Dose escalation study of proton beam therapy with concurrent chemotherapy for stage III non-small cell lung cancer.

The purpose of this study is to determine the recommended dose (RD) of proton beam therapy (PBT) for inoperable stage III non-small cell lung cancer (NSCLC). We tested two prescribed doses of PBT: 66 Gy (relative biological effectiveness [RBE]) in 33 fractions and 74 Gy (RBE) in 37 fractions in arms 1 and 2, respectively. The planning target volume (PTV) included the primary tumor and metastatic lymph nodes with adequate margins. Concurrent chemotherapy included intravenous cisplatin (60 mg/m(2) , day 1) and oral S-1 (80, 100 or 120 mg based on body surface area, days 1-14), repeated as four cycles every 4 weeks. Dose-limiting toxicity (DLT) was defined as grade 3 or severe toxicities related to PBT during days 1-90. Each dose level was performed in three patients, and then escalated to the next level if no DLT occurred. When one patient developed a DLT, three additional patients were enrolled. Overall, nine patients (five men, four women; median age, 72 years) were enrolled, including six in arm 1 and three in arm 2. The median follow-up time was 43 months, and the median progression-free survival was 15 months. In arm 1, grade 3 infection occurred in one of six patients, but no other DLT was reported. Similarly, no DLT occurred in arm 2. However, one patient in arm 2 developed grade 3 esophageal fistula at 9 months after the initiation of PBT. Therefore, we determined that 66 Gy (RBE) is the RD from a clinical viewpoints. (Clinical trial registration no. UMIN000005585).

Machine Learning to Predict Three Types of Outcomes After Traumatic Brain Injury Using Data at Admission: A Multi-Center Study for Development and Validation.

The difficulty of accurately identifying patients who would benefit from promising treatments makes it challenging to prove the efficacy of novel treatments for traumatic brain injury (TBI). Although machine learning is being increasingly applied to this task, existing binary outcome prediction models are insufficient for the effective stratification of TBI patients. The aim of this study was to develop an accurate 3-class outcome prediction model to enable appropriate patient stratification. To this end, retrospective balanced data of 1200 blunt TBI patients admitted to six Japanese hospitals from January 2018 onwards (200 consecutive cases at each institution) were used for model training and validation. We incorporated 21 predictors obtained in the emergency department, including age, sex, six clinical findings, four laboratory parameters, eight computed tomography findings, and an emergency craniotomy. We developed two machine learning models (XGBoost and dense neural network) and logistic regression models to predict 3-class outcomes based on the Glasgow Outcome Scale-Extended (GOSE) at discharge. The prediction models were developed using a training dataset with n = 1000, and their prediction performances were evaluated over two validation rounds on a validation dataset (n = 80) and a test dataset (n = 120) using the bootstrap method. Of the 1200 patients in aggregate, the median patient age was 71 years, 199 (16.7%) exhibited severe TBI, and emergency craniotomy was performed on 104 patients (8.7%). The median length of stay was 13.0 days. The 3-class outcomes were good recovery/moderate disability for 709 patients (59.1%), severe disability/vegetative state in 416 patients (34.7%), and death in 75 patients (6.2%). XGBoost model performed well with 69.5% sensitivity, 82.5% accuracy, and an area under the receiver operating characteristic curve of 0.901 in the final validation. In terms of the receiver operating characteristic curve analysis, the XGBoost outperformed the neural network-based and logistic regression models slightly. In particular, XGBoost outperformed the logistic regression model significantly in predicting severe disability/vegetative state. Although each model predicted favorable outcomes accurately, they tended to miss the mortality prediction. The proposed machine learning model was demonstrated to be capable of accurate prediction of in-hospital outcomes following TBI, even with the three GOSE-based categories. As a result, it is expected to be more impactful in the development of appropriate patient stratification methods in future TBI studies than conventional binary prognostic models. Further, outcomes were predicted based on only clinical data obtained from the emergency department. However, developing a robust model with consistent performance in diverse scenarios remains challenging, and further efforts are needed to improve generalization performance.

Particle therapy using protons or carbon ions for cancer patients with cardiac implantable electronic devices (CIED): a retrospective multi-institutional study.

