Sweat gland function as a measure of radiation change.

BACKGROUND: Radiotherapy may result in dryness of the skin even when no other change can be detected. We describe a system for recording the electrical conductance of skin as a measure of sweat gland function. PATIENTS AND METHODS: In 22 normal volunteers close agreement was obtained between measurements obtained from comparable sites on both sides of the chest. Measurements were subsequently made in 38 patients treated by radiotherapy to one side of the chest for tumours of the breast or lung using one of five different fractionation schedules. Simultaneous readings were obtained from both sides of the chest with the non irradiated side acting as a control. RESULTS: A dose response relationship was demonstrated: five patients who received the equivalent total dose of 15 Gy in 2-Gy fractions showed no change in conductance. Sixteen out of 23 who received an equivalent total dose of 42-46 Gy in 2-Gy fractions had a greater than 22% reduction in mean skin conductance compared with that of the control areas despite the skin appearing normal in the large majority. Marked changes in skin conductance were seen after higher total doses. In a prospective study 18 women receiving breast irradiation underwent weekly readings during treatment. A mean reduction of 40% in skin conductance was noted by the end of the second week of treatment prior to any clinical evidence of radiation change. Skin conductance returned to normal in 44% of patients by 6 months. In the remainder, those patients who showed the greatest reduction in skin conductance during treatment demonstrated the least recovery. CONCLUSIONS: Changes in sweat gland function can be detected and quantified in skin which may otherwise appear normal. Differences may so be demonstrated between areas treated using different fractionation schedules and the method may be applied to the detection during radiotherapy of unusually sensitive patient.

Microregional blood flow in murine and human tumours assessed using laser Doppler microprobes.

A multichannel laser Doppler system has been used to measure microregional fluctuations in perfusion in the HT29 human tumour xenograft and in patients with advanced malignant disease. A comparison is made with previously obtained data for the SaF, a transplantable murine tumour. The 300 microns diameter probes recorded fluctuations in erythrocyte flux in tumour microregions with an estimated volume of 10(-2) mm3. Of the 66 human tumour microregions sampled, 26% showed a change in erythrocyte flux by a factor of 2 or more over the 60 min measurement period, compared with 37% of HT29 and 48% of SaF microregions. In each of the studies more than 50% of changes were completed within 20 min, although slower changes were more common in the human tumours than in the experimental systems. Within the 1 h monitoring period at least 30% of the changes were reversed (human tumours 30%, HT29 45%, SaF 31%). These findings demonstrate that microregional changes in erythrocyte flux, consistent with transient, perfusion-driven changes in oxygenation, are a feature of human malignancies as well as experimental transplanted tumours.

Microregional fluctuations in perfusion within human tumours detected using laser Doppler flowmetry.

PURPOSE: Transient fluctations in erythrocyte flux consistent with perfusion driven hypoxia have been previously reported using experimental tumour models. The present study was designed to establish whether such changes are a common feature of human tumours. METHODS AND MATERIALS: A multi-channel laser Doppler system was used to monitor microregional changes in flow in human tumours. Eight individual tumours were investigated, two primary and one locally recurrent breast carcinoma, two metastatic skin deposits and three metastatic lymph nodes. Six custom designed microprobes (diameter of 300 microns), each monitoring a nominal sampling volume of approximately 10(-2) mm3 were inserted into the tumour and perfusion monitored over a period of 60 min. RESULTS: The results show that in 54% of the regions monitored there was a change in microregional blood flow by a factor of 1.5 or more. Over the whole 60-min period, 19% of the changes were reversed, with a time course of 4-44 min. CONCLUSIONS: This finding demonstrates that microregional fluctuations in perfusion occur frequently in human tumours. Furthermore, the observation that 19% of the changes were reversed implies that at least some of the cells are subject to transient acute hypoxia.

Pattern of disease in spinal cord compression on MRI scan and implications for treatment.

