Effect of histologic type on recurrence pattern in radiation therapy for medically inoperable patients with stage I non-small-cell lung cancer.

Japanese randomized trials showed that there was a significant impact on survival from stage I adenocarcinoma (AD) of the lung by adjuvant chemotherapy with uracil-tegaful after complete resection but there was no effect for patients with squamous cell carcinoma (SQ). The purpose of this study was to examine the correlation of tumor histology and clinical outcome of radiation therapy (RT) for stage I non-small-cell lung cancer (NSCLC) and to consider the necessity of adjuvant chemotherapy after RT for these patients. The subjects were 83 patients, 54 with SQ and 29 with AD; they had received definitive RT with the total dose ranging from 60 to 80 Gy with conventional fractionation at a daily dose of 2 Gy. The differences between SQ and AD with respect to survival and recurrence pattern were investigated. The 5-year overall survival and cause-specific survival rates were 26.5% and 49.1%, respectively. No difference in survival was observed between SQ and AD patients, and the recurrence rates were almost identical (44% for SQ and 45% for AD). However, the 5-year primary control rate of SQ was significantly poorer than that of AD (SQ: 61.5%; AD: 87.6%; p = 0.03). Conversely, the 5-year metastasis-free survival rate of SQ was significantly better than that of AD (SQ: 88.2%; AD: 53.0%; p = 0.005). The different failure pattern, according to tumor histology, indicates that taking into consideration the difference in their clinical behaviors would also be important for planning RT and surgery for early lung cancer.

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.

An eight-year survivor with multiple brain metastases of non-small cell lung cancer: an autopsy case.

BACKGROUND: Patients with brain metastases of non-small cell lung cancer (NSCLC) have a poor prognosis, so chemotherapy and best-supportive care are typically pursued as initial treatments. CASE REPORT: A 52-year-old man presented with symptoms of disorientation and disturbed consciousness as a result of multiple brain metastases. A histopathological examination revealed that the primary tumor was a large cell carcinoma located in the left upper lung. Whole brain irradiation (WBI) with a total dose of 50 Gy was immediately started. Since the brain tumors were successfully controlled, irradiation of the primary lung lesion with a total dose of 60 Gy was initiated 6 months after the WBI. Afterward, the patient was clinically free from lung cancer, but other cancers developed in the cecum and appendix and were surgically removed. He survived for more than 8 years after the WBI but eventually died of respiratory insufficiency caused by multiple lung metastases. The autopsy findings indicated that the lung lesions were metastatic adenocarcinomas from the appendiceal cancer, and the patient had remained disease-free from lung cancer. CONCLUSION: In view of the possibility of long-term survival in patients with stage IV NSCLC and brain metastasis, especially those with only intracranial metastases, careful consideration is be needed in the selection of treatment options.

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.

Acute genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity.

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.

Rectal bleeding after hypofractionated radiotherapy for prostate cancer: correlation between clinical and dosimetric parameters and the incidence of grade 2 or worse rectal bleeding.

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.

External beam radiotherapy for clinically node-negative, localized hormone-refractory prostate cancer: impact of pretreatment PSA value on radiotherapeutic outcomes.

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.

A 104-year-old woman with advanced cervical carcinoma of the uterus.

BACKGROUND: Treatment of elderly patient with advanced cancer includes considerable problems because of their limited life expectancy. CASE: A 104-year-old woman with FIGO stage IIIB uterine cervical carcinoma treated with external beam radiotherapy and high dose-rate brachytherapy. After the treatment, the serum squamous cell carcinoma (SCC) antigen had fallen to normal level. She is now living 66 months after the treatment without recurrent symptoms. CONCLUSION: In this specific case, the significance of this treatment is that the patient is surviving at the age of 109.

Comparable outcomes of radiation therapy without high-dose methotrexate for patients with primary central nervous system lymphoma.

BACKGROUND: The previous trials of radiotherapy conducted for primary central nervous system lymphoma (PCNSL) have not been successful. Therefore, we have investigated the clinical outcomes and the role of radiation therapy in the treatment of PCNSL. METHODS: Thirty-three consecutive patients with PCNSL treated with cranial radiotherapy (30-40 Gy whole brain plus 10-20 Gy boost) without administration of high-dose methotrexate were retrospectively analyzed. Nine patients received whole spinal irradiation (WSI) as an additional therapy. The median age of patients was 58 years (range: 28-78 years), and 70% showed a poor performance status (PS). RESULTS: The median survival time (MST) was 13 months, and the 5-year overall survival rate was 35%. The initial response and the number of tumors were significant prognostic factors, and WSI tended toward significance in a multivariate analysis. Four of five patients, who received prophylactic WSI, were 4-year survivors without a tumor relapse and none of them had tumor involvement in the vertebral canal. One patient developed radiation-induced brain necrosis, however, WSI did not seem to affect the late complications. CONCLUSIONS: We consider it important to reduce severe acute and late complications in patients qualified for receiving an aggressive therapy, and to explore the possible tolerable and curative treatment methods that can be used in order to improve the prognosis for PCNSL. Further modifications, including the application of WSI seem to be necessary in the management of PCNSL.

