Assessment of microtubule-associated protein (MAP)-Tau expression as a predictive and prognostic marker in TACT; a trial assessing substitution of sequential docetaxel for FEC as adjuvant chemotherapy for early breast cancer.

The TACT trial is the largest study assessing the benefit of taxanes as part of adjuvant therapy for early breast cancer. The goal of this translational study was to clarify the predictive and prognostic value of Tau within the TACT trial. Tissue microarrays (TMA) were available from 3,610 patients. ER, PR, HER2 from the TACT trial and Tau protein expression was determined by immunohistochemistry on duplicate TMAs. Two parallel scoring systems were generated for Tau expression ('dichotomised' vs. 'combined' score). The positivity rate of Tau expression was 50 % in the trial population (n = 2,483). Tau expression correlated positively with ER (p < 0.001) and PR status (p < 0.001); but negatively with histological grade (p < 0.001) and HER2 status (p < 0.001). Analyses with either scoring systems for Tau expression demonstrated no significant interaction between Tau expression and efficacy of docetaxel. Contrary to the hypothesis that taxane benefit would be enriched in Tau negative/low patients, the only groups with a suggestion of a reduced event rate in the taxane group were the HER2-positive, Tau positive subgroups. Tau expression was seen to be a prognostic factor on univariate analysis associated with an improved DFS, independent of the treatment group (p < 0.001). It had no prognostic value in ER-negative tumours and the weak prognostic effect of Tau in ER-positive tumours (p = 0.02) diminished, when considering ER as an ordinal variable. On multivariable analyses, Tau had no prognostic value in either group. In addition, no significant interaction between Tau expression and benefit from docetaxel in patients within the PR-positive and negative subsets was seen. This is now the second large adjuvant study, and the first with quantitative analysis of ER and Tau expression, failing to show an association between Tau and taxane benefit with limited utility as a prognostic marker for Tau in ER-positive early breast cancer patients.

Epirubicin, cisplatin and protracted venous infusion 5-Fluorouracil chemotherapy for advanced salivary adenoid cystic carcinoma.

AIMS: Adenoid cystic carcinoma (ACC) is a rare tumour that usually arises in the salivary glands. Initial management is surgery often combined with adjuvant radiotherapy. Chemotherapy is reserved for treatment of symptomatic recurrence. We evaluated the combination of epirubicin, cisplatin and protracted venous infusion 5-fluorouracil (ECF) in the management of ACC. MATERIALS AND METHODS: Patients referred for treatment of advanced, symptomatic ACC were considered. The drugs given were epirubicin 50 mg/m(2) 3-weekly, cisplatin 60 mg/m(2) 3-weekly and protracted venous infusion 5-fluorouracil 200 mg/m(2)/day. RESULTS: Eight patients (median age 46 years) received a median of five cycles of chemotherapy. All patients had had previous surgery, seven had had previous radiotherapy and one had had previous chemotherapy. One patient showed a partial response (duration 34 months) and five showed stable disease (median duration 13.6 months [6.8-15.9+ months]). Median survival was 27 months (3.5-62.3 months). CONCLUSIONS: The activity of ECF in ACC of the head and neck seems to be similar to the combination of cisplatin and 5-fluorouracil and single-agent epirubicin.

Cancer Biology and Survival Analysis in Cancer Trials: Restricted Mean Survival Time Analysis versus Hazard Ratios.

Hazard ratios are commonly used when comparing survival between two groups and make the assumption that the relative event rates do not change markedly during follow-up, i.e. that event rates are proportional. However, there is currently debate about the use of the proportional hazards assumption to summarise the treatment effect in survival analysis compared with restricted mean survival time (RMST) analysis, particularly in cancer trials. In many situations it is unrealistic to assume that relative event rates in two groups will be proportional throughout follow-up and, hence, RMST analysis, which does not make this assumption, may be preferable. Several benefits of the latter approach have been identified but the biological perspective is not often discussed. Biological features such as the patterns of tumour growth and response can also contribute to assessing the relative merit of these two methods; such biological considerations are the subject of this paper. The observation that the most commonly observed approximation to the underlying distribution of time to event data, the lognormal distribution, does not reliably show proportional hazards in the comparison of two groups, lends weight to a statistical approach that is not based on proportional hazards. The proportional hazards assumption should be viewed more critically when estimating treatment effects. An optimum approach may be to include both proportional hazards analysis and RMST analysis when comparing time to event endpoints.

