Are there sex biases in standardized tests of radiation oncology knowledge?

PURPOSE/OBJECTIVE: Recent studies have identified biases directed against women in standardized tests. We tested for the existence of such biases in the American College of Radiology (ACR) In-Training Examination in Radiation Oncology and the American Board of Radiology (ABR) Written Radiation Oncology Board Examination. MATERIALS AND METHODS: Our request to the ABR to permit us to study performance on their examinations, as a function of sex, was refused. We obtained scores, through the cooperation of six academic radiation oncology departments, for residents-in-training taking the in-service examination and candidates taking the written board examination for the first time. Test results for 1984 to 1995 were blinded as to name, but not sex or institution of training. For the in-service examination, scores are reported as percentiles normalized to the year of training. The effect of multiple scores for the same resident was assessed using a repeated-measures analysis of variance. Residents were nested within each sex/institution combination and crossed with training year and calendar year. The effects of three factors (sex, institution, and year the examination was taken) on the results of the biology, physics, and clinical sections were evaluated with an analysis of variance. The interactions of sex with institution and year were included to determine the scope of the sex effect. For the board examination, scores are reported as percentiles, as well as an overall pass/ fail outcome. An analyses of variance was performed similar to that used for the in-service examination. In addition, Fisher's exact test and logistic regression were used to analyze overall outcome (pass/fail). RESULTS: We obtained data for 79 residents (48 men and 31 women, 1.54:1) who took the in-service examinations 165 times. Sixty-two residents (41 men and 21 women, 1.95:1) had an initial sitting for the ABR written examination. On the in-service examination, for the biology, physics, and clinical subsections, calendar year, training year, and sex did not have a significant effect on examinees scores. Institution of training had a significant effect (P < .02) on the scores in biology and physics. The total in-service examination scores were not significantly influenced by calendar year, training year, or sex. Institution of training has a strong influence on overall score (P = .03) and the interaction of sex with training year is near significance level (P = .06). The power for our statistical tests ranged from 0.88 to 0.99. On the board examination, sex, institution of training, year the examination was taken, and interaction of sex with year or sex with institution of training did not have a significant effect on test scores. Pass rates were 90% for men versus 81% for women (P = .43). CONCLUSION: Sex did not significantly influence the results of the in-service examination or the written board examination. Institution of training is the strongest influence on the results of the in-service examination.

Randomized comparison of diaziquone and carmustine in the treatment of adults with anaplastic glioma.

PURPOSE: We conducted a phase III trial comparing intravenous (IV) diaziquone (AZQ) and carmustine (BCNU) as single agents in patients with cerebral anaplastic gliomas who had received surgery and radiotherapy. Its purpose was to compare the efficacy of AZQ with that of BCNU, the standard agent for brain tumor chemotherapy. PATIENTS AND METHODS: Randomization between the two regimens occurred 8 weeks after completion of radiotherapy. A total of 251 patients were randomized to receive either AZQ or BCNU, and there were no significant differences between the two treatment arms in any of the known prognostic variables, including age, histologic grade, and Karnofsky performance status (KPS). RESULTS: There was no significant difference in either time to tumor progression or survival between the two treatment arms. Age and histology were strong predictors of outcome, whereas KPS had relatively less effect. Three groups of patients with distinctly different outcomes could be identified: (1) older age (45+) and glioblastoma/gliosarcoma (GBM/GS) patients had a median survival of 37 weeks after randomization; (2) patients with either older age or GBM/GS had a median survival of 61 weeks; and (3) younger age (< 45) and non-GBM/GS (usually anaplastic astrocytoma) patients had a median survival of 147 weeks. Toxicity was primarily hematologic, although acute gastrointestinal toxicity and chronic pulmonary toxicity were more common with BCNU. Patients randomized to AZQ who had significant hematologic toxicity that required dose reduction after the first treatment cycle had significantly longer time to tumor progression and survival than those who did not require dose reduction (P = .011 and .016, respectively). CONCLUSION: There was no significant difference in efficacy between AZQ and BCNU in patients with anaplastic gliomas as tested in this study, although AZQ was somewhat better tolerated.

