Stereotactic ablative body radiotherapy with a central high dose using CyberKnife for metastatic lung tumors.

BACKGROUND: The CyberKnife system features a robotically-positioned linear accelerator to deliver real-time image-guided stereotactic ablative body radiotherapy (SABR). It achieves steep dose gradients using irradiation from hundreds of different directions and increases the central dose of the gross tumor volume (GTV) without increasing the marginal dose to the planning target volume. We evaluated the effectiveness and safety of SABR with a central high dose using CyberKnife for metastatic lung tumors. METHODS: A total of 73 patients with 112 metastatic lung tumors treated with CyberKnife were retrospectively analyzed. Local control, progression-free survival, and overall survival were calculated using the Kaplan-Meier method. The median age was 69.2 years. The most common primary sites were the uterus (n = 34), colorectum (n = 24), head and neck (n = 17), and esophagus (n = 16). For peripheral lung tumors, the median radiation dose was 52 Gy in 4 fractions, whereas for centrally located lung tumors, it was 60 Gy in 8-10 fractions. The dose prescription was defined as 99% of the solid tumor components of the GTV. The median maximum dose within the GTV was 61.0 Gy. The GTV and planning target volume were enclosed conformally by the 80% and 70% isodose lines of the maximum dose, respectively. The median follow-up period was extended to 24.7 months; it was 33.0 months for survivors. RESULTS: The 2-year local control, progression-free survival, and overall survival rates were 89.1%, 37.1%, and 71.3%, respectively. Toxicities of grade ≥ 2 were noted as grade 2 and 3 radiation pneumonitis in one patient each. The two patients with grade 2 or higher radiation pneumonitis had both received simultaneous irradiation at two or three metastatic lung tumor sites. No toxicity of grade ≥ 2 was observed in patients with metastasis in one lung only. CONCLUSIONS: SABR with a central high dose using CyberKnife for metastatic lung tumors is effective with acceptable toxicity. TRIAL REGISTRATION: Number: 20557, Name: Stereotactic ablative radiotherapy using CyberKnife for metastatic lung tumor, URL: http://www.radonc.med.osaka-u.ac.jp/pdf/SBRT.pdf , Date of registration: April 1, 2021 (retrospectively registered), Date of enrollment: May 1, 2014.

Dosimetric advantages of daily adaptive strategy in IMPT for high-risk prostate cancer.

PURPOSE: To evaluate the dosimetric advantages of daily adaptive radiotherapy (DART) in intensity-modulated proton therapy (IMPT) for high-risk prostate cancer by comparing estimated doses of the conventional non-adaptive radiotherapy (NART) that irradiates according to an original treatment plan through the entire treatment and the DART that uses an adaptive treatment plan generated by using daily CT images acquired before each treatment. METHODS: Twenty-three patients with prostate cancer were included. A treatment plan with 63 Gy (relative biological effectiveness (RBE)) in 21 fractions was generated using treatment planning computed tomography (CT) images assuming that all patients had high-risk prostate cancer for which the clinical target volume (CTV) needs to include prostate and the seminal vesicle (SV) in our treatment protocol. Twenty-one adaptive treatment plans for each patient (total 483 data sets) were generated using daily CT images, and dose distributions were calculated. Using a 3 mm set-up uncertainty in the robust optimization, the doses to the CTV, prostate, SV, rectum, and bladder were compared. RESULTS: Estimated accumulated doses of NART and DART in the 23 patients were 60.81 ± 3.47 Gy (RBE) and 63.24 ± 1.04 Gy (RBE) for CTV D99 (p < 0.01), 62.99 ± 1.28 Gy (RBE) and 63.43 ± 1.33 Gy (RBE) for the prostate D99 (p = 0.2529), and 59.07 ± 5.19 Gy (RBE) and 63.17 ± 1.04 Gy (RBE) for SV D99 (p < 0.001). No significant differences were observed between NART and DART in the estimated accumulated dose for the rectum and bladder. CONCLUSION: Compared with the NART, DART was shown to be a useful approach that can maintain the dose coverage to the target without increasing the dose to the organs at risk (OAR) using the 3 mm set-up uncertainty in the robust optimization in patients with high-risk prostate cancer.

