Search

Purpose: Several investigations have revealed that the alpha/beta ratio for prostate cancer is atypically low, and that hypofractionation or high-dose-rate (HDR) brachytherapy regimens using appropriate radiation doses may be expected to yield tumor control and late sequelae rates that are better or at least as favorable as those achieved with conventional radiation therapy. In this setting, we attempted treating localized prostate cancer patients with HDR brachytherapy combined with hypofractionated external beam radiation therapy (EBRT). The purpose of this study was to evaluate the feasibility of using this approach, with special emphasis on the relationship between the severity of acute genitourinary (GU) toxicity and the urethral dose calculated from the dose-volume histogram (DVH) of HDR brachytherapy., Methods and Materials: Between September 2000 and December 2003, 70 patients with localized prostate cancer were treated by iridium-192 HDR brachytherapy combined with hypofractionated EBRT at the Gunma University Hospital. Hypofractionated EBRT was administered in fraction doses of 3 Gy, three times per week; a total dose of 51 Gy was delivered to the prostate gland and the seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography (TRUS)-guided HDR brachytherapy. The fraction size and the number of fractions in HDR brachytherapy were prospectively changed, whereas the total radiation dose for EBRT was fixed at 51 Gy. The fractionation in HDR brachytherapy was as follows: 5 Gy x 5, 7 Gy x 3, 9 Gy x 2, administered twice per day, although the biologic effective dose (BED) for HDR brachytherapy combined with EBRT, assuming that the alpha/beta ratio is 3, was almost equal to 138 in each fractionation group. The planning target volume was defined as the prostate gland with 5-mm margin all around, and the planning was conducted based on computed tomography images. The number of patients in each fractionation group was as follows: 13 in the 5-Gy group; 19 in the 7-Gy group, and 38 in the 9-Gy group. The tumor stage was T1 in 10 patients, T2 in 36 patients, and T3 in 24 patients. The Gleason score was 2-6 in 11 patients, 7 in 34 patients, and 8-10 in 25 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 14 months (range 3-42 months). The toxicities were graded based on the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria., Results: The main symptoms of acute GU toxicity were dysuria and increase in urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 39 patients (56%), and Grade 2-4, 31 patients (44%). One patient who developed acute urinary obstruction was classified as having Grade 4 toxicity. Comparison of the distribution of the grade of acute GU toxicity among the different fractionation groups revealed no statistically significant differences among the groups. The urethral dose in HDR brachytherapy was evaluated using the following DVH parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. The V30-110 values in the patients with Grade 2-4 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. On the other hand, there were no significant differences in the V120-150 values between patients with Grade 0-1 and Grade 2-4 toxicity. Regarding the influence of the number of needles implanted for the radiation therapy, patients with 11 needles or less showed a significantly higher incidence of Grade 2-4 acute GU toxicity compared with those with 12 needles or more (p < 0.05)., Conclusions: It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer when considered from the viewpoint of acute toxicity. Increase in the fraction dose or reduction in the number of fractions in HDR brachytherapy did not affect the severity of acute GU toxicity, and the volume of urethra receiving an equal or lower radiation dose than the prescribed dose was more closely associated with the grade severity of acute GU toxicity than that receiving a higher than the prescribed dose.

