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Purpose To investigate conventional prognostic factors for ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), and survival after breast-conserving therapy (BCT) in screen-detected and symptomatic cases on surveillance up to 25 years. Patients and Methods A total of 1812 consecutive patients in three cohorts (1981–1989, 1990–1992, and 1993–1998) with T12N01M0 invasive breast cancer were treated with BCT (median follow-up, 14 years). Tumor type and grade were reviewed by a single pathologist. Hormone receptor status was measured by immunohistochemistry on tissue microarrays. A Cox proportional hazards model was used to assess independent prognostic variables for relapse and survival. Results A total of 205 IBTR occurred, with 5-, 10-, 15-, and 20-year actuarial relapse rates of 4.5% (95% confidence interval [CI] 3.35–5.5%), 8.4% (95% CI 7.1–9.8%), 14.1% (95% CI 12.0–16%), and 17.4% (95% CI 14.5–20.2%). Number of nodes, young age, pathologic tumor size, and multifocality were significant factors for IBTR. Three hundred seventy-eight patients developed DM. The actuarial metastatic rate was 12% at 5 years and 17.9% at 10 years. Young age, number of positive nodes, pathologic tumor size, and tumor grade were significant factors for DM relapse. When conventional prognostic indices were taken into account screen-detected cancers showed no improvement in overall relapse or survival rate compared with symptomatic cases but did show a reduced risk of DM after IBTR. After 10 years IBTR relapse continued at a constant rate of 0.87% per annum. Conclusions The Edinburgh BCT series has shown that screen-detected invasive breast cancers do not have significantly different clinical outcomes compared with symptomatic cases when pathologic risk factors are taken into account. This suggests that these patients be managed in a similar way.

We present a review of 111 patients who were treated over an initial 3-year period with erlotinib. The median treatment time was 68 days and 59% of patients had stopped treatment within the first 3 months. However, 20 patients were on erlotinib for more than 12 months. Performance status and smoking history were the significant prognostic factors. The overall 3-year survival in patients who had never smoked was 26%.

Purpose: Neoadjuvant androgen deprivation and radical radiotherapy is an established treatment for localized prostate carcinoma. This study sought to analyze the outcomes of patients treated with relatively low-dose hypofractionated radiotherapy. Methods and Materials: Three hundred patients with T1–T3 prostate cancer were treated between 1996 and 2001. Patients were prescribed 3 months of neoadjuvant androgen deprivation before receiving 5250 cGy in 20 fractions. Patients’ case notes and the oncology database were used to retrospectively assess outcomes. Median follow-up was 58 months. Results: Patients presented with prostate cancer with poorer prognostic indicators than that reported in other series. At 5 years, the actuarial cause-specific survival rate was 83.2% and the prostate-specific antigen (PSA) relapse rate was 57.3%. Metastatic disease had developed in 23.4% of patients. PSA relapse continued to occur 5 years from treatment in all prognostic groups. Independent prognostic factors for relapse included treatment near the start of the study period, neoadjuvant oral anti-androgen monotherapy rather than neoadjuvant luteinizing hormone releasing hormone therapy, and diagnosis through transurethral resection of the prostate rather than transrectal ultrasound. Conclusion: This is the largest reported series of patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy in the United Kingdom. Neoadjuvant hormonal therapy did not appear to adequately compensate for the relatively low effective radiation dose used.

Aims The aim of this retrospective analysis was to review the outcome of patients with germ-cell tumours treated in the Edinburgh Cancer Centre over the past 15 years, and to see whether there had been any changes over three 5-year cohorts. Materials and methods Patients referred with gonadal and extra-gonadal primary germ-cell tumours, between 1988 and 2002, were identified from the departmental database, and survival by stage and prognostic group was analysed. Results and conclusions The proportion of patients with stage I seminoma has significantly increased. The good prognosis of patients with early stage disease is confirmed, with the outcome for some groups of patients being better than expected. There is a non-significant trend to improved results over the three 5-year cohorts. The outcome for patients with stage IV seminoma is worse than would be expected, but numbers are small. The poor prognosis of patients with non-seminomatous germ-cell tumours who fall into the International Germ Cell Consensus Classification (IGCCC) poor-prognostic group is confirmed. Failure of patients with metastatic non-seminomatous germ-cell tumours to achieve a complete response to initial therapy is shown to be a poor prognostic indicator.