Sweat-gland tumours: a clinical review of cases in one centre over 20 years.

AIMS: Sweat-gland tumours (SGTs) are uncommon, but malignant varieties are very rare. We have added our data on 30 new cases seen at the Royal Marsden NHS Foundation Trust to the published literature, particularly concentrating on clinical issues. We include a literature review. MATERIALS AND METHODS: The Royal Marsden NHS Foundation Trust database was searched for cases of SGT from 1972. Data were collected on all cases, including patient demographics and tumour characteristics, treatment and outcome. RESULTS: Thirty cases were confirmed histologically to be SGTs. Fourteen were malignant, 15 benign and the degree of malignancy in one was histologically indistinguishable. Mean age was 55 years (64 for malignant, 47 for benign tumours). The 15 patients with benign tumours were almost all treated with complete excision. Those with local relapse underwent successful re-excision. Their 5-year disease-free survival was 78% and cause-specific survival was 100%. Twelve of the 14 malignant tumours had localised disease at diagnosis, one had nodal disease and one had metastatic tumour nodules. All except one were treated with wide local excision. The patient with nodal involvement also had a lymph-node dissection. Two received adjuvant radiotherapy to the tumour bed. One received a melphalan limb perfusion. Eight of the 14 had no relapse. Six had locoregional relapse, and four of these also developed distant metastases. Visceral disease was always fatal. Radiotherapy and chemotherapy at relapse were unsuccessful. Five-year disease-free survival was 45%, and cause-specific survival was 57%. CONCLUSION: These rare tumours should be treated initially with complete wide local excision. In malignant tumours, lymph-node involvement is a poor prognostic sign. Wide local excision remains the primary treatment. Adjuvant radiotherapy may be useful in high-risk cases.

A case-control study confirms that microsatellite assay can identify patients at risk of developing oral squamous cell carcinoma within a field of cancerization.

Distinguishing true precursor lesions on the basis of clinical or histological features alone is unreliable but is important so that appropriate intervention can be instigated. Preliminary studies have shown that a microsatellite assay may provide important new prognostic information. To build on these observations, we have performed a case-control study to establish whether we can be confident about incorporating this new information into clinical practice. We have determined the frequency of allelic imbalance (AI) within key chromosomal regions, by matching 39 cases with dysplastic oral lesions that developed a tumor on the same side of the mouth, for as many variables as possible, with controls presenting with similar lesions that did not progress to malignancy when followed for the same period. Our findings confirm that the group that developed tumor had precursor lesions that harbor AI at more loci (P = 0.002). However, no consistent patterns of AI were associated with the three grades of dysplasia: mild, moderate, and severe. One-third of the tumors developed at the same site as the dysplastic lesion and two-thirds at a different site, which revealed that the presence of these aberrations in a dysplastic lesion provided information about the risk of malignant change within a larger field. This suggests that the process of field cancerization is more widespread than previously recognized. On the basis of these findings, we advocate complete excision of all suspicious areas that show AI at two or more key loci, regardless of the degree of dysplasia. However, because the remaining mucosa is also "at risk," these cases should also be targeted to receive dietary advice and chemoprevention, to minimize their risk of tumor formation at a distant site.

Impact of doxorubicin on survival in advanced ovarian cancer.

