Relocatable fixation systems in intracranial stereotactic radiotherapy. Accuracy of serial CT scans and patient acceptance in a randomized design.

PURPOSE: The goal was to provide a quantitative evaluation of the accuracy of three different fixation systems for stereotactic radiotherapy and to evaluate patients' acceptance for all fixations. METHODS: A total of 16 consecutive patients with brain tumours undergoing fractionated stereotactic radiotherapy (SCRT) were enrolled after informed consent (Clinical trials.gov: NCT00181350). Fixation systems evaluated were the BrainLAB® mask, with and without custom made bite-block (fixations S and A) and a homemade neck support with bite-block (fixation B) based on the BrainLAB® frame. The sequence of measurements was evaluated in a randomized manner with a cross-over design and patients' acceptance by a questionnaire. RESULTS: The mean three-dimensional (3D) displacement and standard deviations were 1.16 ± 0.68 mm for fixation S, 1.92 ± 1.28 and 1.70 ± 0.83 mm for fixations A and B, respectively. There was a significant improvement of the overall alignment (3D vector) when using the standard fixation instead of fixation A or B in the craniocaudal direction (p = 0.037). Rotational deviations were significantly less for the standard fixation S in relation to fixations A (p = 0.005) and B (p = 0.03). EPI imaging with off-line correction further improved reproducibility. Five out of 8 patients preferred the neck support with the bite-block. CONCLUSION: The mask fixation system in conjunction with a bite-block is the most accurate fixation for SCRT reducing craniocaudal and rotational movements. Patients favoured the more comfortable but less accurate neck support. To optimize the accuracy of SCRT, additional regular portal imaging is warranted.

The addition of a boost dose on the primary tumour bed after lumpectomy in breast conserving treatment for breast cancer. A summary of the results of EORTC 22881-10882 "boost versus no boost" trial.

PURPOSE: To investigate the impact of the boost dose to the primary tumour bed in the framework of breast conserving therapy on local control, cosmetic results, fibrosis and overall survival for patients with early stage breast cancer. PATIENTS AND METHODS: Five thousand five hundred and sixty-nine patients after lumpectomy followed by whole breast irradiation of 50 Gy were randomised. After a microscopically complete lumpectomy (5318 patients), the boost doses were either 0 or 16 Gy, while after a microscopically incomplete (251 patients) lumpectomy randomisation was between 10 and 26 Gy. The results at a median follow-up of 10 years are presented. RESULTS: At 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the 0 Gy and the 16 Gy boost groups (p < 0.0001) and 17.5% versus 10.8% for the 10 and 26 Gy boost groups, respectively (p > 0.1). There was no statistically significant interaction per age group but recurrences tended to occur earlier in younger patients. As younger patients had a higher cumulative risk of local relapse by year 10, the magnitude of the absolute 10-year risk reduction achieved with the boost decreased with increasing age. Development of fibrosis was significantly dependent on the boost dose with a 10-year rate for severe fibrosis of 1.6% after 0 Gy, 3.3% after 10 Gy, 4.4% after 16 Gy and 14.4% after 26 Gy, respectively. CONCLUSION: An increase of the dose with 16 Gy improved local control for patients after a complete lumpectomy only. The development of fibrosis was clearly dose dependent. With 10 years median follow-up, no impact of survival was observed.

Simple non-invasive assessment of advanced glycation endproduct accumulation.

AIMS/HYPOTHESIS: The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a non-invasive tool for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We validated its use by comparing the values obtained using the AFR with the AGE content measured in extracts from skin biopsies of diabetic and control subjects. METHODS: Using the AFR with an excitation light source of 300-420 nm, fluorescence of the skin was measured at the arm and lower leg in 46 patients with diabetes (Type 1 and 2) and in 46 age- and sex-matched control subjects, the majority of whom were Caucasian. Autofluorescence was defined as the average fluorescence per nm over the entire emission spectrum (420-600 nm) as ratio of the average fluorescence per nm over the 300-420-nm range. Skin biopsies were obtained from the same site of the arm, and analysed for collagen-linked fluorescence (CLF) and specific AGE: pentosidine, N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL). RESULTS: Autofluorescence correlated with CLF, pentosidine, CML, and CEL ( r=0.47-0.62, p

Can patient-, treatment- and pathology-related characteristics explain the high local recurrence rate following breast-conserving therapy in young patients?

