Effective bladder preservation strategy with low-dose radiation therapy and concurrent intraarterial chemotherapy for muscle-invasive bladder cancer.

PURPOSE: The aim of this study was to evaluate retrospectively the toxicity and response, bladder preservation, and survival of patients with muscle-invasive bladder cancer treated with multimodality therapy consisting of low-dose radiation therapy (RT) and concurrent intraarterial chemotherapy (IACT). METHODS AND MATERIALS: . Between November 1999 and July 2005, a total of 27 consecutive, previously untreated patients with muscle-invasive bladder cancer underwent transurethral bladder tumor resection followed by concurrent low-dose RT and IACT. Patients who achieved a complete response (CR) were followed up closely without further therapy, and patients who did not achieve a CR underwent further treatment. RESULTS: Complete response was achieved in 22 of 27 patients (81%). Of these 22 patients, 7 developed recurrences, and 3 died of their disease. In five patients who did not achieve CR, one died from bone metastases. The 3-year overall survival rate was 81%, with a median follow-up time of 27 months; and 22 of 27 patients (81%) with a preserved bladder were tumor-free at the last follow-up. Three patients (11%) developed grade 3 acute hematological toxicity. CONCLUSION: Multimodality therapy consisting of low-dose RT and concurrent IACT for muscle-invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation and minimal adverse effects.

Prognostic significance of HIF-2alpha expression on tumor infiltrating macrophages in patients with uterine cervical cancer undergoing radiotherapy.

Hypoxia-inducible factor (HIF)-2alpha, a basic helix-loop-helix (bHLH)-PAS protein, is the principal regulator of the hypoxic transcriptional response. An immunohistochemical study reported strong HIF-2alpha expression in the cytoplasm of tumor infiltrative macrophages (TIMs). Thus we assessed the expression of HIF-2alpha in human cervical cancer tissue before radiation therapy and its relationship to the clinical outcome. Seventy three patients with histologically proven primary advanced squamous cell carcinoma of the uterine cervix underwent radiotherapy in Tokushima University Hospital after biopsy specimens were taken. Among 73 specimens stained for HIF-2alpha, 53 (72.6%) exhibited HIF-2alpha immunoreactivity in the TIMs. In only 5 of 73 cases, HIF-2alpha immunoreactivity was observed in the nuclei of tumor cells. The HIF-2alpha positive cell count ratio in TIMs was associated with disease-free survival (DFS) with the worst DFS (p=0.024) being in cases in the group with a high positive cell count ratio. A high HIF-2alpha positive cell count ratio in TIMs increased the risk of local recurrence (p=0.0142). These findings might suggest that the ratio of the HIF-2alpha positive cell in TIMs may be a new predictive indicator for prognosis before radiation therapy for uterine cervical cancer.

Can Kampo therapy prolong the life of cancer patients?

Our policy regarding the performance of radiotherapy to squamous cell carcinoma of the uterine cervix has not changed since 1969. We have already reported the treatment results which were as good as those from other institutions. Since 1978, Kampo therapy was first introduced in the treatment of cancer patients in dealing with problems such as the side effects of radiotherapy and chemotherapy and various types of general malaise. We analyzed our treatment results in order to re-evaluate the chemo-radiotherapy in combination with Kampo. Survival rates for 5, 10 and 15 years, respectively, were 90.9%, 71.6% and 71.6% for Stage IB, 78.9%, 61.8% and 41.8% for Stage II, 62.3%, 49.1% and 41.2% for Stage III and 53.1%, 36.5% and 16.7% for Stage IV. The Kampo significantly extended the survival of patients with uterine cervical cancer. We intend to perform further research with more patients to explore how this therapy contributes to the prolonging of patients survival.

Radiation therapy for cervical cancer in the elderly.