PURPOSE: Our study examined the impact of the addition of doxorubicin to ovarian cancer regimens in general, while removing the confounding influence of other drugs. MATERIALS AND METHODS: We performed an overview using the data from two large analyses, the Advanced Ovarian Cancer Trialists Group (AOCTG [Br Med J 303:884-893, 1991] and Williams et al [Seminars in Oncol 19:120-128, 1992 (suppl 2)]) and the Ovarian Cancer Meta-Analysis Project (OCMP [J Clin Oncol 9:1668-1674, 1991]). RESULTS: Our data suggest that the addition of doxorubicin significantly improves survival (hazards ratio, 0.85; 95% confidence interval [CI], 0.76 to 0.95; P = .003) and that the size of this benefit is of a similar magnitude to that of platinum. CONCLUSION: The implication of our results is that the basic drugs for the standard treatment of advanced ovarian should be a combination of platinum and doxorubicin. The addition of an alkylating agent may add toxicity and lead to a dose reduction of these two drugs. In view of recent data on combination therapy with paclitaxel and platinum, it would be appropriate to compare this regimen with a combination of doxorubicin and platinum.

Natural history and prognosis of untreated stage I epithelial ovarian carcinoma.

PURPOSE: The aim of this study was to investigate the independent significance of prognostic factors in stage I invasive epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Between 1980 and 1994, all patients with stage I EOC (borderline tumors excluded) following surgical resection were entered onto this study. No patient received adjuvant therapy and patients were monitored as follows: years 1 to 2-physical examination and serum CA125 every 3 months and computed tomographic (CT) scan every 6 months; years 3 to 5-physical examination and serum CA125 every 6 months and CT scan yearly; years 5 to 10-annual physical examination and serum CA125, with CT scan if clinically indicated. RESULTS: A total of 194 patients entered the study. The median patient age was 54 years (range, 15 to 83), and the median follow-up duration 54 months (range, 7 to 157). Five-year survival rates were as follows: stage IA, 93.7%; stage IB, 92%; and stage IC, 84%. Multivariate analysis using Cox's regression identified grade (P < .001), presence of ascites (P = .05), and surface tumor (P < .01) as independent poor prognostic factors. International Federation of Gynecology and Obstetrics (FIGO) substage did not appear to have independent prognostic significance. Intraoperative capsule rupture was not found to be prognostically significant. The impact of pre-operative rupture remains unclear. CONCLUSION: This is an important series, as no patient received adjuvant therapy, and represents the natural history of surgically resected stage I EOC.

Natural history of stage IV epithelial ovarian cancer.

PURPOSE: In this report we present the natural history, prognostic factors, and therapeutic implications of stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: We reviewed 192 patients with stage IV EOC as defined in 1985 by the International Federation of Gynecology and Obstetrics. RESULTS: The site of stage IV-defining disease was cytologically positive pleural effusion in 63 patients, liver in 50 patients, lymph nodes in 26 patients, lung in six patients, other sites in 15 patients, and disease at multiple stage IV-defining metastatic sites in 32 patients. Surgery was performed before chemotherapy in 169 patients; 25 patients (14.8%) were left with only microscopic residual disease or less than 2 cm of macroscopic residual disease. The overall response rate to chemotherapy was 56%; the complete response rate was 18%. The median progression-free survival was 7.1 months, and the median overall survival was 13.4 months. The median overall survival of patients with positive pleural effusions only was 13.4 months as compared with 10.5 months for patients with visceral disease only, but this difference was not statistically significant. The 5-year survival rate was 7.6%, with only six patients surviving more than 5 years. Univariate and multivariate analysis showed that two parameters were associated with a shorter survival time: visceral involvement (lung or liver) and diagnosis before 1984. CONCLUSION: Patients with stage IV EOC initially respond to chemotherapy as often as those with less advanced disease, but the long-term prognosis is very poor. The size of residual disease is not a prognostic factor in this group of patients, and, therefore, the role of debulking surgery in these patients needs to be reconsidered.

Results of external beam radiotherapy in differentiated thyroid carcinoma: a retrospective study from the Royal Marsden Hospital.