PURPOSE: To evaluate the outcomes of particle therapy in cancer patients with cardiac implantable electronic devices (CIEDs). MATERIALS AND METHODS: From April 2001 to March 2013, 19,585 patients were treated with proton beam therapy (PBT) or carbon ion therapy (CIT) at 8 institutions. Of these, 69 patients (0.4%, PBT 46, CIT 22, and PBT + CIT 1) with CIEDs (64 pacemakers, 4 implantable cardioverter defibrillators, and 1 with a cardiac resynchronization therapy defibrillator) were retrospectively reviewed. All the patients with CIEDs in this study were treated with the passive scattering type of particle beam therapy. RESULTS: Six (13%) of the 47 PBT patients, and none of the 23 CIT patients experienced CIED malfunctions (p = 0.105). Electrical resets (7) and over-sensing (3) occurred transiently in 6 patients. The distance between the edge of the irradiation field and the CIED was not associated with the incidence of malfunctions in 20 patients with lung cancer. A larger field size had a higher event rate but the test to evaluate trends as not statistically significant (p = 0.196). CONCLUSION: Differences in the frequency of occurrence of device malfunctions for patients treated with PBT and patients treated with CIT did not reach statistical significance. The present study can be regarded as a benchmark study about the incidence of malfunctioning of CIED in passive scattering particle beam therapy and can be used as a reference for active scanning particle beam therapy.

Brain imaging modality before systemic thrombolysis for ischemic stroke within three hours.

OBJECTIVE: In Japan, MRI-based thrombolysis after CT screening is the most common imaging strategy prior to intravenous thrombolysis (IVT) with tissue plasminogen activator (tPA) within 3 h after ischemic stroke. A choice of MRI with MR angiography (MRA) provides a higher diagnostic accuracy, but may delay an initiation of thrombolysis. METHODS: In our neuro-unit, brain CT is the first screening image for suspected stroke. We retrospectively examined a delay to thrombolysis, imaging modality, diagnostic accuracy, and clinical outcomes at 3 months by the modified Rankin Scale in patients receiving IVT within 3 h. RESULTS: Among 67 patients receiving IVT with tPA, brain imaging prior to IVT was solely CT in 10 (15%) patients and CT + MRI/MRA in 57 (85%) patients. Final diagnosis of brain ischemia was 100%. Patients receiving CT + MRI had significantly shorter pre-hospital delay (mean 54 vs. 83 min; p = 0.012), but longer door-to-needle time (mean 90 vs. 57 min; p = 0.019) than those receiving CT only. Finally, time from onset to thrombolysis was not different between the two groups and clinical outcomes were also comparable. The earlier patients arrived, the longer door-to-needle times were (p < 0.001). CONCLUSIONS: The imaging strategy of initial CT screening with optional MRI/MRA scans prior to IVT was feasible. However, it resulted in an additional 30 min in-hospital delay of tPA administration, which may affect clinical outcomes.

Liver phantom design and dosimetric verification in participating institutions for a proton beam therapy in patients with resectable hepatocellular carcinoma: Japan Clinical Oncology Group trial (JCOG1315C).

BACKGROUND AND PURPOSE: In Japan, the first domestic clinical trial of proton beam therapy for the liver was initiated as the Japan Clinical Oncology Group trial (JCOG1315C: Non-randomized controlled study comparing proton beam therapy and hepatectomy for resectable hepatocellular carcinoma). Purposes of this study were to develop a new dosimetric verification system and to carry out a credentialing for the JCOG1315C clinical trial. MATERIALS AND METHODS: Accuracy and differences in doses in proton treatment planning among participating institutions were surveyed and investigated. We designed and developed a suitable water tank-type liver phantom for a dosimetric verification of proton beam therapy for liver. In a visiting survey of five institutions participating in the clinical trial, we performed the dosimetric verification using the liver phantom and an air-filled ionization chamber. RESULTS: The shape of the dose distributions calculated in proton treatment planning was characteristic and dependent on the manufacturers of the proton beam therapy system, the proton treatment planning system and the setup at the participating institutions. Widths of the lateral penumbra were 5.8-12.7 mm among participating institutions. The accuracy between the calculated and the measured doses in the proton irradiation was within 3% at five measurement points including both points on the isocenter and off the isocenter. CONCLUSIONS: These findings confirmed the accuracy of the delivery doses in the institutions participating in the clinical trial, and the clinical trial with integration of all institutions (five institutions) could be initiated.

Measurement of neutron ambient dose equivalent in passive carbon-ion and proton radiotherapies.

