Ovarian ablation by radiation therapy: is it still an option for the ablation of ovarian function in endocrine responsive premenopausal breast cancer patients?

Surgical or medical ovarian ablation is likely to be the treatment of choice at the current time, radiation ablation (RA) can be still a reasonable alternative. The efficacy and toxicity of radiation therapy (RT) for ovarian function suppression in 118 premenopausal breast cancer patients were retrospectively evaluated. The median age was 39 years (range 21-52 years). RT was given with either Co-60 or 15MV photons of the linear accelerator. The median total dose was 15Gy in 4 consecutive fractions (range 5Gy single fraction-36Gy in 18 fractions over 3.5 weeks). The endpoint for treatment efficacy was menstrual status. Amenorrhea was noted in 113 of 118 patients (96%) in 6 months following RA. Five patients (4%) who had still normal menstrual functioning after 6 months of RA underwent estradiol and follicle stimulating hormone measurements and were found to have premenopausal levels. No acute Grade 3 or 4 (according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria) toxicities were noted. With a median follow-up of 24.5 months (range: 6-167), no late severe complications that could be attributable to RT were reported. RA should be considered as an option for endocrine responsive premenopausal breast cancer patients and can be easily delivered when postoperative or palliative irradiation is given.

Skeletal muscle: an unusual site of distant metastasis in gastric carcinoma.

UNLABELLED: Gastric cancer metastatic to skeletal muscle is an unusual entity. Surgery, systemic chemotherapy, or radiotherapy to the metastatic mass can be treatment options for achiving palliation. CASE REPORT: A patient with multiple skeletal muscle metastases that occurred during follow-up after gastrectomy and adjuvant chemo-radiotherapy is reported. Magnetic resonance imaging (MRI) demonstrated soft-tissue masses involving the posterior right paralumbar and posterior left paradorsal muscles. Biopsy showed metastatic infiltrating adenocarcinoma. The patient did not respond to palliative chemotherapy. Palliative radiotherapy was administered to the painful mass. Based on this case, the diagnosis of muscle metastases and treatment options for palliation are discussed.

The effects of tamoxifen on radiation-induced pulmonary fibrosis in Wistar albino rats: results of an experimental study.

This study was performed to evaluate the effects of tamoxifen on pulmonary fibrosis, given concurrently with or after irradiation in Wistar albino rats. Twenty-one female Wistar albino rats were randomized into three groups. The first group (Group A) had tamoxifen, which was started after the completion of irradiation. The second group (Group B) had tamoxifen concomitant with irradiation. The third group (Group C) had only thoracic irradiation and did not receive tamoxifen. Whole lungs were irradiated to a total dose of 30Gy in ten fractions with Co60. Tamoxifen was continued until the animals were sacrificed 16 weeks after the start of irradiation. As an end point the percentage of lung with fibrosis for each rat was quantified with image analysis of histological sections of the lung. Groups were compared using the one-way ANOVA method and Bonferroni post hoc test. The mean percentage values of fibrosis were 10.03 for Group A, 36.81 for Group B, and 3.87 for group C (P<0.001). When the percentages of fibrosis were compared for each group, the difference was statistically significant between Group A and Group B (P<0.001) and between Group B and Group C (P<0.001). Concomitant use of tamoxifen appears to increase radiation-induced pulmonary fibrosis and it seems more convenient to delay tamoxifen until the completion of irradiation.

Toxicity and survival results of a phase II study investigating the role of postoperative chemo-radioimmunotherapy for gastric adenocarcinoma.

BACKGROUND AND PURPOSE: To investigate the role of postoperative concomitant chemo-radioimmunotherapy in gastric adenocarcinoma patients. PATIENTS AND METHODS: 59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m(2)/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m(2)/day 5-FU and 25 mg/m(2)/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months). RESULTS: Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. CONCLUSION: Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.

Corneal topography in thyroid orbitopathy after orbital irradiation.

