Clinical results of image-guided interstitial brachytherapy with or without external beam radiotherapy for postsurgical vaginal recurrence of cervical and endometrial cancers.

PURPOSE: This study aimed to evaluate the clinical outcome and efficacy of image-guided interstitial brachytherapy (ISBT) for postsurgical vaginal recurrence of cervical and endometrial cancers. MATERIALS AND METHODS: The study included 11 patients who received CT-based image-guided high-dose-rate ISBT with or without external beam radiotherapy (EBRT). Local control, progression-free survival, and treatment-related toxicities were evaluated retrospectively. RESULTS: Of the 11 patients, 4 underwent ISBT with EBRT and the other 7 ISBT alone; two of the latter patients received previous pelvic radiotherapy. After a median follow-up of 43.9 months (range 3.9-92.7 months), the 2-year local control rate was 100%. The median equivalent doses in 2 Gy fractions received by at least 90% of the clinical target volume for ISBT with versus without EBRT were 82.2 Gy (range 60.4-84.2 Gy) versus 69.0 Gy (range 50.8-98.2 Gy). The 2-year progression-free survival rates after ISBT with versus without EBRT were 75% versus 80%, and the difference was not significant (p = 0.74). Grade 3 late toxicities occurred in two patients. CONCLUSION: Our radiotherapy strategy using image-guided ISBT, either with or without EBRT, for postsurgical vaginal recurrence showed effective treatment outcomes.

Achieving PSA < 0.2 ng/ml before Radiation Therapy Is a Strong Predictor of Treatment Success in Patients with High-Risk Locally Advanced Prostate Cancer.

BACKGROUND: To predict long-term treatment outcome of radiation therapy (RT) plus androgen deprivation therapy (ADT) for high-risk locally advanced prostate cancer. METHODS: In total, 204 patients with the National Comprehensive Cancer Network (NCCN) high risk locally advanced prostate cancer (PSA > 20 ng/ml, Gleason score ≧ 8, clinical T stage ≧ 3a) were treated with definitive RT with ADT. Median follow up period was 113 months (IQR: 95-128). Median neoadjuvant ADT and total ADT duration were 7 months (IQR: 6-10) and 27 months (IQR: 14-38), respectively. RESULTS: PSA recurrence-free survival (PSA-RFS), cancer specific survival (CSS), and overall survival (OS) rates at 5 years were 84.1%, 98.5%, and 93.6%, respectively, and 67.9%, 91.2%, and 78.1%, respectively, at 10 years. Pre-RT PSA less than 0.2 ng/ml was associated with superior outcomes of PSA-RFS (HR = 0.42, 95% CI: 0.25-0.70, p = 0.001), CSS (HR = 0.27, 95% CI: 0.09-0.82, p = 0.013), and OS (HR = 0.48, 95% CI: 0.26-0.91, p = 0.021). On multivariate analysis, age (≥70 y.o.) and pre-RT PSA (≥0.2 ng/ml) were factors predictive of poorer OS (p = 0.032) , but iPSA, T stage, Gleason score, number of NCCN high-risk criteria, a combination with anti-androgen therapy and neoadjuvant ADT duration were not predictive of treatment outcome. CONCLUSION: In patient with high-risk prostate cancer, RT plus ADT achieved good oncologic outcomes. PSA < 0.2 ng/ml before radiation therapy is a strong independent predictor for long overall survival.

Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan.

OBJECTIVE: Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese. METHODS: Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II-IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70mg/m2 for level 0, 80mg/m2 for level 1, and 100mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200mg/m2, response rate, and incidences of adverse events. RESULTS: A CDDP dose of 100mg/m2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m2. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200mg/m2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event. CONCLUSION: The present phase I study indicated that a CDDP dose of 80mg/m2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80mg/m2 as compared with a dose of 100mg/m2, and a dose of 80mg/m2 is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).

Risk Factors and Time to Occurrence of Genitourinary Toxicity After External Beam Radiotherapy for Prostate Cancer.