Secondary neutron ambient dose equivalents per the treatment absorbed dose in passive carbon-ion and proton radiotherapies were measured using a rem meter, WENDI-II at two carbon-ion radiotherapy facilities and four proton radiotherapy facilities in Japan. Our measured results showed that (1) neutron ambient dose equivalent in carbon-ion radiotherapy is lower than that in proton radiotherapy, and (2) the difference to the measured neutron ambient dose equivalents among the facilities is within a factor of 3 depending on the operational beam setting used at the facility and the arrangement of the beam line, regardless of the method for making a laterally uniform irradiation field: the double scattering method or the single-ring wobbling method. The reoptimization of the beam line in passive particle radiotherapy is an effective way to reduce the risk of secondary cancer because installing an adjustable precollimator and designing the beam line devices with consideration of their material, thickness and location, etc., can significantly reduce the neutron exposure. It was also found that the neutron ambient dose equivalent in passive particle radiotherapy is equal to or less than that in the photon radiotherapy. This result means that not only scanning particle radiotherapy but also passive particle radiotherapy can provide reduced exposure to normal tissues around the target volume without an accompanied increase in total body dose.

Post-licensed 1-year experience of systemic thrombolysis with tissue plasminogen activator for ischemic stroke in a Japanese neuro-unit.

OBJECTIVE: In Japan, intravenous thrombolysis with tissue plasminogen activator (tPA) for ischemic stroke within 3h of onset was officially approved in October 2005. METHODS: We report initial 1-year clinical experience of intravenous alteplase at 0.6mg/kg in a Japanese neuro-unit. RESULTS: Twenty patients received intravenous tPA, corresponding to 12% of all ischemic strokes (n=166) and 38% of ischemic strokes within 3h of onset (n=52). The mean age was 68 years old and 15% had pre-morbid dependency with modified Rankin Scale (mRS) of 3 or 4. The median baseline National Institute of Health Stroke Scale score was 19 points (range; 5-37). Average time from stroke onset to tPA delivery was 136 min (range; 87-180). Of 18 (90%) patients receiving pretreatment vascular imaging, 16 (80%) patients had a large arterial occlusion. At 3 months, excellent outcome with mRS of 0 or 1 was 25%, and good outcome with mRS of 0-2 was 35%. One patient (5%) developed symptomatic intracranial hemorrhage within 36 h. Mortality rate was 15%. CONCLUSIONS: Intravenous tPA within 3h was safe and feasible, and possibly effective in clinical practice. The higher stroke severity in our cohort precluded to compare the sufficient effectiveness with clinical trials. In Japan, a post-licensed national surveillance is currently under way.

Simplified estimation method for dose distributions around field junctions in proton craniospinal irradiation.

In radiotherapy involving craniospinal irradiation (CSI), field junctions of therapeutic beams are necessary, because a CSI target is generally several times larger than the maximum field size of the beams. The purpose of this study was to develop a simplified method for estimating dose uniformity around the field junctions in proton CSI. We estimated the dose profiles around the field junctions of proton beams using a simplified field-junction model, in which partial lateral dose distributions around the field edge were assumed to be approximated using the error function. We measured the lateral dose distributions of the proton beams planned for the CSI treatment using a two-dimensional (2D) ionization chamber array. Although dose hot spots and cold spots tend to be underestimated by a chamber array because of the partial volume effect of the sensitive volume and discrete chamber positions, the model estimation results were fairly consistent with the measurements obtained using a 2D chamber array subjected to CSI-simulated serial irradiation. The simplified junction model enabled us to estimate the dose distributions and dependence of the setup position gap on the dose uniformity around the field junctions on the basis of the field-by-field dose profiles measured using the 2D chamber array.

Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients.

To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose-volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al. were calculated for the same patient. All the published dose-response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means ± standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 ± 0.52% (n = 7, P = 0.0021), (ii) 23.3 ± 17.2% (n = 8, P = 0.0065), (iii) 16.6 ± 19.9% (n = 8, P = 0.0497) and (iv) 50.0 ± 21.1% (n = 3, P = 0.0274), respectively (one tailed t-test). The numbers needed to treat (NNT) were (i) 98.0, (ii) 4.3, (iii) 6.0 and (iv) 2.0 for WCNS, respectively. In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. Although a validation study is required, it is suggested that the LAR would be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques.

Extended collimator model for pencil-beam dose calculation in proton radiotherapy.

We have developed a simple collimator model to improve the accuracy of penumbra behaviour in pencil-beam dose calculation for proton radiotherapy. In this model, transmission of particles through a three-dimensionally extended opening of a collimator is calculated in conjunction with phase-space distribution of the particles. Comparison of the dose distributions calculated using the new three-dimensional collimator model and the conventional two-dimensional model to lateral dose profiles experimentally measured with collimated proton beams showed the superiority of the new model over the conventional one.