The aim of this study was to identify patient-, tumour- or treatment-related factors associated with young age that might explain the higher risk of ipsilateral breast recurrence that occurs after breast-conserving therapy (BCT) in young breast cancer patients. In the 'boost versus no boost trial', 5569 early-stage breast cancer patients were entered. All patients underwent tumorectomy followed by whole breast irradiation of 50 Gy. Patients having a microscopically complete excision were randomised between receiving no boost or a 16-Gy boost, while patients with a microscopically incomplete excision were randomised between receiving a boost dose of 10 or 26 Gy. The 5-year local control rate was 82% for patients 60 years of age (P<0.0001). In young patients, the tumour was significantly larger and more often oestrogen and progesterone receptor-negative. Invasive carcinoma and the intraductal component were more often of a high grade. The intraductal component was more frequently incompletely resected in young patients. Re-excisions were performed more often (most probably due to a more frequent incomplete excision at the first attempt). The total volume of breast tissue removed at the tumorectomy was smaller in the younger patient group, even after including the volume removed during re-excision. When relating all these parameters (including age itself) to local control, the multivariate analysis stratified by treatment showed that age was the only independent prognostic factor for local control (P=0.0001). Including the boost treatment as a separate covariate, the analysis retained age and boost treatment as significant factors related to local control (P<0.0001). It was shown that the boost dose significantly reduced the 5-year local recurrence rate from 7 to 4% for patients with a complete excision (P<0.001). For patients 40 years of age or younger, the boost dose reduced the local recurrence rate from 20 to 10% (P=0.002). This large European Orgnaization for Research and Treatment of Cancer (EORTC) trial demonstrated an increased local recurrence rate in young patients. Although several associations between patient, tumour and treatment factors and age were found, that might explain the high local recurrence rate in the younger patients, it appears that age itself and the boost dose were the only factors that were independently related to local control.

Shortened irradiation scheme, continuous infusion of 5-fluorouracil and fractionation of mitomycin C in locally advanced anal carcinomas. Results of a phase II study of the European Organization for Research and Treatment of Cancer. Radiotherapy and Gastrointestinal Cooperative Groups.

The European Organization for Research and Treatment of Cancer (EORTC) 22861 randomised trial established that combined radiochemotherapy is the standard treatment for locally advanced anal cancer. This EORTC phase II study (#22953) tests the feasibility of reducing the gap between sequences to 2 weeks, to deliver Mitomycin C (MMC) in each radiotherapy sequence and 5-FU continuously during the treatment. The first sequence consisted of 36 Gy over 4 weeks. 5-FU 200 mg/m(2)/days 1-26, MMC 10 mg/m(2)/day 1 gap 16 days. Then a second sequence of 23.4 Gy over 17 days, 5-FU 200 mg/m(2)/days 1-17 and, MMC 10 mg/m(2)/day 1 was given. 43 patients with a World Health Organization (WHO) status of 0 (n=27) or 1 (n=16) and with T2-T4, N0-3 tumours were included. Compliance with the planned treatment, doses and duration was 93%. The complete response rate was 90.7%. Grade 3 toxicities of 28, 12 and 2% were observed for skin, diarrhoea and haematological toxicities, respectively. The 3-year estimated rates for trials 22861 and 22953 are: 68 and 88% for local control; 72 and 81% for colostomy-free interval, 62 and 84% for severe late toxicity-free interval, and 70 and 81% for survival, respectively. The 22953 scheme is feasible and the results are promising. This is now considered as the new standard scheme by the EORTC.