Between 1969 and 1991, 113 patients with differentiated thyroid carcinoma (follicular and papillary) received radical dose megavoltage external beam radiotherapy. There were 70 females and 43 males, mean age 53 years (range 11-84). Radiotherapy was delivered to both sides of the neck and superior mediastinum, using either megavoltage photons via anterior and posterior portals, delivering a 60 Gy mid-plane dose in 30 fractions and treating daily over 6 weeks (with spinal cord shielding from the posterior field after 40 Gy), or matched 20 MeV and 35 MeV electron beams (to the neck and superior mediastinum, respectively) delivering a 75 Gy applied dose in 30 daily fractions. All patients received suppressive thyroid hormone and 74 radioiodine. Local recurrence, mostly within field, occurred in 19% of 53 patients with probable and definite residual microscopic disease (both follicular and papillary histologies). For gross residual disease (both follicular and papillary) in 49 patients, complete regression was obtained in 37.5%, partial regression in 25% and no regression in 37.5%. Median follow-up from diagnosis was 49 months (range 3-335). Overall 5-year survival rates were 85% for residual microscopic disease but only 27% for gross disease. 61 patients have died. Nineteen deaths were due to unrelated causes, 15 to distant metastases, 15 to uncontrolled local disease and 12 died with both local and distant tumours.

The early diagnosis of breast cancer--a twenty-year experience at the Royal Marsden Hospital.

Over 30,000 women with minimal symptoms were examined between 1968 and 1987 for the detection of early stage breast cancer. Subsequent follow-up screening was selected for women at higher risk because of family history, previous significant benign breast change (e.g. epitheliosis) and hormone replacement therapy. 552 cases of cancer were diagnosed and the current prevalent detection rate is 8.5 per 1000 women examined. Incident cancer (screen-detected and interval) occurred in 6.2 per 1000 women-years at risk. Of the prevalent cancers, 47% were in early T stages of development (TIS, T0 and T1) and this proportion rose to 70% in the screened group. Survival is stage-dependent but the group has not reached its median survival at 15 years. Actuarial estimates of the percentages surviving at 10 years are 73% in the prevalent group and 80% in the incident group.

Combining platinum, paclitaxel and anthracycline in patients with advanced gynaecological malignancy.

Two meta-analyses have suggested that the addition of an anthracycline to platinum-based chemotherapy may improve survival in advanced ovarian cancer, and two randomised trials have demonstrated superiority of paclitaxel over cyclophosphamide in platinum combinations. A combination of platinum, anthracycline and paclitaxel would, therefore, be a reasonable experimental arm of any future randomised trial in patients with epithelial ovarian carcinoma (EOC). Patients who required chemotherapy for EOC but were ineligible for standard trials or had other gynaecological tumours that required similar platinum-based chemotherapy were considered for this pilot. The platinum/anthracycline/paclitaxel regimen (G-CAT) was given 3-weekly and consisted of doxorubicin 50 mg/m(2) or epirubicin 60 mg/m(2) intravenously (i.v.) bolus, paclitaxel 175 mg/m(2) (i.v.) over 3 h and either cisplatin 75 mg/m(2) (i.v.) or carboplatin AUC 6, with granulocyte colony-stimulating factor (G-CSF) at the neutrophil nadir. Different combinations were used in order to determine the least toxic regimen. Toxicity and response were assessed according to CTC and WHO criteria, respectively. 26 patients entered the study, 13 with EOC and 13 with other gynaecological cancers (peritoneal, fallopian tube, mixed Mullerian). Median age was 49 years (range: 27-67). 8 patients received carboplatin/doxorubicin/paclitaxel, 8 cisplatin/doxorubicin/paclitaxel and 10 carboplatin/epirubicin/paclitaxel. A total of 135 cycles of chemotherapy were delivered, with a median of 6 cycles per patient (range: 2-6). 54 (40%) cycles required G-CSF support and 17 (65%) patients required at least one dose reduction. All patients experienced grade 4 neutropenia and 13 (50%) patients developed grade 3-4 thrombocytopenia (12 of whom had received carboplatin). There were 4 (15%) patients with grade 3/4 infections but no septic deaths. Non-haematological toxicities were manageable, lethargy occurred in 75% of cisplatin-treated patients. Grade 1/2 cardiotoxicity, as assessed pre- and post-treatment by left ventricular ejection fraction, was observed in 6/13 (46%) patients who had received doxorubicin and 2/7 (29%) epirubicin-treated patients. No clinically detectable cardiac toxicity was encountered. The response rate in 25 evaluable patients was 76% (12 CR, 7 PR). Dose intensity was highest in the carboplatin/epirubicin/paclitaxel combination. G-CAT shows high activity and can be administered safely, but only very fit patients are suitable for this regimen as it is associated with considerable toxicity. Carboplatin/epirubicin/paclitaxel was the best tolerated regimen overall.