AIM: To retrospectively investigate the risk factors and time to occurrence of genitourinary (GU) toxicity after radiotherapy for localized prostate cancer. PATIENTS AND METHODS: The study included 320 patients. The radiotherapy planning target volume encompassed the prostate with a 1-cm margin in the transverse plane and a 1-cm margin (Group A) or a 1.5-cm margin (Group B) in the longitudinal plane. Incidence rates, risk factors and time to occurrence of GU toxicity were evaluated. RESULTS: After a median follow-up of 38.2 months, the rate of late grade 2-3 GU toxicity was 5.9% and the median interval was 18.3 months. The wider longitudinal margin was the single significant independent factor. The 2-year cumulative incidence rates of late grade ≥2 GU toxicity were 2.8% and 7.5% in Group A and B patients. CONCLUSION: A wider radiotherapy margin increased the risk of GU toxicity and led to earlier occurrence.

Timing and characteristics of radiation pneumonitis after stereotactic body radiotherapy for peripherally located stage I lung cancer.

BACKGROUND: This study was conducted to determine the timing and characteristics of radiation pneumonitis (RP) associated with stereotactic body radiotherapy (SBRT) for stage I lung cancer. METHODS: Two hundred thirty-one patients treated with SBRT using 52 Gy in 4 fractions were identified. Control rate, RP incidence rate, and predictive factors and timing of RP were evaluated retrospectively. RESULTS: The 3-year overall survival and local control rates were 80.7 and 92.0 %, respectively. The grade ≥2 RP rate was 13.0 %; no grade 4-5 RP occurred. The most statistically significant predictive factor of grade ≥2 RP was V10. The median intervals to first graphical appearance were 4.2 and 2.5 months for grade 1 and grade 2-3 RP, respectively. Median intervals to maximum radiological density change were 6.0 and 4.6 months for grade 1 and grade 2-3 RP, respectively. A significantly different interval to first graphical appearance between grade 1 and grade 2-3 RP was observed; no significantly different interval to maximum radiological density change was noted. CONCLUSIONS: The first graphical appearance of grade ≥2 RP was earlier than that of grade 1 RP, although the timing of maximum radiological density change was not significantly different.

Long-term results of chemoradiotherapy for locally advanced esophageal cancer, using daily low-dose 5-fluorouracil and cis-diammine-dichloro-platinum (CDDP).

BACKGROUND: We evaluated the efficacy and toxicity of radiation combined with daily, low-dose protracted chemotherapy for locally advanced esophageal cancer. METHODS: We analyzed data for 68 patients with locally advanced esophageal cancer, including 18 surgical candidates. Standard fractionation (total dose range, 60 to 70 Gy) was used for radiotherapy. The chemotherapy consisted of a daily 5-fluorouracil dose of 250 mg/m2, with a cis-diammine-dichloro-platinum dose of 3 mg/m2 administered on radiotherapy days. RESULTS: Sixty-four patients (94%) received at least 60 Gy. Grade 3 acute hematological toxicity was observed in 13 (19%) patients; there was no grade 4 hematological toxicity. Complete response, partial response, no change, and progressive disease were obtained in 22, 35, 7, and 4 patients, respectively. Minimum follow-up for surviving patients was 45 months. Locoregional progression-free rates at 3 and 5 years were 47% and 47%. Four patients died of late cardiac toxicity; the primary site for all 4 patients was the middle thoracic esophagus. Overall survival rates at 2, 3, and 5 years were 40%, 32%, and 20%. The 3- and 5-year survival rates in patients with T2-3M0 disease were 43% and 27%, and the rates were 24% and 15% in patients with T4/M1. CONCLUSION: Given the large proportion of patients in this study with inoperable disease (roughly three quarters), our treatment seemed to provide equivalent efficacy and less hematological toxicity than standard-dose chemoradiotherapy.

Risk factors for enlargement of cardiac silhouette on chest radiography after radiotherapy for esophageal cancer.