Multicenter prospective study of stereotactic body radiotherapy for previously untreated solitary primary hepatocellular carcinoma: The STRSPH study.

AIM: To prospectively evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for patients with previously untreated solitary primary hepatocellular carcinoma (HCC). METHODS: The main eligibility criteria included the following: (1) primary solitary HCC; (2) no prior treatment for HCC; (3) Child-Turcotte-Pugh score of seven or less; and (4) unsuitability for or refusal of surgery and radiofrequency ablation (RFA). The prescribed dose of SBRT was 40 Gy in five fractions. The primary endpoint was 3-year overall survival (OS); the secondary endpoints included local progression-free survival (LPFS), local control (LC), and adverse events. The accrual target was 60 patients, expecting a 3-year OS of 70% with a 50% threshold. RESULTS: Between 2014 and 2018, 36 patients were enrolled; enrollment was closed early because of slow accrual. The median tumor size was 2.3 cm. The median follow-up at the time of evaluation was 20.8 months. The 3-year OS was 78% (95% confidence interval [CI]: 53%-90%). The 3-year LPFS and LC proportion were 73% (95% CI: 48%-87%) and 90% (95% CI: 65%-97%), respectively. Grade 3 or higher SBRT-related toxicities were observed in four patients (11%), and grade five toxicities were not observed. CONCLUSIONS: This study showed acceptably low incidence of SBRT-related toxicities. LC and OS after SBRT were comparable for previously untreated solitary HCC for patients unfit for resection and RFA. Although a definitive conclusion cannot be drawn by this study, the promising results indicate that SBRT may be an alternative option in the management of early HCC.

Treatment outcomes of stereotactic body radiation therapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinomas.

AIM: To report the outcomes of stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinoma patients. METHODS: From January 2005 to July 2018, 63 patients with 74 lesions with a maximum diameter ≤52 mm were treated by stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system. No patient with a Child-Pugh Score ≥9 was included, and 85.6% had a score of 5 or 6. Using the biological effective dose (BED) with an α/ß ratio of 10 (BED10 ), the median dose in BED10 at the reference point was 76.8 Gy (range 60-122.5 Gy). Overall survival (OS) and local control rates were assessed using the Kaplan-Meier method. RESULTS: With a median follow-up period of 24.6 months (range 0.9-118.4 months), the 1-year and 2-year OS rates were 86.8% (95% confidence interval [95% CI] 75.8-93.3) and 71.1% (57.8-81.6), respectively. The 2-year OS was 89.6% in patients with the baseline modified albumin-bilirubin (mALBI) grade =1, and 61.7% in patients with grade ≥2a. In the multivariate analysis, the mALBI grade (=1 vs. ≥2a) was a significant factor for OS (p = 0.028, 95% CI 1.11-6.18). The 1-year and 2-year local control rates were 100% (100-100%) and 92.0% (77.5-97.5%). The local control rates were significantly higher in the BED10 ≥100 Gy group than in the BED10 <100 Gy group (2-year 100% vs. 86.5%, p = 0.049) at the reference point. CONCLUSION: This retrospective study of stereotactic body radiotherapy using real-time tumor-tracking radiotherapy for hepatocellular carcinoma showed favorable outcomes with lower incidence of toxicities, especially in patients treated with BED10 ≥100 Gy to the reference point.

Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas.

PURPOSE: To investigate potential advantages of adaptive intensity-modulated proton beam therapy (A-IMPT) by comparing it to adaptive intensity-modulated X-ray therapy (A-IMXT) for nasopharyngeal carcinomas (NPC). METHODS: Ten patients with NPC treated with A-IMXT (step and shoot approach) and concomitant chemotherapy between 2014 and 2016 were selected. In the actual treatment, 46 Gy in 23 fractions (46Gy/23Fx.) was prescribed using the initial plan and 24Gy/12Fx was prescribed using an adapted plan thereafter. New treatment planning of A-IMPT was made for the same patients using equivalent dose fractionation schedule and dose constraints. The dose volume statistics based on deformable images and dose accumulation was used in the comparison of A-IMXT with A-IMPT. RESULTS: The means of the Dmean of the right parotid gland (P < 0.001), right TM joint (P < 0.001), left TM joint (P < 0.001), oral cavity (P < 0.001), supraglottic larynx (P = 0.001), glottic larynx (P < 0.001), , middle PCM (P = 0.0371), interior PCM (P < 0.001), cricopharyngeal muscle (P = 0.03643), and thyroid gland (P = 0.00216), in A-IMPT are lower than those of A-IMXT, with statistical significance. The means of, D0.03cc , and Dmean of each sub portion of auditory apparatus and D30% for Eustachian tube and D0.5cc for mastoid volume in A-IMPT are significantly lower than those of A-IMXT. The mean doses to the oral cavity, supraglottic larynx, and glottic larynx were all reduced by more than 20 Gy (RBE = 1.1). CONCLUSIONS: An adaptive approach is suggested to enhance the potential benefit of IMPT compared to IMXT to reduce adverse effects for patients with NPC.

