Reading the prognosis of the individual with breast cancer.

AIM: To obtain better survival estimates for the individual than is provided by placement in an NPI group. METHOD: Consecutive primary operable breast cancers treated at Nottingham City Hospital 1990-1999. Ten year % actuarial survivals plotted for 10 ranges of NPI from 2.0 to 6.9. There is an excellent inverse correlation between median NPI value for each range and survival at 10 years. To enable estimation of survival for all individual values of NPI, a curve fitting technique applied to these results (by G.B.) gave the formula to estimate survival from the individual's NPI score: 10 year % survival for the individual=-3.0079 x NPI(2)+12.30 x NPI+83.84. This gave an r(2) of 0.98. RESULTS AND CONCLUSION: Greater accuracy in individual survival prediction is obtained by dividing women into 10 groups by NPI scores than in the originally described six groups; rank order of survival in relation to NPI score is preserved. A curve fitting technique has been applied to these data to give a formula for the prediction of 10 year survival for every 0.1 value of NPI.

Survival of invasive breast cancer according to the Nottingham Prognostic Index in cases diagnosed in 1990-1999.

UNLABELLED: The Nottingham Prognostic Index (NPI) is a well established and widely used method of predicting survival of operable primary breast cancer. AIMS: Primary: To present the updated survival figures for each NPI Group. Secondary: From the observations to suggest reasons for the reported fall in mortality from breast cancer. METHODS: The NPI is compiled from grade, size and lymph node status of the primary tumour. Consecutive cases diagnosed and treated at Nottingham City Hospital in 1980-1986 (n=892) and 1990-1999 (n=2,238) are compared. Changes in protocols towards earlier diagnosis and better case management were made in the late 1980s between the two data sets. RESULTS: Case survival (Breast Cancer Specific) at 10 years has improved overall from 55% to 77%. Within all Prognostic groups there are high relative and absolute risk reductions. The distribution of cases to Prognostic groups shows only a small increase in the numbers in better groups. CONCLUSION: The updated survival figures overall and for each Prognostic group for the NPI are presented.

Estrogen receptor assay in primary breast cancer and early recurrence of the disease.

Estrogen receptor assays of primary breast tumors have been related to early recurrence of the disease. A significantly longer disease-free interval was found in women whose primary tumor was estrogen receptor positive. Although there was no relationship of receptor content to stage of disease at mastectomy, the greatest difference between recurrence rates was found when the tumor had spread to the lymph nodes, especially to those in the apex of the axilla or in the internal mammary chain. Presence of estrogen receptor is closely related to histologically well-differentiated tumors, but it was found that poorly differentiated estrogen receptor-negative tumors recurred earlier than poorly differentiated receptor-positive tumors and had a very unfavorable prognosis.

LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial.

PURPOSE: The purpose of this randomized trial was to compare the efficacy of eight cycles of chlorambucil, vincristine, procarbazine, and prednisone (LOPP) with four cycles of LOPP that alternate with four cycles of etoposide, vinblastine, Adriamycin (doxorubicin; Familitalia Carlo Erba, Ltd, UK), and prednisone (EVAP) in patients with advanced Hodgkin's disease. PATIENTS AND METHODS: Between June 1983 and December 1989, 594 patients were entered onto the study. Of the 594, 295 patients were allocated to receive LOPP, and 299 were allocated to receive LOPP/EVAP. RESULTS: The complete remission (CR) rates were 57% and 64%, respectively, after initial chemotherapy (difference not significant [NS]), and 65% and 75%, respectively, after the subsequent administration of radiotherapy to residual masses (P less than .01). The procedure associated mortality in the LOPP and LOPP/EVAP arms was 1% and 3%, respectively. The actuarial CR relapse-free survival was significantly greater in the LOPP/EVAP arm (P less than .001) as was the overall survival (P less than .05). The CR relapse-free rate, disease-free survival (DFS) rate, and overall survival rate at 5 years were 52%, 32%, and 66%, respectively, in the LOPP arm, compared with 72%, 47%, and 75% in the LOPP/EVAP arm, respectively. CONCLUSION: These results indicate that LOPP and EVAP is superior to LOPP alone as initial treatment for advanced Hodgkin's disease.

Cardiac doses in post-operative breast irradiation.