Phase II treatment of medulloblastoma and pineoblastoma with melphalan: clinical therapy based on experimental models of human medulloblastoma.

We conducted a phase II study of intravenous (IV) melphalan in the treatment of children with recurrent medulloblastoma and in the initial treatment of children with poor-prognosis medulloblastoma and pineoblastoma. There was one complete response (CR) and two partial responses (PRs) among the 12 children with recurrent medulloblastoma. There were three PRs in the four patients initially treated with melphalan for poor-prognosis medulloblastoma or pineoblastoma. Toxicity was limited to severe myelosuppression with marked neutropenia and thrombocytopenia. These results support our laboratory studies demonstrating melphalan activity in human medulloblastoma, suggest that similar activity may be demonstrated against pineoblastoma, and support further trials with this agent (administered prior to radiotherapy) in the treatment of patients with newly diagnosed poor-prognosis medulloblastoma.

Efficacy and toxicity of 9-beta-D-arabinofuranosylguanine (araG) as an agent to purge malignant T cells from murine bone marrow: application to an in vivo T-leukemia model.

9-beta-D-Arabinofuranosylguanine (araG), an analog of deoxyguanosine which is not degraded by purine nucleoside phosphorylase, has been previously shown in in vitro studies by our laboratory to be effective in purging malignant T cells from human bone marrow (1). We now describe studies in a murine model of T-cell acute lymphoblastic leukemia (ALL) in which we tested whether bone marrow, contaminated with malignant T cells and purged ex vivo with araG, could reconstitute both the lymphoid and myeloerythroid lineages in the absence of leukemic relapse. The model utilized 6C3HED tumor cells, derived from a Thy 1.2+ malignant murine T-cell line, which were shown to cause lethal leukemia in C3H/HeN mice. Intravenous injection of 10(6) 6C3HED cells resulted in 100% mortality within 18 days, with autopsy revealing tumor infiltration of multiple organs. 100% of non-leukemia bearing lethally irradiated C3H/HeN mice transplanted with syngeneic bone marrow, treated ex vivo with 100 microM of araG for 18 hours, survived > 365 days post-transplant with full lymphohematopoietic reconstitution. Evidence of araG's ability to purge bone marrow of malignant tumor cells without causing significant toxicity to normal marrow derived hematopoietic progenitor cells was documented in experiments in which 75% of lethally irradiated mice transplanted with syngeneic bone marrow, contaminated with 6C3HED tumor cells and treated ex vivo with 100 microM araG for 18 hours, survived for > 250 to > 400 days. Death in 25% of mice was secondary to infection which developed before marrow reconstitution occurred. Reconstitution of the lymphoid, myeloid, and erythroid lineages with donor cells in surviving mice was documented. The data presented indicate that araG may effectively purge bone marrow of malignant T cells without irreversible toxicity to hematopoietic stem cells. This purging regimen is recommended for consideration for clinical trials in patients with T-cell malignancies undergoing autologous bone marrow transplantation and may also be a viable option for T-cell depletion as a strategy to prevent graft-versus-host disease.

Establishment and characterization of the human medulloblastoma cell line and transplantable xenograft D283 Med.