Pineal and CNS germ cell tumors: Royal Marsden Hospital experience 1962-1987.

A retrospective analysis has been made of all patients with pineal and CNS germ cell tumors who were treated at The Royal Marsden Hospital between 1962-1987. A total of 67 new cases were seen: 17 had initial histological verification of tumor type and the remainder were tested for radiosensitivity with a dose of 20 Gy following a shunting procedure. Patients with germ cell or radiosensitive tumors were treated with a uniform policy of whole neuraxis radiotherapy giving 50 Gy to the local tumor and 30 Gy to the remaining brain and spinal cord. Nonresponding lesions continued with local fields to a dose of 50 Gy. Patients were divided into three groups (a) germinoma and radiosensitive tumours, 34 cases; (b) malignant teratoma, 12 cases; (c) non-germ cell, 21 cases. Median follow-up is 83 months (range 2-246 months). Overall and cause specific actuarial 5/10 year survival were for group 1, 81.7%/69.4% and 86.5%;/86.5%; group 2, 18.2%/18.2% and 18.2%/18.2%, and group 3, 64.3%/46.8% and 64.3%/52.6%, respectively. No patient in group 1 treated during the last 12 years has recurred. Univariate analysis of factors at presentation, showed that neurological performance status (p less than .001) as well as tumor type (p less than .001) correlated with outcome. Recurrence was confined to the primary site in only 1 of 4 patients in group 1 compared to 6 of 9 patients in group 2 and 9 of 10 patients in group 3. No isolated spinal recurrence occurred in group 1 patients. A total of eight patients have received platinum containing chemotherapy for recurrence (6 cases) or adjuvant therapy (4 cases). Germinomas appear to respond better than teratomas, all of which have recurred rapidly following initial partial response. Shunting and radiosensitivity testing remains the treatment of choice for tumors compatible with germinoma. Craniospinal irradiation is associated with low morbidity providing spinal growth is complete and is recommended in older patients as salvage following spinal recurrence is unsatisfactory. Aggressive combined modality approaches with surgery, radiotherapy and chemotherapy need to be investigated to improve results in CNS teratoma.

The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity.

A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts.

Prediction of local recurrence of ductal carcinoma in situ of the breast using five histological classifications: a comparative study with long follow-up.

The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening and the more widespread use of breast-conserving surgery have led to a search for histological features associated with the risk of recurrence. In a case control study of 141 patients with long follow-up, we compared the ability of five morphological classifications to predict recurrence after local excision. A significant correlation was not found between recurrence and growth pattern when a traditional classification based on architecture was used nor with necrosis when a scheme based principally on this feature was employed. A correlation was, however, found between recurrence and "differentiation" as defined by nuclear features and cell polarization in a classification recently formulated by the European Pathologists Working Group (EPWG), but this failed to reach statistical significance at the 5% level. A stronger and statistically significant correlation was found between nuclear grade as defined by the EPWG and recurrence when cell polarization was disregarded, using the classification currently employed by the UK National Health Service and European Commission-funded Breast Screening Programmes. This was attributable to a small number of recurring cases being downgraded as a consequence of exhibiting polarized cells. A significant correlation between histology and recurrence was also observed using the Van Nuys classification, which is based on nuclear grade and necrosis. Whether the tumor recurred as in situ or invasive carcinoma was unrelated to histological classification, as was the time course over which it occurred. These findings strongly support the use of nuclear grade to identify cases of DCIS at high risk of recurrence after local excision, but further work is necessary to determine whether nuclear grade or necrosis is more appropriate to subdivide the non-high-grade cases.

Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b).

A scoring system, based on the immunophenotypic analysis of a panel of five membrane markers (CD5, CD22, CD23, FMC7, SmIg) was shown to be useful in the distinction between chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative diseases (non-CLL). We investigated whether the monoclonal antibody SN8 (CD79b) could improve our previous scoring system. Peripheral blood samples of 298 patients with CLL and 166 patients with non-CLL were analyzed by flow cytometry. Using the five standard markers, the accuracy of the scoring system was 91.8%, using a cutoff of 4 points or higher, to distinguish CLL from non-CLL. This was increased to 96.6% if SN8 was added and a cutoff of 4 points or higher was also used. A similar accuracy, 96.8%, was observed if CD22 was excluded and a cutoff of 3 points or higher was used. Thus, the replacement of CD22 by SN8 in the original scoring system significantly increases its potential to discriminate between CLL and other B-cell lymphoproliferative diseases.

The leukemic presentation of mantle-cell lymphoma: disease features and prognostic factors in 58 patients.

Mantle-cell lymphoma (MCL) is a B-cell malignancy with distinct molecular genetics and pathological features. Peripheral blood involvement has been reported with variable frequency, but information on the natural history of cases presenting with leukemia is lacking. This study aimed to determine the clinical and prognostic features of such cases. We studied clinical features, tumor characteristics, prognostic factors and outcome in 58 patients with leukemic presentation of MCL. Diagnosis was based on morphology, immunophenotype, presence of t(11;14), histology and cyclin D1 expression. The median age was 62 years and male:female 2.4:1. Presenting features included splenomegaly (74%), lymphadenopathy (45%), hepatomegaly (17%) and, in a minority, gastro-intestinal involvement or involvement of Waldeyer's ring; 10% had lymphocytosis alone. Six patients developed central nervous system disease. Median lymphocyte count was 58 x 10(9)/l, 55% had anemia and 17% had thrombocytopenia. Morphology of peripheral blood showed small-cell MCL in 15% of cases, typical MCL in 46% and blastoid MCL in 39%. Immunological markers showed a typical phenotype (CD5+ CD23 -) in 68%, and atypical phenotypes, CD5- CD23- in 17% or CD5+ CD23+ in 15%. CLL scores were 0, 1 or 2 in 96%. Median overall survival was 36 months. Good response to first-line treatment (P = 0.0008) and splenomegaly (P = 0.03) were favorable prognostic factors, while other features including morphology and CD38 expression had no impact on survival or treatment response. This analysis demonstrates that except for splenomegaly, survival of MCL patients presenting with leukemia is not significantly influenced by clinical or tumor characteristics. Splenectomy is a useful treatment option in this group of patients.

Cisplatin and 5-fluorouracil for symptom control in advanced salivary adenoid cystic carcinoma.

Adenoid cystic carcinoma is a relatively rare tumour which arises in the parotid and submandibular salivary glands. Initial management is surgical, often with post-operative radiotherapy, but local relapse is common and distant metastasis not infrequent. Chemotherapy is generally reserved for cases where symptoms are not controlled by other means, since the tumour is slow growing and the response rate frequently disappointing. Cisplatin and 5-fluorouracil (5-FU) both show single agent activity in this disease but had not been previously investigated in combination. All patients referred for palliative chemotherapy of metastatic, symptomatic, histologically confirmed adenoid cystic carcinoma between November 1990 and February 1994 were considered for this study. The drugs were administered as follows: cisplatin 100 mg/m2 with appropriate pre- and post-hydration and 5-FU on a 4-day schedule of 1 g/m2/day. A total of 11 patients (7 male, 4 female) with median age 53 years (range 34-69) received 46 courses of chemotherapy (median four, range one to six). All patients had prior surgery and 8 had previously received radiotherapy. There were no objective responses of > 50% reduction in tumour size. 3 patients had a minor response and two progressed on treatment. The symptomatic response rate, however, was 64%, which compares favourably with other previously reported regimens. Toxicity was manageable. The median time to tumour progression was 9 months (range 0-38) and median survival was 12 months (range 1-65). This cisplatin/5-FU regimen would appear to produce a low rate of objective response but useful palliative benefits in advanced symptomatic adenoid cystic carcinoma. Prior series suggest that a higher objective response rate may be possible with a platinum/anthracycline/fluorouracil combination, and investigation of such a regimen is warranted.