Clinical relevance of apoptotic markers in breast cancer not yet clear.

Currently, the mainly used characteristics to predict outcome or treatment response in patients with breast cancer are tumor size, N-status, histological grade and receptor status (ER/PgR). However, these conventional clinico-pathological characteristics are of limited value. More accurate determinators are needed to select patients who are most likely to benefit from treatment in terms of prognosis as well as treatment response. Proliferation and apoptosis are assumed to play a key role in tumor progression as well as response to treatment. Currently, an increasing number of molecular factors controlling apoptosis as well as proliferation is known. The clinical relevance of apoptotic tumor markers in the treatment strategy of patients with breast cancer is the subject of this review. In addition, potential future developments are discussed.

Adjuvant chemo-hormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate (MPA) for node-positive cancer patients, update at 12 years follow up.

An update with 10 years of follow up of a study adding adjuvant MPA to CAF chemotherapy is presented. A total of 409 patients were entered, of which 200 were randomized to receive 500 mg of MPA i.m. on days 1-28 and twice per week thereafter for 6 months. There was a significant improvement in metastases-free and overall survival in women >60 years of age receiving MPA (P=0.01 and P=0.02 respectively). A detrimental effect of MPA was seen in women <40 years. Possible reasons for these results are discussed.

The influence of patient, tumor and treatment factors on the cosmetic results after breast-conserving therapy in the EORTC 'boost vs. no boost' trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups.

PURPOSE: To analyze the influence of different patient, tumor, and treatment parameters on the cosmetic outcome after breast-conserving therapy at 3-year follow-up. A subjective and an objective cosmetic scoring method was used and the results of both methods were compared. PATIENTS AND METHODS: In EORTC trial 22881/10882, 5569 early-stage breast cancer patients were treated with tumorectomy and axillary dissection, followed by tangential fields irradiation of the breast to a dose of 50 Gy in 5 weeks, at 2 Gy per fraction. A total of 5318 patients, having a microscopically complete tumorectomy, were randomized between no further treatment and a boost of 16 Gy to the primary tumor bed. The cosmetic result at 3-year follow-up was assessed by a panel for 731 patients, and by digitizer measurements, measuring the displacement of the nipple, for 1141 patients. Univariate and multivariate analyses were used to evaluate the correlation between various patient, tumor, and treatment factors and cosmesis. RESULTS: The factors associated with a worsened cosmesis according to the panel evaluation were: an inferior tumor location, a large excision volume, the presence of postoperative breast complications, and the radiotherapy boost. According to the digitizer measurements, a central/superior tumor location, a large excision volume, an increased pathological tumor size, an increased radiation dose inhomogeneity, and an increased bra cup size resulted in an increased asymmetry in nipple position. It appeared that the evaluation of the nipple position (whether by panel or by digitizer) is only moderately representative of the overall cosmetic outcome. CONCLUSION: To achieve a good cosmesis, it is necessary to excise the tumor with a limited margin, to avoid postoperative complications, to assess the need for a boost in the individual patient, and to give the radiation dose as homogeneously as possible. As far as the method of evaluation is concerned, the panel evaluation is the most appropriate method for giving an overall impression of the cosmetic result after breast-conserving therapy (BCT). The use of the digitizer is recommended for comparing the cosmetic outcome of two different approaches to BCT or for analyzing cosmetic changes over time.

Anti-apoptotic phenotype is associated with decreased locoregional recurrence rate in breast cancer.

