Intraoperative single fraction high-dose-rate brachytherapy for head and neck cancers.

PURPOSE: To report on the use of single fraction high-dose-rate brachytherapy in delivering localized intraoperative radiation therapy to sites in the head and neck region inaccessible to intraoperative electron beam radiotherapy (IOERT). METHODS AND MATERIALS: After maximal surgical resection, 7.5-20 Gy intraoperative high-dose-rate brachytherapy (IOHDR) was delivered to 65 patients using custom-made surface applicators. RESULTS: The 1-, 3-, and 5-year local control rates for the entire group were 77%, 69%, and 59%, respectively. The 1-, 3-, and 5-year overall survival rates were 83%, 63%, and 42%, respectively, with a median overall survival of 50 months. There were no major intraoperative or postoperative complications. CONCLUSIONS: IOHDR can be used to treat selected locally advanced head and neck tumors arising at sites inaccessible to IOERT or at institutions not using IOERT. A prospective multi-institutional study with a larger number of patients treated with IOHDR is needed to firmly establish the efficacy of IOHDR in this population group.

Intraoperative high-dose-rate brachytherapy for paranasal sinus tumors.

PURPOSE: Advanced and recurrent tumors of the paranasal sinuses can be difficult to irradiate to high doses with standard external beam radiotherapy (EBRT), conventional brachytherapy, or intraoperative electron beams. We, therefore, explored the role of intraoperative high-dose-rate brachytherapy (IOHDR) as a boost to EBRT in primary tumors or as sole adjuvant treatment in recurrent disease. METHODS AND MATERIALS: Between 1992 and 1998, 34 patients with locally advanced tumors arising in the paranasal sinuses were treated with IOHDR after maximal surgical excision. Twenty-seven patients with new primaries underwent gross resection and 10-12.5 Gy IOHDR followed by 45-50 Gy EBRT. Seven previously irradiated (45-63 Gy) patients with recurrent disease were treated with 15-20 Gy of IOHDR alone after gross excision. Local control and overall survival were analyzed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: After a mean follow-up of 6 years (range 34-120 months), the 1-, 3-, and 5-year actuarial survival rate was 80%, 62%, and 44%, respectively. The overall local control rate at 1 and 5 years was 75% and 65%, respectively, and distant failure was documented in 44% of patients. Subgroup analysis revealed that the presence of gross disease after surgical resection was the strongest prognosticator, with a 5-year survival and local control rate of 17% and 50%, respectively, compared with 60% and 68%, respectively, for microscopic disease. The local control rates of patients with new primaries were similar to those of patients treated for recurrent disease (63% vs. 71%), probably because gross residual disease occurred only in the group of patients with new primaries. The addition of EBRT to IOHDR increased the 5-year disease-free survival rate from 27% to 44% but had no effect on local control (64% vs. 65%). CONCLUSION: IOHDR can be safely used to deliver a high radiation dose to locally advanced and recurrent tumors in the paranasal sinuses. In an attempt to improve outcome, we are now adding limited-dose EBRT (20-30 Gy) after 17.5 Gy of IOHDR in previously irradiated patients and increasing the EBRT dose for both microscopic (50-54 Gy) and gross residual disease (60-65 Gy) after 15 Gy of IOHDR in previously unirradiated patients. Chemosensitization should also be considered in previously irradiated patients and in those with gross residual disease. Interstitial boosting techniques, which can deliver higher doses at depth, should also be considered in patients with gross residual disease.

Structures of d(Gm5)CGm5CGCGC) and d(GCGCGm5CGm5C): effects of methylation on alternating DNA octamers.

The crystal structures of two alternating octamers d(Gm(5)CGm(5)CGCGC) and d(GCGCGm(5)CGm(5)C) have been determined at 1.7 and 1.9 A resolution with R(work)/R(free) of 16.9/19.6% and 17.9/19.8%, respectively. The two octamers crystallized in the same tetragonal space group P4(3)2(1)2, with unit-cell parameters a = b = 43.0, c = 24.9 A and a = b = 43.1, c = 24.7 A, respectively. Both structures adopt the A-type double helix and the abutting crystal packing. Despite the different positions of the methylated cytosine in the sequence, the two octamers display essentially the same conformation. The close similarity of the two structures indicates that methylation at different positions in a DNA sequence does not affect the helical conformation of the alternating DNA octamer. Investigation of other related crystal structures implies that methylation of cytosine stabilizes the A-type conformation for alternating DNA sequences beginning with a 5'-purine but is beneficial to the Z-type conformation for alternating DNA sequences beginning with a 5'-pyrimidine.

