Takahiro Kato

Dose-Volume Comparison of Proton Radiotherapy and Stereotactic Body Radiotherapy for Non-Small-Cell Lung Cancer

PURPOSE This study designed photon and proton treatment plans for patients treated with hypofractionated proton radiotherapy (PT) at the Southern Tohoku Proton Therapy Center (STPTC). We then calculated dosimetric parameters and compared results with simulated treatment plans for stereotactic body radiotherapy (SBRT), using dose--volume histograms to clearly explain differences in dose distributions between PT and SBRT. METHODS AND MATERIALS Twenty-one patients with stage I non-small-cell lung cancer (stage IA, n = 15 patients; stage IB, n = 6 patients) were studied. All tumors were located in the peripheral lung, and total dose was 66 Gray equivalents (GyE) (6.6 GyE/fraction). For treatment planning, beam incidence for proton beam technique was restricted to two to three directions for PT, and seven or eight noncoplanar beams were manually selected for SBRT to achieve optimal planning target volume (PTV) coverage and minimal dose to organs at risk. RESULTS Regarding lung tissues, mean dose, V5, V10, V13, V15, and V20 values were 4.6 Gy, 13.2%, 11.4%, 10.6%, 10.1%, and 9.1%, respectively, for PT, whereas those values were 7.8 Gy, 32.0%, 21.8%, 17.4%, 15.3%, and 11.4%, respectively, for SBRT with a prescribed dose of 66 Gy. Pearson product moment correlation coefficients between PTV and dose--volume parameters of V5, V10, V15, and V20 were 0.45, 0.52, 0.58, and 0.63, respectively, for PT, compared to 0.52, 0.45, 0.71, and 0.74, respectively, for SBRT. CONCLUSIONS Correlations between dose--volume parameters of the lung and PTV were observed and may indicate that PT is more advantageous than SBRT when treating a tumor with a relatively large PTV or several tumors.

A comparison of prone three-dimensional conformal radiotherapy with supine intensity-modulated radiotherapy for prostate cancer: which technique is more effective for rectal sparing?

The purpose of this study was to assess the potential dose reductions to the rectum with three-dimensional conformal radiotherapy in the prone position (prone 3D-CRT) compared with intensity-modulated radiotherapy in the supine position (supine IMRT) for prostate cancer. 17 prostate cancer patients underwent treatment planning CT scans in the supine and prone positions. Prone 3D-CRT and supine IMRT plans were constructed for each patient and compared in terms of the volume of rectum exposed to the V90 (volume of rectum receiving at least 90% of the prescription dose) as the high dose region. It was confirmed that supine IMRT was significantly superior to prone 3D-CRT (p = 0.023). Although, in some cases, the distance between the seminal vesicles and the rectum could change by more than 20 mm in the transition from supine to prone, the change in distance was approximately 5 mm in many other cases. While prone 3D-CRT resulted in significant improvements in some patients in terms of rectal sparing, the degree of the effect may be dependent on a patients anatomy and physical condition in prone 3D-CRT compared with supine IMRT. If the cases in which prone 3D-CRT was more effective in rectal dose reduction could be extracted using some anatomical predictor before treatment planning, prone 3D-CRT may be appropriate in such a case. We consider that prone 3D-CRT still warrants further investigation because of its advantages in terms of simplicity, cost-effectiveness and labour saving; continued research to find an appropriate anatomical predictor is required.

Preliminary treatment results of proton beam therapy with chemoradiotherapy for stage I–III esophageal cancer

The effect of proton beam therapy (PBT) on various cancers is controversial. We aimed to evaluate the efficacy and safety of PBT with alternating chemoradiotherapy (ACRT) for patients with stage I–III esophageal cancer. Two cycles of systemic chemotherapy with a continuous infusion of 5‐fluorouracil (5‐FU) on days 1–5 and a 5h infusion of nedaplatin (NDP) on day 6 were accompanied by thoracic irradiation using X‐ray therapy and PBT. During the first half of the treatment, X‐rays were delivered to the prophylactic area. During the second half of the treatment, proton beams were used to irradiate the involved field. To reduce the dose of cardiac irradiation, proton beams were delivered with posterior and posterior oblique angles. Between January 2009 and December 2012, 47 patients were enrolled in this study. The median follow‐up duration was 29 months for all patients and 40 months for survivors. The 3 year overall survival rate, progression‐free survival rate, and local control rate were 59.2%, 56.3%, and 69.8%, respectively. With respect to grade 3–4 late toxicities, there were no pleural or pericardial effusions, but two patients (4.3%) had esophageal stenosis, one patient (2.1%) had fistula, and two patients (4.3%) developed radiation pneumonitis. PBT with ACRT might have the potential to reduce the risk of cardiac damage and might become one of the primary methods of esophageal cancer treatment.

