Re-irradiation and external hyperthermia in locally advanced, radiation recurrent, hormone refractory prostate cancer: a preliminary report.

The purpose of this report is to present the preliminary results of re-irradiation and external hyperthermia in patients with locally advanced, previously irradiated, hormone refractory prostate cancer. Three consecutive patients with symptomatic, locally advanced, previously irradiated and hormone refractory prostate cancer were treated with further irradiation (30.6-50 Gy) and external hyperthermia (5-8 treatments). All patients had complete resolution of symptoms lasting for 12-24 months. Significant tumour shrinkage, including complete tumour response, was demonstrated by CT and endoscopy. In one case, at 2 years after re-treatment, there is continued tumour regression and bone regeneration in the pelvis. Two patients had local control of tumour, which continued until most recent follow-up at 12 months and more than 24 months, respectively. Another case developed local recurrence at 17 months. At most recent follow-up, no patient has experienced significant treatment-related side effects. In these patients with no other therapeutic alternatives, re-irradiation and hyperthermia can provide durable tumour response for more than a year, resulting in significant improvement in quality of life. Further clinical studies are warranted.

Repositioning accuracy with the Laitinen frame for fractionated stereotactic radiation therapy in adult and pediatric brain tumors: preliminary report.

PURPOSE: To determine the repositioning accuracy, patient tolerance, and clinical efficacy of stereotactic radiation therapy for brain tumors in children and adults performed with the Laitinen stereotactic localizer and head holder. MATERIALS AND METHODS: In this retrospective analysis, stereotactic frame tolerance was assessed by recording patient discomfort or pain in the ear and nose during each treatment in 34 patients, including 21 children and 13 adults with 37 lesions treated with fractionated stereotactic radiation therapy. Radiation doses ranged from 10-60 Gy at 1.0-4.0 Gy per fraction. Repositioning accuracy was assessed by comparing portal radiographs with setup fields on computed tomographic (CT) scout images. Clinical efficacy was assessed by analyzing posttreatment CT and magnetic resonance images. RESULTS: The stereotactic localizer was well tolerated. The mean isocenter shifts observed after studying 305 portal radiographs were x-coordinate shift of 1.0 mm +/- 0.7 (SD), y-coordinate shift of 0.8 mm +/- 0.8, and z-coordinate shift of 1.7 mm +/- 1.0. At a median follow-up of 16 months, local control was achieved in 18 of 22 primary and in one of eight of recurrent tumors. CONCLUSION: The Laitinen stereotactic localizer is well tolerated with accurate reproducibility during stereotactic radiation therapy. Preliminary local control rates are consistent with those in other reports.

Clinical outcome in children with recurrent craniopharyngioma after primary surgery.

PURPOSE: The purpose of this article is to report the clinical outcome in children with recurrent craniopharyngioma after primary surgery. PATIENT AND MATERIALS: Fourteen children with craniopharyngioma treated with primary surgery developed local recurrence. The median time to recurrence from primary surgery was 19 months (range, 2-156 months). At first recurrence (n = 14), seven children (50%) underwent reoperation. Five children (36%) received radiotherapy, and two children did not undergo any treatment. At second recurrence (n = 7), six children underwent radiotherapy (86%), and one had surgery. External-beam radiation was delivered with 6-MV or 10-MV x-rays by use of three-dimensional conformal technique (n = 4) or fractionated stereotactic radiotherapy (n = 7) using the Laitinen stereoadapter. Total dose ranged from 54 to 55.8 Gy at 1.8 Gy/fraction. RESULTS: The median follow-up from primary surgery is 8.5 years (range, 3-15.8 years). The 5-, 10-, and 15-year overall survival was 100%, 86%, and 86%, respectively, and the disease-free survival was 92%, 60%, and 60%, respectively. The median follow-up from date of first relapse was 6 years (range, 2.5-10 years). After treatment for first recurrence, the 2- and 5-year second-recurrence-free survival was 71% and 29%, respectively. After radiotherapy, the 2- and 5-year second-recurrence-free survival was 100% and 100%, respectively, compared with 43% and 0%, respectively, for surgery alone. Univariate analysis revealed significantly superior local control with radiotherapy compared with surgery. The local control rate at last follow-up, after stratifying for treatment at first and second recurrence, were analyzed at first and second relapse was 90% and 0% after radiotherapy and surgery, respectively. If radiotherapy was used for first or second recurrence, the 5-, 10-, and 15-year relapse-free survival was 100%, 83%, and 83%, respectively, compared with 67%, 0%, and 0%, respectively, for surgery alone. The median time to second relapse after surgery for first relapse was 12 months (range, 2-36 months). After primary surgery, all 14 children developed panhypopituitarism, requiring lifelong hormone supplementation. After surgery at recurrence, three children (3/7, 43%) experienced intraoperative bleeding, resulting in permanent neurologic deficits in two. No child has shown any signs of radiation-induced optic neuropathy. DISCUSSION: In children with recurrent craniopharyngioma after radical resection, the use of three-dimensional conformal radiotherapy or fractioned stereotactic radiotherapy results in very good local control with a low incidence of complications. In young children with stable tiny recurrences, a policy of close surveillance could be adopted for the brain to mature before beginning radiotherapy. The use of secondary surgery for recurrent tumors is associated with a low cure rate and a high risk of complications.