Rapid tumor growth with glial differentiation of central neurocytoma after stereotactic radiosurgery.

Although stereotactic radiosurgery (SRS) is effective for central neurocytoma (CN), the long-term outcome of SRS remains unclear. We present a case of recurrent CN that was diagnosed 10years after surgical resection and consecutive stereotactic radiotherapy. The patient was treated with SRS for the recurrent tumor, but underwent two-staged surgery once again due to rapid tumor growth. Histological features of the recurrent tumor were consistent with the diagnosis of CN. However, an increased Ki-67 proliferation index (3.4%), aberrant angiogenesis and glial differentiation of the tumor cells were observed, which were not identified in the initial CN. In addition, vascular endothelial growth factor (VEGF) and VEGF receptor were highly expressed in the recurrent tumor cells, as well as in the vascular endothelial cells. Our case suggests that malignant transition with aberrant angiogenesis and glial differentiation may be attributable to SRS.

Patient positioning method based on binary image correlation between two edge images for proton-beam radiation therapy.

A new technique based on normalized binary image correlation between two edge images has been proposed for positioning proton-beam radiotherapy patients. A Canny edge detector was used to extract two edge images from a reference x-ray image and a test x-ray image of a patient before positioning. While translating and rotating the edged test image, the absolute value of the normalized binary image correlation between the two edge images is iteratively maximized. Each time before rotation, dilation is applied to the edged test image to avoid a steep reduction of the image correlation. To evaluate robustness of the proposed method, a simulation has been carried out using 240 simulated edged head front-view images extracted from a reference image by varying parameters of the Canny algorithm with a given range of rotation angles and translation amounts in x and y directions. It was shown that resulting registration errors have an accuracy of one pixel in x and y directions and zero degrees in rotation, even when the number of edge pixels significantly differs between the edged reference image and the edged simulation image. Subsequently, positioning experiments using several sets of head, lung, and hip data have been performed. We have observed that the differences of translation and rotation between manual positioning and the proposed method were within one pixel in translation and one degree in rotation. From the results of the validation study, it can be concluded that a significant reduction in workload for the physicians and technicians can be achieved with this method.

A model-based analysis of a simplified beam-specific dose output in proton therapy with a single-ring wobbling system.

In radiation therapy, it is necessary to preset a monitor unit in an irradiation control system to deliver a prescribed absolute dose to a reference point in the planning target volume. The purpose of this study was to develop a model-based monitor unit calculation method for proton-beam therapy with a single-ring wobbling system. The absorbed dose at a calibration point per monitor unit had been measured for each beam-specific measurement condition without a patient-specific collimator or range compensator before proton therapeutic irradiation at Shizuoka Cancer Center. In this paper, we propose a simplified dose output model to obtain the output ratio between a beam-specific dose and a reference field dose, from which a monitor unit for the proton treatment could be derived without beam-specific measurements. The model parameters were determined to fit some typical data measured in a proton treatment room, called a Gantry 1 course. Then, the model calculation was compared with 5456 dose output ratios that had been measured for 150-, 190- and 220 MeV therapeutic proton beams in two treatment rooms over the past decade. The mean value and standard deviation of the difference between the measurement and the model calculation were respectively 0.00% and 0.27% for the Gantry 1 course, and -0.25% and 0.35% for the Gantry 2 course. The model calculation was in good agreement with the measured beam-specific doses, within 1%, except for conditions less frequently used for treatment. The small variation for the various beam conditions shows the high long-term reproducibility of the measurement and high degree of compatibility of the two treatment rooms. Therefore, the model was expected to assure the setting value of the dose monitor for treatment, to save the effort required for beam-specific measurement, and to predict the dose output for new beam conditions in the future.

Semi-analytical model for output factor calculations in proton beam therapy with consideration for the collimator aperture edge.

