BACKGROUND:Herpes simplex virus 1716 (HSV1716), a selectively replication competent mutant of HSV1, is under investigation as an oncolytic viral therapy in human malignant glioma. As with similar therapies, a technique for measurement of viral replication and distribution over time following virus administration is required. Imaging expression of the HSV-thymidine kinase (HSV-tk) gene offers an opportunity for non-invasive assessment of viral distribution in living subjects. This is the first study to explore the use of HSV-tk as a reporter gene and radiolabelled thymidine analogue 5-[(123)I]iodo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil ((123)I-FIAU) as a marker substrate to non-invasively monitor HSV1716 replication in humans during treatment of high-grade glioma. METHODS:I-FIAU brain SPECT imaging was undertaken in eight patients receiving intra-tumoural injection of HSV1716, before and after administration of the virus. Baseline images were acquired 3 days prior to virus administration and between 1 and 5 days following virus administration. Region of interest analysis was used to investigate whether there was an increase in (123)I-FIAU concentration following virus administration due to HSV-tk expression. RESULT:Increased (123)I-FIAU accumulation due to HSV-tk expression was not detected in this study. The possible explanations for this finding are explored and design options for future studies are discussed.

BACKGROUND:The role of chemotherapy in the treatment of patients with primary central nervous system lymphoma (PCL) remains unclear, with no randomized trials available to aid in the interpretation of the current data. The Medical Research Council therefore conducted the current randomized trial to assess the impact on survival of postradiotherapy chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in nonimmunocompromised adult patients with pathologically proven PCL. METHODS:After surgery, patients were randomized at a ratio of 1:2 to radiotherapy alone (RT: 40 grays [Gy] in 20 fractions to the whole brain followed by a 14-Gy boost to the tumor plus a 2-cm tumor margin) or to the same radiotherapy followed by six cycles of CHOP chemotherapy given at 3-week intervals (RT-CHOP). The target sample size was 90 patients, which allowed 90% power to detect a doubling of the median survival time. RESULTS:Between 1988 and 1995, 53 patients were randomized: Fifteen patients were randomized to RT, and 38 patients were randomized to RT-CHOP. The trial closed earlier than planned through poor accrual. The median patient age was 57 years, 57% of the patients were male, and 75% of the patients had unifocal disease. The median number of chemotherapy cycles received was 6 (mean, 4 cycles). Forty-three patients have died, and the median follow-up of survivors is 5 years (range, 1-9 years). There was no evidence of a benefit from RT-CHOP with respect to overall survival (hazard ratio [HR], 1.19; 95% confidence interval, 0.51-2.76) after adjustment for prognostic factors (patient age and neurologic performance status) in an analysis in which HR > 1 favored the control (RT) group. CONCLUSIONS:CHOP has no clear role in the postradiotherapy treatment of patients with PCL. Chemotherapy is poorly tolerated and largely palliative in older, less fit patients. In younger patients, initial chemotherapy designed to penetrate the blood-brain barrier warrants further investigation.

A shape analysis technique has been developed to quantify intracranial deformation as a means of objectively assessing treatment for brain tumor. Conventional measurements of tumor volume are prone to ambiguity and error, so instead the authors are investigating the secondary space occupying effects of tumor, namely the deformation of structures within the brain. In order to avoid surface segmentation problems in MR images and to facilitate computation, the B-splines method has been introduced to approximate digital 3-D image surfaces. Using the mean curvature and the Gaussian curvature the authors classify a surface into 4 basic types: planar, parabolic, elliptic, and hyperbolic. The deformation of a surface can be described by measuring the geometric changes in these basic types. The method is independent of size, domain (translation), and viewpoint (rotation). These invariance properties are important as they overcome problems caused by wide variations in brain size within the normal population as well as small differences in patient orientation during acquisition. Experimental results show the potential of the technique in objectively monitoring patient response to treatment.< >

Psychometric ratings for both anxiety and depression in 30 cancer patients were significantly elevated compared with values in 16 controls. The scores were especially high in the 14 patients who did not have breast cancer. This group also had significantly greater platelet monoamine oxidase activity than either the breast cancer patients or controls. Platelet monoamine oxidase activity values correlated significantly with both depression and anxiety scores in the whole cancer group.

Thirty one patients with very advanced tumours of the maxillary sinus were treated with fast neutrons. Tumour regressed completely in 29 (94%) and subsequently recurred in four (14%). No surgical excision of bone, skin, or nerve was required, and an artificial eye was well tolerated in cases where the eye received the tumour dose and had to be removed. Complications occurred in 10 patients, two of whom had already received radical x ray treatment. The overall duration of neutron treatment was four weeks, and admission to hospital was usually unnecessary. These results compared well with those obtained with surgery. Surgery with curative intent for even moderately advanced tumours of the facial region, particularly the paranasal sinuses, results in deformity, which is often severe and always irreversible. Even so, the cure rate is only about 35%. The high rates of tumour control and the avoidance of severe cosmetic and functional defects after fast neutron treatment make it an alternative to radical surgery in the management of malignant tumours of the facial area.

Phenolsulphotransferase and monoamine oxidase inactivate a wide range of dietary and endogenous phenols/monoamines by sulphoconjugation and oxidative deamination respectively. In this study, both enzymes were measured in platelets from cancer patients and controls. Of the two variants of phenolsulphotransferase, activity of the P form was normal in all groups. Activity of the M form was, however, significantly less than control values in patients with cancer of the rectum and bowel but not in other cancer patient groups. If this finding reflects enzyme activity elsewhere in the body and is not merely a manifestation of an abnormal platelet population, the deficit could expose affected subjects to the action of potentially carcinogenic dietary phenols. Platelet monoamine oxidase activity was significantly raised in the cancer group as a whole, and in all sub-types investigated apart from breast cancer. The increase in the cancer group as a whole was independent of sex, age, drugs, radiotherapy, smoking or platelet count. Its mechanism and significance are unknown but there may be links with the patients' psychiatric state.