Recent trends in the management of bone metastases include the use of prophylactic bisphosphonates and low dose single fraction radiotherapy in favour of high dose fractionated radiotherapy. A recent animal model [1] suggests that cord compression is often associated with predominant soft tissue epidural disease, with bone collapse as a late event. In the present study, potential implications were investigated by retrospective evaluation of the pattern of disease on MRI scans of patients with spinal cord compression. The dominant component of spinal cord compression was determined in 62 patients. Two main patterns were identified, 45 (73%) had predominant soft tissue epidural disease and 15 (24%) had bone collapse. There were two with intrathecal deposits. The patterns were correlated with response to radiotherapy. Positive response was observed in 64% of those with soft tissue epidural disease and 27% of those with bone collapse. These data support the animal model, suggesting soft tissue epidural disease rather than collapse as the predominant cause of cord compression. This implies that prophylactic bisphosphonates alone would be unlikely to reduce the incidence of spinal cord compression. It also introduces concern about the long term safety of low dose single fraction radiotherapy for bone metastases in patients with a medium term life expectancy (e.g. > 2 years). These patients may benefit from more than a single fraction of radiotherapy to produce longer growth delay for sub-clinical epidural disease.

The long-term outcome after radical radiotherapy for advanced head and neck cancer.

The patterns of local failure, salvage treatment, metastasis, second primary tumour and intercurrent disease are observed in 99 patients with advanced head and neck tumours, who were entered into a pilot study of CHART. The patients were treated between January 1985 and March 1990 and have a median follow-up of 59 months. All patients presented with squamous cell carcinoma of one of the major sites in the head and neck region, with 85% having T3-4 and/or N3 stage disease. Complete regression of locoregional disease was achieved in 89% of patients, but this fell to 49% at 5 years, 95% of those relapsing did so in the first 24 months. Using univariant analysis, N-stage influenced local tumour control, with N0 disease having a 5-year local tumour control rate of 62% compared with 33% for N+ disease. Local tumour control was not influenced by T-stage due to the disproportionate number of patients with T1-2 tumours who had nodal disease. Three of the 11 patients with residual disease underwent salvage therapy with surgery or further radiation; but failed to obtain local tumour control. Of the 39 patients judged to have recurrent disease two had no histological evidence of tumour when surgery was performed. Of the 21 who had salvage surgery 13 maintained local tumour control to last follow-up or death. Distant metastases occurred in 11 patients, all of whom also showed local failure. Thirteen of the 99 patients developed second primary tumours; these occurred most frequently after treatment for oral cavity tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

The long-term outcome after radical radiotherapy for advanced localized non-small cell carcinoma of the lung.

The incidence of locoregional failure, distant metastases and intercurrent disease was observed in 76 patients with advanced localized non-small cell lung cancer (NSCLC) entered into a pilot study of CHART. Patients were treated between January 1985 and March 1990 and have a median follow-up of 62 months. All patients had advanced, apparently localized, NSCLC and 76% were considered to show mediastinal involvement. Serial computed tomographic (CT) scans were used to assess patients' response to treatment, allowing us to determine the contribution of locoregional disease to death. Locoregional control was achieved in 32 (42%) of the 76 patients, with the figure falling to 23% at 2 years. Metastatic disease was demonstrated in 44 patients and, once detected, the median survival time was 3.8 months. Overall median survival for the group was 12.8 months, with patients attaining locoregional control faring better, with a median survival of 27.9 months compared with 9.9 months for those who did not achieve locoregional control. The life-tables show a 52% survival probability at 1 year for the whole group, but those attaining locoregional control showed a 75% survival probability compared with 39% for patients failing to achieve complete regression; these figures fell to 62% and 6% respectively at 2 years. To date, six patients remain alive and without evidence of disease at any site, and death has occurred in 12 without evidence of locoregional disease. The remaining 58 patients died with locoregional disease, with 35 also showing evidence of distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)