Purpose: To investigate the incidence and severity of rectal bleeding after high-dose hypofractionated radiotherapy (RT) for prostate cancer, and to explore the factors affecting the incidence of Grade 2 or worse rectal bleeding., Methods and Materials: The data of 52 patients who had been treated by external beam RT for localized prostate cancer between 1999 and 2002 were analyzed. All the patients had received hypofractionated external beam RT to a total dose of 69 Gy in 3-Gy fractions, three fractions weekly. The clinical and dosimetric factors affecting the incidence of Grade 2 or worse late rectal bleeding were analyzed by univariate and multivariate analyses. The effect of the percentage of the whole rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose (V(30), V(50), V(80), and V(90), respectively) on the incidence of rectal bleeding was evaluated., Results: Of the 52 patients, 13 (25%) developed Grade 2 or worse rectal bleeding. One patient who needed laser coagulation and blood transfusion for the treatment of rectal bleeding was classified as having Grade 3 rectal bleeding. The median time to the development of Grade 2 or worse rectal bleeding was 11 months. The results of the univariate analysis revealed that the presence of a history of diabetes mellitus (p < 0.001), and V(30) >/= 60%, V(50) >/= 40% (p < 0.05), V(80) >/= 25%, and V(90) >/= 15% (p < 0.001) were statistically significant risk factors for the occurrence of Grade 2 or worse rectal bleeding. The results of the multivariate analysis revealed that a history of diabetes mellitus was the most statistically significant risk factor for the occurrence of rectal bleeding after hypofractionated RT for prostate cancer (p < 0.05)., Conclusion: A history of diabetes mellitus was the most statistically significant risk factor for the occurrence of Grade 2 or worse rectal bleeding after high-dose hypofractionated RT, although dosimetric factors were also closely associated with the risk of rectal bleeding.

Purpose: To analyze the results of clinically node-negative, localized hormone-refractory prostate cancer treated with external beam radiotherapy (EBRT) and to investigate the potential prognostic factors that influenced the therapeutic outcome., Methods and Materials: Fifty-three patients who had developed localized hormone-refractory prostate cancer were treated with EBRT between 1994 and 2001. According to the 1992 American Joint Committee on Cancer clinical stage, 4 patients had T2 and 49 had T3 at the start of RT, and 14 patients had a Gleason score <7, 14 had a Gleason score of 7, and 23 had a Gleason score of 8-10. All patients were treated with EBRT using the unblocked oblique four-field technique, with a total dose of 69 Gy. The fraction dose was 3 Gy three times weekly. The median follow-up after RT was 35 months (range, 8-96 months) and after androgen ablation was 73 months (range, 42-156 months)., Results: Of 53 patients, 15 patients subsequently developed clinical relapse, including locoregional and/or distant metastases. The site of first relapse was bone metastasis in 10, lymph nodes in 3, and local failure in 2 patients; 3 patients died of prostate cancer during the analysis period. The 3-year and 5-year cause-specific survival rate was 94% and 87%, respectively, and the 3-year and 5-year clinical relapse-free survival rate was 78% and 56%, respectively. The univariate analysis revealed that a short prostate-specific antigen (PSA) doubling time and high PSA value at the start of RT and a high Gleason score were statistically significant factors for the risk of clinical relapse. Multivariate analysis demonstrated that the PSA value (PSA or=15 ng/mL) at the start of RT was an independent prognostic factor., Conclusion: EBRT could be a treatment of choice for clinically node-negative, localized, hormone-refractory prostate cancer.

Purpose: To analyze the results of radiotherapy (RT) for malignant lymphoma of the orbit and to evaluate them compared with the World Health Organization (WHO) classification published in 2001., Methods and Materials: The data from 29 patients with malignant lymphoma of the orbit treated with RT at Gunma University Hospital between 1978 and 2001 were retrospectively analyzed. Pathologic slides from 23 cases were available and were reviewed by a hematopathologist according to the WHO classification. The original and reviewed diagnoses, patient characteristics, treatment results, and complications were analyzed. In principle, patients with low-grade or indolent lymphoma were treated with RT alone, using 30 Gy as the tumor dose. Survival data were calculated using the Kaplan-Meier method., Results: One case that proved to be a pseudotumor was excluded from evaluation. Of the 28 cases, 25 were Stage IAE, 1 was Stage IIAE, and 2 were Stage IVAE. The median follow-up was 71 months. According to the original classification and the Working Formulation, the 5- and 10-year overall survival rate of patients with low-grade lymphoma was 94% and 73%, respectively. The corresponding rates for those with intermediate-grade lymphoma were 67% and 67% (p = 0.15). In contrast, the WHO classification showed a significant difference in the survival curves. The 5- and 10-year overall survival rate of patients with mucosa-associated lymphoid tissue (MALT) lymphoma was 100% and 88%, respectively; for diffuse large B-cell patients, the rates were both 0% (p < 0.001). In patients with MALT lymphoma, one local and four distant relapses developed; two of them >10 years after initial treatment. All of the relapsed MALT lymphomas were controlled by salvage therapy., Conclusion: Excellent local control and survival can be achieved for patients with orbital MALT lymphoma using RT alone. A precise histopathologic diagnosis using the WHO classification and long-term follow-up for >10 years is recommended.