In the development of an external radiotherapy treatment planning system, the output factor (OPF) is an important value for the monitor unit calculations. We developed a proton OPF calculation model with consideration for the collimator aperture edge to account for the dependence of the OPF on the collimator aperture and distance in proton beam therapy. Five parameters in the model were obtained by fitting with OPFs measured by a pinpoint chamber with the circular radiation fields of various field radii and collimator distances. The OPF model calculation using the fitted model parameters could explain the measurement results to within 1.6% error in typical proton treatment beams with 6- and 12 cm SOBP widths through a range shifter and a circular aperture more than 10.6 mm in radius. The calibration depth dependences of the model parameters were approximated by linear or quadratic functions. The semi-analytical OPF model calculation was tested with various MLC aperture shapes that included circles of various sizes as well as a rectangle, parallelogram, and L-shape for an intermediate proton treatment beam condition. The pre-calculated OPFs agreed well with the measured values, to within 2.7% error up to 620 mm in the collimator distance, though the maximum difference was 5.1% in the case of the largest collimator distance of 740 mm. The OPF calculation model would allow more accurate monitor unit calculations for therapeutic proton beams within the expected range of collimator conditions in clinical use.

Reconstruction of biologically equivalent dose distribution on CT-image from measured physical dose distribution of therapeutic beam in water phantom.

From the standpoint of quality assurance in radiotherapy, it is very important to compare the dose distributions realized by an irradiation system with the distribution planned by a treatment planning system. To compare the two dose distributions, it is necessary to convert the dose distributions on CT images to distributions in a water phantom or convert the measured dose distributions to distributions on CT images. Especially in heavy-ion radiotherapy, it is reasonable to show the biologically equivalent dose distribution on the CT images. We developed tools for the visualization and comparison of these distributions in order to check the therapeutic beam for each patient at the National Institute of Radiological Sciences (NIRS). To estimate the distribution in a patient, the dose is derived from the measurement by mapping it on a CT-image. Fitting the depth-dose curve to the calculated SOBP curve also gives biologically equivalent dose distributions in the case of a carbon beam. Once calculated, dose distribution information can be easily handled to make a comparison with the planned distribution and display it on a grey-scale CT-image. Quantitative comparisons of dose distributions can be made with anatomical information, which also gives a verification of the irradiation system in a very straightforward way.

Cadaveric and clinical study of endoscope-assisted microneurosurgery for cerebral aneurysms using angle-type rigid endoscope.

Highly advanced optical equipment enables endoscopic surgery to be performed in neurosurgery. We developed an angle-type rigid endoscope having an angled shaft, and has performed endoscope-assisted surgery in neck clipping of 50 cerebral aneurysms. Anatomical study concerning the perforating branch was made through a pterional approach using 3 cadavers. By using endoscope, we can observe the posterior communicating artery and anterior choroidal artery behind the internal carotid artery without retract the internal carotid artery and the surrounding structures. Furthermore IIIrd~VIIIth cranial nerve in opposite side and basilar artery in the posterior fossa can be observed. As the clinical study, we used endoscope in 50 clipping of cerebral aneurysms (29 Internal carotid artery aneurysms, 6 anterior communicating artery aneurysms, 2 anterior cerebral artery aneurysms, 7 middle cerebral artery aneurysms, 5 vertebral artery-posterior inferior cerebellar artery aneurysm, and basilar bifurcation aneurysms). The endoscopic image showed in incomplete clipping in 2 cases, where additional clipping was then performed. In all subject, complete clipping was performed using both microscopic and endoscopic view. Use of the angle-type rigid endoscope together with Doppler ultrasound, should increase the feasibility of complete clipping procedure, resulting in reduced complication rate.

A revision of proton machine quality assurance for wobbled-proton-beam therapy.

Periodic checks for proton machine quality assurance (QA) are significant for machine users safely and accurately to provide proton-beam treatment for cancer. Our aim in this study was to describe a revision to proton machine QA procedures for wobbled-proton-beam therapy at the Shizuoka Cancer Center (SCC) in Japan. The previous daily, monthly, and annual QA procedures were determined by reference to our past operational experience and to QA papers for medical accelerators. The revised QA procedures were initiated in May 2011 after preliminary measurements to decide baselines for the QA procedures. This paper presents the proton machine QA procedures and the results of representative QA measurements. Three action levels were decided on by reference to the American Association of Physicists in Medicine Task Group 142 report. Tolerances of inspection action were decided on based on the provisional operational results and actual fluctuations of the QA measurement for a year, and those of scheduled action and stop-treatment action were determined by reference to the machine QA papers and those of the inspection action. No deviation from the tolerance of the scheduled action has been observed so far. Although a few QA procedures exceeded the tolerance of the inspection action, these excesses were resolved by inspection and improvement of the respective measuring procedure within the designated QA time. Hereafter, the proton machine QA procedures proposed in this study will be performed continuously at the SCC to assure patient safety and accurate operation of proton therapy.

Microdosimetric calculation of relative biological effectiveness for design of therapeutic proton beams.