A new continuous cell line and transplantable xenograft, D283 Med, was derived from the peritoneal implant and ascitic fluid of a child with metastatic medulloblastoma and grew in vitro in suspension culture with spontaneous macroscopic spheroid formation. The in vitro population doubling time was 52.55 hours. Mean colony forming efficiency in an agarose medium was 1.83 +/- 0.56%. The cell line, D283 Med, grew in athymic mice as serially transplantable intracranial and subcutaneous xenografts. Intracranial tumors grew as masses of small cells with scant cytoplasm and abundant mitotic figures and prominent anuclear zones resembling neuroblastic rosettes. Subcutaneous (SQ) tumors were markedly cellular neoplasms but did not contain rosettes. They expressed glutamine synthetase, neuron-specific enolase and neurofilament protein. Glial fibrillary acidic protein and S-100 protein were not detected. The SQ tumors grew to 500 mm3 with a latency of 52.55 +/- 12.5 days and a doubling time of 9.33 +/- 2.39 days. The stemline karyotypes of the peritoneal implant and ascitic fluid cells contained an extra copy of chromosome number 11 and three marker chromosomes (8q+, 17p+, 20q+). The cultured cell line and subcutaneous and intracranial xenografts retained the three marker chromosomes and differed from the original karyotype only in that they lacked the additional copy of chromosome number 11. This cell line and transplantable xenograft may allow further analysis of the biological properties and therapeutic sensitivity of human medulloblastoma.

Intracranial atherosclerosis following radiotherapy.

We describe a case of severe intracranial atherosclerosis in a young man who had received therapeutic radiation for a presumed brain neoplasm. Since there was no evidence of vascular disease outside the radiation ports, we speculate that accelerated atherosclerosis was induced by radiation and that hyperlipidemia may have predisposed him to this effect.

Cyclophosphamide, doxorubicin, vincristine, and prednisone for primary central nervous system lymphoma: short-duration response and multifocal intracerebral recurrence preceding radiotherapy.

The activity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the treatment of primary central nervous system lymphoma (PCNSL) prior to radiotherapy was studied in six patients. Primary lesions were reduced by 80% or more on contrast-enhancing cross-sectional area in four patients and to a lesser extent in two others after two cycles of chemotherapy. The primary lesion sites demonstrated no contrast enhancement in the three patients who completed four cycles of therapy. However, concurrent with response at the primary disease sites, multiple lesions occurred at distant, noncontiguous CNS parenchymal sites in five patients after two to four cycles of chemotherapy. Median survival was 8.5 months for the six enrolled patients and 16.5 months for the four patients completing craniospinal radiotherapy. PCNSL is highly responsive to standard systemic non-Hodgkin's lymphoma chemotherapy regimens, but the pattern and rapidity of relapse suggest mechanisms of failure including inherent or rapidly evolving antineoplastic drug resistance and perhaps limited drug delivery to occult sites of disease in the brain.

Criteria for termination of phase II chemotherapy for patients with progressive or recurrent brain tumor.

We report six patients with progressive primary tumors of the brain who had prolonged periods with stable contrast-enhancing CT lesions following initial responses to chemotherapy. Chemotherapy was discontinued after 21 to 36 months, despite the persistence of apparent disease in each patient. PET using (F-18) fluorodeoxyglucose was performed in three patients, revealing hypometabolic lesions. All six patients are alive and well, with no clinical or radiographic evidence of progressive disease at 24 to 57+ months following termination of treatment. The usual criteria for terminating phase II chemotherapy in patients with a recurrent brain tumor are evidence of progressive disease or unacceptable toxicity. However, chemotherapeutic success mandates that these criteria be expanded to include patients whose response following the initiation of phase II treatment is followed by prolonged (greater than 1 year) radiographic and clinical stability. Complete response, ie, disappearance of all evidence of disease, is unusual in patients with recurrent primary brain tumors, even with highly effective therapy. Continued improvement in the therapy of patients with these tumors will allow wider application of these criteria.

Event-free survival of children with biologically favourable neuroblastoma based on the degree of initial tumour resection: results from the Pediatric Oncology Group.

