Initial Investigation into Microbleeds and White Matter Signal Changes following Radiotherapy for Low-Grade and Benign Brain Tumors Using Ultra-High-Field MRI Techniques.

BACKGROUND AND PURPOSE: External beam radiation therapy is a common treatment for many brain neoplasms. While external beam radiation therapy adheres to dose limits to protect the uninvolved brain, areas of high dose to normal tissue still occur. Patients treated with chemoradiotherapy can have adverse effects such as microbleeds and radiation necrosis, but few studies exist of patients treated without chemotherapy. MATERIALS AND METHODS: Ten patients were treated for low-grade or benign neoplasms with external beam radiation therapy only and scanned within 12-36 months following treatment with a 7T MR imaging scanner. A multiecho gradient-echo sequence was acquired and postprocessed into SWI, quantitative susceptibility mapping, and apparent transverse relaxation maps. Six patients returned for follow-up imaging approximately 18 months following their first research scan and were imaged with the same techniques. RESULTS: At the first visit, 7/10 patients had microbleeds evident on SWI, quantitative susceptibility mapping, and apparent transverse relaxation. All microbleeds were within a dose region of >45 Gy. Additionally, 4/10 patients had asymptomatic WM signal changes evident on standard imaging. Further analysis with our technique revealed that these lesions were venocentric, suggestive of a neuroinflammatory process. CONCLUSIONS: There exists a potential for microbleeds in patients treated with external beam radiation therapy without chemotherapy. This finding is of clinical relevance because it could be a precursor of future neurovascular disease and indicates that additional care should be taken when using therapies such as anticoagulants. Additionally, the appearance of venocentric WM lesions could be suggestive of a neuroinflammatory mechanism that has been suggested in diseases such as MS. Both findings merit further investigation in a larger population set.

3D prostate histology reconstruction: an evaluation of image-based and fiducial-based algorithms.

PURPOSE: Evaluation of in vivo prostate imaging modalities for determining the spatial distribution and aggressiveness of prostate cancer ideally requires accurate registration of images to an accepted reference standard, such as histopathological examination of radical prostatectomy specimens. Three-dimensional (3D) reconstruction of prostate histology facilitates these registration-based evaluations by reintroducing 3D spatial information lost during histology processing. Because the reconstruction accuracy may constrain the clinical questions that can be answered with these data, it is important to assess the tradeoffs between minimally disruptive methods based on intrinsic image information and potentially more robust methods based on extrinsic fiducial markers. METHODS: Ex vivo magnetic resonance (MR) images and digitized whole-mount histology images from 12 radical prostatectomy specimens were used to evaluate four 3D histology reconstruction algorithms. 3D reconstructions were computed by registering each histology image to the corresponding ex vivo MR image using one of two similarity metrics (mutual information or fiducial registration error) and one of two search domains (affine transformations or a constrained subset thereof). The algorithms were evaluated for accuracy using the mean target registration error (TRE) computed from homologous intrinsic point landmarks (3-16 per histology section; 232 total) identified on histology and MR images, and for the sensitivity of TRE to rotational, translational, and scaling initialization errors. RESULTS: The algorithms using fiducial registration error and mutual information had mean ± standard deviation TREs of 0.7 ± 0.4 and 1.2 ± 0.7 mm, respectively, and one algorithm using fiducial registration error and affine transforms had negligible sensitivities to initialization errors. The postoptimization values of the mutual information-based metric showed evidence of errors due to both the optimizer and the similarity metric, and variation of parameters of the mutual information-based metric did not improve its performance. CONCLUSIONS: The extrinsic fiducial-based algorithm had lower mean TRE and lower sensitivity to initialization than the intrinsic intensity-based algorithm using mutual information. A model relating statistical power to registration error for certain imaging validation study designs estimated that a reconstruction algorithm with a mean TRE of 0.7 mm would require 27% fewer subjects than the method used to initialize the algorithms (mean TRE 1.3 ± 0.7 mm), suggesting the choice of reconstruction technique can have a substantial impact on the design of imaging validation studies, and on their overall cost.

Assessing fitness to drive in brain tumour patients: a grey matter of law, ethics, and medicine.

