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Background: There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice.Methods: This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder. Patients completed the questionnaire at baseline pretherapy and subsequently at 2 months. Following this, the psychometric properties of reliability, validity, scale structure and responsiveness to change were analysed.Results: Analysis of the QLQ-BIL21 scales showed appropriate reliability with Cronbach's α-coefficients >0.70 for all scales overall. Intraclass correlations exceeded 0.80 for all scales. Convergent validity >0.40 was demonstrated for all items within scales, and discriminant validity was confirmed with values <0.70 for all scales compared with each other. Scale scores changed in accordance with Karnofsky performance status and in response to clinical change.Conclusions: The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder. [ABSTRACT FROM AUTHOR]

Radiation-induced G[SUB1] arrest was studied in four classes of early passage skin fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutation-carriers, two homozygous (mut/-) TP53 mutation-carriers and 16 strains from nine Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP53 mutation has been found, despite sequencing of all exons, exon-intron boundaries, 3′ and 5′ untranslated regions and promoter regions. In an assay of p53 allelic expression in yeast, cDNAs from these non-mutation strains behaved as wild-type p53. Using two different assays, we found G[SUB1] arrest was reduced in heterozygous strains with mis-sense mutations and one truncation mutation, when compared to the range established for the normal cells. Heterozygous strains with mutations at splice sites behaved like normal cells, whilst homozygous (mut/-) strains showed either extremely reduced, or no, arrest. Strains from all nine non-mutation families gave responses within the normal range. Exceptions to the previously reported inverse correlation between G[SUB1] arrest and clonogenic radiation resistance were observed, indicating that these phenotypes are not strictly interdependent. [ABSTRACT FROM AUTHOR]

A study was made of the prognostic value of measurements of pretreatment serum marker levels in patients with carcinoma of the uterine cervix undergoing radiotherapy. The markers studied were carcinoma antigen 125 (CA125), squamous cell carcinoma antigen (SCC) and tissue polypeptide antigen (TPA). The levels of all three markers increased with disease stage. In a univariate analysis stratifying patients according to either median values or cut-off levels representing the top of the normal range, pretreatment levels predicted patient survival (follow-up times 1-4 years). In a multivariate analysis, disease stage was the most important prognostic variable and, after allowing for stage, only CA125 was a significant independent predictor of treatment outcome. These data suggest that, in carcinoma of the cervix treated with radiotherapy, pretreatment measurements of CA125, but not SCC and TPA, may have a role to play in defining prognosis.

The intrinsic radiosensitivity of cervical carcinoma has been measured using a soft agar clonogenic assay. All patients received radical radiotherapy alone with a minimum of 2 years post-treatment follow-up. Only women with stage I, II and III disease were included in the analysis. Values for cell surviving fraction at 2 Gy (SF2) were obtained for 88 tumours with an assay success rate of 73%. The 53 patients alive and well at the time of analysis had tumours with a mean SF2 that was significantly lower than the value from the 22 patients with locoregional failure (P < 0.01). Patients with radioresistant tumours (SF2 > 0.40, the median) had a significantly lower 3 year survival level than those with sensitive tumours (SF2 < or = 0.40) (P = 0.002). Also the frequency of local recurrence was higher (P = 0.001) whether these were central (P = 0.009) or peripheral (P = 0.046). Cell surviving fraction at 3.5 Gy was obtained for 46 tumours and the 3 year patient survival rate was significantly higher for those with SF3.5 values less than the median (P = 0.043). There was, however, no difference in the level of local recurrence (P = 0.24). The ability to grow in culture was not associated with significantly poorer patient survival (P = 0.56) or failure to control the primary disease (P = 0.17). While high colony forming efficiencies were associated with an increased rate of local recurrence (P = 0.029) they did not predict for overall patient survival (P = 0.32). These data suggest that, for cervical carcinoma treated with radical radiotherapy, intrinsic radiosensitivity is important in determining treatment outcome.

An assessment has been made of the reproducibility of measuring tumour proliferation using in vivo iododeoxyuridine (IUdR) labelling and flow cytometry. The variation that occurs between different institutions (Paterson Institute for Cancer Research, Manchester and the Gray Laboratory, Northwood), different observers and different runs on the same flow cytometer have been measured on 139 samples from 53 patients with colorectal cancer. The results demonstrate that the IUdR technique for measuring tumour proliferation is reproducible. Correlations were seen between measurements of Tpot obtained by different individuals and on separate machines. However, direct comparisons of the measured parameters showed that there were highly significant differences in the values obtained between institutes and observers (P < 0.001). Despite these variations, there were still significant detectable differences in Tpot measurements between individual tumours (P < 0.001). Analysis of the results obtained by running the same samples on two separate occasions on the same machine showed that the technique was highly reproducible and that the staining procedure was stable. Eighty per cent of the samples were similarly assigned to either above or below the median Tpot value, regardless which observer/laboratory combination was utilised. These data suggest that large clinical trials using Tpot should employ a single centre and a single individual to prepare, run and analyse samples.

The aim of this study was to determine the proliferative activity within the epithelial cells of the normal human breast in 122 patients (6 reduction mammoplasties and 116 fibroadenoma excisions) in relation to age and the phase of the menstrual cycle. Thirty three of the patients were on oral contraceptives and 33 were parous. Thin tissue slices were incubated with tritiated thymidine and processed for autoradiography. Other samples were fixed directly and prepared for histology. The labelling, mitotic and apoptotic indices (LI, MI and AI) were determined and all illustrated considerable variability. The labelling indices are significantly (P less than 0.05) influenced by both patient age and stage during the menstrual cycle and ranged from 0-11.5%. Maximum LI values were obtained on the 20.8th day of the cycle. A square root transformation of the data was used to reduce the skewness of the data to a more normal distribution. The square root of the LI declined by 0.22 per decade. The mitotic data showed similar significant (P less than 0.05) correlations against age and day of cycle with a peak on the 21.5th day of the cycle, a decline by 0.072 per decade and a range from 0-0.6%. The data for apoptotic cells were less clearly influenced by the stage of the menstrual cycle but showed a significant (P less than 0.5) decline with age. The AI in parous patients was significantly higher than that in non-parous patients. There was no significant effect of oral contraceptives on any of the parameters measured when age and stage of cycle were taken into account. The considerable variability in the data could not be fully accounted for by either technical factors, the age of the patients, or the day of the cycle. We conclude that proliferation is negatively related to age and is influenced by the menstrual cycle but that additional as yet unknown factors must account for a large part of the variability seen in the data.