Whole-abdominal radiation in endometrial carcinoma: an analysis of toxicity, patterns of recurrence, and survival.

PURPOSE: The purpose of this study was to determine the toxicity, patterns of recurrence, and survival in high-risk endometrial cancer patients treated with whole-abdominal radiation. MATERIALS AND METHODS: All patients with endometrial cancer treated at Northwestern University since 1994 and at Rush University since 1993 were retrospectively reviewed. Patients believed to be at high risk for intra-abdominal recurrence and who received whole-abdominal radiation were reviewed for this study. RESULTS: A total of 30 patients completed whole-abdominal radiation (WAR) and were available for study. The mean and median follow-up was 2.3 and 2.1 years, respectively, with a range of 0.13 to 6.1 years. Seventy-eight percent of the cohort received surgical staging with bilateral salpingo-oophorectomy/total abdominal hysterectomy/lymph node sampling. Forty-seven percent of the patients were found to have serous histology as a component of their tumor. Surgical staging results included 19% stage 1B, 4% stage IC, 8% stage IIB, 37% stage IIIA, 26% stage IIIC, and 7% stage IVB. Two patients had gross residual disease at the completion of surgery. Megestrol acetate (Megace) was used as an adjuvant treatment in 37% of patients, and no cases received initial chemotherapy. All patients received WAR with a mean total dose and dose per fraction of 2620 and 143 cGy, respectively. Twenty-two percent of patients received a para-aortic boost. The mean total pelvic dose was 4956 cGy. Seventy percent of patients received a vaginal cuff boost. Eight percent of patients had grade 3 acute gastrointestinal morbidity, and 4% had grade 4 acute gastrointestinal morbidity. No other grade 3 or greater acute or long-term morbidity was noted. At last follow-up, seven (23%) patients had experienced recurrence. The pattern of first recurrence was 0% in the vaginal cuff, 3% other vaginal, 7% pelvic, 7% upper abdominal, 3% lung, 7% bone, and 7% para-aortic lymph nodes. Ultimate recurrences were similar. At last follow-up, 77% patients had no evidence of disease, 13% were alive with disease, and 10% had died of disease. CONCLUSIONS: Utilizing a conservatrive total whole-abdominal radiation dose and limited para-aortic nodal boost resulted in very tolerable treatments. The patterns of recurrence and survival in this early report are encouraging.

Adverse impact of multileaf collimator field shaping on lens dose in children with acute leukemia receiving cranial irradiation.

PURPOSE: This study was designed to investigate the impact of multileaf collimator (MLC) on lens dose in children with leukemia undergoing cranial irradiation. METHODS AND MATERIALS: This is a prospective study utilizing three common cranial irradiation techniques. Technique A uses a half-beam, nondivergent radiation field. Technique B has the anterior divergent field edge at the lateral bony canthus. Technique C is similar to B, but with a field collimator angle. Thermoluminescent dosimeter (TLD) lens dose measurements were obtained in children and phantom with all three techniques. RESULTS: Seventeen children were studied. Lens dose measurements were obtained in 14 children with technique A using MLC and blocks. In 7 of 14 children, dose measurements were obtained with MLC only. One child was treated with technique B and 2 children were treated with C, with MLC +/- blocks. In all 3 techniques, with MLC alone, the lens dose increased by 64%, 119%, and 72%, respectively. Similar results were obtained in phantom. CONCLUSION: This study demonstrates that independent of irradiation technique, additional custom blocking is required to maximally protect the lens with MLC shaped fields. This is due to the lack of conformity between MLC and the desired field edge at the lateral bony canthus.

Fractionated stereotactic radiotherapy for pediatric brain tumors: the Chicago children's experience.

Thirty-three children with a total of 35 benign/malignant brain and eye neoplasms were treated with fractionated stereotactic radiotherapy. In the first 11 children immobilization for treatment was achieved with plaster of Paris casts or aquaplast masks. In the remaining 22 children the Laitinen stereoadapter was used. Radiation was delivered with noncoplanar static or rotational beams. The dose fractionation used was 50.4-60 Gy in 28-30 fractions in patients receiving treatment with curative intent, and 10-32 Gy at 2-4 Gy/fraction for reirradiation. The accuracy of daily treatment was < 2 mm. After a median follow-up of 27 months, 22 of the 25 children treated with curative intent achieved local control. One child had progressive brain necrosis following 54 Gy in 30 fractions for a pontine astrocytoma. The exact etiology of this complication is unknown. This series demonstrates that in children fractionated stereotactic radiotherapy using the Laitinen stereoadapter is well tolerated and accurate and results in good local control.

Racial differences in prostate cancer related to loss of heterozygosity on chromosome 8p12-23.