BACKGROUND: Neurocognitive deficits from brain tumours may impair the ability to safely operate a motor vehicle. Although certain jurisdictions in Canada legally require that physicians report patients who are unfit to drive, criteria for determining fitness are not clearly defined for brain tumours. METHODS: Patients receiving brain radiotherapy at our institution from January to June 2009 were identified using the Oncology Patient Information System. In addition to descriptive statistics, details of driving assessment were reviewed retrospectively. The Fisher exact test was used to determine factors predictive of reporting a patient to the Ontario Ministry of Transportation (mto) as unfit to drive. A logistic regression model was constructed to further determine factors predictive of reporting. RESULTS: Of the 158 patients available for analysis, 48 (30%) were reported to the mto, and 64 (41%) were advised to stop driving. With respect to the 53 patients with seizures, a report was submitted to the mto for 30 (57%), and a documented discussion about the implications of driving was held with 35 (66%). On univariate analysis, younger age, a central nervous system primary, higher brain radiotherapy dose, unifocal disease, and the presence of seizures were predictive of physician reporting (p < 0.05). On logistic regression modelling, the presence of seizures (odds ratio: 3.9) and a higher radiotherapy dose (odds ratio: 1.3) remained predictive of reporting. INTERPRETATION: Physicians frequently do not discuss the implications of driving with brain tumour patients or are not properly documenting such advice (or both). Clear and concise reporting guidelines need to be drafted given the legal, medical, and ethical concerns surrounding this public health issue.

Multidisciplinary assessment of fitness to drive in brain tumour patients in southwestern Ontario: a grey matter.

BACKGROUND: Neurocognitive impairments from brain tumours may interfere with the ability to drive safely. In 9 of 13 Canadian provinces and territories, physicians have a legal obligation to report patients who may be medically unfit to drive. To complicate matters, brain tumour patients are managed by a multidisciplinary team; the physician most responsible to make the report of unfitness is often not apparent. The objective of the present study was to determine the attitudes and reporting practices of physicians caring for these patients. METHODS: A 17-question survey distributed to physicians managing brain tumour patients elicited Respondent demographicsKnowledge about legislative requirementsExperience of reportingBarriers and attitudes to reporting Fisher exact tests were performed to assess differences in responses between family physicians (fps) and specialists. RESULTS: Of 467 physicians sent surveys, 194 responded (42%), among whom 81 (42%) were specialists and 113 (58%) were fps. Compared with the specialists, the fps were significantly less comfortable with reporting, less likely to consider reporting, less likely to have patients inquire about driving, and less likely to discuss driving implications. A lack of tools, concern for the patient-physician relationship, and a desire to preserve patient quality of life were the most commonly cited barriers in determining medical fitness of patients to drive. CONCLUSIONS: Legal requirements to report medically unfit drivers put physicians in the difficult position of balancing patient autonomy and public safety. More comprehensive and definitive guidelines would be helpful in assisting physicians with this public health issue.

Fitness to drive in patients with brain tumours: the influence of mandatory reporting legislation on radiation oncologists in Canada.

BACKGROUND: Certain jurisdictions in Canada legally require that physicians report unfit drivers. Physician attitudes and patterns of practice have yet to be evaluated in Canada for patients with brain tumours. METHODS: We conducted a survey of 97 radiation oncologists, eliciting demographics, knowledge of reporting laws, and attitudes on reporting guidelines for unfit drivers. Eight scenarios with varying disability levels were presented to determine the likelihood of a patient being reported as unfit to drive. Statistical comparisons were made using the Fisher exact test. RESULTS: Of physicians approached, 99% responded, and 97 physicians participated. Most respondents (87%) felt that laws in their province governing the reporting of medically unfit drivers were unclear. Of the responding physicians, 23 (24%) were unable to correctly identify whether their province had mandatory reporting legislation. Physicians from provinces without mandatory reporting legislation were significantly less likely to consider reporting patients to provincial authorities (p = 0.001), and for all clinical scenarios, the likelihood of reporting significantly depended on the physician's provincial legal obligations. CONCLUSIONS: The presence of provincial legislation is of primary importance in determining whether physicians will report brain tumour patients to drivers' licensing authorities. In Canada, clear guidelines have to be developed to help in the assessment of whether brain tumour patients should drive.

Sci-Fri PM: Delivery - 11: Accuracy considerations in modern radiation oncology: An update.