Data were collected on radiation doses given to the heart and coronary arteries during primary breast irradiation in order to analyze factors which might be important in the aetiology of subsequent cardiac-related disease. Twenty eight patients with breast cancer were studied. Fourteen patients treated from 1957 to 1984 were studied retrospectively (group 1), and 14 treated from 1988 to 1989 were studied prospectively (group 2). All patients had stage I or II disease at presentation, and were under 70 years of age. None had chemotherapy as a primary form of treatment. Patients were given a computed tomography scan of the chest, and three-dimensional reconstruction was made of the heart, lung and body contour. Original dose distributions were super-imposed on these outlines, and doses to the total cardiac volume and three main coronary arteries were estimated using an alpha/beta ratio of 4 Gy. Nine out of 14 patients in group 1 had a mastectomy followed mainly by orthovoltage radiation with similar techniques used up until 1984. Thirteen out of 14 patients in group 2 had conservative surgery followed by a modern two- or four-field megavoltage technique. We found that for patients with left-sided tumours (n = 20), the heart volume irradiated to a minimum extrapolated target dose of 5 Gy is significantly decreased for patients treated with a modern technique (group 2) when compared with those treated with earlier techniques (group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen receptors and breast cancer.

Estrogen receptors have been assayed in a series of primary breast cancers from postmenopausal women; 59% of which were estrogen-receptor positive. These patients survived for a significantly longer period of time than those whose tumors were estrogen-receptor negative. The effect of estrogen-receptor status was only seen (and then markedly accentuated) in patients who had lymph-node invasion at the time of mastectomy. Such determinations also appear to be of value in preselecting those patients who, on recurrence, will benefit from tamoxifen therapy.

The use of the Gompertz function to relate changes in life expectancy to the standardized mortality ratio.

BACKGROUND: Change in life expectancy may be more readily appreciated by a lay person as a measure of risk than the standardized mortality ratio (SMR). METHODS: The linear increase in the logarithm of the age-specific mortality rates with age (the Gompertz function) is used to deduce formulae connecting SMR with change in life expectancy. Their validity is checked by a comparison between the 1992 and 1952 mortality data for England and Wales, and between smokers and non-smokers in the American Cancer Society's second Cancer Prevention Study. RESULTS: It is shown that the Gompertz function is a good fit to mortality data for England and Wales from age 30 years upwards. Changes in life expectancy at ages 15, 25, 45 and 65 are presented for values of SMR from 0.5 to 3. A very simple formula connecting the two is valid at ages 15 and 25, and provides a reasonable approximation at age 45. CONCLUSIONS: The Gompertz relationship can be used to calculate the change in life expectancy corresponding to a particular SMR over a greater range than have previous methods, and, although subject to some uncertainties, can provide a quick method of judging the change in life expectancy that is associated with a given SMR value.

Should years lost always be equated with life expectancy?

BACKGROUND: The 'years lost' by a person dying prematurely from some cause is usually equated with life expectancy at the age of death derived from a life table for either the general population or a population in which the cause does not operate. It is suggested that this procedure may not always be valid. METHODS: The calculation of years lost by individuals dying prematurely from smoking-related deaths is taken as an example using data from the American Cancer Society Cancer Prevention Study (ACS CPS II) and from Peto et al. An alternative hypothesis, whereby smoking advances the age of death by an amount considerably less than the life expectancy, is examined. RESULTS: It is shown that when smoking-related deaths are removed from the ACS CPS II data, the life expectancy of the smokers is still less than that of the non-smokers. Secondly, it is demonstrated that, if the alternative hypothesis is used to predict a survival curve in the absence of smoking, it would be incorrect to equate years lost with life expectancy calculated from that curve. CONCLUSIONS: Years lost cannot automatically be equated with life expectancy. In the case of smoking, estimates of years lost must still be subject to considerable uncertainty. Further research is needed to see if smokers dying at a given age have comparable physical and social characteristics to all smokers living at that age.

The predictive value of tumor classification compared with results of the British Institute of Radiology fractionation trial in the treatment of laryngopharyngeal carcinoma.

Data from a clinical trial involving 734 patients have shown the value and the deficiencies of the current Union Internationale Contre le Cancer's tumor, node, and metastasis classification system for prognostic purposes. The tumor-category classification provides a good discriminant for both nodal involvement and survival; however, the previous node classification system only discriminated between node-negative and node-positive patients, as nodal fixity was not found to be a discriminator. The current anatomical site classification is ambiguous for some laryngeal and pharyngeal subsites, and modifications to the present system based on prognostic values are proposed. A difference in patient age between tumor categories has been shown, and various differences in incidence and survival data for the sexes have been demonstrated. Differences in observed and expected survival rates are related to continued late deaths from tumor. Multivariate analyses have shown that stage grouping is the most powerful prognostic discriminator, followed by anatomical site and age.

A widely applicable method for computing dose distributions from external megavoltage beams.