The updated outcomes of bladder-preserving trimodal therapy using a real-time tumor-tracking radiotherapy system for patients with muscle-invasive bladder cancer.

OBJECTIVE: Bladder-preserving trimodal therapy is recognized as a promising alternative treatment for muscle-invasive bladder cancer. We report the updated outcomes of muscle-invasive bladder cancer patients that were treated using our treatment protocol, which involves radiotherapy delivered with a real-time tumor-tracking radiotherapy system. METHODS: Thirty-eight patients who were diagnosed with T2-T4N0M0 bladder cancer between 1998 and 2016 and had clinically inoperable disease or refused to undergo surgery were enrolled. The treatment protocol included maximal transurethral resection followed by whole-bladder radiotherapy (40 Gy). Concurrent nedaplatin-based chemotherapy was administered to patients with adequate renal function. At the time of the first evaluation (via transurethral resection of the tumor bed), fiducial markers were endoscopically inserted into the bladder wall around the tumor. A boost of 25 Gy was administered using the real-time tumor-tracking radiotherapy system. The second evaluation (via transurethral resection of the tumor bed) was performed 6 months after the start of treatment. The Kaplan-Meier method and Cox hazards analysis were used to analyze overall survival and cancer-specific survival. RESULTS: The median duration of the follow-up period was 28 months (range: 3-161 months). The 5- and 10-year overall survival rates were 54.9 and 41.2%, respectively. Twenty-five (65.8%) and twenty (74.1%) patients had achieved complete responses to chemoradiation at the first and second evaluations, respectively. In univariate and multivariate analyses, performance status was found to be significantly associated with overall survival [P = 0.03, hazard ratio: 3.48, 95% confidence interval: 1.15-10.6] and cancer-specific survival [P = 0.02, hazard ratio: 4.57, 95% confidence interval: 1.32-16.9], and sex was shown to be significantly associated with cancer-specific survival [P = 0.03, hazard ratio: 3.07, 95% confidence interval: 1.09-8.30]. CONCLUSIONS: Our bladder-preserving trimodal therapy protocol, which involves the use of a real-time tumor-tracking radiotherapy system, produced an acceptable overall survival rate. This therapy is a reasonable alternative for patients that are medically unfit for or do not want to undergo cystectomy.

Dynamic gating window technique for the reduction of dosimetric error in respiratory-gated spot-scanning particle therapy: An initial phantom study using patient tumor trajectory data.

Spot-scanning particle therapy possesses advantages, such as high conformity to the target and efficient energy utilization compared with those of the passive scattering irradiation technique. However, this irradiation technique is sensitive to target motion. In the current clinical situation, some motion management techniques, such as respiratory-gated irradiation, which uses an external or internal surrogate, have been clinically applied. In surrogate-based gating, the size of the gating window is fixed during the treatment in the current treatment system. In this study, we propose a dynamic gating window technique, which optimizes the size of gating window for each spot by considering a possible dosimetric error. The effectiveness of the dynamic gating window technique was evaluated by simulating irradiation using a moving target in a water phantom. In dosimetric characteristics comparison, the dynamic gating window technique exhibited better performance in all evaluation volumes with different effective depths compared with that of the fixed gate approach. The variation of dosimetric characteristics according to the target depth was small in dynamic gate compared to fixed gate. These results suggest that the dynamic gating window technique can maintain an acceptable dose distribution regardless of the target depth. The overall gating efficiency of the dynamic gate was approximately equal or greater than that of the fixed gating window. In dynamic gate, as the target depth becomes shallower, the gating efficiency will be reduced, although dosimetric characteristics will be maintained regardless of the target depth. The results of this study suggest that the proposed gating technique may potentially improve the dose distribution. However, additional evaluations should be undertaken in the future to determine clinical applicability by assuming the specifications of the treatment system and clinical situation.