High-dose proton beam therapy for stage I non-small cell lung cancer: Clinical outcomes and prognostic factors

Abstract Background. Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of two proton beam therapy (PBT) protocols for stage I NSCLC and to determine prognostic factors. Material and methods. This study included patients clinically diagnosed with stage I NSCLC. Based on the location of the tumor, one of the two PBT protocols was administered. Patients with peripherally located tumors were given 66 Gy relative biological dose effectiveness (RBE) over 10 fractions (Protocol A) while patients with centrally located tumors were given 80 Gy (RBE) over 25 fractions (Protocol B). Results. Between January 2009 and May 2012, 56 eligible patients were enrolled (protocol A: 32 patients; protocol B: 24 patients). The three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 81.3% [95% confidence interval (CI) 75.9–86.7%], 73.4% (95% CI 67.2–79.6%), and 96.0% (95% CI 93.2–98.8%), respectively. There were no significant differences in outcomes between the two protocols. Late grade 2 and 3 pulmonary toxicities were observed in nine patients (13.4%) and one patient (1.5%), respectively; no grade 4 or 5 toxicities were observed. Sex, age, performance status, T-stage, operability, and tumor pathology were not associated with OS and PFS. Only maximum standardized uptake value (SUVmax; < 5 vs. ≥ 5) was identified as a significant prognostic factor for OS and PFS. Conclusion. Both high-dose PBT protocols achieved high LC rates with tolerable toxicities in stage I NSCLC patients, and SUVmax was a significant prognostic factor.

Feasibility of CBCT-based proton dose calculation using a histogram-matching algorithm in proton beam therapy

The aim of this study was to confirm On-Board Imager cone-beam computed tomography (CBCT) using the histogram-matching algorithm as a useful method for proton dose calculation. We studied one head and neck phantom, one pelvic phantom, and ten patients with head and neck cancer treated using intensity-modulated radiation therapy (IMRT) and proton beam therapy. We modified Hounsfield unit (HU) values of CBCT and generated two modified CBCTs (mCBCT-RR, mCBCT-DIR) using the histogram-matching algorithm: modified CBCT with rigid registration (mCBCT-RR) and that with deformable image registration (mCBCT-DIR). Rigid and deformable image registration were applied to match the CBCT to planning CT. To evaluate the accuracy of the proton dose calculation, we compared dose differences in the dosimetric parameters (D2% and D98%) for clinical target volume (CTV) and planning target volume (PTV). We also evaluated the accuracy of the dosimetric parameters (Dmean and D2%) for some organs at risk, and compared the proton ranges (PR) between planning CT (reference) and CBCT or mCBCTs, and the gamma passing rates of CBCT and mCBCTs. For patients, the average dose and PR differences of mCBCTs were smaller than those of CBCT. Additionally, the average gamma passing rates of mCBCTs were larger than those of CBCT (e.g., 94.1±3.5% in mCBCT-DIR vs. 87.8±7.4% in CBCT). We evaluated the accuracy of the proton dose calculation in CBCT and mCBCTs for two phantoms and ten patients. Our results showed that HU modification using the histogram-matching algorithm could improve the accuracy of the proton dose calculation.