Aims Sex cord–stromal tumours of the testis are uncommon tumours, accounting for around 5% of testicular neoplasms. Treatment is primarily surgical, with no adjuvant therapy of proven benefit. We present a single-centre experience over a period of 15 years. Materials and methods From 1988 to 2002, 18 patients with a diagnosis of sex cord–stromal tumour were referred to our centre. A retrospective analysis of their case notes was made and a pathological review undertaken. Results Sixteen were Leydig-cell tumours and two were Sertoli cell. For the Leydig-cell tumours, the median age at presentation was 42 years, 50% presented with a testicular mass and 31% with gynaecomastia. Two patients followed a malignant course: one revealing disease dissemination at initial staging, and a second 12 months after potentially curative orchidectomy. Salvage retroperitoneal lymphadenectomy in the latter patient proved unsuccessful. Clinical outcome correlated strongly with the presence of adverse pathological features described previously in the literature. After a median follow-up of 46 months, two patients have developed progressive disease, and two patients have died, one of metastatic Leydig-cell tumour. No patient defined as being of low malignant potential on pathological examination has relapsed outside our review period of 2 years. Conclusion We confirm the overall excellent prognosis for most of the patients with sex cord–stromal tumours of the testis. Compared with most previous reports, pathological features seem to predict with reasonable accuracy the risk of malignant behaviour, and can adequately inform the subsequent review policy.

To determine whether palliation of chest symptoms from a 10 Gy single fraction (regimen 1) was equivalent to that from 30 Gy in 10 fractions (regimen 2).Patients with cytologically proven, symptomatic lung cancer not amenable to curative therapy, with performance status 0-3, were randomised to receive either 30 Gy in 10 fractions or a 10 Gy single fraction. Local symptoms were scored on a physician-assessed, five-point categorical scale and summed to produce a total symptom score (TSS). This, performance status, Hospital Anxiety and Depression (HAD) score and Spitzer's quality-of-life index were noted before treatment, at 1 month after treatment and every 2 months thereafter. Palliation was defined as an improvement of one point or more in the categorical scale. Equivalence was defined as less than 20% difference in the number achieving an improvement in the TSS.We randomised 149 patients and analysed 74 in each arm. According to the design criteria, palliation was equivalent between the two arms. TSS improved in 49 patients (77%) on regimen 1, and in 57 (92%) patients on regimen 2, a difference of 15% (95% confidence interval [CI] 3-28) in the proportion improving between the two regimens. A complete resolution of all symptoms was achieved in three (5%) on regimen 1, and in 14 (23%) patients on regimen 2 (P0.001), a difference in the proportion between the two regimens of 21% (95% CI 10-33). A significantly higher proportion of patients experienced palliation and complete resolution of chest pain and dyspnoea with regimen 2. No differences were observed in toxicity. The median survival was 22.7 weeks for regimen 1 and 28.3 weeks for regimen 2 (P = 0.197).Although this trial met the pre-determined criteria for equivalence between the two palliative regimens, significantly more patients achieved complete resolution of symptoms and palliation of chest pain and dyspnoea with the fractionated regimen.