Difference in LET-based biological doses between IMPT optimization techniques: Robust and PTV-based optimizations.

PURPOSE: While a large amount of experimental data suggest that the proton relative biological effectiveness (RBE) varies with both physical and biological parameters, current commercial treatment planning systems (TPS) use the constant RBE instead of variable RBE models, neglecting the dependence of RBE on the linear energy transfer (LET). To conduct as accurate a clinical evaluation as possible in this circumstance, it is desirable that the dosimetric parameters derived by TPS ( D RBE = 1.1 ) are close to the "true" values derived with the variable RBE models ( D v RBE ). As such, in this study, the closeness of D RBE = 1.1 to D v RBE was compared between planning target volume (PTV)-based and robust plans. METHODS: Intensity-modulated proton therapy (IMPT) treatment plans for two Radiation Therapy Oncology Group (RTOG) phantom cases and four nasopharyngeal cases were created using the PTV-based and robust optimizations, under the assumption of a constant RBE of 1.1. First, the physical dose and dose-averaged LET (LETd ) distributions were obtained using the analytical calculation method, based on the pencil beam algorithm. Next, D v RBE was calculated using three different RBE models. The deviation of D v RBE from D RBE = 1.1 was evaluated with D99 and Dmax , which have been used as the evaluation indices for clinical target volume (CTV) and organs at risk (OARs), respectively. The influence of the distance between the OAR and CTV on the results was also investigated. As a measure of distance, the closest distance and the overlapped volume histogram were used for the RTOG phantom and nasopharyngeal cases, respectively. RESULTS: As for the OAR, the deviations of D max v RBE from D max RBE = 1.1 were always smaller in robust plans than in PTV-based plans in all RBE models. The deviation would tend to increase as the OAR was located closer to the CTV in both optimization techniques. As for the CTV, the deviations of D 99 v RBE from D 99 RBE = 1.1 were comparable between the two optimization techniques, regardless of the distance between the CTV and the OAR. CONCLUSION: Robust optimization was found to be more favorable than PTV-based optimization in that the results presented by TPS were closer to the "true" values and that the clinical evaluation based on TPS was more reliable.

Quantitative analysis of treatments using real-time image gated spot-scanning with synchrotron-based proton beam therapy system log data.

A synchrotron-based real-time image gated spot-scanning proton beam therapy (RGPT) system with inserted fiducial markers can irradiate a moving tumor with high accuracy. As gated treatments increase the beam delivery time, this study aimed to investigate the frequency of intra-field adjustments corresponding to the baseline shift or drift and the beam delivery efficiency of a synchrotron-based RGPT system. Data from 118 patients corresponding to 127 treatment plans and 2810 sessions between October 2016 and March 2019 were collected. We quantitatively analyzed the proton beam delivery time, the difference between the ideal beam delivery time based on a simulated synchrotron magnetic excitation pattern and the actual treatment beam delivery time, frequency corresponding to the baseline shift or drift, and the gating efficiency of the synchrotron-based RGPT system according to the proton beam delivery machine log data. The mean actual beam delivery time was 7.1 min, and the simulated beam delivery time in an ideal environment with the same treatment plan was 2.9 min. The average difference between the actual and simulated beam delivery time per session was 4.3 min. The average frequency of intra-field adjustments corresponding to baseline shift or drift and beam delivery efficiency were 21.7% and 61.8%, respectively. Based on our clinical experience with a synchrotron-based RGPT system, we determined the frequency corresponding to baseline shift or drift and the beam delivery efficiency using the beam delivery machine log data. To maintain treatment accuracy within ± 2.0 mm, intra-field adjustments corresponding to baseline shift or drift were required in approximately 20% of cases. Further improvements in beam delivery efficiency may be realized by shortening the beam delivery time.

Analysis of treatment process time for real-time-image gated-spot-scanning proton-beam therapy (RGPT) system.