We analysed the 2-year event-free survival (EFS) of 49 patients 1 year of age and older, with stage 2B or 3 neuroblastoma, treated on Pediatric Oncology Group protocols 8742 and 9244, with respect to the degree of tumour resection at diagnosis. The 2-year EFS rate for 21 children whose tumours were completely resected at diagnosis was 85% (SE = 10%) compared with an EFS rate of 70% (SE = 9%) for the 28 children whose tumours were incompletely resected at diagnosis. Despite the observed trend in favour of complete resection, these EFS curves were not statistically significantly different (P = 0.259). Patients with favourable Shimada histology tumours had an EFS rate of 92% (SE = 7%) compared with a rate of 58% (SE = 15%) for patients with unfavourable histology tumours. EFS curves for the two histologic groups were significantly different (P = 0.009). The impact of aggressive surgery and adjuvant chemotherapy on the outcome of patients with biologically favourable regional neuroblastoma is still unclear.

Concerning the inferior portion of the spinal radiotherapy field for malignancies that disseminate via the cerebrospinal fluid.

PURPOSE: Many radiotherapists widen the inferior aspect of the craniospinal irradiation field to encompass the sacroiliac joints and "cover the sacral nerve roots." This is commonly referred to as a "spade" field. Other therapists, however, reject the notion of widening the bottom of the field--feeling that straight field borders are adequate. We have evaluated this controversy by an anatomical study. METHODS AND MATERIALS: Twenty-five skeletons were measured to ascertain the distance between the outermost portions of the posterior pedicles of L3, L4, and L5; the distance between the outermost portions of the intervertebral foramina between L3-L4, L4-5, and L5-S1 through which the spinal nerves pass; and the width of the most lateral portions of the posterior and anterior foramina of S1 and S2 through which the sacral spinal nerves would pass. Twenty-two cranial spinal irradiation simulator films of patients with medulloblastoma were used to measure the distance between the outermost portions of the posterior pedicles of L3, L4, and L5 and the foramina of S1 and S2. These measurements were then corrected for film magnification. RESULTS: Skeleton measurements showed that the mean width between the outer portions of the posterior pedicles of L3 and 4.1 cm, for L4 it was 4.4 cm, and for L5 it was 5.1 cm. Measurements of the mean maximum width of the intervertebral foramen for nerve root exit at the bottom of L3 was 4.1 cm, for L4 4.4 cm, and for L5 4.7 cm. The mean distance between the outermost portions of the intervertebral foramen for nerve root exit at the front of S1 was 5.9 cm while it was 5.0 cm for the back of S1. The mean distance between the outermost portions of the anterior foramen of S2 was 5.7 cm and 4.8 cm for the back. Measurements from the 22 simulation films show that the mean maximum width between the outer portion of the posterior pedicles of L3 was 3.3 cm, for L4 3.5 cm, and for L5 3.8 cm. The mean maximum width of the intervertebral foramen for nerve root exit at the bottom of S1 was 4.4 cm and 4.5 cm for S2. CONCLUSIONS: While the caudal end of the craniospinal field needs to be widened by 1.2 to 1.8 cm to encompass the increase in distance between nerve root exits as one moves inferiorly down the spine, coverage of the sacroiliac joints is not necessary.

Impact of radiation technique upon the outcome of treatment for medulloblastoma.

Craniospinal irradiation (CSI) is an essential component of the therapy of medulloblastoma. Because medulloblastoma disseminates via the cerebrospinal fluid (CSF), CSI technique involves the irradiation of all CSF-bearing areas which are at risk for tumor seeding. Underdosing with radiation because of inadequacies in CSI technique will produce dose "cold spots" which have the potential of serving as a nidus for tumor recurrence. A simple mathematic model of subclinical disease in medulloblastoma based on the available data concerning the radiosensitivity of medulloblastoma cell lines as well as the known clinical dose-response relationships support the hypothesis that for most cases of medulloblastoma, the radiotherapist is working in a range of doses arrayed on the steep portion of the tumor control probability curve. Underdosing of CSF-bearing areas because of technical problems at the junction of the cranial and spinal fields of irradiation, placement of shielding blocks in the cribiform plate-subfrontal region, and/or anatomic errors in the design of the caudal end of the CSI fields may lead to significant risks of tumor relapse. One may debate the necessity of a posterior fossa boost encompassing the entire anatomic posterior fossa rather than the primary tumor volume with a margin. This review critically evaluates the potential impact of CSI technique upon the outcome of treatment for medulloblastoma, and suggests future areas of inquiry.