ABSTRACT: The objective of this study was to review the results of our policy of primary radiotherapy (RT) and salvage cystectomy for transitional carcinoma (TCC) of the bladder in the light of changes in our radiotherapy planning procedure, in particular the introduction of CT planning. The case notes of 163 patients treated with radical radiotherapy using a CT planning technique were examined. The main endpoint for assessment was response at the time of the check cystoscopy 6 months after the completion of treatment. In addition survival was estimated by stage of disease and by response at the time of first cystoscopy. Patterns of relapse and time to relapse were analysed. All percentages quoted in the text use the initial 163 patients as the denominator. One hundred patients (61%) achieved a complete response. The complete response rate was significantly related to T stage at presentation being 90% for TI, 75% for T2, and 53% for T3 disease respectively. Of these patients 78 remain disease free in the bladder (47%). Twenty-two have relapsed in the bladder, of whom 5 have also relapsed at metastatic sites. Fifteen patients have relapsed outside the bladder whilst remaining disease free within the bladder. At the time of last follow up or death from other causes 63 of the 100 patients who had a complete response remained disease free with an intact bladder. There were 18 (11%) partial responders. Seven of these patients went on to have a cystectomy. Ten remain alive, 7 disease free, 4 with intact bladders. In 24 patients (15%) there was no response and these patients have all died, the median survival being 10 months. In 21 patients (13%) a postradiotherapy cystoscopy was not performed. In all but one patient, who was lost to follow up, this was because of progressive disease. The median survival of these 20 patients was 6 months. Of the 163 patients 35% are alive and well with an intact bladder. If patients dying from other causes are included then 42% were rendered disease free. Cause specific survival was significantly related to stage of disease at presentation with 5 year actuarial survival being 87%, 48% and 26%, for T1, T2 and T3 disease respectively. Survival was also related to response to treatment at 6 months with 5 year survival being 64%, and 52% for complete and partial responders respectively. Survival was extremely poor for non-responders with only 37.5% surviving 1 year and none 5 years. There was a highly significant relationship between response and the development of, and the time to developing metastatic disease. Of those who exhibited a response 21% developed metastatic disease compared to 78% of non-responders. Salvage cystectomy offers the possibility of cure in those who achieve a complete or partial response with 42% of such patients being rendered disease free. Results however are poor in those who did not respond with all patients dying of their disease. Response rates for all stages, and survival for stages T1 and T2 are much improved from those previously reported from this centre and compare favourably with other published series. These results confirm the place of radiotherapy and salvage cystectomy in the management of TCC of the bladder in selected patients. In about one-third of patients the desired outcome of curing the patient of their cancer with organ preservation is achieved. The prognostic significance of cystoscopic response at 6 months and stage at presentation is confirmed. The outcome for patients with early stage disease is excellent. The relationship between response and the development of metastatic disease would suggest that even if these patients had had a primary cystectomy they may have fared badly, a conclusion supported by the fact that these results are comparable with surgical series. This series supports the role of radiotherapy in the management of this disease and suggests that modern RT techniques including CT planning have had a beneficial effect on the results of radical radiotherapy.

The aim of palliative thoracic radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) is to alleviate symptoms. This study was designed to determine whether any patients achieved long-term survival after this treatment. In Edinburgh, between 1974 and 1993, 4531 patients were treated with palliative radiotherapy for NSCLC, receiving ten fractions or fewer. We reviewed the case notes of the long-term survivors. Sixty-one (1.3%; 95% confidence interval (CI) 1.0-1.6) patients survived for more than 5 years; 43 (70%) had histological confirmation of cancer; 28 (46%) had stage Stage I or II, 28 (46%) Stage III and one Stage IV disease; 53 (87%) patients were treated with doses of 30-35 Gy in ten daily fractions, seven (12%) received 20 Gy in five daily fractions and one received a 10 Gy single fraction. Forty-two (69%) patients had a radiological complete response, 16 (26%) a partial response and the remainder stable disease. Clinically significant radiation pneumonitis occurred in one (2%) patient, radiation myelopathy in two (3%) and multiple rib fractures in one (2%). There did not appear to be an association between long-term survival and a radiosensitive phenotype. On univariate analysis, long-term survival was more frequent in patients receiving ten-fraction regimens than in those who underwent a shorter course of radiotherapy (chi 2 = 19.5, P < 0.001). Thirty-four (0.8%; 95% CI 0.6-1.0) patients were disease free at death or at last review (median 10 years; range 5-17). We conclude that palliative thoracic radiotherapy produces long-term survival in 1.3% and personal cure in up to 1% of patients with advanced NSCLC.