PURPOSE: Tumor stage and nodal status are the most important factors predicting locoregional recurrence in breast cancer. We wanted to investigate the prognostic value of some newer molecular genetic markers for the occurrence of a locoregional recurrence, in order to improve the selection of patients for locoregional adjuvant therapy. METHODS: Bcl-2, p53, MIB-1, pS2 and CD44v6 were determined immunohistochemically on formalin-fixed and paraffin embedded tumour tissues of 163 patients treated by modified radical mastectomy between 1982 and 1987. Postoperative irradiation was given to 35 patients to the intermammary chain only and to only 13 (8%) patients to the chest wall with or without the regional lymph nodes. Node-positive patients were treated with CAF adjuvant chemotherapy and were randomized for whether or no additional Medroxyprogesteroneacetate (MPA). A multivariate analysis was performed on a number of potential prognostic factors. The risk for locoregional recurrence was estimated using the competing risk approach. RESULTS: After a median period of 7.5 years 28 patients developed a locoregional recurrence. The cumulative incidence of loco-regional recurrence at 10 years was 17%. Bcl-2 and p53 were found to be independent factors predicting locoregional recurrence, whereas a trend was found for MIB-1. Increased Bcl-2 as well as p53 expression were associated with a decreased risk, whereas the increased presence of MIB-1 was associated with an increased risk. CONCLUSION: Results indicate that molecular markers of apoptosis as well as proliferation provide additional information for the risk of locoregional recurrence after modified radical mastectomy. If confirmed, these markers may play a role in the selection of appropriate locoregional adjuvant treatment after primary surgery.

The influence of the boost in breast-conserving therapy on cosmetic outcome in the EORTC "boost versus no boost" trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. European Organization for Research and Treatment of Cancer.

PURPOSE: To evaluate the influence of a radiotherapy boost on the cosmetic outcome after 3 years of follow-up in patients treated with breast-conserving therapy (BCT). METHODS AND MATERIALS: In EORTC trial 22881/10882, 5569 Stage I and II breast cancer patients were treated with tumorectomy and axillary dissection, followed by tangential irradiation of the breast to a dose of 50 Gy in 5 weeks, at 2 Gy per fraction. Patients having a microscopically complete tumor excision were randomized between no boost and a boost of 16 Gy. The cosmetic outcome was evaluated by a panel, scoring photographs of 731 patients taken soon after surgery and 3 years later, and by digitizer measurements, measuring the displacement of the nipple of 3000 patients postoperatively and of 1141 patients 3 years later. RESULTS: There was no difference in the cosmetic outcome between the two treatment arms after surgery, before the start of radiotherapy. At 3-year follow-up, both the panel evaluation and the digitizer measurements showed that the boost had a significant adverse effect on the cosmetic result. The panel evaluation at 3 years showed that 86% of patients in the no-boost group had an excellent or good global result, compared to 71% of patients in the boost group (p = 0.0001). The digitizer measurements at 3 years showed a relative breast retraction assessment (pBRA) of 7.6 pBRA in the no-boost group, compared to 8.3 pBRA in the boost group, indicating a worse cosmetic result in the boost group at follow-up (p = 0.04). CONCLUSIONS: These results showed that a boost dose of 16 Gy had a negative, but limited, impact on the cosmetic outcome after 3 years.

Loco-regional recurrences after mastectomy in breast cancer: prognostic factors and implications for postoperative irradiation.

PURPOSE: Potential risk factors including DNA flow cytometric-derived parameters predicting loco-regional recurrence (LRR) in early breast cancer were investigated. MATERIALS AND METHODS: This study included 608 patients treated by modified radical mastectomy between 1982 and 1987. Recommendations regarding local treatment as well as adjuvant systemic therapy did not change during this period. Patients treated by adjuvant chemotherapy were randomized to receive additional medroxyprogesterone acetate (MPA) treatment. Only 59 (10%) patients received postoperative irradiation (XRT) to the chest wall and/or axillary lymph nodes; another 121 (20%) patients received XRT to the internal mammary nodes because of centromedially located tumours. RESULTS: Patients were followed for a median period of 7.5 years. The event-free survival at 10 years was 50%. The cumulative incidence rate of LRR at 10 years was 18% (n = 93), either with (n = 30) or without (n = 63) concurrent distant metastases. The chest wall, regional lymph nodes or both were involved in 41 (44%), 38 (41%) and 12 (13%) patients, respectively. Multivariate analysis according to the Cox model revealed two factors associated with LRR, i.e. pT (P < 0.05) and nodal status (P < 0.05). In node-positive patients extracapsular tumour extension (ECE) and pT were independent risk factors. DNA ploidy and S-phase fraction did not yield additional information. Based on pT, nodal status and extracapsular extension of tumour growth a high risk (> 10%) and low risk (< 10%) group for LRR could be identified. CONCLUSIONS: Results indicate that T-stage and nodal status, combined with ECE, may help to identify patients at risk for loco-regional recurrence, whereas DNA flow cytometry does not.