Long-term morbidity in children treated with fractionated high-dose-rate brachytherapy for soft tissue sarcomas.

BACKGROUND: The purpose of this study was to determine the long-term local control, disease-free survival, and morbidity of fractionated high-dose-rate brachytherapy (F-HDR) in infants and children with soft tissue sarcomas. PATIENTS AND METHODS: Fifteen children (13 girls and 2 boys, ages 5-101 months) with soft tissue sarcomas were treated with chemotherapy, organ-preserving surgery, and F-HDR (36 Gy in 12 fractions) to post-chemotherapy volumes. External beam radiotherapy was not part of the primary treatment, although four patients (27%) subsequently received salvage external beam radiotherapy after treatment failure. Chemotherapy was administered to all patients based on their tumor histology and stage. RESULTS: After a median follow-up of 10 years (range 32-154 months), 12 patients (80%) were alive without evidence of disease. Ten-year overall survival and local control rates were both 80% (12/15 children). The overall survival was better (91%) for children with microscopic residual versus gross residual disease (75%). With longer follow-up, grade 3 to 4 brachytherapy-related late morbidities increased from 8% (1/12) to 20% (3/15) and included trismus/osteonecrosis, vaginal stenosis, and periurethral fibrosis. There were two late complications associated with puberty that occurred 8 to 10 years after the initial treatments. Acute toxicity occurred in five patients (38%) and consisted primarily of grade 1 to 3 skin and mucosal reactions. CONCLUSIONS: As the sole radiation modality, F-HDR achieved excellent local control and disease-free survival in properly selected children with soft tissue sarcomas while preserving normal bone and organ development. A significant percentage of patients experience adverse late sequelae as a result of this treatment.

Intraoperative electron beam treatment for pediatric malignancies: The Ohio State University experience.

PURPOSE: To report the result of intraoperative electron beam radiation therapy (IOERT) in patients with extensive pediatric tumors. METHOD: From October 1989 through June 2000, 13 children were treated with chemotherapy, maximal surgery, and 10-15 Gy IOERT at a total of 18 sites. IOERT was used for palliative purposes in 5 children with metastatic disease and in 3 others who were previously treated with external beam radiation (EBRT). The remaining five patients received definitive IOERT. Postoperative EBRT of 35.4-45 Gy was given in 5 patients. RESULTS: After a median follow-up of 42 months (range = 18-63 months), 4 patients were alive and without evidence of disease. Overall and 3 year actuarial survival rates were 31% (4/13) and 26%, respectively. Local control was achieved at 13/18 sites (72%). Poor prognostic factors included metastatic disease, recurrent disease, and the absence of adjuvant EBRT. Two children with Wilms tumors had 100% local control, disease-free survival, and overall survival without the addition of EBRT. CONCLUSION: A boost dose of IOERT allows for reduction in the dose of EBRT, thereby limiting growth-related morbidity without compromising local control or disease-free survival. Except for Wilms tumors, which achieved 100% local control and disease-free survival, adjuvant EBRT is necessary for successful local control and survival in children with soft tissue sarcomas. Based on this study and others, intraoperative irradiation should be considered for inclusion in prospective, multi-institutional trials designed to treat localized malignancies in young children.

Brachytherapy for pediatric tumors.

PURPOSE: Pediatric tumors are generally managed with a multi-modality treatment program that includes surgery, chemotherapy, and teletherapy. The use of teletherapy in young children can result in significant long-term toxicity (especially retardation of growth of bones and organs). The use of brachytherapy is an attractive alternative because brachytherapy irradiates small volumes and can thus potentially minimize complications. METHODS AND MATERIALS: The brachytherapy techniques used are similar to those used in adults. Low-dose-rate brachytherapy with manually-afterloaded removable 192Ir is commonly used though it is associated with some radiation exposure hazards. Low energy radionuclides and remote afterloading technology have been used to reduce the radiation exposure hazards. Teletherapy is often added in the treatment of more extensive tumors, especially in older children. RESULTS: Brachytherapy (as the sole radiation modality) to small volumes in conjunction with chemotherapy and surgery has produced good local control with growth preservation and acceptable late complications in selected patients with localized tumors. CONCLUSION: Brachytherapy increases local control with a decrease in the probability of late complications (especially altered bone and organ growth) in comparison to EBRT. Low energy radionuclides and remote afterloading technology (HDR, IOHDR, and PDR) have been used to extend treatment to infants and younger children while reducing the radiation exposure to patients, family, and medical personnel.