The most recent reviews of accuracy requirements in radiation oncology were published in the 1990s, primarily in an era that was transitioning from 2-D to 3-D conformal radiation therapy (CRT). Since then, the technology associated with radiation oncology has changed dramatically. The combination of various forms of imaging for radiation therapy planning, treatment planning software, dose delivery technology including 4-D considerations as well as in-room daily image guidance has resulted in new perspectives on accuracy considerations. The underlying hypothesis for the use of these advanced technologies is that loco-regional control of cancer remains a significant barrier to cancer cure for many common cancers and that better dose distributions will translate into better outcomes. However, further clinical gain using these new technologies may be limited by single or compounded uncertainties associated with the entire treatment process. Thus, it is important to understand what factors should be considered in determining accuracy requirements as well as the realistic expectations of uncertainties that exist within the total treatment process. The need for accuracy is based on clinical requirements such as the steepness of dose-response curves, inherent heterogeneity in patient response to treatment, and the level of accuracy that is practically achievable. Statements on accuracy are dependent on the technology used and the reality of what is practically achievable and necessary. This review highlights some of the major differences between accuracy requirements as determined in the 2-D RT and 3-D CRT era versus the modern era of intensity modulated, image-guided, 4-D radiation therapy.

Neurocytomas: long-term experience of a single institution.

There is a lack of studies reporting on outcomes of control and treatment toxicities for neurocytomas. A 25-year retrospective review of a tertiary center's experience with neurocytomas was completed to report on these outcomes. All cerebral neurocytoma cases (19 patients; median age, 31 years; range, 18-62 years; 18 intraventricular and 1 extraventricular) treated between 1984 and 2009 were analyzed, including central pathology and radiology reviews. Median follow-up was 104.5 months (range, 0.75-261.7 months). Primary treatment was surgery alone (n = 18 patients), followed by surgery and adjuvant radiotherapy (n = 1). The crude local control rate after surgery was 68% for all cases (cerebral neurocytomas) and 74% for central neurocytomas. Salvage therapies included further surgery (n = 4), radiation (n = 3), and chemotherapy (n = 1). Ten-year Kaplan-Meier overall and relapse-free survival rates were 82% and 62% and 81% and 57%, respectively, for all cases and for central neurocytomas only. The median overall survival and relapse-free survival were 104.5 and 79.3 months, respectively, for all cases and for central neurocytomas. Ten patients had grade 3/4 toxicity, and 1 patient had a grade 5 perioperative hemorrhage that resulted in death 23 days after surgery. Late grade 3/4 toxicities occurred in 9 patients. Three patients had permanent grade 2 motor or cognitive deficits. We provide the first report outlining toxicities and survival outcomes in a series of 19 patients. Our experience suggests that initial surgery provides durable local control rates in two-thirds of patients, with low risk for significant permanent deficits. Salvage therapy with surgery and/or radiation provides durable local control in tumors that recur after surgery.

Sci-Thurs PM: Delivery-07: Evaluation of prospects to use daily megavoltage CT studies for adaptive radiotherapy.

PURPOSE: To evaluate gross tumor volume (GTV) changes for non-small cell lung cancer (NSCLC) patients using daily megavoltage CT (MVCT) studies acquired before each treatment fraction on helical tomotherapy, and to relate the potential benefit of adaptive image-guided radiotherapy to changes in GTV. METHODS: 17 patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for NSCLC at London Regional Cancer Program from December 2005 to March 2007. The GTV was contoured on the daily MVCT studies of each patient. Adapted plans were created using merged MVCT-kVCT image sets to investigate the advantages of replanning for patients with differing GTV regression characteristics. RESULTS: The average GTV change observed over 30 fractions was -38%, ranging from -12 to -87%. No significant correlation was observed between GTV change and patient's physical or tumor features. The pattern of GTV changes of the 17 patients could be broadly divided into 3 groups with distinctive potential for benefit from adaptive planning. CONCLUSIONS: GTV changes are difficult to predict quantitatively based on patient or tumor characteristics. If changes do occur, there are points in time during the treatment course when it may be appropriate to adapt the plan to improve sparing of normal tissues. If the GTV decreases by greater than 30% at any point in the first twenty fractions of treatment, adaptive planning is appropriate to further improve the therapeutic ratio.

Dosimetric impact of image-guided 3D conformal radiation therapy of prostate cancer.