Neonatal neoplasms.

PURPOSE: To describe neoplasms diagnosed in children

Pediatric brain stem tumors: patterns of treatment failure and their implications for radiotherapy.

There have been conflicting opinions regarding the correct volume to be used in radiotherapy fields for brain stem tumors of childhood. Whereas many clinicians recommend limited fields designed to cover the tumor volume with a margin, some have advocated whole brain radiotherapy. Using our clinical experience at Duke University Medical Center, we have made an attempt to determine the proper irradiation volume in this group of tumors. We have evaluated 38 patients with brain stem tumors in children less than 18 years of age. The most common presenting symptoms were headache, ataxia, and hemiparesis. Thirteen patients had a histologic diagnosis made prior to treatment or post-mortem. All had either an anaplastic astrocytoma or a glioblastoma multiforme. Tumors were located in the thalamus, hypothalamus, or midbrain in 9 patients and in the pons or medulla oblongata in the remaining 29 patients. All patients received a course of radiotherapy. The mean minimum tumor dose was 52.6 +/- 5 Gy given at 1.7 to 2.0 Gy/fraction. Twenty-three patients received radiation to a limited field and 14 received whole brain irradiation. In one patient, the field size could not be ascertained. The five year survival of the total group was 39%. The survival of patients with thalamic, hypothalamic, or midbrain tumors was 73% compared with 28% for those with tumors of the pons or medulla oblongata (p = 0.0159). Eighty-eight percent of the tumor recurrences in evaluable patients (22/25) occurred within the radiotherapy fields. Patients were stratified for tumor location and no difference was observed in survival or relapse-free survival among those individuals treated with limited irradiation fields or whole brain irradiation fields. When our results are examined in conjunction with previously published data, the bulk of existing evidence supports the use of limited fields for irradiation of brain stem tumors of childhood.

Radiation therapy in the management of neuroblastoma: the Duke University Medical Center experience 1967-1984.

We have evaluated the role of radiotherapy in providing local control of primary tumors and to palliate metastases from neuroblastoma (NB). Fifty-five children with histologically verified NB were evaluated and treated from 1967 to 1984. In univariate analysis, the actuarial survival of eight children with thoracic primaries (85%) was significantly better than the survival of 39 children with intra-abdominal primaries (35%, p = 0.0287). The survival of 28 children less than or equal to 18 months of age at diagnoses was 73%, whereas 27 children older than 18 months had a survival probability of 10% (p = 0.0001). The survival by Evans stage was: I 100% (2 patients), II 85% (7), III 60% (13), IV 4% (27) and IV-S 100% (6). According to the Pediatric Oncology Group (POG) staging system, the survival was: A 100% (3), B 66% (9), C 66% (9), D 23% (34). A multivariable analysis indicated that the Evans staging system was a more powerful indicator of prognosis than the POG system. The analysis also indicated that Evans stage and patient age were independent determinants of survival. The primary tumor site did not add significant prognostic information beyond these two factors. Children with Stage I disease were treated with surgery alone. Most children with Stages II and III disease were treated with surgery, irradiation, and Cyclophosphamide or Cyclophosphamide plus Vincristine. All seven patients with Stage II disease received post-operative irradiation to the primary tumor and were locally controlled with doses of 4.8 to 26.5 Gy. Eleven of the 13 patients with Stage III disease were irradiated post-operatively. Seven of these 11 patients were locally controlled with doses of 12 to 48.4 Gy. The four Stage III patients with in-field recurrences were older children with large radiotherapy fields and/or low doses administered. The Radiation Therapy Oncology Group pain score system was used to evaluate response of painful bony metastases to irradiation. A response was observed in 65% of the sites irradiated. A response was observed at 67% of the soft tissue metastases irradiated. Hepatomegaly causing respiratory embarrassment or inferior vena cava obstruction was treated with irradiation in seven patients. All patients responded with doses ranging from 5 to 24.4 Gy. Five of the 17 children who survived for more than 5 years following treatment had significant scoliosis or kyphosis secondary to vertebral body abnormalities in irradiated bones. All five children were irradiated at a young age with megavoltage equipment.(ABSTRACT TRUNCATED AT 400 WORDS)