Purpose: A retrospective analysis was performed with emphasis on the patterns of recurrence, latent period, and prognosis in patients with cervical squamous cell carcinoma of the uterus treated with definitive radiation therapy alone. Late recurrence, which was observed more than 5 years after the initial radiation therapy, was finally focused on and discussed., Materials and Methods: Between 1976 and 1994, 256 patients with squamous cell carcinoma of the uterine cervix without hematogenous metastasis were treated with definitive radiation therapy alone. The patients were staged as follows according to the FIGO classification: 26 in Stage I, 56 in Stage II, 124 in Stage III, 28 in Stage IVa, and 22 in Stage IVb. All the patients were treated with external beam irradiation and low-dose-rate intracavitary brachytherapy., Results: A total of 74 patients had recurrence. The recurrence appeared in 67 cases (90.5%) within 5 years. Metastasis to para-aortic and/or supraclavicular nodes developed later than other types of recurrence. Among patients with lymphogenous metastasis, there were more 5-year survivors after recurrence than with other types of recurrence. Patients with early recurrence, within 2 years of the initial therapy, had a worse prognosis than those with recurrence more than 2 years after treatment. Seven patients (2.7%) in all developed late recurrence more than 5 years after the treatment. The first site of recurrence was an abdominal para-aortic or supraclavicular node in all patients, excluding one patient who developed intrapelvic lymph node metastasis. Six patients had pelvic node metastasis detected with lymphangiography at the initial treatment. Median survival after late recurrence was 16.0 months. Two of 7 patients survived more than 3 years after secondary radiation therapy, and the remainder died of recurrent disease., Conclusion: Patients with para-aortic and/or supraclavicular node metastasis that developed late after the initial treatment are more likely to survive due to secondary radiation therapy. Careful follow-up is emphasized for long-term survivors.

Purpose: We reported that two established rat yolk sac tumor cell lines differ in their radiosensitivity by 1.7 fold, and the variation is most likely manifested by the differences seen in their apoptotic response. We investigated the relationship between radiosensitivity and p53 in these cell lines., Methods and Materials: We assessed the status of p53 in cell lines by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequence analysis, and also analyzed protein expression of p53, p21, and bax as a function of time after irradiation to determine the signal transduction for p53 by immunoblotting., Results: A band shift was observed only in exon 7 for the radioresistant NMT-1R cells and no band shift was detected for the radiosensitive NMT-1 cells. A band shift was confirmed also at the mRNA level. Exon 7 of p53 DNA showed a three base substitution of DNA at codon 267 to 268. Expression of p53, p21, and bax proteins in NMT-1R cells did not change after 10 Gy irradiation; however, in NMT-1 cells, the expression of these proteins was increased from 1-12 h after irradiation., Conclusion: A loss of p53 function by radiation-induced mutation of p53 decreased the radiosensitivity in these cell lines.