Meta-analysis of cancer trials: a new approach to the assessment of treatment.

Meta-analysis of clinical trials offers the opportunity to pool results from a number of randomised studies so increasing the statistical ability to detect the value of treatment. More accurate estimates of the likely size of such effects can also be obtained. Subset analysis, which is seldom reliable in individual clinical trials, can be made more trustworthy. Meta-analysis of randomised trials of adjuvant therapy in early breast cancer illustrates the value of such analyses. These have helped not only routine clinical practice but also thrown light upon biological mechanisms and directed future research. Meta-analyses or overviews are playing an increasingly prominent role in cancer research. They offer the opportunity to maximise the use of information about a given treatment by combining the results from multiple randomised trials in a meaningful way. Whilst data from studies examining the same issue cannot simply be combined (due to trial heterogeneity), summation of the treatment effect across trials can be performed. It is reasonably assumed that differences between studies are differences in magnitude rather than differences in direction. The net result of such a process is to produce a result which is more accurate in its estimate of treatment benefit than its component parts.

An audit of outcome of adjuvant post-operative radiotherapy for 52 women with stage II carcinoma of the endometrium.

A retrospective review was undertaken of the medical records of 52 women with stage II carcinoma of the endometrium who received adjuvant radiotherapy following surgery. The information was obtained from medical notes and a hospital database. Actuarial disease-free survival was 68% at 5 years for those women with stage IIA disease, and 70% at 5 years for those women with stage IIB disease. 6 of the women (11.5%) had side effects from treatment. In contrast to the literature, the only statistically significant prognostic factor in this study was histological differentiation; patients with poorly differentiated tumours fared worse (p = 0.05). This may indicate that a greater number than 52 women is needed to demonstrate weaker prognostic factors such as substage. A larger review is being undertaken of the remaining women recorded on the database, with stage I, III and IV disease.

The role of diagnostic CT scanning of the brachial plexus and axilla in the follow-up of patients with breast cancer.

In order to assess the value of computed tomographic scanning of the axilla and brachial plexus in the management of patients with arm symptoms following treatment for breast cancer, the case notes and diagnostic films of 102 such patients who underwent scanning between 1985 and 1990 at this institution were analysed retrospectively. The clinical indications for requesting computed tomography (CT) of the brachial plexus and axilla included arm oedema (52 patients, 51%), brachial plexus neuropathy (73 patients, 72%), and/or the presence of a palpable axillary mass (18 patients, 18%). Of 102 CT scans, 80 showed either no abnormality (31 patients, 30%), or axillary fibrosis (49 patients, 48%), and 22 (21%) showed radiological evidence of recurrent tumour. Only 4 of 84 patients with no palpable mass had computed tomographic evidence of occult recurrent tumour; all of these had concurrent evidence of distant metastatic disease (lung, liver, bone). Patients have been followed up for from between 1 and 15 years from diagnosis (median 5.5 years). The extremely low yield of tumour recurrence on computed tomographic scanning in the absence of a palpable axillary mass (4/84 patients, 5%; 95% CI 1-12), cannot justify CT as a method of screening for clinically occult axillary relapse in patients with arm symptoms following axillary surgery and radiotherapy for breast cancer. Computed tomographic scanning in these patients should only be employed to confirm the clinical suspicion of tumour as a baseline prior to further treatment.