Medulloblastoma: the Duke University Medical Center experience.

We have reviewed the clinical experience in the treatment of medulloblastoma with radiotherapy at Duke University Medical Center. One hundred and twenty-seven patients treated between January 1, 1940 and December 31, 1983 were evaluated. The irradiation technique was reviewed and all irradiation doses were recalculated as minimum tumor doses in Gray (Gy). The mean follow-up was 24.4 years and the median follow-up was 26.5 years. The energy of the treatment machine was known in 102 cases. Sixty patients were treated with orthovoltage equipment and 42 patients were treated with megavoltage equipment. As a gross assessment of the impact of the details of radiotherapy treatment upon outcome, patients were grouped into excellent, good, fair, and poor treatment groups. Patients undergoing cranio-spinal axis (CSA) irradiation and receiving greater than or equal to 52 Gy to the posterior fossa and greater than or equal to 30 Gy to the clinically uninvolved remainder of the CSA were classified as having "excellent" technique. Patients undergoing CSA irradiation and receiving 40 to 52 Gy to the posterior fossa and greater than or equal to 20 Gy to the remainder of the CSA were classified as "good." Patients receiving 20 to 40 Gy to the posterior fossa and greater than or equal to 10 Gy to the spinal axis with or without prophylactic cranial irradiation were designated "fair." Any patient not fulfilling the above minimum criteria was categorized as "poor." The actuarial 5-year survival for the entire population was 33%. The 10-year survival was 21%. In 93 patients for whom records were detailed enough to allow categorization of treatment technique, 5-year actuarial survivals were: Excellent 37% (n = 17), Good 55% (n = 13), Fair 35% (n = 23), Poor 20% (n = 40). A complete surgical resection was not correlated with improved disease-free survival (DFS) in the excellent and good groups, but was correlated with an improved DFS in the fair and poor groups. The posterior fossa accounted for 62% of the failures in the 55 patients completing irradiation where the initial site of failure was known. An examination of patterns of failure in the spinal canal failed to demonstrate a dose response relationship above 10 Gy for spinal canal prophylactic irradiation. No patient developed recurrence beyond their period of risk as defined by "Collins' Law."(ABSTRACT TRUNCATED AT 400 WORDS)

The management of desmoid tumors.

