Multi-modality megatherapy with [131I]meta-iodobenzylguanidine, high dose melphalan and total body irradiation with bone marrow rescue: feasibility study of a new strategy for advanced neuroblastoma.

New therapeutic approaches are needed for advanced neuroblastoma as few patients are currently curable. We describe an innovative strategy combining [131I]meta-iodobenzylguanidine ([131I]mIBG) therapy with high dose chemotherapy and total body irradiation. The aim of combining these treatments is to overcome the specific limitations of each when used alone to maximise killing of neuroblastoma cells. Five children received combined therapy with [131I]mIBG followed by high dose melphalan and fractionated total body irradiation. Autologous bone marrow transplantation was undertaken in 3 patients and allogeneic in 2 patients. One patient received additional localised radiotherapy to residual bulk disease. One patient is alive without relapse 32 months after treatment. 4 patients relapsed after remissions of 9, 10, 14 and 21 months. These results indicate that this combined modality approach is feasible and safe, but further evaluation is necessary to establish whether it has advantages over conventional megatherapy using melphalan alone.

Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: ten years experience.

PURPOSE: To report our experience in the use of interstitial iridium-192 implantation combined with external radiotherapy in anal cancer. METHODS AND MATERIALS: From 1984 to 1994, 79 patients with anal cancer were treated with radical intent using radiotherapy (plus chemotherapy) at Beatson Oncology Centre, Glasgow, Scotland. The mean and median age at presentation were 68 and 70 years, respectively (range 34-85) with a male-to-female ratio of 0.39. The histologic distribution was as follows: 48 squamous, 16 basaloid, 14 adenocarcinoma, and 1 basal cell carcinoma. The T stages were: 8 T1, 40 T2, 26 T3, and 5 T4 lesions. Twelve (15%) patients had nodal involvement at presentation. All patients underwent interstitial implantation using iridium-192 as part of the initial treatment. Seventy-six patients were treated with external radiotherapy followed by implant with a mean delay of 37 days after the end of radiotherapy. Twelve patients also received chemotherapy with 5-fluorouracil and mitomycin-C concurrently with external radiotherapy. Follow-up ranged from 6 to 123 months, with a median of 37 months. RESULTS: Seventy-nine patients were analyzed to assess local control, survival, and complications. A complete response rate of 91% (72 of 79) was achieved after planned radiation treatment. At the end of external radiotherapy, 29% (22 of 76) had achieved complete response, 58% (7 of 12) with chemotherapy and 23% (15 of 64) without it. Local control was achieved in 62 of 79 (78%) patients and 8 of 17 (47%) local failures were salvaged by abdominoperineal resection. Five patients developed inguinal node failure; four of these were salvaged. Overall, 10% of all patients developed distant metastasis as the first site of failure and 25% failed at any site after salvage therapy. Time to unsalvageable relapse was significantly different on comparing T stage (p = 0.005) and histology (p = 0.029) of tumor. Major complications requiring surgical intervention were seen in six (7.5%) patients. Anal function preservation with local control was possible in 56 of 79 (71%) patients. CONCLUSION: We report excellent results with radiotherapy in T1 and T2 lesions. The role of chemoradiotherapy as radical treatment of anal cancer should be defined in the context of locally advanced tumors.

Clinical governance: risks and quality control in radiotherapy.

The professions involved in radiotherapy constantly strive to improve quality and to minimize errors and their effects. We are aware of our shortcomings but sometimes are powerless to take corrective action. We have seen that clinical governance requires some change in the medical culture but much has yet to be achieved in the standardization of medical processes. We would gain by sharing experiences of system failures, whether that be by reporting near misses or by disseminating details of litigation cases. In a specialty that depends on human processes and interactions, it is no surprise to find a measurable incidence of human errors. Sometimes this is also related to technological or design deficiencies and we rely too much on human interventions to overcome these. We would like to take positive steps to improve quality, such as those inherent in the new ISO9000 standards, but we are hindered by a variety of constraints--manpower, old technology, pressure to achieve high patient throughput. We need to make decisions for the future development of radiotherapy in the UK. We could settle for a system that is characterized by high throughput and high risk. Hopefully, we will receive the necessary encouragement and resources to strive for high standards of treatment and low risk.

Diffusion of sugars and acids in human dental plaque in vitro.