The authors attempt to establish the relative biological effectiveness (RBE) calculation for designing therapeutic proton beams on the basis of microdosimetry. The tissue-equivalent proportional counter (TEPC) was used to measure microdosimetric lineal energy spectra for proton beams at various depths in a water phantom. An RBE-weighted absorbed dose is defined as an absorbed dose multiplied by an RBE for cell death of human salivary gland (HSG) tumor cells in this study. The RBE values were calculated by a modified microdosimetric kinetic model using the biological parameters for HSG tumor cells. The calculated RBE distributions showed a gradual increase to about 1cm short of a beam range and a steep increase around the beam range for both the mono-energetic and spread-out Bragg peak (SOBP) proton beams. The calculated RBE values were partially compared with a biological experiment in which the HSG tumor cells were irradiated by the SOBP beam except around the distal end. The RBE-weighted absorbed dose distribution for the SOBP beam was derived from the measured spectra for the mono-energetic beam by a mixing calculation, and it was confirmed that it agreed well with that directly derived from the microdosimetric spectra measured in the SOBP beam. The absorbed dose distributions to planarize the RBE-weighted absorbed dose were calculated in consideration of the RBE dependence on the prescribed absorbed dose and cellular radio-sensitivity. The results show that the microdosimetric measurement for the mono-energetic proton beam is also useful for designing RBE-weighted absorbed dose distributions for range-modulated proton beams.

Assessment of organ dose reduction and secondary cancer risk associated with the use of proton beam therapy and intensity modulated radiation therapy in treatment of neuroblastomas.

BACKGROUND: To compare proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT) with conformal radiation therapy (CRT) in terms of their organ doses and ability to cause secondary cancer in normal organs. METHODS: Five patients (median age, 4 years; range, 2-11 years) who underwent PBT for retroperitoneal neuroblastoma were selected for treatment planning simulation. Four patients had stage 4 tumors and one had stage 2A tumor, according to the International Neuroblastoma Staging System. Two patients received 36 Gy, two received 21.6 Gy, and one received 41.4 Gy of radiation. The volume structures of these patients were used for simulations of CRT and IMRT treatment. Dose-volume analyses of liver, stomach, colon, small intestine, pancreas, and bone were performed for the simulations. Secondary cancer risks in these organs were calculated using the organ equivalent dose (OED) model, which took into account the rates of cell killing, repopulation, and the neutron dose from the treatment machine. RESULTS: In all evaluated organs, the mean dose in PBT was 20-80% of that in CRT. IMRT also showed lower mean doses than CRT for two organs (20% and 65%), but higher mean doses for the other four organs (110-120%). The risk of secondary cancer in PBT was 24-83% of that in CRT for five organs, but 121% of that in CRT for pancreas. The risk of secondary cancer in IMRT was equal to or higher than CRT for four organs (range 100-124%). CONCLUSION: Low radiation doses in normal organs are more frequently observed in PBT than in IMRT. Assessments of secondary cancer risk showed that PBT reduces the risk of secondary cancer in most organs, whereas IMRT is associated with a higher risk than CRT.

A treatment planning comparison of passive-scattering and intensity-modulated proton therapy for typical tumor sites.

Intensity-modulated proton therapy (IMPT) is expected to improve treatment results with fewer side effects than other proton therapies. The purpose of this study was to evaluate the tumor sites for which IMPT was effective under the same beam calculation conditions by planning IMPT for typical cases treated with passive scattering proton therapy (PSPT). We selected 16 cases of nasal cavity, lung, liver or prostate cancers as typical tumor sites receiving PSPT. The dose distributions and dose volume histograms optimized by the IMPT were compared with those optimized by the PSPT. We took particular note of the doses to the skin and organs at risk (OAR) when PSPT was replaced by IMPT. Furthermore, an improvement of the beam angles was also performed to obtain better dose distributions in the IMPT. The IMPT with the same beam angles resulted in near-maximum doses to the skin of average 78%, 64%, 84% and 99% of the PSPT doses for nasal cavity, lung, liver, and prostate cancers, respectively. However, it was difficult to improve the dose homogeneity of the target volume. The change of the IMPT beam angles could reduce the doses to OARs and skin in the case of the nasal cavity, while it had limited effect in the other cases. We concluded that IMPT was effective for reducing the doses to some OARs when treating nasal cavity, lung, liver and prostate cancers. The selection of beam angles was important in the IMPT optimization, especially for nasal cavity cancers.