PURPOSE: To determine the efficacy of different treatment modalities for desmoid tumors. MATERIALS AND METHODS: We reviewed the treatment of 40 patients with histologically confirmed desmoid tumors seen at Duke University Medical Center between 1974 and 1990. RESULTS: Radiotherapy was administered to 16 patients (Group I)--14 with recurrent disease s/p surgery and in two as initial treatment. The average size of the irradiated lesions was 9.3 +/- 3.9 X 8.4 +/- 3.5 cm. With a median follow-up of 57.5 months and a median administered dose of 5400 cGy (mean 5286 cGy, range 4960-5620 cGy), local control has been obtained in 15/16 patients (94%). Complete regression (5/16), partial regression (5/16), or stable disease (5/16) was produced in 15 patients while one patient failed and was salvaged via gross total resection. Continued regression has been seen up to 60 months after treatment. Fourteen patients underwent primary gross total resection and two underwent subtotal resection (Group II). None received post-operative radiotherapy. Three of 14 patients (21%) recurred after gross total resection. All three were salvaged with subsequent gross total resection. After subtotal resection, 2/2 patients recurred. With a mean follow-up of 52 months, 14 patients are without evidence of disease, one is dead with disease (unrelated cause of death), and one was lost to follow-up after recurrence. Eight patients have been treated with combinations of chemotherapy, NSAIDS, anti-estrogens, and immunotherapy with mixed results (Group III). A subset of seven patients with retroperitoneal disease taken from all three groups had large tumor burden (mean size 17 X 15 cm), an infiltrative nature, as well as a difficult location. The disease was surgically resectable in three patients. One is without evidence of disease 9 years after gross total resection alone. Disease has been stabilized with radiotherapy in the other two patients after multiple unsuccessful surgical resections. Of four patients with unresectable disease, two are dead of disease, one died of unrelated causes with disease, and regression of disease was obtained in the other with Gamma-interferon after unsuccessful treatment with tamoxifen and vincristine, doxorubicin, and cyclophosphamide chemotherapy. CONCLUSION: Gross total resection is the indicated initial therapy, if it can be performed without significant disfigurement. Radiotherapy is also excellent for obtaining local control, even in patients with a large burden of recurrent disease. Doses in the range of 50 to 55 Gy give a chance of local control equal to that obtained with higher doses previously reported.

A double-blind, randomized, prospective trial to evaluate topical vitamin C solution for the prevention of radiation dermatitis. CNS Cancer Consortium.

PURPOSE: The object of this study was to ascertain the value of topical ascorbic acid in the prevention of radiation dermatitis. METHODS AND MATERIALS: Patients with primary or metastatic brain tumors were eligible. Patients applied a topical solution, twice per day prior to and throughout the course of radiotherapy, to the left and right sides of the head. The radiotherapist and the patient were blinded as to the contents of the solutions. The bottle for one side of the head contained topical ascorbic acid solution. The bottle for the other side of the head contained only vehicle. During and after the course of treatment the radiotherapist scored the skin reaction on both the left and right sides of the irradiated head using a skin reaction scale. The data were analyzed with a matched pair analysis. Since each patient received both treatments (ascorbic acid and control solutions) the statistical analysis concentrated on the paired difference in scores based on the probability of a "preference" for the treatment or control. RESULTS: Eighty-four patients entered the study. Sixty-five were suitable for analysis. In 10 patients there was a preference for ascorbic acid solution (15%), in 20 patients there was a preference for placebo (31%), and there was a preference for neither in 35 patients (54%). Ascorbic acid solution could be considered to have an effect if the percentage of preferences favoring ascorbic acid over placebo, among those subjects with a preference, significantly exceeded the 50% expected by chance. The observed percentage of preferences for ascorbic acid was only 33% (10 of 30 with a preference; p = .10, two-sided sign test). Patient age, race, sex, and total dose of irradiation had no detectable influence on the comparative skin toxicity scores. CONCLUSION: There is no discernible benefit to ascorbic acid lotion, in the manner in which we used it in this trial, for the prevention of radiation dermatitis.

Radiation therapy treatment planning in supratentorial glioblastoma multiforme: an analysis based on post mortem topographic anatomy with CT correlations.