[Locoregional radiotherapy after mastectomy and chemotherapy for breast cancer: prolonged survival and better local tumor control]. / Locoregionale radiotherapie na mastectomie en chemotherapie wegens mammacarcinoom: verlengde overleving en betere lokale tumorcontrole.

In two recent randomized clinical trials from Denmark and Canada the usefulness of radiotherapy was evaluated in premenopausal patients with breast cancer who had been operated and in whom the findings indicated a poor prognosis. Over 2000 patients participated. After follow-up periods of 10 and 15 years, respectively, addition of locoregional therapy to mastectomy and chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF) was found to result in better locoregional control and a better disease-free survival. These studies also demonstrated, for the first time, that the overall survival was increased after postoperative radiotherapy. In view of these findings, the indication for postoperative locoregional radiotherapy in breast cancer in the Netherlands should be reconsidered.

Increased proliferative activity and p53 expression in normal glandular breast tissue after radiation therapy.

Radiation used in breast-conserving therapy (BCT) for early breast cancer, to eradicate residual malignant cells after tumour resection, induces DNA damage and cell death. Little is known about the effect of the commonly used doses of radiation therapy on normal breast tissue. Under physiological conditions, p53 plays a role in maintaining genomic stability and regulating progression through the cell cycle. In normal glandular breast tissue, p53 expression is very low, as is proliferative activity. The purpose of this study was to investigate the levels of p53 expression and proliferative activity in non-malignant glandular epithelium of the breast after BCT. The immunohistochemical expression of p53 and Ki-67 was semiquantitatively correlated in non-malignant glandular epithelium in biopsies before and after BCT in 24 women with breast cancer. In 18 cases, a recurrence was diagnosed and in the remaining cases, the clinical suspicion was not histologically confirmed. In addition, in six cases with contralateral breast cancer, the same immunohistochemical evaluation was performed in tissue from both breasts. The mean interval between the two surgical interventions was 50 months. The percentage of p53 immunoreactive epithelial cells in normal breast tissue was significantly (P < 0.01) higher after radiation therapy than before in the ipsilateral side (0.2 per cent +/- 0.3 and 4.6 per cent +/- 4.5, respectively). Ki-67 immunoreactivity was also significantly increased (P < 0.001) after radiation therapy, from 0.6 per cent to an average of 4.8 per cent in epithelial cells. In contrast, in the patients with contralateral breast cancer, the levels of p53 and Ki-67 immunoreactivity in the normal glandular breast tissue were comparable to the ipsilateral side (P = 0.7 and P = 0.1, respectively). In conclusion, increased expression of p53 and Ki-67 is present in normal glandular breast tissue, even 2-5 years after radiation therapy.

The prognostic significance of steroid receptor activity in tumor tissues of patients with primary breast cancer.