We developed a synchrotron-based real-time-image gated-spot-scanning proton-beam therapy (RGPT) system and utilized it to clinically operate on moving tumors in the liver, pancreas, lung, and prostate. When the spot-scanning technique is linked to gating, the beam delivery time with gating can increase, compared to that without gating. We aim to clarify whether the total treatment process can be performed within approximately 30 min (the general time per session in several proton therapy facilities), even for gated-spot-scanning proton-beam delivery with implanted fiducial markers. Data from 152 patients, corresponding to 201 treatment plans and 3577 sessions executed from October 2016 to June 2018, were included in this study. To estimate the treatment process time, we utilized data from proton beam delivery logs during the treatment for each patient. We retrieved data, such as the disease site, total target volume, field size at the isocenter, and the number of layers and spots for each field, from the treatment plans. We quantitatively analyzed the treatment process, which includes the patient load (or setup), bone matching, marker matching, beam delivery, patient unload, and equipment setup, using the data obtained from the log data. Among all the cases, 90 patients used the RGPT system (liver: n = 34; pancreas: n = 5; lung: n = 4; and prostate: n = 47). The mean and standard deviation (SD) of the total treatment process time for the RGPT system was 30.3 ± 7.4 min, while it was 25.9 ± 7.5 min for those without gating treatment, excluding craniospinal irradiation (CSI; head and neck: n = 16, pediatric: n = 31, others: n = 15); for CSI (n = 11) with two or three isocenters, the process time was 59.9 ± 13.9 min. Our results demonstrate that spot-scanning proton therapy with a gating function can be achieved in approximately 30-min time slots.

Percutaneous insertion of hepatic fiducial true-spherical markers for real-time adaptive radiotherapy.

Purpose: This study evaluated the success rate and complications of percutaneous implantation of hepatic fiducial true-spherical gold markers for real-time adaptive radiotherapy (RAR), which constitutes real-time image-guided radiotherapy with gating.Material and methods: We retrospectively evaluated 100 patients who underwent 116 percutaneous intrahepatic implantations of 2-mm-diameter, spherical, gold fiducial markers before RAR from 1999 to 2016, with Seldinger's method. We defined technical success as marker placement at the intended liver parenchyma, without mispositioning, and clinical success as successful tracking of the gold marker and completion of planned RAR. Complications related to marker placement were assessed.Results: The technical success rate for true-spherical gold marker implantation was 92.2% (107/116). Nine of 116 markers migrated (intra-procedurally in seven patients, delayed in two patients). Migration out of the liver (n = 4) or intrahepatic vessels (n = 5) occurred without complications; these markers were not retrieved. The clinical success rate was 100.0% (115/115). Abdominal pain occurred in 16 patients, fever and hemorrhage in seven patients each, and pneumothorax and nausea in one patient each. No major complications were encountered.Conclusions: Percutaneous transhepatic implantation of true-spherical gold markers for RAR is feasible and can be conducted with a high success rate and low complication rate.

Impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with intensity-modulated radiotherapy.

PURPOSE: Interplay effects may influence dose distributions to a moving target when using dynamic delivery techniques such as intensity-modulated radiotherapy (IMRT). The aim of this study was to evaluate the impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with IMRT. METHODS: Ten patients who had been treated with IMRT for stomach lymphomas were enrolled. The clinical target volume (CTV) was contoured as the whole stomach. Considering interfractional uncertainty, the internal target volume (ITV) margin was uniformly 1.5 cm to the CTV and then modified based on the 4DCT images in case of the large respiratory motion. The planning target volume (PTV) was created by adding 5 mm to the ITV. The impact of organ motion on the volumetric and dosimetric parameters was evaluated retrospectively (4D simulation). The organ motion was reproduced by shifting the isocenter on the radiation treatment planning system. Several simulation plans were created to test the influence of the beam-on timing in the respiration cycle on the dose distribution. The homogeneity index (HI), volume percentage of stomach covered by the prescribed dose (Vp ), and D99 of the CTV were evaluated. RESULTS: The organ motion was the largest in the superior-inferior direction (10.1 ± 4.5 mm [average ± SD]). Stomach volume in each respiratory phase compared to the mean volume varied approximately within a ± 5% range in most of the patients. The PTV margin was sufficiently large to cover the CTV during the IMRT. There was a significant reduction in Vp and D99 but not in HI in the 4D simulation in free-breathing and multiple fractions compared to the clinically-used plan (P < 0.05) suggesting that interplay effects deteriorate the dose distribution. The absolute difference of D99 was less than 1% of the prescribed dose. CONCLUSIONS: There were significant interplay effects affecting the dose distribution in stomach IMRT. The magnitude of the dose reduction was small when patients were treated on free-breathing and multiple fractions.