The goal of this work is to quantify the impact of image-guided conformal radiation therapy (CRT) on the dose distribution by correcting patient setup uncertainty and inter-fraction tumour motion. This was a retrospective analysis that used five randomly selected prostate cancer patients that underwent approximately 15 computed tomography (CT) scans during their radiation treatment course. The beam arrangement from the treatment plan was imported into each repeat CT study and the dose distribution was recalculated for the new beam setups. Various setup scenarios were then compared to assess the impact of image guidance on radiation treatment precision. These included (1) daily alignment to skin markers, thus representing a conventional beam setup without image guidance, (2) alignment to bony anatomy for correction of daily patient setup error, thus representing on-line portal image guidance, and (3) alignment to the 'CTV of the day' for correction of inter-fraction tumour motion, thus representing on-line CT or ultrasound image guidance. Treatment scenarios (1) and (3) were repeated with a reduced CTV to PTV margin, where the former represents a treatment using small margins without daily image guidance. Daily realignment of the treatment beams to the prostate showed an average increase in minimum tumour dose of 1.5 Gy, in all cases where tumour 'geographic miss' without image guidance was apparent. However, normal tissue sparing did not improve unless the PTV margin was reduced. Daily realignment to the tumour combined with reducing the margin size by a factor of 2 resulted in an average escalation in tumour dose of 9.0 Gy for all five static plans. However, the prescription dose could be escalated by 13.8 Gy when accounting for changes in anatomy by accumulating daily doses using nonlinear image registration techniques. These results provide quantitative information on the effectiveness of image-guided radiation treatment of prostate cancer and demonstrate that the dosimetric impact is patient dependent.

Validation of contour-driven thin-plate splines for tracking fraction-to-fraction changes in anatomy and radiation therapy dose mapping.

The goal of this study is to validate a deformable model using contour-driven thin-plate splines for application to radiation therapy dose mapping. Our testing includes a virtual spherical phantom as well as real computed tomography (CT) data from ten prostate cancer patients with radio-opaque markers surgically implanted into the prostate and seminal vesicles. In the spherical mathematical phantom, homologous control points generated automatically given input contour data in CT slice geometry were compared to homologous control point placement using analytical geometry as the ground truth. The dose delivered to specific voxels driven by both sets of homologous control points were compared to determine the accuracy of dose tracking via the deformable model. A 3D analytical spherically symmetric dose distribution with a dose gradient of approximately 10% per mm was used for this phantom. This test showed that the uncertainty in calculating the delivered dose to a tissue element depends on slice thickness and the variation in defining homologous landmarks, where dose agreement of 3-4% in high dose gradient regions was achieved. In the patient data, radio-opaque marker positions driven by the thin-plate spline algorithm were compared to the actual marker positions as identified in the CT scans. It is demonstrated that the deformable model is accurate (approximately 2.5 mm) to within the intra-observer contouring variability. This work shows that the algorithm is appropriate for describing changes in pelvic anatomy and for the dose mapping application with dose gradients characteristic of conformal and intensity modulated radiation therapy.

Tracking the dose distribution in radiation therapy by accounting for variable anatomy.

The goal of this research is to calculate the daily and cumulative dose distribution received by the radiotherapy patient while accounting for variable anatomy, by tracking the dose distribution delivered to tissue elements (voxels) that move within the patient. Non-linear image registration techniques (i.e., thin-plate splines) are used along with a conventional treatment planning system to combine the dose distributions computed for each 3D computed tomography (CT) study taken during treatment. For a clinical prostate case, we demonstrate that there are significant localized dose differences due to systematic voxel motion in a single fraction as well as in 15 cumulative fractions. The largest positive dose differences in rectum, bladder and seminal vesicles were 29%, 2% and 24%, respectively, after the first fraction of radiation treatment compared to the planned dose. After 15 cumulative fractions, the largest positive dose differences in rectum, bladder and seminal vesicles were 23%, 32% and 18%, respectively, compared to the planned dose. A sensitivity analysis of control point placement is also presented. This method provides an important understanding of actual delivered doses and has the potential to provide quantitative information to use as a guide for adaptive radiation treatments.

Multidisciplinary management of adult anaplastic oligodendrogliomas and anaplastic mixed oligo-astrocytomas.