OBJECTIVE: To evaluate the long-term results of radical radiation therapy (RT) for cervical cancer in elderly patients. METHODS: We reviewed the clinical records of 727 patients with cervical cancer who underwent radical RT at the Tokushima University Hospital and compared the treatment results of three age groups: /=75 years (older group [OG], 132 patients). RESULTS: At the last follow-up, 155 YG (46%), 77 YOG (30%), and 48 OG patients (36%) had died of cervical cancer; the median follow-up periods were 82, 87, and 68 months, respectively. The 5-/10-year disease-specific survival rates were 60%/52% in YG, 76%/68% in YOG, and 66%/57% in OG. Differences between OG and the other groups were not significant. The 5-/10-year disease-specific survival rate of YOG was significantly superior to that of YG (p<0.001). Clinical stage was the only significant prognostic variable (p<0.001). Late radiation morbidity of grades 2-4 in the bladder and/or rectum occurred in 22% of YG, 31% of YOG, and 8% of OG patients. CONCLUSIONS: RT was well tolerated in elderly patients, and age was not a significant prognostic factor. In the management of cervical cancer, advanced age is not a contraindication to radical RT.

Quality assurance of I-125 seeds for prostate brachytherapy using an imaging plate.

PURPOSE: OncoSeed is delivered in a sterile environment in the form of a cartridge, so it is impractical to resterilize and reload seeds after calibration. We investigated a new method using an imaging plate dosimetry system to characterize all seeds in the OncoSeed cartridge in a sterile environment. METHODS AND MATERIALS: Seeds within the cartridge were placed on an imaging plate, and the imaging plate irradiated. To remove scatter radiation, and improve spatial resolution of seed images, we used X-ray parallel cross grids. The irradiated imaging plate was scanned using a Bio-imaging Analyzer System, and radioactivity intensities of seed images were given in counts. Counts could be translated to profiles, and each seed within the cartridge was analyzed. RESULTS: Results showed a good correlation between counts and total radioactivity of the seeds within the cartridge. Thus, using a least-squares line, it was possible to characterize a cartridge with unknown apparent activity. By analyzing the profiles, it was possible not only to detect a miscalibrated seed in the cartridge from its relative difference in counts, but also to identify its position in the cartridge. No significant changes in counts were seen between sterile and nonsterile environments. CONCLUSION: Using an imaging plate dosimetry system, all seeds in a cartridge could be characterized in a sterile environment.

Randomized phase II study of immunomodulator Z-100 in patients with stage IIIB cervical cancer with radiation therapy.

OBJECTIVE: To find the optimal dose of immunomodulator Z-100 in patients with stage IIIB squamous cell carcinoma of the cervix in combination with radiation therapy. METHODS: The patients were randomly assigned to the dosage levels of 2, 20 or 40 mug of Z-100. Z-100 was subcutaneously injected twice a week during radiotherapy and once in two weeks during the maintenance period. The response rate after radiotherapy was evaluated, and the optimal clinical dosage was then determined. Safety of Z-100 was evaluated during the radiation therapy and maintenance therapy. Survival was also evaluated. RESULTS: A total of 116 patients were entered. The adverse reactions were not dose-dependent and no serious toxicities were observed. The response rates were 72.2% (26/36) in the 2 microg group, 84.6% (33/39) in the 20 microg group and 94.3% (33/35) in the 40 microg group (P = 0.006). However, the survival was not significantly different. CONCLUSIONS: The optimal dose of Z-100 was determined to be 40 mug in combination with radiation therapy for stage IIIB cervical cancer. However, impact of Z-100 on survival must be determined by the placebo controlled randomized trial, because survival benefit was not observed in this small population study.

Chemoradiation therapy for cervical cancer: toxicity of concurrent weekly cisplatin.