[Angiomyolipoma with Epithelial Cysts (AMLEC) of the Kidney].

A 49-year-old man was demonstrated to have two tumors in the right kidney by computed tomographic scan during an examination for cholelithiasis. One was a fat rich solid tumor which was clinically diagnosed as angiomyolipoma, and the other was an unconfirmed cystic tumor. Cholecystectomy and radical nephrectomy were performed. Based on pathological findings, the solid tumor was diagnosed as common angiomyolipoma and the cystic tumor as angiomyolipoma with epithelial cysts (AMLEC). The cystic tumor consisted of 3 components : an epithelial cyst lined with single flat to cuboidal cells, a subepithelial compact stroma and an external layer of muscle predominant angiomyolipoma. Immunohistochemical examinations showed strong intense staining of pan-cytokeratin in the epithelium lining the cyst. The subepithelial compact stroma was stained with both CD10 and HMB45. The muscle predominant angiomyolipoma exhibited expression of HMB45. AMLEC is a recently recognized rare variant of angiomyolipoma.

Total number of lymph node metastases is a more significant risk factor for poor prognosis than positive lateral lymph node metastasis.

PURPOSE: Lateral lymph nodes (LLNs) along the iliac vessels are an important indicator of local recurrence; however, we are unaware of any study that investigates whether the number of LLN metastases influences the prognosis of patients with lower rectal cancer. METHOD: We analyzed retrospectively the records of 154 patients who underwent radical resection of T1-4 lower rectal adenocarcinoma at a single institution. RESULTS: Among the 88.3 % of patients who underwent LLN dissection, 13 (8.4 %) had LLN metastasis. The Cox proportional hazard model indicated that sex, histological grade, lymphatic or venous invasion, and LLN metastasis were not significantly associated with tumor recurrence, whereas tumor depth and more than three lymph node metastases were risk factors for recurrence (p = 0.002 and p = 0.02, respectively). Of the 13 patients with LLN metastasis, 6 whose mesenteric lymph nodes (MLNs) had been well dissected and examined did not have MLN metastasis. CONCLUSIONS: The presence of one or two LLN metastases in patients who have undergone LLN dissection with surgery for lower rectal cancer is not associated with poor prognosis. The number of LLN metastases is a more significant risk factor for poor prognosis.

Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly.

OBJECTIVE: Recently, COL4A1 mutations have been reported in porencephaly and other cerebral vascular diseases, often associated with ocular, renal, and muscular features. In this study, we aimed to clarify the phenotypic spectrum and incidence of COL4A1 mutations. METHODS: We screened for COL4A1 mutations in 61 patients with porencephaly and 10 patients with schizencephaly, which may be similarly caused by disturbed vascular supply leading to cerebral degeneration, but can be distinguished depending on time of insult. RESULTS: COL4A1 mutations were identified in 15 patients (21%, 10 mutations in porencephaly and 5 mutations in schizencephaly), who showed a variety of associated findings, including intracranial calcification, focal cortical dysplasia, pontocerebellar atrophy, ocular abnormalities, myopathy, elevated serum creatine kinase levels, and hemolytic anemia. Mutations include 10 missense, a nonsense, a frameshift, and 3 splice site mutations. Five mutations were confirmed as de novo events. One mutation was cosegregated with familial porencephaly, and 2 mutations were inherited from asymptomatic parents. Aberrant splicing was demonstrated by reverse transcriptase polymerase chain reaction analyses in 2 patients with splice site mutations. INTERPRETATION: Our study first confirmed that COL4A1 mutations are associated with schizencephaly and hemolytic anemia. Based on the finding that COL4A1 mutations were frequent in patients with porencephaly and schizencephaly, genetic testing for COL4A1 should be considered for children with these conditions.