PURPOSE: The orbital tonus changes in thyroid orbitopathy, so it may be expected that corneal topographic results also change. Orbital irradiation may reduce the orbital tonus, and thus, it may affect the topographic changes. Corneal topographic results were examined before and after orbital irradiation in patients with thyroid orbitopathy to determine whether there was a difference. METHODS: Twenty eyes of 10 patients with thyroid orbitopathy were included in this study. Corneal topography was performed with Topographic Modeling System 2 (Tomey). The refractive power of the corneal curvature was measured at the center of the corneal apex and in each of the eight quadrants, 1.5 mm and 3 mm from the corneal apex, on the corneal topographer. A total dose of 20 Gy was given in 10 fractions over 2 weeks to the orbital structures sparing the lens, and corneal topography was performed 6 weeks and 8 months later. The measures of the refractive power of the cornea were taken again. Repeated-measures analysis of variance was used to evaluate the differences between the measures. RESULTS: There were no statistically significant differences in refractive power of the cornea in the topographic maps obtained before the radiotherapy and the two follow-up examinations after the radiotherapy. CONCLUSIONS: Thyroid orbitopathy is an orbital disease and may affect corneal topographic results. Orbital irradiation reduces or eliminates pathogenic orbital lymphocyte infiltration, thereby reducing orbital and extraocular muscle edema in patients with thyroid orbitopathy. In the current study group, corneal topographic changes were observed minimally as a result of the orbital irradiation, but they were not statistically significant.

The effect of treatment interruptions in the postoperative irradiation of breast cancer.

OBJECTIVE: There is much evidence for the detrimental effect of treatment interruptions on tumor control, particularly in head and neck cancer. In order to determine the outcome of the treatment interruptions in postoperative irradiation of breast cancer, 853 female patients treated between 1990 and 1999 inclusive were retrospectively analyzed. METHODS: Locally advanced breast cancer patients who received neoadjuvant chemotherapy were not included in the study. Five hundred and forty-six patients (64%) treated with mastectomy and 307 patients (36%) with breast-conserving surgery were analyzed. A total dose of 50 Gy (46--54 Gy) was given to the chest wall/breast and regional lymph nodes in 1.8- to 2-Gy daily fractions, 5 times per week. A 14-Gy (10- to 20-Gy) photon or electron boost was given to the tumor bed of the patients with breast-conserving surgery. Unplanned treatment interruptions occurred in 741 (87%) of the patients and the median duration of the gaps was 13 days (1--91 days). A total of 348 patients (41%) had no treatment break or interruptions of 1 week or less, whereas 505 patients (59%) had treatment interruptions of more than 1 week. The locoregional control (LC) and overall survival (OS) rates were estimated with the Kaplan-Meier method. A Cox proportional hazard regression model was used to evaluate the influence of host- and treatment-related factors on LC and OS (age, menopausal status, histological subtype, grade, hormonal receptor status, pT stage, pN stage, type of surgery, adjuvant treatment, number of gaps and duration of gaps). RESULTS: For all patients LC rates for 5 and 10 years were 95 and 87%, respectively, and OS rates were 78% for 5 years and 62% for 10 years. LC rates for the group of patients with no treatment break or interruptions of 1 week or less, for 5 and 10 years were 94 and 90%, whereas the LC rates for 5 and 10 years were 89 and 86%, for the group of patients with interruptions of more than 1 week (p=0.019). Treatment interruptions of more than 1 week and premenopausal status appeared to be independent adverse prognostic factors in multivariate analyses affecting the LC (p=0.043 and p=0.005, respectively). The OS rates for the patients without treatment interruptions or interruptions of 1 week or less were also significantly better than for the patients with treatment interruptions of more than 1 week (p=0.026) in multivariate analyses. CONCLUSION: Interruptions more than 1 week during postoperative irradiation of breast cancer adversely affect the treatment outcome.

Pentoxifylline in the treatment of radiation-related pelvic insufficiency fractures of bone.