Once thought to be rare, oligodendroglial tumors might actually represent up to 25% of primary glial neoplasms. In recent years, the histologic criteria for the diagnosis of oligodendroglioma have been broadened to include most small cell, monomorphic glial neoplasms. These refinements have led to an increased recognition of oligodendroglial neoplasms, but uniform definitions of pure versus mixed oligodendroglioma as well as the criteria for high-grade (anaplastic) versus low-grade tumors remain elusive. From a prognostic standpoint, the presence of an oligodendroglial component in a malignant glioma predicts longer survivals times for patients treated with surgery, and radiation therapy with or without chemotherapy. High rates of response to PCV (procarbazine, CCNU and Vincristine) chemotherapy also have been noted among patients with anaplastic oligodendroglial neoplasms. Ongoing prospective trials seek to clarify the role of PCV chemotherapy when added to radiation therapy and surgery. In addition, the role of molecular markers as diagnostic aides and guides to therapy and prognosis are being explored for patients with pure and mixed anaplastic oligodendroglial tumors.

Nontraumatic osteonecrosis after chemotherapy for testicular cancer: a systematic review.

Nontraumatic osteonecrosis is a well-documented late complication of chemotherapy for hematologic malignancies, with prolonged corticosteroid exposure implicated. Reports of this treatment complication in patients treated with chemotherapy for solid tumors are sparse. We reviewed our institutional experience and the published medical literature to explore an association between chemotherapy for testicular cancer and the occurrence of nontraumatic osteonecrosis. Two databases of men with testicular cancer were reviewed. Search of the medical literature included MEDLINE, CANCERLIT, and EMBASE. Two of 107 men with testicular cancer treated with chemotherapy at our center were identified with nontraumatic osteonecrosis. Literature review identified 14 reports describing patients with 39 solid tumors with osteonecrosis after chemotherapy. Of 38 adults, 28 had testicular cancer and 6 had breast cancer. All patients with testicular cancer had received cisplatin, vinblastine, and bleomycin, or bleomycin, etoposide, and cisplatin. Twenty-seven of 28 had received corticosteroids. Diagnosis was subacute in three and delayed a mean of 26 months (range, 12-47 months) in 26. The femoral head was involved in 26 patients, with bilateral involvement in 18. Crude incidence was 1.5% (95% CI, 0.9-2.1). Nontraumatic osteonecrosis is an infrequent but disabling late complication of cancer chemotherapy reported most commonly in adult patients with testicular cancer. Corticosteroid exposure makes this association plausible.

Palliative chemoirradiation for transitional carcinoma of the bladder: a case report.

Palliation of locally advanced transitional carcinoma of the bladder is a major problem that has not been well investigated. Recent reports from the curative literature suggest improved tumor response rates using platinum based chemoirradiation over radiotherapy alone. Because of the poor symptomatic responses seen with conventional palliative radiotherapy, we have been treating selected cases of locally advanced bladder carcinoma palliatively with low dose chemoirradiation. We present a case of an elderly female treated this way with an excellent clinical response.

Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas.

INTRODUCTION: Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients. MATERIALS AND METHODS: We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined. RESULTS: Fifty-five patients (29 male, 26 female; ages 18-75 years; median, 44 years; KPS 50-90, median 80) were irradiated for either a WHO Grade II (n = 19) or Grade III (n = 36) oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy. The median radiation dose was 54 Gy in 30 fractions. Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumors and absent in 19. Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p (p < 0.001). On both univariate and multivariate analyses, chromosome lp loss was the principal independent predictor of longer progression-free survival for patients with Grade II and III oligodendrogliomas. For Grade III oligodendrogliomas, chemotherapy as an adjunct to radiotherapy prolonged tumor control for those patients whose tumors harbored allelic loss of chromosome 1p (p = 0.004). CONCLUSION: These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy +/- chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of oligodendroglioma.

Simulation for localized prostate cancer: a comparison of urethrography techniques.

Forty-five patients having conventional fluoroscopic, or CT scan simulation of the prostate gland from January 1999 to June 1999 were studied. Patients were consecutively assigned (not randomized) in groups of 15 to 3 different urethrography techniques: air contrast alone (group 1), hypaque contrast alone (group 2), and xylocaine jelly and hypaque contrast (group 3). Outcome measures were pain scores, visualization of the apex (indicated by urethrogram tip), and frequency of corrections necessary on the basis of verification port films. Group 3 patients had the lowest mean pain score and required fewer lateral setup corrections at the time of portal imaging on the first day of treatment. A comparison of radiographs also revealed that group 2 and 3 patients (hypaque contrast) had better delineation of the prostatic anatomy than group 1 patients (air contrast). We found that of the 3 techniques tested, urethrography utilizing xylocaine jelly and hypaque was associated with the least amount of pain, least amount of corrective shifts, and best quality in defining the prostatic anatomy.