PURPOSE: To retrospectively evaluate the toxicity of concurrent weekly cisplatin and radiation therapy (RT) for locally advanced cervical cancer. MATERIALS AND METHODS: Between April 2001 and December 2004, 21 consecutive previously untreated patients with locally advanced cervical cancer were treated with concurrent chemoradiation therapy (CCRT) at the Tokushima University Hospital. Clinical stages were II: 5, III: 15, IVA: 1. External beam radiation therapy (EBRT) was delivered with 10 MV X-rays, 2 Gy fraction per day; total dose to the whole pelvis was 50 Gy. Iridium-192 high-dose-rate (HDR) intracavitary radiation therapy was performed with 10-30 Gy (median, 24 Gy) targeted at point A. Concurrent chemotherapy consisted of cisplatin, administered weekly at a dose of 40 mg/m2 for patients who were younger than 65 years and 30 mg/m2 for those 65 years or over. A maximum single dose of cisplatin, up to 70 mg/body, was administered in 5 cycles during EBRT. RESULTS: A total of 86 cycles of cisplatin were administered to the 21 patients, with a median of 4 cycles (range, 2-5). Severe hematological toxicity occurred in 18 patients (86%), including grade 3 in 17 patients (81%) and grade 4 in one patient (4.8%). Moderate or severe gastrointestinal toxicity occurred in 11 patients (52%), including grade 2 in 10 patients (48%) and grade 3 in one patient (4.8%). The grades of hematological toxicity were significantly greater in the 40 mg/m2 group than in the 30 mg/m2 group. All of the patients who were administered 40 mg/m2 of cisplatin developed grade 3 or greater hematological toxicity, including one patient with grade 4 toxicity. In the 30 mg/m2 group, 3 of 10 patients developed less than grade 3 toxicity, and all patients completed radiation therapy without interruption. CONCLUSION: The incidence of severe acute hematological toxicity was significantly higher in this study than in previously reported randomized controlled trials (RCTs), especially in the group of 40 mg/m2 cisplatin. A dose of 30 mg/m2 of cisplatin was considered to be feasible in weekly cisplatin and radiation therapy.

Phase III double-blind randomized trial of radiation therapy for stage IIIb cervical cancer in combination with low- or high-dose Z-100: treatment with immunomodulator, more is not better.

BACKGROUND: To evaluate the efficacy of low or high-dose immunomodulator, Z-100, in combination with radiotherapy for cervical cancer. METHODS: Between 1995 and 1999, 221 patients with stage IIIb squamous cell carcinoma of the cervix were randomly assigned to treatment with Z-100 either at 0.2 microg or 40 microg in a double-blind manner in combination with radiotherapy. RESULTS: The 5-year survival of patients with high-dose and low-dose Z-100 was 41.5% (95% CI: 31.7-51.3%) and 58.2% (95% CI: 48.7-67.7%), respectively, showing a 30% reduction in the death rate (hazard ratio: 0.670 [95% CI: 0.458-0.980], P = 0.039). Survival of high-dose group was equivalent to the 4-year survival of the radiotherapy plus hydroxyurea arm (49.7%) of GOG120 study, and that of low-dose group was similar to the survival of the cisplatin-based chemoradiation arm. The progression-free survival was also significantly improved in favor of low-dose group (hazard ratio: 0.667 [95% CI: 0.447-0.997], P = 0.048). The survival of low-dose group was similar to the survival of the cisplatin-based chemoradiation arms of the GOG120 study. CONCLUSIONS: Unexpectedly, the survival of patients with advanced cervical cancer treated by lower dose of Z-100 in combination with radiotherapy was significantly better than those treated with higher dose Z-100, which was equivalent to the survival with radiotherapy alone. The hypothesis that lower dose of Z-100 enhances the efficacy of radiation therapy is now being tested by placebo-controlled randomized trial.

Quality assurance of I-125 seed permanent implant therapy using a self-color developing reflection-type dosimetry sheet film.

PURPOSE: We evaluated a self-color developing sheet-type film for the detection of dead seeds in I-125 permanent implant therapy for prostate cancer. MATERIALS AND METHODS: As a preliminary study, we irradiated X-rays to a self-developing reflection-type sheet film and created a relational curve between absorbed dose and film density. I-125 seeds were placed on a film and the approximate absorbed dose of I-125 was calculated from the relational curve of X-rays. A cartridge in which a dead seed was loaded among 10 I-125 seeds was placed on the film and the detectability of the dead seed was evaluated. RESULTS: Using the relational curve of X-rays, it was possible to measure the approximate absorbed dose of I-125 seeds and to easily detect a dead seed at a glance. Using sterilized film, it was possible to detect a dead seed. CONCLUSION: The self-developing film method is feasible for the detection of a dead seed in a cartridge without re-sterilization of seeds.