Purpose: To investigate the effect of radiation on E-cadherin and alpha-catenin expression in a human lung cancer cell line, and also evaluate invasive capacity in the membrane invasion culture system using the Boyden Chamber., Materials and Methods: The immunoblot and immunofluorescence analyses were performed using the human lung cancer cell line A549 to examine altered expression of E-cadherin and alpha-catenin after irradiation. We also compared invasive capacity of untreated cells with that of irradiated cells., Results: Immunoblot analysis revealed that the expression of E-cadherin increased after irradiation. In a time-course analysis, the expression was increased 6 h after irradiation with 10 Gy and reached its peak level at 24 h, being 2.3 times the control value, whereas expression at 1 and 3 h after irradiation was almost equivalent to that of the control. A slight increase in expression was observed after irradiation of 2 Gy and the expression reached peak levels after 5 Gy. After fractionated irradiation, the increase in expression of both E-cadherin and alpha-catenin was observed, and the alteration of alpha-catenin was more prominent than that after a single irradiation of the same total dose. In the immunofluorescence study for E-cadherin antibody analyzed by confocal laser scanning microscopy, increased intensity in irradiated cells produced as a nondisrupted and continuous line at cell-cell contact sites. In an invasive assay, the number of migrated cells in irradiated cells after a dose of 5 and 10 Gy was reduced significantly compared to untreated cells., Conclusion: The results indicate that irradiation of A549 increased the expression of E-cadherin, possibly preserving their functional property.

Purpose: Phosphorus-31 magnetic resonance spectra (31P-MRS) were obtained from highly apoptotic murine lymphoma xenografts before and up to 24 hr following graded doses of radiation ranging from 2 to 30 Gy. Radiation-induced apoptosis was also estimated up to 24 hr by scoring apoptotic cells in tumor tissue., Methods and Materials: Highly apoptotic murine lymphoma cells, EL4, were subcutaneously transplanted into C57/BL mice. At 7 days after transplantation, radiation was given to the tumor with a single dose at 3, 10, and 30 Gy. The beta-ATP/Pi, PME/Pi, and beta-ATP/PME values were calculated from the peak area of each spectrum. Radiation-induced apoptosis was scored with counting apoptotic cells on hematoxylin and eosin stained specimens (% apoptosis)., Results: The values of % apoptosis 4, 8, and 24 hr after radiation were 21.8, 19.6, and 4.6% at 3 Gy, 35.1, 25.6, and 14.8% at 10 Gy, 38.4, 38.0, and 30.6% at 30 Gy, respectively (cf. 4.4% in control). There was no correlation between early change in beta-ATP/Pi and % apoptosis at 4 hr after radiation when most of the apoptosis occurred. An early decrease in PME/Pi was observed at 4 hr after radiation dose at 30 Gy. For each dose, the values of beta-ATP/Pi 24 hr after radiation were inversely related to radiation dose., Conclusion: The increase in beta-ATP/Pi observed by 31P-MRS was linked to the degree of histological recovery from radiation-induced apoptosis.

Purpose: To investigate changes in E-cadherin expression after X-ray irradiation of a human cancer cell line in vitro and in vivo., Methods and Materials: E-cadherin expression on a human squamous cell carcinoma of the thyroid gland (T-SCC cell), which was established in our laboratory, at 24 h after graded single doses of irradiation and at 7 successive times after 10-Gy irradiation were investigated in vitro by immunoblot analysis with the monoclonal antibody to human E-cadherin. The changes in E-cadherin expression caused by irradiation of T-SCC tumors that were transplanted into athymic nude mice were also determined in vivo by immunohistochemical staining and immunoblot analysis in a similar fashion to that in vitro., Results: In vitro studies revealed that E-cadherin expression had increased significantly on T-SCC cells at 24 h after irradiation with doses of 2 to 10 Gy and that, in a time-course analysis, the expression had increased significantly at 3 to 72 h after irradiation compared with an unirradiated control cell, although it was not observed at 1 h after irradiation. In in vivo studies, a significant increase in E-cadherin expression was observed at 24 h after irradiation with 5 and 10 Gy by immunohistochemical staining and time-course studies demonstrated that E-cadherin increased temporarily at 12 to 24 h after 10-Gy irradiation; however, immunoblot analysis did not show alteration of E-cadherin expression by irradiation., Conclusion: X-ray irradiation upregulated E-cadherin expression on T-SCC cells in vitro and in vivo.