Effects of radiation on a three-dimensional model of malignant glioma invasion.

An experimental model of malignant glioma growth involving implantation of spheroids into a gel matrix of collagen type I has been developed. This model has been used to characterize changes in glioma cell invasion in response to single dose and fractionated radiation treatment. Suspensions of C6 astrocytoma cells were grown in spinner culture flasks to yield spheroids of varying size (300-1000 microm). Implantation of spheroids into a gel matrix of collagen type I was associated with measurable invasion of the surrounding gel by individual tumor cells. Changes in the distance of invasion in response to single dose and fractionated radiation were measured. Changes in apoptosis and proliferative indices in different regions of the spheroids in response to radiation were also assessed. In unirradiated gels, maximum depth of invasion, 1300-1750 microm, was achieved by 5 days after implantation. A radiation dose-dependent inhibition of invasion was noted and was most profound for larger spheroids. Fractionation of the radiation dose was associated with a partial recovery of invasion. Changes in apoptotic and proliferative indices in response to radiation depended on the region of the spheroid examined. Increases in apoptosis were noted for cells at the surface of the spheroid and invading cells while cells at the centre of the spheroid demonstrated virtually no increase in apoptosis. Likewise, a dose-dependent decrease in proliferative indices following radiation was noted among the invading cells and cells at the surface of the spheroid but not at the centre of the spheroid. We have described a model of malignant glioma invasion which possesses many of the qualities of in vivo malignant gliomas. Within this model, invasion appeared to be inhibited by radiation in a dose- and fractionation-dependent fashion. Measurement of apoptotic and cell proliferation indices favour a direct cytotoxic effect on the invading cells as the most likely mechanism for this phenomenon.

Analysis of the clinical benefit of 5-fluorouracil and radiation treatment in locally advanced pancreatic cancer.

PURPOSE: To assess the palliative benefit of 5-fluorouracil (5-FU) and radiotherapy in patients with surgically unresectable localized pancreatic cancer. METHODS AND MATERIALS: Twenty-five patients with locally advanced surgically unresectable symptomatic pancreatic cancer received 5-FU chemotherapy and local radiation therapy. They were retrospectively reviewed in regard to their clinical benefit response (a composite of measurement of pain assessment, weight, and Karnofsky performance status [KPS]), as well as radiological response, time to progression, and overall survival. RESULTS: Median survival for the 25 patients was 9 months and median progression-free survival was 6 months. Thirty-two percent of patients survived in excess of 1 year. Analgesic requirements increased >50% in 2 patients and KPS deteriorated in 10 patients. Of the 13 remaining patients, 2 sustained a >7% weight loss and 2 gained weight post-treatment. Six patients improved in one parameter of analgesic consumption, weight loss or KPS without deteriorating in any others. Thus, the clinical benefit response index for 5-FU-radiation was 6/25 (24%). In terms of tumor response, 8 patients (44%) demonstrated a reduction in tumor volume post-treatment, 4 of whom (22%) experienced a >50% reduction. Four additional patients had radiologically stable disease. CONCLUSION: In this retrospective analysis, the clinical benefit response index for 5-FU-radiation was 24%, a value similar to the 23.8% reported for single agent gemcitabine. The median survival of 7 months was also similar to the 5.65 months reported for gemcitabine. The radiological partial response rate of 22% and the 1-year survival of 32% were higher for 5-FU-radiation than the reported values for gemcitabine. A randomized trial would be necessary to compare 5-FU-radiation to gemcitabine directly; however, from this review it did not appear that the overall palliative benefit of 5-FU-radiation was inferior to gemcitabine.

Effects of radiation on a model of malignant glioma invasion.

We sought to characterize the effects of radiation alone and in combination with BCNU and dexamethasone on malignant glioma invasion. A model of malignant glioma invasion into a gel matrix of collagen type I was used to characterize response to radiation treatment for four malignant glioma cell lines (C6, U251, U373, A172) and nine primary human glioblastoma explants. A radiation dose dependent inhibition of invasion was noted for the C6 astrocytoma cell line but not the other cell lines or explants. Addition of BCNU and dexamethasone to radiation produced additional inhibition of invasion among the cell lines and explants but could not suppress invasion entirely.