Interaction of radiation and etoposide on two cell lines with different radiosensitivities in vitro.

PURPOSE: To investigate the differences between two rat yolk sac tumor cell lines with different radiosensitivities in etoposide sensitivity and in the sensitizing effect of etoposide in combination with irradiation. MATERIALS AND METHODS: NMT-1 is a parent radiosensitive cell line and NMT-1R is a variant radioresistant cell line. The effects were assessed by clonogenic assay. Apoptosis was evaluated by DNA fragmentation to investigate the mechanism of cell death. RESULTS: Etoposide potentiation of radiation sensitivity was manifested by elimination of the initial shoulder of the cell survival curve in radioresistant NMT-1R cells. However, there was no enhancement effect in radiosensitive NMT-1 cells. The incidence of apoptosis was elevated in NMT-1R cells treated with etoposide and radiation. CONCLUSION: Etoposide had a supra-additive effect in combination with irradiation for radioresistant NMT-1R cells due to the induction of apoptosis. However, a suppra-additive effect was not seen in radiosensitive NMT-1 cells.

Treatment results of radiotherapy for malignant lymphoma of the orbit and histopathologic review according to the WHO classification.

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.

Comparison of primary thyroid lymphoma with anaplastic thyroid carcinoma on computed tomographic imaging.

PURPOSE: Primary non-Hodgkin's lymphoma (LY) and anaplastic carcinoma (AC) of the thyroid gland are rare malignant tumors, and the initial symptoms of these diseases are very similar. The aim of our study was to compare the characteristics of the two diseases using computed tomographic (CT) scans in order to make an accurate differential diagnosis. MATERIALS AND METHODS: Ten patients with LY and 10 with AC were analyzed. Differences in the CT findings of the two diseases were evaluated before treatment and statistically tested with either Student's t-test or the chi-square test. RESULTS: In the analysis of characteristics of CT imaging, the existence of calcification and necrosis, and heterogeneous tumor were dominant findings in AC, and there was a statistically significant difference in frequency between the two diseases (p < 0.01). Calcification detected in AC was usually multiple and/or gross (mean size: phi8.2 mm). All lymphadenopathies were delineated as having the same homogeneous attenuation as the tumors in the thyroid gland in LY, but were shown as irregular rim enhancement in AC. CONCLUSION: The CT features of the two diseases are characteristic in terms of calcification, necrosis, and tumor composition. Evaluation by means of CT imaging is useful in distinguishing between LY and AC.

Combined effect of hyperthermia at 42 degrees C and irradiation dose of 2 Gy on two rat yolk sac tumor cell lines with different radio-thermosensitivity in vitro.

BACKGROUND: Two rat yolk sac tumor cell lines, NMT-1 and NMT-1R, are of the same origin and of different sensitivity to irradiation and to heat. The aim of this study was to investigate the sensitivities of these two cell lines to combined treatments of low-dose irradiation at 2 Gy and hyperthermia at 42 degrees C. MATERIALS AND METHODS: The cell survival was assayed by soft agar clonogenic assay. After the survival curves of radiation alone and of heat alone at various temperatures were estimated, not only the effect of irradiation on heat, but the effect of heat on irradiation were evaluated with sequential treatments in both cell lines. These effects on survival curves were evaluated by the enhancement ratios at isosurvival levels of 37%, 10% and 1%, respectively. RESULTS: NMT-1 was more sensitive to radiation but more resistant to heat than NMT-1R. For 1% survival level, radiosensitivity in NMT-1 was 1.32 times that in NMT-1R, while thermal sensitivity at 42 degrees C in NMT-1R was 2.73 times that in NMT-1. For sequential treatment, thermosensitization by a radiation dose of 2 Gy in radiosensitive NMT-1 was greater than that in radioresistant NMT-1R. Following heat at 42 degrees C for 1 hour, increased radiosensitivity in NMT-1R was significant, whereas the same heat treatment produced an increase in the radiation sensitivity of NMT-1 with a reduction of the survival curve shoulder but with less slope modification. There was no difference in the surviving fraction in the time-course of a combination of heat and irradiation at various intervals within 6 hours for NMT-1 except for heating immediately after irradiation. However a significant increase in survival was observed when heat was applied more than 3 hours after 2 Gy irradiation for NMT1-R. CONCLUSION: These results from our cell lines with the same origin were useful for investigation into the interaction of irradiation with heat.