Purpose: The efficacy of radiation therapy for Kasabach-Merritt syndrome, which is characterized by a huge hemangioma with consumption coagulopathy, remains controversial. In this study, we retrospectively investigated the treatment outcome of radiation therapy for seven neonates with Kasabach-Merritt syndrome., Methods and Materials: During the past 25 years we have seen seven children with Kasabach-Merritt syndrome who were treated with radiation therapy. Their ages ranged from 1 day to 5 months, with a median age of 1 month. The hemangioma was located in the extremities in four of seven children. Tumor sizes ranged from 70 cm to more than 150 cm in greatest diameter. Initial platelet counts were all less than 40,000/mm3 except for one patient. In principle, the total dose applied to the hemangioma was 8-10 Gy, with a daily dose of 1 Gy five times a week., Results: Four of seven hemangiomas responded dramatically, with a concomitant rise of the platelet count to radiation therapy. Although the remaining three hemangiomas, all of which were ill circumscribed by widespread overlying shiny, dusky purple skin, became less tense during radiation therapy. Disseminated intravascular coagulopathy was not improved, but they have responded favorably to two or three courses of radiation therapy with an extended radiation field by 1.5 years of age. As a result, all seven patients are now surviving with no evidence of hemangioma or hematological abnormalities. Shortening of the extremity was observed in three patients who received multiple courses of radiation therapy., Conclusions: Radiation therapy appears to be one of the effective treatment options for Kasabach-Merritt syndrome despite the risk of growth delay and malignancy.

Purpose: A retrospective analysis was performed to investigate the treatment outcome and the significance of radiation therapy for esophageal cancer in patients over 80 years old., Methods and Materials: Between 1971 and 1990, 257 patients with squamous cell carcinoma of the esophagus were treated by radiation therapy. Of these, 40 patients over eighty years old were investigated. The reasons for radiation therapy were advanced age alone in 22 patients, Stage IV disease in 13, and medical problems in 5. Of these, 33 patients (83%) could be irradiated over 60 Gy. The cases with Stage I to III disease who received 60 Gy or more were defined as the curative radiation therapy group, and the others were defined as the palliative radiation therapy group. Actuarial survival rates were determined by the Kaplan-Meier method., Results: The 5-year disease-specific survival rate for the curative radiation therapy group (n = 25) was 34% with three intercurrent deaths. None of the patients in the palliative radiation therapy group (n = 15), including 13 cases with Stage IV and two given-up cases, survived over 2 years. No severe radiation damage was observed in either group. The 5-year disease-specific survival rate was 64% for complete response cases of local response, and 8% for partial response and no change cases (p < 0.01). The 5-year disease-specific survival rate was 64% for the patients with tumors less than 5 cm in length, and 8% for the patients with tumors over 5 cm in length (p < 0.001). No significant survival differences were found in regard to sex and tumor location. The patients with superficial spreading type and polypoid type tumors according to the radiologic findings had better prognoses than the patients with ulcerative type and circumferential type tumors., Conclusions: Radiation therapy is a safe and effective treatment for esophageal cancer in patients over 80 years old.