PURPOSE: To determine if there is a racial difference in prostate cancer related to loss of heterozygosity (LOH) on chromosome 8p12-23, the region most frequently altered in prostate cancer. METHODS AND MATERIALS: A total of 51 prostate cancer patients, consisting of 23 African Americans and 28 Caucasians, were included in this study. All patients underwent radical prostatectomy, and patients in the two racial subgroups were matched for median serum PSA, Gleason score, and pathological stage of cancer. Paired normal prostate and cancer tissue DNA was isolated and amplified with 13 polymorphic markers mapped to 8p12-23 by radiolabeled polymerase chain reaction. The amplified products were resolved by polyacrylamide gel electrophoresis, autoradiographed, and analyzed for allelic losses. RESULTS: The overall incidence of LOH at 8p12-23 was 53%, and 16% showed homozygous deletions. The incidence of LOH in Caucasians was 68% compared to 35% in African Americans. On univariate (p = 0.02) and multivariate logistic regression analysis (p = 0.02), only Caucasian race was a significant predictor for LOH. The other clinicopathologic parameters did not have any significant effect on incidence of LOH. CONCLUSION: These results highlight the independent influence of Caucasian race on incidence of LOH at 8p12-23, and suggest that genetic differences at specific tumor suppressor loci may be a factor responsible for racial variations observed in prostate cancer.

Improved trigeminal and facial nerve tolerance following fractionated stereotactic radiotherapy for large acoustic neuromas.

The purpose of this study was to demonstrate improved cranial nerve tolerance following fractionated stereotactic radiotherapy for large acoustic neuromas, defined as tumours with pons-petrous distance (A) > 1 cm and midporous transverse diameter (A + Y) > 2 cm. Of 28 patients with acoustic neuromas treated with fractionated stereotactic radiotherapy, 19 had large tumours at high risk for radiosurgery-induced cranial neuropathy. Six patients received 36 Gy in six, weekly, fractions and 13 patients received 30 Gy in six, weekly, fractions. 15 patients had evaluable trigeminal nerve function and 16 had evaluable facial nerve function. At a median follow-up of 4.5 years, tumour shrinkage was seen in 10 patients and tumour size was stable in nine. None of the patients developed any evidence of transient, or permanent, trigeminal or facial neuropathy at any time during their follow-up period. Fractionated stereotactic radiotherapy may offer a superior therapeutic ratio to single fraction stereotactic radiosurgery in the management of large acoustic neuromas, as evidenced by the absence of post-treatment trigeminal and facial neuropathy.

Acute hyperthermia following stereotactic radiosurgery for pituitary adenoma.

A 71-year-old male presented with a large pituitary adenoma with superior extension into the optic chiasm and suprasellar cistern. He was treated with stereotactic radiosurgery to a dose of 16 Gy. Approximately 1 h after radiosurgery he developed fever; his temperature peaked at 105.1 degrees F and normalized about 20 h later. This case demonstrates that acute hyperthermia is a potential complication following high dose stereotactic radiosurgery for large pituitary tumours.

Pediatric radiotherapy. An overview.

The use of RT in pediatric cancer has been virtually eliminated in certain diseases (NHL); greatly reduced in some (Wilms' tumor, ALL, neuroblastoma); and refined and modified in others (rhabdomyosarcoma, Ewing's sarcoma). At present, however, it seems clear that RT will continue to be an important modality (particularly in brain tumors) and a much greater understanding of its effects has been achieved and utilized. The knowledge of the occurrence of late effects and SMN in a child cured of cancer is continuing to modify initial treatment strategies: A classic example of such an effort is the common use of lower RT doses and nonalkylator-based chemotherapy in Hodgkin's disease. Further, the use of DNA testing in children may be able to identify the presence of germline RB and p53 mutations, which may identify a child at high risk for SMN, so that appropriate therapeutic modifications may be made. In addition, knowledge of these late consequences in children mandates that they be carefully monitored and closely followed, so that prompt and effective treatment can be administered to give them a better chance for a long and healthy life.

Intracranial meningiomas: factors that influence the development of cerebral edema after stereotactic radiosurgery and radiation therapy.

PURPOSE: To evaluate causative factors of cerebral edema after stereotactic radiosurgery or stereotactic radiation therapy in intracranial meningiomas. MATERIALS AND METHODS: Of 43 adult patients with intracranial meningiomas, three received 13.5-18-Gy single-fraction stereotactic radiosurgery; one received 19.8 Gy in three fractions, one received 42 Gy in six fractions, and 31 received 32-36 Gy in six to eight fractions of stereotactic radiation therapy; and seven received 45-54-Gy external-beam radiation with 20-28 Gy in five to seven fractions as concomitant stereotactic boosts. Brain edema was estimated by calculating the edema index. RESULTS: After irradiation, all 11 patients with parasagittal and four patients with nonparasagittal tumors developed worsening cerebral edema that necessitated the administration of steroids (P < .001). The statistically significant factors for the development of edema were parasagittal location, presence of pretreatment edema, sagittal sinus occlusion, and the use of more than 6 Gy per fraction. Five patients with parasagittal tumors developed life-threatening panhemispheric edema, which was fatal in one. The causative factors of panhemispheric edema were a large tumor, single-fraction stereotactic radiosurgery, or use of more than 6 Gy per fraction. CONCLUSION: A smaller dose per fraction and aggressive use of steroids may help prevent life-threatening complications due to worsening edema.