The reported incidence of bone complications after radiation therapy is quite low. The most commonly seen bone complication is insufficiency fractures of the pubis and sacrum. Treatment of insufficiency fractures consists of conservative care, and mineral replacement may be useful. The resolution of symptoms takes at least one year with these treatments. Vascular damage has an important role in the etiology of late radiation injury in normal tissues. Progressive ischemic changes further weaken the bone structure, which can cause fractures, and healing is also delayed. Pentoxifylline is a methylxanthine derivative that is shown to increase tissue blood flow. Here, we present a 63-year-old male patient with pelvic insufficiency fractures due to postoperative pelvic irradiation for rectal adenocarcinoma. The patient received pelvic radiotherapy to a total dose of 50.4 Gy with concomitant 5-FU. Six months after the completion of radiotherapy, the patient presented with severe pelvic pain. Pelvic magnetic resonance imaging (MRI) demonstrated abnormal signal intensity with insufficiency fractures at the sacrum and bone marrow edema near the fractures, but not an abnormal intensity that revealed bone metastases. Neither distant nor locoregional recurrence was observed at his work-up. The final diagnosis was insufficiency fractures of the pelvic bones owing to irradiation, and pentoxifylline (400 mg, 3 times daily, peroral, 1,200 mg/day) was used for eight months as treatment. Dramatic clinical improvement was obtained in six months, and objective healing was revealed with MRI. We concluded that pentoxifylline is a cost-effective drug with minimal adverse effects in treating radiation damage of bone.

Medulloblastoma in adults: treatment results and prognostic factors.

PURPOSE: To investigate the treatment outcome and prognostic factors of adult medulloblastoma patients who received postoperative craniospinal irradiation (RT). METHODS AND MATERIALS: Between 1983 and 2000, 30 adult patients (17 men and 13 women, age >or=16 years, median 27, range 16-45) underwent postoperative RT. The median duration of symptoms was 2 months (range 1-9). The tumor location was lateral in 16 (53%). A desmoplastic variant was seen in 12 (40%). Tumor resection was complete in 20 (67%) and incomplete in 10 (33%). All patients received craniospinal RT. The median dose to the whole brain was 40 Gy (range 36-51), to the posterior fossa 54 Gy (range 49-56), and to the spinal axis 36 Gy (range 24-40). The median interval between surgery and the start of RT was 31 days (range 12-69), and the median duration of RT was 45 days (range 34-89). Ten patients (33%) received adjuvant chemotherapy. The median follow-up was 51 months (range 5-215). RESULTS: The 5- and 8-year overall survival and disease-free survival rates were 65% and 51% and 63% and 50%, respectively. Twelve patients (40%) developed relapse, with a median follow-up of 51 months. The posterior fossa was the most common site of relapse (6 patients). The median time to relapse was 26 months (range 4-78). Fifty percent of the relapses occurred after 2 years, 17% after 5 years. In univariate analysis, M stage and the interval between surgery and the start of RT were significant prognostic factors for disease-free survival. At 5 years, 70% of M0 patients were estimated to be disease-free, but none of the 3 M3 patients reached 5 years without recurrence (p = 0.0002). The 5-year disease-free survival rate for the patients whose interval between surgery and the start of RT was <3 weeks, between 3 and 6 weeks, and >6 weeks was 0%, 85%, and 75%, respectively (p = 0.002). The 5-year posterior fossa control rate for patients who received >or=54 Gy or <54 Gy to the posterior fossa was 91% and 33%, respectively (p = 0.05). CONCLUSION: The survival results for medulloblastomas in adults compare favorably with those in children. However, late relapses, lateral tumor location, and desmoplastic histologic features are more frequent in adults. Spinal seeding at presentation is a poor prognostic factor for disease-free survival. A minimal dose of 54 Gy to the posterior fossa is essential for adequate tumor control. The interval between surgery and the start of RT, which was found to be a significant prognostic factor, is an interesting issue that requires further study.