Purpose: A retrospective analysis was performed to evaluate external beam therapy and three brachytherapy fractions for patients with squamous cell carcinoma of the uterine cervix, compared with those with other histological types., Methods and Materials: Three hundred and twenty-two patients with carcinoma of the uterine cervix received external pelvic irradiation combined with three sessions of low dose rate intracavitary irradiation within 6 weeks. Two hundred and ninety-three patients had squamous cell carcinoma (SCC), whereas 29 patients had nonsquamous cell histology (N-SCC): 18 had adenocarcinoma, 5 had undifferentiated carcinoma, 4 had adenosquamous carcinoma, and 2 had adenoacanthoma. Survival rates, patterns of failure, local control rates, and complications in the patients with SCC were compared with those in the patients with N-SCC., Results: The 5-year overall actuarial survival rates for the patients with SCC and for those with N-SCC were: 84% and 100% in Stage I disease, 72% and 38% in Stage II disease, 52% and 17% in Stage III disease, and 29% and 0% in Stage IV disease, respectively. The 5-year cause specific survival rates for the patients with SCC in Stages I to IV disease were 100%, 87%, 72%, and 39%. Corresponding rates for the patients with N-SCC were 100%, 43%, 25%, and 0%. There was a statistically significant difference between the survival curves for two histological types in Stage II B, III B, and IV A diseases. The local control for the patients with N-SCC was worse than in the patients with SCC. The crude moderate and severe rectal complication rates (Grades 3 and 4) for the patients with SCC and for the patients with N-SCC were 7.5% and 3.4%, respectively. Only one patient with SCC developed chronic small intestinal injury in this series. We observed four patients with SCC who developed Grade 2 and four with Grade 4 urinary bladder complications., Conclusions: Three sessions of intracavitary brachytherapy were a safe and effective procedure for the patients with SCC and the outcome of radiation therapy in the patients with SCC was satisfactory even in advanced cases. However, local control of N-SCC is difficult to achieve by this method and the prognosis for patients with N-SCC was significantly worse than that for patients with SCC.

Purpose: A retrospective analysis was performed to investigate the radioprotective effects of amifostine on the long-term outcome of radiation therapy for the patients with carcinoma of the uterine cervix., Methods and Materials: Eighty-three patients with histologically proven epidermoid carcinoma (Stage II-IVA disease) of the uterine cervix were treated with definitive radiation therapy between January 1978 and December 1984. Forty-six patients treated with radiation alone, whereas 37 patients treated with radiation plus amifostine. Amifostine was given intravenously 30 min prior to every radiation. Most patients received 75 mg/m2 of amifostine daily from the initiation of the course of radiation therapy. The median total dose of amifostine given was 1300 mg/m2, with a range of 280 mg/m2 to 3700 mg/m2., Results: The 5-year overall actuarial survival for the patients treated with radiation alone and with radiation plus amifostine were: 72% and 88% in Stage II disease (p = 0.45); 52% and 50% in Stage III disease (p = 0.68); and 40% and 43% in Stage IVA disease (p = 0.51), respectively. The 5-year intra-pelvic recurrence rates in the patients treated with amifostine were almost the same as those observed in the patients treated without amifostine (0% vs. 6% in Stage II disease; 15% vs. 10% in Stage III disease; 25% vs. 40% in Stage IVA disease). There was also no statistically significant difference of the chronic rectal or bladder complication rate between the groups treated by each regimen., Conclusion: We concluded that any radioprotective effects of amifostine on tumor tissue and any beneficial effects of amifostine against chronic radiation injury were not observed in the patients with cervical cancer followed up for more than 5 years after radiation therapy.

We have previously reported that Amifostine, a radioprotective agent, was effective in treating acute radiation mucositis in the head and neck region. We found that when a considerable amount of Amifostine accumulates in the salivary glands, it may be useful in preventing chronic disturbances of salivary secretion. We have observed an increase in the uptake of Ga-67-citrate to the salivary glands when they were irradiated. In this paper, the radioprotective effects of Amifostine, in treating chronic radiation injury of the salivary glands, were studied, using the cessation of an increase in uptake of Ga-67-citrate after radiotherapy as the criterion. The subjects were 105 patients, (280 salivary glands in Ga-scintigrams) with malignancy of the head and neck region treated by irradiation from 1978 to 1984. Ga-negative glands were recognized in 97%, that is, 36 out of 37 glands, before irradiation, and the figure decreased to 19%, seven out of 37, within 1 to 2 weeks (10Gy less than or equal to) after the start of radiotherapy. In patients who were irradiated with more than 30 Gy and in whom scintigraphy was performed at 6 months or more after radiotherapy, Ga-negative glands were recognized in 18 out of 41 glands, 44%, with Amifostine, compared with 13%, four out of 32 glands, without Amifostine. A difference was recognized between these two groups in the negative change in Ga-67 uptake after radiotherapy (p less than 0.05). These facts suggest that Amifostine may have a radioprotective effect on chronic radiation injury.