Using a clearance technique, diffusion coefficients, D, were measured in plaque samples in which metabolic activity was eliminated by fixation with glutaraldehyde. Diffusion coefficients for sucrose, sodium acetate and sodium lactate at 37 degrees C were 3.0, 5.0 and 4.8 x 10(-6) cm2 s-1, respectively. Diffusion rate in plaque was between 2- and 5-fold slower than in water with uncharged species retarded less than charged species. However, diffusion in thin layers of plaque (100 microns) was rapid with clearance-halving times. T1/2, of about 6 s for acetate and lactate and 9 s for sucrose. Acetic and lactic acids diffuse faster than sucrose in plaque. Thus, the prolonged lowering of plaque pH following exposure to dietary carbohydrate is due to continued acid production in the plaque rather than to a restriction of diffusion of acid.

Effect of extracellular polysaccharides on diffusion of NaF and [14C]-sucrose in human dental plaque and in sediments of the bacterium Streptococcus sanguis 804 (NCTC 10904).

It has been postulated that extracellular polysaccharides form a barrier to diffusion in dental plaque. Diffusion coefficients, D, were measured for NaF and [14C]-sucrose in glucan-free and glucan-containing sediments of Strep. sanguis 804 at 37 degrees C. There was a tendency for NaF and [14C]-sucrose to diffuse faster as the carbohydrate concentration in the sediments increased. NaF diffused only 38 per cent more slowly in cell-free glucan sediment than in water, suggesting that glucan per se does not form a barrier to diffusion. The diffusion coefficient for NaF was positively correlated with carbohydrate concentration in individual plaque samples from 15 subjects and incubation of 3 plaque samples with sucrose resulted in both an increase in carbohydrate concentration in the plaque and an increase in D for NaF. Thus the presence of extracellular polysaccharides in plaque leads to slightly faster rates of diffusion. Nevertheless, the total time for diffusion through plaque may be increased if the presence of extracellular polysaccharides results in thicker layers of plaque.

An audit of 3D treatment planning facilities and practice in the UK.

The availability and use of 3D treatment planning facilities in the UK was investigated by questionnaire. Fifty-eight of the 62 UK radiotherapy centres responded (94%). There was considerable variation in the facilities available and in the manner in which they were used. Although 36 centres (62%) have the facilities to undertake complex, non-coplanar treatment planning, only 12 did so on a regular basis. More surprising was the inconsistent implementation of coplanar CT planning. It is suggested that we need to work towards reaching a consensus on best practice in radiotherapy planning. This will require the creation of systems for guidance and further training of the various staff involved.

Interstitial iridium-192 implantation for recurrent and/or locally advanced head and neck cancer.

We report our experience with the use of interstitial iridium-192 implantation in the management of patients with recurrent and locally advanced squamous cell carcinoma of the head and neck. Between June 1992 and July 1998 this technique was employed in the management of two groups of patients: (1) a primary group, comprising 42 patients who had presented for the first time with advanced head and neck disease, and had therefore not undergone any previous treatment; and (2) a salvage group of 16 patients with recurrent disease previously treated with external beam radiotherapy (four received therapy to the neck, one to the cheek, eight to the tongue and three to the floor of the mouth). The follow-up in each group was short, ranging from 3 to 56 months. The overall response in the primary group was 38/42 (90%). A complete response was achieved in 35/42 (83%). In the salvage group, the overall response was 13/16 (81%); 4/16 (25%) showed a complete response and 9/16 (56%) a partial response. The estimated percentage surviving at 1 year for patients with primary disease is 70% (95% confidence interval (CI) 54-86). For those receiving salvage therapy the estimated percentage surviving at 1 year is 45% (95% CI 19-71).

A technical and clinical evaluation of the Disa uroflowmeter.

This investigation reveals that there is a marked reduction in the rotational speed of the transducer disc as the stream flowrate is increased, although the non-linearity is partly reduced by electronic compensation within the instrument. The inaccuracy at low flowrates is probably unimportant in routine clinical applications. However, significant errors are recorded at high flowrates when the stream strikes the grid intersections or when the point of impact is close to the edge of the rotating disc. For these reasons, it is desirable that the patient should avoid micturating directly on to the grid. To obtain acceptable clinical recordings, an instrument time constant of 0-5 sec must be used. Although some characteristic tracings can be identified, the clinical measurements indicate that the effects of the volume voided and stream movement must be taken into consideration when the flow patterns are being interpreted.

Instrumentation for measurement of dental plaque thickness in situ.

A commercial digital micrometer has been modified mechanically and electronically to allow the measurement, in situ, of the thickness of dental plaque. The device detects initial contact between a moving probe and the plaque, and measures subsequent probe displacement through to the tooth surface. Instrument accuracy is +/- 5 micron over a displacement range of 0-5 mm, with 1 micron resolution. In practice, after a short 'learning' phase, reliable clinical results can be obtained.