A method of computing megavoltage dose distributions using an empirical mathematical model is described. The dose at a point in a medium is calculated as the product of a central axis percentage depth dose, a crossplot factor and a wedge factor. For a given set of conditions (i.e. type of machine, source-skin distance and wedge) 16 parameters are required to calculate the values of the three factors and hence the dose at any point. These parameters can be obtained from a relatively small number of experimental measurements. Dose distributions from a variety of different treatment machines have been computed by the method, and some comparisons of the calculated and measured doses have been made using "Goodness of Fit" score values. These show that the use of the method as a basis for computer treatment planning should be clinically acceptable.

A simple after-loading technique for the treatment of cancer of the cervix.

A simple manual after-loading system for the treatment of carcinoma of the cervix has been developed. Radiochemical Centre J-type caesium sources are used made up in PVC tubes which can be inserted into PVC uterine tubes or rubber ovoids after these have been packed in position in the patient. Radiation exposure to theatre staff has been reduced by a factor of about four.

The Cancer Research Campaign (King's/Cambridge) trial for early breast cancer: an analysis of the radiotherapy data.

A detailed study has been made of the patients receiving routine post-operative radiotherapy in the Cancer Research Campaign trial for early breast cancer. Particular attention has been paid to the routine dose delivered and the incidence of recurrence in different areas. Little difference was apparent in the incidence of local recurrence in groups of patients receiving different levels of dosage, although there was a threefold reduction in five-year local recurrence-free rates compared with that for patients who received no irradiation. Moderate or severe telangiectasis occurred more frequently as the dose increased. When analysed in terms of survival, there was a tendency for the patients receiving more than 1510 ret to do a little better, but this was not statistically significant and could be due to some unexplained patient selection or higher dosage. There was no suggestion that irradiation might cause reduced survival.

An on-line computer graphics terminal for radiotherapy treatment planning.

A programmed graphics terminal has been connected on-line to a large time-shared computer for calculating dose distributions in radiotherapy treatment planning and provides a viable alternative to dedicated systems and batch working. The terminal equipment is based on a mini-computer and includes a function-key devise for outline input, a large-screen refresh oscilloscope for viewing results and an X-Y plotter for hard-copy. Radiotherapy dose computation programs in standard Fortran are stored and run on a large remote computer with graphical interaction at the terminal. External beam programs can calculate dose distributions for most commonly used treatment situations and can compute in off-axis planes. Data input is fully interactive and easy to understnad. Dose distributions are displayed as isodose contours. Advantages of the system include accuracy, speed, ease of use and maintenance, and transferability of the programs between different host computers.

A computer-based radiotherapy clinical record system using mark-sense forms.

A computer-based system for radiotherapy clinical records is described. Its main features are the use of a single mark-sense form for input of data at all stages of the patient's progress, and the provision of a plain language print-out of the patient's record after each updating. The programs are written in Fortran and are implemented on a Rank Xerox Sigma 6 computer.

Normal tissue reactions in the British Institute of Radiology Study of 3 fractions per week versus 5 fractions per week in the treatment of carcinoma of the laryngo-pharynx by radiotherapy.

The radiobiological data obtained from a multicentre clinical trial of the British Institute of Radiology, which compared the treatment of carcinoma of the laryngo-pharynx by 3 fractions per week (3F/wk) with 5 fractions per week (5F/wk) radiotherapy, have been studied. The trial involved an intake of 734 patients between 1966 and 1975. The number of fractions, overall treatment time and total doses used by different treatment centres ranges from 9 to 40 fractions, 18 to 70 days and 3880 to 7800 cGy, respectively. An 11-13% reduction in the total radiation dose was applied for treatments with 3F/wk as compared with 5F/wk in centres treating over 6 weeks and 3 weeks, respectively. All patients were followed for 10 years from the start of treatment. Different types of early and late normal-tissue reactions were investigated, ranging from a low percentage incidence of perichondritis to 95% for slight early reactions. Greater than 80% of the late normal-tissue reactions seen were observed within the first year after the start of treatment, and 96% were observed within the first 5 years. There was no statistically significant difference in the normal-tissue event-free rates between the 3F/wk and 5F/wk treatment groups. This finding did not differ when different major treatment centres were studied separately. For a number of end-points, alpha/beta ratios and N- and T-exponents of a modified nominal standard dose (NSD) formula have been calculated.

Final report of the general clinical results of the British Institute of Radiology fractionation study of 3F/wk versus 5F/wk in radiotherapy of carcinoma of the laryngo-pharynx.