Background : The optimum dose and fractionation schedule for the palliative irradiation of painful bone metastases is controversial. Purpose : To compare the efficacy, side-effects and effect on quality of life of two commonly used radiotherapy schedules in the management of painful bone metastases. Materials and methods : In a prospective trial, 280 patients were randomised to receive either a single 10 Gy treatment or a course of 22.5 Gy in five daily fractions for the relief of localised metastatic bone pain. Results : Response rates have been calculated from 240 assessable treated sites of pain. The overall response rates were 83.7% (single treatment) and 89.2% (five fractions). The complete response rates were 38.8% (single treatment) and 42.3% (five fractions). The median duration of pain control was 13.5 weeks (single treatment) and 14.0 weeks (five fractions). None of these differences was statistically significant. There were no differences between the groups in the effect of treatment on a variety of quality of life parameters. Conclusions : It is concluded that a single 10 Gy treatment is as effective as a course of 22.5 Gy in five fractions in the management of painful bone metastases.

Four staging systems for breast cancer have been introduced in turn and have been in general use in the United Kingdom since 1948. Each of these systems has been applied to a cohort of nearly 4000 patients treated in the Radiotherapy Department in Edinburgh between 1954 and 1964 to determine the effect of such changes on prognosis and, presumably, also on management for the various stage groupings. The changes in staging systems over the years have highlighted the importance of some factors, e.g. tumour size and extent of nodal involvement. However, the overall effect on survival of these changes is minimal and the value of frequent changes in staging systems at less than 10-year intervals is questionable. Even the most recent changes in the UICC staging system make assumptions which are not validated by this review.

An anonymous questionnaire study was designed to assess sexual function after orchidectomy and radiotherapy for testicular cancer. Questionnaires were sent to: (1) 237 patients treated with orchidectomy and abdominal radiotherapy in Edinburgh from 1974 to 1988; (2) 32 patients under “surveillance” following orchidectomy alone; (3) 402 “normal” age-matched controls. All were asked questions concerning sexual function over the preceding 6 months. All the patients were also asked the same questions with reference to the first 6 months after completion of treatment. Completed questionnaires were returned from 137 (62%) radiotherapy patients, 18 (56%) surveillance patients and 121 (35%) controls. There was a significant difference between the radiotherapy patients and the controls in almost all the parameters looked at including erection, ejaculation and libido with the treated group performing less well. In addition, almost 24% of the radiotherapy patients felt disabled or disfigured by the treatment, most commonly because of the presence of only one testicle. A deterioration in sexual function was observed with increasing age. In the radiotherapy group of patients there was no difference in response between the two time periods or in any of the treatment variables. The clinical significance of these observations are unclear but together with the increasing information on other toxicities emerging following this therapy the role of radiation for early stage seminoma is being brought into question. This study also confirms the morbidity of orchidectomy. We suggest that testicular implants should be offered more widely.

Fifty-four consecutive patients underwent 61 orthopaedic operations for metastatic bone disease affecting the upper and lower limbs. These patients were subsequently managed using a consistent postoperative radiotherapy (RT) policy. There were 27 prophylactic internal fixations and 34 internal fixations of pathological fractures. There was a marked difference in survival between these groups. The median postoperative survival of the prophylactic (P) group was 15 months whereas that of the fracture (F) group was 2 months (P less than 0.0001). Ninety-three per cent of the P group and 59% of the F group were able to be discharged home following treatment. Subsequent local fracture requiring further surgical intervention occurred in 11% of the P group and in none of the F group. Seventy-eight per cent of the P group and 62% of the F group did not suffer any further sequelae at the operation site until the time of death or last follow-up. Patient mobility following surgery and RT for metastatic lesions occurring in the lower limb was significantly improved in both the P group (P less than 0.05) and in the F group (P less than 0.0001) such that 91% and 58%, respectively, of these patients were subsequently able to walk.

A retrospective analysis of malignant melanoma of the upper aerodigestive tract treated in Scotland between 1976 and 1988 has been performed to define the incidence clinical features and response to treatment. Using the Scottish Melanoma Group database and pathology and oncology department registers 32 patients, 20 female, 12 male, were identified, representing a population incidence of approximately 0.5 per million per year. The median age was 69 years, range 38–86. Tumour arose in the nose or sinuses in 23 cases and the oral cavity or pharynx in eight cases. Metastases were present at presentation in four cases. Radical treatment was attempted in 27 patients: radiotherapy alone in 13, surgery alone in 10 and combined modality treatment in four. Complete regression, which was sustained in five cases occurred in eight of the 13 radically irradiated patients; whereas sustained local control was achieved by radical surgery in only four of ten patients. The median survival is 14 months, none lived more than 63 months. Only one patient is alive and disease free, three more survive with disease. Of the 28 who have died, nine had local tumour only, nine metastases only and ten both local and distant disease. Outcome was not affected by age, sex, primary site or nodal spread.

