinal RBE values ranged from 1.01 to 1.08 for protons and from 1.15 to 1.88 for carbon ions. The skin RBE value was 2.16 at C320/6 cm spread-out Bragg peak (SOBP) center. CONCLUSION: The radiobiologic measurements of proton and carbon ion beams at Hyogo Ion Beam Medical Center are consistent with previous reports using proton beams in clinical settings and carbon ion beams with similar linear energy transfer (LET) values.

Usefulness of positron-emission tomographic images after proton therapy.

PURPOSE: To examine the positron emission tomography (PET) image obtained after proton irradiation and investigate the usefulness of the image for confirmation of the irradiated volume in proton radiotherapy (RT). METHODS AND MATERIALS: A homogenous phantom was irradiated separately by carbon-ion and proton beams and the images obtained were compared. The PET images of cancer patients just after proton RT were then taken after informed consent. RESULTS: In the PET image produced by carbon-ion beams, the high pixel counts in the image corresponded to the Bragg peak; however, in that produced by proton beams, they were visible throughout the entire track of the proton beams and were not related to the Bragg peak. The PET image of patients treated with proton RT was similar to that of the phantom experiment. CONCLUSION: The PET image after proton RT was different from that of carbon-ion RT. It was found that the PET image was very useful in proton RT to verify treatment planning.