The 10 year follow-up of a clinical trial involving the comparison of 3F/wk versus 5F/wk in radiotherapy of squamous cell carcinoma of the larynx and hypopharynx has now been completed. The trial involved an intake of 734 patients between 1966 and 1975. The classification of all patients has been revised to conform with the latest TNM publication. A reduction in total dose was made for 3F/wk compared with 5F/wk. This varied between 13% and 11% in centres treating over 3 weeks and 6 weeks, respectively. No statistically significant differences have been found between the two arms (3F/wk versus 5F/wk) of the trial in any of the main group analyses. A number of sub-group analyses relating to survival, tumour-free and laryngectomy-free rates and to the comparison of acute or late normal-tissue radiation damage have also been performed. No differences have been found that could be considered to be statistically significant in relation to the particular sub-group. Previous interim reports suggested minor differences in sub-group analyses between the 3F/wk and 5F/wk regimes in this trial; these have diminished now that the full follow-up data are available. This trial has provided evidence on which clinicians may base their choice between either a 3F/wk fractionation regime or a conventional 5F/wk treatment protocol in the treatment of carcinoma of the laryngo-pharynx.

Final report on the second British Institute of Radiology fractionation study: short versus long overall treatment times for radiotherapy of carcinoma of the laryngo-pharynx.

The second British Institute of Radiology trial of dose fractionation in radiotherapy compared two groups of prospectively randomized patients with squamous carcinoma of the laryngo-pharynx; one group was treated in a short (less than or equal to 4 weeks) and the other in a long (greater than 4 weeks) overall time. Treatment in any one centre could be given, with no planned gap in the course of treatment, either as a conventional, daily (5 fractions per week regime) or as 3 fractions per week. A total of 611 patients were allocated to treatment, of whom nine have had to be excluded from the analysis for a lack of information. Patients were admitted to the trial from January 1976 to December 1985 and were followed up for a maximum of 10 years and a minimum of 3 years. A reduction in total dose was made for use in the short compared with the long treatment regime. This reduction in total dose varied between 18% and 22% depending on whether 5 fractions or 3 fractions per week regimes were used. Overall, no statistically significant differences have been found between the two arms of the trial. The patients treated with 5 fractions per week in a short overall treatment time showed fewer late normal tissue effects. An analysis based on stratification by age, stage and anatomical site gave a relative risk (short/long overall treatment time) for deaths of 1.23 with a 95% confidence interval from 0.96 to 1.59. Analyses stratified for stage and site gave relative risks with 95% confidence intervals of 1 x 10 (0.84-1.44) for local recurrences/tumour persistence, and 1.01 (0.70-1.45) for laryngectomies.

First interim progress report on the second British Institute of Radiology Fractionation Study: short versus long overall treatment times for radiotherapy of carcinoma of the laryngopharynx.

Preliminary data from a second British Institute of Radiology Fractionation Trial comparing short (less than or equal to 4 weeks) and long (greater than 4 weeks) overall treatment times are reported. The intake of patients ran from January, 1975 to December, 1985 when 611 patients with carcinoma of the laryngo-pharynx were registered in this prospective, randomized, multicentre clinical trial. No significant differences have, so far, been demonstrated between the two arms of the trial with respect to observed survival rates, tumour-free or laryngectomy-free rates. Further long-term follow-up is continuing.

Sixth interim progress report of the British Institute of Radiology fractionation study of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx.

The results are reported of the multicentre BIR fractionation trial of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx. 687 patient records have been analysed with respect to survival rates, recurrence-free rates and laryngectomy-free rates. For the group as a whole these analyses show no difference between the two fractionation regimes. Analysis of the sub-group which had early disease confined to the vocal cords does, however, show a better recurrence-free and laryngectomy-free rate for those patients treated with 5F/week, though the survival rate for the two groups remains similar. Acute and late normal tissue reactions are reported for up to six years after treatment. It appears that treatment with 3F/week can be given safely to patients with advanced disease. The differences between the two treatment groups who had early disease of the vocal cords are discussed, but until more data become available in the future the problems raised cannot be resolved.

Seventh interim progress report of the british institute of radiology fractionation study of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx.

A fresh analysis of the data entered into the multicentre BIR fractionation trial of 3F/week versus 5F/week in radiotherapy of the laryngopharynx has been undertaken. Completed records of the 732 patients initially entered into the trial have now risen from 687 at the last report to 706. The data have been analysed in a manner similar to that adopted previously so as to measure the effects of the two regimes on both tumour and normal tissues, and some additional analyses have now also been made. There have been some modifications in the results in the various sub-groups which may be due to an inadequate number of patients having been followed up for long enough at the time of the previous analyses. More data for late radiation damage to normal tissues and new radiobiological findings have suggested possible explanations for the differences which have emerged between the two groups. The apparent differences between the sub-groups containing patients with highly localized tumours, which were reported in our previous report, are now less marked and not statistically significant.