Prior to 1982 the standard radiation tissue absorbed dose administered to the chest wall following mastectomy was 40.0-42.5 Gy in 10 alternate day fractions over 4 weeks. From 1982 the standard maximum dose was 45.0 Gy administered in 20 daily fractions over 4 weeks. On review of the records of the 770 patients treated between 1979 and 1984, 19 (2.5%) had symptoms of acute radiation pneumonitis, 7/484 (1.4%) treated by the earlier technique and 12/286 (4.2%) by the later technique (X2 = 4.56, P less than 0.05). The mean 4 cm depth doses on the chest wall were 33.98 Gy and 36.84 Gy respectively in the earlier and later populations (t = 5.06, P less than 0.001) and 33.62 Gy and 38.30 Gy in those developing acute pneumonitis. Comparison of these two schedules gives an alpha/beta ratio of 8.5 Gy. It is suggested that the sparing of symptomatic acute reactions in human lung by smaller doses per fraction may be less than currently believed.

A series of 88 cases of male breast cancer was compared with 241 cases of female breast cancer randomly selected from Departmental records. Cases of male breast cancer differed significantly from control female cases with regard to stage of the disease, age of onset and liability to the development of a second carcinoma. In 11 of the 88 cases (12.5%) of male breast cancer another primary malignant tumour developed. In seven instances the large bowel or rectum was the site of the other carcinoma. When correction was made for age and for the stage of the disease the prognosis of breast cancer in men and women was found to be similar. Only minor histological differences were found between male and female cases. Two of 54 cases examined for X-chromatin proved to be Barr-positive.

The results of treatment of 838 patients who were irradiated for germ cell tumours of the testis between 1950 and 1969 are presented. The overall 10-year survival rate was 61.8%. For seminomas alone it was 75.3% and for teratomas 37.7%. No increase in survival was found which could be attributed to the introduction of megavoltage beams.

Sixty-four patients (37 stage I and 27 stage II) with low grade non-Hodgkin's lymphoma were treated by surgical excision alone (two patients) or with radiotherapy (53 patients), chemotherapy (five patients) or both (four patients). Actuarial survival was 80.7% at 5 years and 77.9% at 10 years. Actuarial recurrence-free survival at 10 years was 49.4% for stage I and 38.0% for stage II patients. Local control was achieved in 52 out of 56 (93%) patients treated with a radiation dose of 30 Gy or greater. There was no advantage for extended compared with involved, field irradiation. A multivariate analysis identified age, sex, stage and disease site as independent prognostic variables for survival.

A retrospective analysis has been made of a consecutive series of 3924 cases of breast carcinoma in women seen in one centre subject to a consistent management policy between 1954 and 1964. Survival was studied in relation to the clinical stages of the disease as defined by three different staging systems, Manchester, International TNM and that of the International Union Against Cancer and the American Joint Committee on Cancer Staging and End Results Reporting (UICC/AJC). In spite of considerable differences in the distribution of cases between stages according to the system applied there was markedly little difference in survival rates up to 20 years when each stage was compared with the other two. The most important prognostic factor used in staging is the size of the primary tumour. Although the frequency of clinical evidence of spread outside the breast is related to tumour size, significantly higher 20-year survival rates were found for patients in whom the tumour appeared to be confined to the breast on clinical examination when compared with patients in whom there was clinical evidence of spread beyond the breast only for tumours less than 5 cm maximum diameter. These results suggest that staging systems relying wholly on restricted clinical criteria are of limited value in terms of prognosis and their overfrequent modification is not justified.

The case records of 116 patients treated with radical megavoltage X-ray therapy for carcinoma of the prostate have been reviewed. The age-corrected actuarial 5-year survival rate was 60.0% and the 10-year rate was 31.5%. Multivariate analysis demonstrated that T classification was the strongest prognostic variable but a long delay between diagnosis and radiotherapy also had a detrimental effect on prognosis. The incidence of severe acute and late radiation morbidity was low. Radical radiotherapy has been shown to be a safe and effective form of management for localised carcinoma of the prostate.