Effect of DIR uncertainty on prostate passive-scattering proton therapy dose accumulation

Deformable image registration (DIR) is important in dose accumulation. Currently, the impact of DIR-algorithm-associated uncertainties in proton therapy is unclear. Here, we quantify the effect of DIR uncertainties on prostate passive-scattering proton therapy (PSPT) dose accumulation. Ten patients with an intermediate risk for prostate cancer formerly treated by PSPT (PTV D95=78GyE) were studied. Dose distributions from all verification CT images (five images per patient) were warped and accumulated in the planning CT geometries with DIR. The dose-volume histogram parameters (Dmean, V40, and V70) for rectum and bladder were calculated. Two commercially available DIR software packages were employed: Velocity AI (Varian Medical Systems) and RayStation (RaySearch Laboratories). The dice similarity coefficient (DSC) and surface distance, which were calculated between planning CT contours and deformed contours, were used for DIR validation, with the relationship between the dose parameter and DIR uncertainty ultimately investigated. On average, when using RayStation, the DSC increased by 0.14 and surface distance decreased by 6.4mm, as compared to Velocity. For Dmean, V40, and V70 to the rectum, the average differences between the RayStation and Velocity were 3.9GyE, 5.5%, and 3.2%, respectively. For the bladder, the differences were 5.2GyE, 5.8%, and 5.4%, respectively. The maximum differences in V40 between RayStation and Velocity were 14.4% and 22.8% for the rectum and bladder, respectively, when the average DSC and surface distance differences were more than 0.14 and 6.4mm, respectively. Such results suggest that DIR uncertainties might significantly affect prostate PSPT dose accumulations.

Effect of anatomical change on dose distribution during radiotherapy for maxillary sinus carcinoma: passive scattering proton therapy versus volumetric-modulated arc therapy

Objective: Maxillary sinus carcinomas are anatomically situated next to many organs at risk (OARs), and anatomical change is often observed during radiotherapy. We analyzed the effect of anatomical change on dose distribution of passive scattering proton therapy (PSPT) and volumetric-modulated arc therapy (VMAT) for 20 patients. Methods: The first plans were generated based on the first CT images. The second CT images were acquired after 3 weeks, and the second plans were generated by copying the first plans to the second CT images. The effect of anatomical change was estimated by comparing both plans. Results: Target volume change was observed in all cases, however, the influence on dose coverage of clinical target volume tended to be small. Alternatively, the doses to almost all OARs were increased. In particular, the increase in the dose to brainstem (p < 0.001) and optic chiasm (p < 0.001) was significantly higher in the second PSPT plan than in the first PSPT plan. Although PSPT is sensitive to anatomical change, the dose to OARs remained significantly lower in PSPT plans than that in VMAT plans. Conclusion: PSPT was confirmed to be more effective than VMAT even the effect of anatomical change was taken into account. Therefore, it is expected that the contralateral vision can be preserved reliably while optimal target coverage is provided. Advances in knowledge: PSPT allowed significant sparing of OARs even in the result of the second plans affected by the anatomical change. PSPT offers benefits over VMAT in reducing dose to several OARs.

Dosemetric Parameters Predictive of Rib Fractures after Proton Beam Therapy for Early-Stage Lung Cancer

Proton beam therapy (PBT) is the preferred modality for early-stage lung cancer. Compared with X-ray therapy, PBT offers good dose concentration as revealed by the characteristics of the Bragg peak. Rib fractures (RFs) after PBT lead to decreased quality of life for patients. However, the incidence of and the risk factors for RFs after PBT have not yet been clarified. We therefore explored the relationship between irradiated rib volume and RFs after PBT for early-stage lung cancer. The purpose of this study was to investigate the incidence and the risk factors for RFs following PBT for early-stage lung cancer. We investigated 52 early-stage lung cancer patients and analyzed a total of 215 irradiated ribs after PBT. Grade 2 RFs occurred in 12 patients (20 ribs); these RFs were symptomatic without displacement. No patient experienced more severe RFs. The median time to grade 2 RFs development was 17 months (range: 9-29 months). The three-year incidence of grade 2 RFs was 30.2%. According to the analysis comparing radiation dose and rib volume using receiver operating characteristic curves, we demonstrated that the volume of ribs receiving more than 120 Gy3 (relative biological effectiveness (RBE)) was more than 3.7 cm(3) at an area under the curve of 0.81, which increased the incidence of RFs after PBT (P < 0.001). In this study, RFs were frequently observed following PBT for early-stage lung cancer. We demonstrated that the volume of ribs receiving more than 120 Gy3 (RBE) was the most significant parameter for predicting RFs.