Prospective phase II study of image-guided local boost using a real-time tumor-tracking radiotherapy (RTRT) system for locally advanced bladder cancer.

OBJECTIVE: The real-time tumor-tracking radiotherapy system with fiducial markers has the advantage that it can be used to verify the localization of the markers during radiation delivery in real-time. We conducted a prospective Phase II study of image-guided local-boost radiotherapy for locally advanced bladder cancer using a real-time tumor-tracking radiotherapy system for positioning, and here we report the results regarding the safety and efficacy of the technique. METHODS: Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection and 40 Gy irradiation to the whole bladder was followed by the transurethral endoscopic implantation of gold markers in the bladder wall around the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor while maintaining the displacement from the planned position at less than ±2 mm during radiation delivery using a real-time tumor-tracking radiotherapy system. The toxicity, local control and survival were evaluated. RESULTS: Among the 20 patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each observed in one patient. The local-control rate, overall survival and cause-specific survival with the native bladder after 5 years were 64, 61 and 65%. CONCLUSIONS: Image-guided local-boost radiotherapy using a real-time tumor-tracking radiotherapy system can be safely accomplished, and the clinical outcome is encouraging. A larger prospective multi-institutional study is warranted for more precise evaluations of the technological efficacy and patients' quality of life.

Positive peritoneal washing cytology is a potential risk factor for the recurrence of curatively resected colorectal cancer.

PURPOSES: Whether free peritoneal cancer cells should be considered peritoneal dissemination in colorectal cancer patients remains controversial. The aim of this study was to investigate the clinical significance of positive peritoneal washing cytology (PWC) in patients with colorectal cancer. METHODS: We retrospectively analyzed the records of 771 sequential patients diagnosed with stage 0-III colorectal cancer who underwent R0 resection and had no distant metastases or peritoneal dissemination. RESULTS: PWC was performed on all 771 patients. Sixty-eight patients experienced metastasis recurrence, 10 of whom experienced peritoneal recurrence. Of the 10 patients with peritoneal recurrence, 6 had positive PWC. Out of the 771 patients, 21 had positive PWC. Of these 21 patients, 6 had peritoneal recurrence, while 4 had distant metastasis and no peritoneal recurrence during the observation period. The 5-year disease-free survival was 89.0 % in the patients with negative PWC vs. 46.8 % in the patients with positive PWC (p < 0.0001, log-rank test). A Cox proportional hazards model revealed that positive PWC was the strongest independent risk factor for cancer-specific recurrence. CONCLUSIONS: Our study highlights PWC as a useful prognostic tool in patients undergoing curative surgery for colorectal cancer, since positive PWC was shown to be a potential risk factor for recurrence.

[Advanced radiation therapy project for cancer treatment--from Hokkaido to the world, the world access to Hokkaido].

Cancer is the most major cause of death in Japan recently. In this symposium, we explained advanced treatment technology for cancer treatment, now used and that will be used in near future at the Hokkaido University Hospital. Intensity Moderated Radiation Therapy (IMRT) and Proton Beam Therapy (PBT) are considered to be the most promising and advanced technologies for cancer treatment. Various kinds of radiation treatment equipment and methods have been developed and constructed at the Hokkaido University. One of the most worlds wide famous one is the real time tumor tracking radiotherapy system. The FIRST (Funding for World-Leading Innovative R&D on Science and Technology) Program has been supporting us to produce cutting-edge technology. We hope that this symposium would help the audience to understand the latest technology for cancer treatment especially in the field of radiation therapy and also we wish the audience would recognize the importance of the research aspect that have been performed at Hokkaido University and its Hospital.

Technical Note: Improving the workflow in a carbon ion therapy center with custom software for enhanced patient care.

Carbon-ion radiation therapy (CIRT) is an up-and-coming modality for cancer treatment. Implementation of CIRT requires collaboration among specialists like radiation oncologists, medical physicists, and other healthcare professionals. Effective communication among team members is necessary for the success of CIRT. However, the current workflows involving data management, treatment planning, scheduling, and quality assurance (QA) can be susceptible to errors, leading to delays and decreased efficiency. With the aim of addressing these challenges, a team of medical physicists developed an in-house workflow management software using FileMaker Pro. This tool has streamlined the workflow and improved the efficiency and quality of patient care.