In a previous study of the brains of 15 adults with glioblastoma multiforme who received minimal or no radiotherapy we determined the topographic distribution of tumor cells. All 15 brains had been fixed and then cut in the coronal or horizontal plane. The distribution of neoplastic cells was determined and entered onto tracings of the whole mount histologic sections. The last CT scans obtained prior to death of 11 of the patients were reviewed independently by a neuroradiologist who traced, on the CT scans, the outer edge of both the contrast-enhancing area and the peritumoral low density "edema". Presented with the neuroradiologist's assessment of the contrast enhancing rim of tumor and of the "edema", a radiotherapist and a radiation dosimetrist, in the present study, prepared treatment plans for a 6 MeV linear accelerator. In 9 of the 11 cases in which immediately antemortum CT scans were available, radiation treatment of the contrast enhancing area alone with a 1 cm margin would have missed portions of the histologically identified tumor. Treatment of the contrast enhancing area along with the peritumoral "edema", with a 1 cm margin, would have covered histologically identified tumor in six of the 11 cases. Treatment of the contrast enhancing area, all "edema", and a 3 cm margin around the "edema" would have covered histologically identified tumor in all cases. Tumors tended to track along nerve pathways. In those lesions near the midline it was common for tumor to cross the corpus callosum. We conclude that radiotherapy with fields designed to treat the contrast enhancing region alone or this region plus "edema" with a tight margin will frequently miss tumor which can be histologically identified by our technique.

Fractionated external-beam radiation therapy for meningiomas of the cavernous sinus.

PURPOSE: Despite advances in microsurgical technique, many cavernous sinus meningiomas remain unresectable or only partially resectable, prompting referral of patients for radiation therapy. Stereotactic radiosurgery is recommended as therapy at some institutions. We evaluated our experience with fractionated radiotherapy to permit comparison with single-fraction radiosurgery. MATERIALS AND METHODS: Between July 1985 and January 1998, 21 women and 7 men were treated for primary (21) or recurrent (7) cavernous sinus meningiomas. Of these, 22 tumors were subtotally resected and 6 were unresectable. Of the 28 lesions, 26 were categorized histologically as benign (16), aggressive-benign (7), or malignant (3); 2 were not biopsied. All patients were treated with fractionated photon irradiation to a median dose of 53.1 Gy. We assessed prognostic factors for overall (OS) and progression-free survival (PFS), including age, gender, presentation (primary vs. recurrent), extent of surgical resection, radiotherapy dose, and technique. Influence of radiotherapy dose and technique on acute and late treatment toxicities was analyzed. RESULTS: One patient died of disease and 2 others were alive with progressive disease at last follow-up, yielding 8-year actuarial OS and PFS of 96% and 81%, respectively. Univariate analysis showed that none of the prognostic factors tested was significantly associated with OS or PFS. There were two late side effects of treatment: an orbital sac fibrosis and a 6-month decline of cognitive function documented by formal neuropsychiatric testing. Neither radiotherapy dose nor technique significantly influenced late toxicity. CONCLUSION: For unresectable or subtotally resected cavernous sinus meningiomas, fractionated radiotherapy provides patients with excellent progression-free survival and minimal treatment-related toxicity.

Defining the superior border of posterior fossa radiation treatment fields.

PURPOSE: Lateral posterior fossa treatment fields are usually defined on traditional simulation films based on bony landmarks. The superior field border, intended to include the apex of the tentorium cerebelli, is frequently difficult to define. While sagittal magnetic resonance imaging (MRI) images or three-dimensional treatment planning tools are good means to locate the tentorial apex, these are not always available. We herein describe a method for locating the tentorial apex based on bony landmarks. METHODS AND MATERIALS: Midsagittal magnetic resonance images of 53 patients were reviewed. Using a Cartesian grid, the geometric relationship between the tentorial apex and several bony landmarks was assessed. Two lines were defined: the first connected the posterior clinoid and the internal occipital protuberance (AB). The second was perpendicular to the first, included the tentorial apex, and extended from the base of the skull inferiorly to the "crown" of the skull superiorly (DE). Relationships between measurements were made using linear regression and least square fits. RESULTS: Line DE was within 5 mm of the perpendicular bisector of line AB in 83% (44/53) of patients. The tentorial apex was located within 10 mm of the midpoint of DE in 91% (48/53) of patients. CONCLUSION: In the majority of patients, the location of the tentorial apex can be estimated based on bony landmarks, to within approximately 10 mm. The technique described is a useful means of estimating the location of the tentorial apex in patients where sagittal MRI imaging or three-dimensional treatment planning tools are not available.