PURPOSE: To evaluate the incidence and risk factors of enlargement of cardiac silhouette on chest radiographs after radiotherapy for esophageal cancer. MATERIALS AND METHODS: We analyzed 67 patients with esophageal cancer who received external beam radiation therapy with a total dose of >or=50 Gy and were followed for >or=6 months. Sixteen patients received radiation alone, and the remaining 51 received chemoradiotherapy. The difference between the cardiothoracic ratio (CTR) on the pretreatment chest radiograph and that on the posttreatment radiograph with maximum cardiac silhouette for each patient was used for the analysis. RESULTS: The average maximum increase in CTR for the entire group was 4.5%, which was statistically significant. Only the area of the cardiac silhouette in the initial radiation field was a significant risk factor for enlargement of the cardiac silhouette. Pericardial effusions were observed in all patients who underwent computed tomography with severe enlargement of the cardiac silhouette. CONCLUSION: The CTR value significantly increased after radiotherapy for esophageal cancer. Radiation-induced pericardial effusion may be the main cause of enlargement of the cardiac silhouette. The irradiated cardiac area was the only significant risk factor for enlargement of the cardiac silhouette; the use of chemotherapy was not.

Outcomes of locally advanced prostate cancer: a single institution study of 209 patients in Japan.

AIM: To investigate the outcomes for Asian populations with locally advanced/clinical stage III prostate cancer (PCa) treated with currently prevailing modalities. METHODS: We reviewed the record of 209 patients with clinical stage III PCa, who were treated at Niigata Cancer Center Hospital between 1992 and 2003. Treatment options included hormone therapy-combined radical prostatectomy (RP+HT), hormone therapy-combined external beam irradiation (EBRT+HT) and primary hormone therapy (PHT). RESULTS: The 5- and 10-year overall survival rates were 80.3% and 46.1% in all cohorts, respectively. The survival rates were 87.3% and 66.5% in the RP+HT group, 94.9% and 70.0% in the EBRT+HT group and 66.1% and 17.2% in the PHT group, respectively. A significant survival advantage was found in the EBRT+HT group compared with that in the PHT group (P < 0.0001). Also, the RP+HT group had better survival than the PHT group (P = 0.0107). The 5- and 10-year disease-specific survival rates for all cases were 92.5% and 80.0%, respectively. They were 93.8% and 71.4% in the RP+HT group, 96.6% and 93.6% in the EBRT+HT group and 88.6% and 62.3% in the PHT group, respectively. A survival advantage was found in the EBRT+HT group compared with the PHT group (P = 0.029). No significant difference was found in disease-specific survival between the EBRT+HT and RP+HT groups or between the RP+HT and PHT groups. CONCLUSION: Although our findings indicate that radiotherapy plus HT has a survival advantage in this stage of PCa, we recommend therapies that take into account the patients'social and medical conditions for Asian men with clinical stage III PCa.

A multi-institutional retrospective analysis of external radiotherapy for mucosal melanoma of the head and neck in Northern Japan.

PURPOSE: A multi-institutional retrospective study was performed in northern Japan to analyze the outcome of external radiotherapy as the definitive treatment modality for localized mucosal melanoma of the head and neck. PATIENTS AND METHODS: Thirty-one patients with localized mucosal melanoma of the head and neck treated by external radiotherapy at nine institutions of the Northern Japan Radiation Therapy Oncology Group between 1980 and 1999 were enrolled in this study. Radiotherapy alone was performed in 21 patients, and the remaining 10 patients received postoperative radiotherapy for gross residual tumors. The fraction size of radiotherapy varied from 1.5-13.8 Gy, with the total dose ranging from 32-64 Gy (median, 50 Gy). The follow-up periods ranged from 1-214 months (median, 16 months). RESULTS: Complete or partial responses were observed in 9 patients (29%) and 18 patients (58%), respectively. Local recurrence occurred in 13 patients (41.9%) and distant metastasis occurred in 11 patients (35.5%). Most incidences of local recurrence and distant metastasis developed within 2 years after the initial treatment. Overall cause-specific survival rates of patients at 1 and 3 years were 73% and 33%, respectively. Univariate analysis showed that high dose per fractionated radiotherapy doses (>or=3 Gy) was associated with better prognosis for both local control (p = 0.048) and survival (p = 0.045). Multivariate analysis indicated that age (better prognosis in younger patients, p = 0.046) was the only significant factor. Radiotherapy for gross residual lesions after surgery did not seem to impact the significant gain of local control and survival. We observed two fatal late complications of mucosal ulcer and bleeding in the high dose per fractionated radiotherapy group. CONCLUSION: Radiotherapy at a dose of 3 Gy or more per fraction was effective in gaining local control in patients with localized mucosal melanoma of the head and neck, and subsequently better survival was possible, especially in younger patients.