Hitoshi Wada

Carbon Ion Radiation Therapy for Primary Renal Cell Carcinoma: Initial Clinical Experience

PURPOSE Renal cell carcinoma (RCC) is known as a radioresistant tumor, and there are few reports on radiotherapy for primary RCC. We evaluated the efficacy of carbon ion radiotherapy (CIRT) for patients with RCC. METHODS AND MATERIALS Data for patients with RCC who received CIRT were analyzed. A median total dose of 72 GyE (gray equivalents) in 16 fractions was administered without any additional treatment. Clinical stage was determined based on TNM classification by the International Union Against Cancer (UICC). Local recurrence was defined as definite tumor regrowth after treatment. RESULTS Data for 10 patients were included in the analyses, including 7 patients with Stage I and 3 patients with Stage IV (T4NxM0 or TxN2M0) disease. The median maximum diameter of the tumor was 43 mm (24-120 mm). The median follow-up for surviving patients was 57.5 months (9-111 months). The 5-year local control rate, progression-free survival rate, cause-specific survival rate, and overall survival rates were 100%, 100%, 100%, and 74%, respectively. Interestingly, treated tumors showed very slow shrinkage, and the tumor in 1 case has been shrinking for 9 years. One patient with muscular invasion (T4 tumor) developed Grade 4 skin toxicity, but no other toxicity greater than Grade 2 was observed. CONCLUSIONS This is one of the few reports on curative radiotherapy for primary RCC. The response of the tumor to treatment was uncommon. However despite inclusion of T4 and massive tumors, favorable local controllability has been shown. The results indicate the possibility of radical CIRT, as well as surgery, for RCC.

INTRAOPERATIVE RADIOTHERAPY FOR UNRESECTABLE PANCREATIC CANCER: A MULTI-INSTITUTIONAL RETROSPECTIVE ANALYSIS OF 144 PATIENTS

PURPOSE To retrospectively analyze the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy (EBRT) for resected pancreatic cancer. METHODS AND MATERIALS The records of 210 patients treated with gross complete resection (R0: 147 patients; R1: 63 patients) and IORT with or without EBRT were reviewed. One hundred forty-seven patients (70.0%) were treated without EBRT and 114 patients (54.3%) were treated in conjunction with chemotherapy. The median doses of IORT and EBRT were 25 Gy (range, 20-30 Gy) and 45 Gy (range, 20-60Gy), respectively. The median follow-up of the surviving 62 patients was 26.3 months (range, 2.7-90.5 months). RESULTS At the time of this analysis, 150 of 210 patients (71.4%) had disease recurrences. Local failure was observed in 31 patients (14.8%), and the 2-year local control rate in all patients was 83.7%. The median survival time and the 2-year actuarial overall survival (OS) in all 210 patients were 19.1 months and 42.1%, respectively. Patients treated with IORT and chemotherapy had a significantly more favorable OS than those treated with IORT alone (p = 0.0011). On univariate analysis, chemotherapy use, degree of resection, carbohydrate antigen 19-9, and pathological N stage had a significant impact on OS and on multivariate analysis; these four factors were significant prognostic factors. Late gastrointestinal morbidity of NCI-CTC Grade 4 was observed in 7 patients (3.3%). CONCLUSION IORT yields an excellent local control rate for resected pancreatic cancer with few frequencies of severe late toxicity, and IORT combined with chemotherapy confers a survival benefit compared with that of IORT alone.

Long‐Term Results of Radiotherapy for T1a and T1bN0M0 Glottic Carcinoma

Objective/Hypothesis: The purpose of this study is to determine the prognostic factors for local control and significance of total radiation dose in T1 glottic cancer.

Fatal hemorrhage in irradiated esophageal cancer patients

Between 1980 and 1994, 423 patients with esophageal cancer were given curative radiation therapy. Of these patients, 31 died of massive hemorrhage and were used as the subjects of analysis in this study. The incidence of massive hemorrhage in all patients was 7% (31/423). In the 31 patients who died of massive hemorrhage, 27 had local tumors and two had no tumors at hemorrhage (two unknown cases). The mean time interval from the start of radiation to hemorrhage was 9.2 months. In 9 autopsy cases the origin of hemorrhage was a tear of the aorta in 5 cases, necrotic local tumor in 3 cases and esophageal ulcer in 1 case. The positive risk factors for this complication seemed to be excess total dose, infection, metallic stent, and tracheoesophageal fistula. Chest pain or sentinel hemorrhage proceeding to massive hemorrhage was observed in about half of the patients.

Advantage of accelerated fractionation regimens in definitive radiotherapy for stage II glottic carcinoma.

Objectives: We evaluated the prognostic factors for local control of T2 glottic cancer and verified the efficacy of accelerated fractionation regimens such as hyperfractionation and accelerated hyperfractionation. Methods: A total of 86 patients with T2 NO MO glottic squamous cell carcinoma, who were treated with definitive radiotherapy, were analyzed retrospectively by multivariate analysis. Results: Overall treatment time of radiotherapy (p = .0003) and total dose (p = .0036) were the significant prognostic factors for local control on multivariate analysis. The group with a higher total dose (>67 Gy versus <67 Gy) showed a favorable prognosis (5-year local control rate of 91% versus 60%, respectively; p = .0013, log-rank test). Likewise, the group with a shorter overall treatment time of radiotherapy (<54 days versus >54 days) showed a favorable prognosis (5- year local control rate of 87% versus 71%, respectively; p = .023). Conclusions: A radiotherapy total dose of >67 Gy delivered for a shorter period is required for T2 glottic cancer. The fractionation regimens of hyperfractionation and accelerated hyperfractionation are more effective than conventional fractionation in terms of shortening overall treatment time and delivering a high total dose with acceptable toxicity.

Treatment outcomes of patients with FIGO Stage I/II uterine cervical cancer treated with definitive radiotherapy: a multi-institutional retrospective research study

The purpose of this study was to analyze the patterns of care and outcomes of patients with FIGO Stage I/II cervical cancer who underwent definitive radiotherapy (RT) at multiple Japanese institutions. The Japanese Radiation Oncology Study Group (JROSG) performed a questionnaire-based survey of their cervical cancer patients who were treated with definitive RT between January 2000 and December 2005. A total of 667 patients were entered in this study. Although half of the patients were considered suitable for definitive RT based on the clinical features of the tumor, about one-third of the patients were prescribed RT instead of surgery because of poor medical status. The RT schedule most frequently utilized was whole-pelvic field irradiation (WP) of 30 Gy/15 fractions followed by WP with midline block of 20 Gy/10 fractions, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) of 24 Gy/4 fractions prescribed at point A. Chemotherapy was administered to 306 patients (46%). The most frequent regimen contained cisplatin (CDDP). The median follow-up time for all patients was 65 months (range, 2–135 months). The 5-year overall survival (OS), pelvic control (PC) and disease-free survival (DFS) rates for all patients were 78%, 90% and 69%, respectively. Tumor diameter and nodal status were significant prognostic indicators for OS, PC and DFS. Chemotherapy has potential for improving the OS and DFS of patients with bulky tumors, but not for non-bulky tumors. This study found that definitive RT for patients with Stage I/II cervical cancer achieved good survival outcomes.

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.

Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer

The purpose of this study was to clarify the efficacy and toxicities of re‐irradiation using proton beam therapy combined with weekly intra‐arterial chemotherapy for recurrent oral cancer.

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.

Clinical results of proton beam therapy for hepatocellular carcinoma over 5 cm

This study aimed to evaluate the safety and efficacy of proton beam therapy for large hepatocellular carcinoma (HCC).