A total of 443 patients with bronchogenic carcinoma were treated by radical radiotherapy. Their 5-year survival rate was 10.5%, median survival 57 weeks. Of these patients 42 (9.5%) had postoperative residual or recurrent tumour. Their 5-year survival rate was 14.3%, median 80 weeks. The corresponding figures for the 401 patients who had had no previous therapy were 10.2% and 54 weeks. The tumour was histologically confirmed in 277 patients; their 5-year survival rate was 6.9%, median 54 weeks. The corresponding figures for the 166 patients who had no positive histology were 16.9% and 61 weeks. The 5-year survival rate of 235 patients with positive histology who had no surgery was 5.5%, median 51 weeks. Age and sex had no significant influence on survival. Tumour size and regional lymph node status had a marked influence on survival. The 5-year survival rate was 27.5% for patients who had T1 tumours and 8.2% for those with T2/3 tumours (P less than 0.001), median 125 and 51.5 weeks, respectively. The lymph node status was recorded in 72% of patients. The 5-year survival rate of patients who had nodal involvement was 7.4% (median 44 weeks) and 18.6% for those who had no apparent lymph node involvement (median 71 weeks), P less than 0.001. Histological type and grade had no influence on survival; in particular the survival of patients who had small cell carcinoma was similar to those of other carcinomas. Dose had no influence on survival in this series.

Ninety-four patients with invasive transitional-cell carcinoma of the bladder were randomised to receive three different doses of megavoltage X-rays. Doses of 50.0 Gy, 52.5 Gy and 57.5 Gy were given in 20 daily fractions. Patients were stratified into two groups by tumour size: less than 5.0 cm and 5.0-7.0 cm in diameter. The large tumours were more advanced (higher T stage) and included a larger number of patients with less well differentiated tumours. Comparisons of morbidity are made in each dose group defined by tumour size. Early and late morbidity was carefully assessed during follow-up and was found to be unacceptably high in the group who received 57.5 Gy in 20 daily fractions.

The case records of 90 patients developing brain metastases from carcinoma of the breast have been reviewed. Brain metastases developed more commonly in those patients who had Stage III disease at first diagnosis of breast cancer and in those who were pre- or perimenopausal at that time. Patients given whole-brain irradiation for brain metastases lived longer, from the date of central nervous system involvement, than those not given radiotherapy.

The implications of the new staging system for breast carcinoma proposed in 1973 by the International Union Against Cancer (UICC) in conjunction with the American Joint Committee on Cancer Staging and End Results (AJC) has been examined both in terms of staging distribution and the presentation of survival results as compared with the currently used International staging classification in a large consecutive series of patients referred for treatment between 1960–62. The new UICC/AJC system, if accepted, will require some 23% of cases at present Stage II (International) to be allocated to Stage I depending on a clinical assessment as to whether the nodes are involved or not. It will result in the reporting of increased survival rates for Stage I and Stage II disease, and this change is sufficiently large to be of statistical significance in Stage I disease at five and ten years.

The value of hospital follow-up in the detection of first locoregional or metastatic relapse was assessed in 276 patients with histologically confirmed FIGO Stage IB carcinoma of the cervix. All were treated by intracavitary and external beam irradiation. The maximum period of follow-up studied was 10 years (median follow-up was 55 months) during which 3190 routine and interval clinical visits were made. Fifteen (44%) of locoregional relapses (LRR) and eight (38%) of metastatic relapses were detected at routine visits (137 visits per relapse detected). Seventy-five per cent of relapses occurred within the first 5 years. Nine LRR occurred in the second quinquennium. Five (14.7%) of LRR underwent salvage surgery, three of whom were asymptomatic at the time of relapse. If routine visits had been stopped at 5 years the number of clinical visits would have been reduced by 15%, possibly at the cost of one patient whose asymptomatic LRR might not have been amenable to salvage surgery, had she not presented until she was symptomatic. Routine follow-up beyond 5 years is of dubious benefit in the detection of relapse.