The prognostic significance of steroid-receptor activity is still debatable. Discrepancies in results are probably attributable to few patients, heterogeneous patient populations, and short follow-up. We investigated the prognostic significance of estrogen- and progesterone-receptor (ER and PgR, respectively) activity as a continuous variable in a homogeneous patient population. The prognostic significance of steroid-receptor activity was examined in 329 node-negative and 320 node-positive unselected breast cancer patients. In node-negative patients, ER values of primary tumors between 100 and 400 fmol/mg protein appeared to be a significant predictor for low risk of recurrence, whereas high ER (> 400) revealed an unfavorable prognosis. The classic cutoff level of ER (< 10 fmol/mg proteins) had no prognostic significance, however. In patients receiving adjuvant chemotherapy--the node-positive breast cancer patients--the classic cutoff value of ER (10 fmol/mg protein) predicts significantly distant metastases-free survival and overall survival only in the first 4 years of follow-up after diagnosis. Progesterone receptor is a time-dependent prognosticator in node-negative breast cancer patients (cutoff point for PgR, 80 fmol/mg). In node-positive breast cancer patients treated with chemotherapy or a combination of chemo- and hormonal therapy, PgR values lower than 60 fmol/mg had a worse prognosis. The results show the poor performance of standard cutoff points for ER and PgR positivity in predicting prognosis. Better prognosis is related to higher receptor levels but this relation is predominantly time-dependent. Moreover, patients who have high ER levels have a prognosis that is worse when compared with intermediate ER levels. Standard cutoff points for steroid receptors should not be used to select patients for prognosis.

Validity of the stage of lung cancer in records of the Maastricht cancer registry, The Netherlands.

Information collected in a clinical study on a random sample of 99 patients with inoperable lung cancer, treated with radiotherapy, was compared to the staging information in the Maastricht cancer registry. Validity of sex (0% disagreements), date of birth (0%), histology (1% major disagreements) and treatment (1%) was high, but the validity of stage was lower: 12% major and 23% minor disagreements. The misclassification of stage did not result in a shift in the survival estimates. If cancer registries intend to use stage in comparisons of survival, more validation studies are necessary.

Prognostic significance of etiological risk factors in early breast cancer.

Several risk factors for the etiology of breast cancer have also been correlated with the prognosis of breast cancer. However, the published studies have yielded conflicting results. Women under 71 years of age with stage I, II, or III breast cancer were eligible for inclusion in a clinical study. 866 patients with breast cancer entered the study, of whom 463 had positive lymph nodes. Survival was analysed using Cox's proportional hazards model. Age at menarche parity, age at menopause and family history were not consistently related to survival. Young age at first full-term pregnancy was related to decreased survival (adjusted relative risk (RR): 1.69, 95% confidence intervals (95% CI): 1.04-2.68), but it cannot be excluded that this result was due to chance alone. Use of oral contraceptives was not correlated with survival (RR: 1.10, 95% CI: 0.80-1.51) nor was family history (RR: 0.93, 95% CI: 0.66-1.30). This study provided little support for the hypothesis that risk factors for breast cancer are related to survival.

A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844.

PURPOSE: Cerebral low-grade gliomas (LGG) in adults are mostly composed of astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. There is at present no consensus in the policy of treatment of these tumors. We sought to determine the efficacy of radiotherapy and the presence of a dose-response relationship for these tumors in two multicentric randomized trials conducted by the European Organization for Research and Treatment of Cancer (EORTC). The dose-response study is the subject of this article. METHODS AND MATERIALS: For the dose-response trial, 379 adult patients with cerebral LGGs were randomized centrally at the EORTC Data Center to receive irradiation postoperatively (or postbiopsy) with either 45 Gy in 5 weeks or 59.4 Gy in 6.6 weeks with quality-controlled radiation therapy. All known parameters with possible influences on prognosis were prospectively recorded. Conventional treatment techniques were recommended. RESULTS: With 343 (91%) eligible and evaluable patients followed up for at least 50 months with a median of 74 months, there is no significant difference in terms of survival (58% for the low-dose arm and 59% for the high-dose arm) or the progression free survival (47% and 50%) between the two arms of the trial. However, this prospective trial has revealed some important facets about the prognostic parameters: The T of the TNM classifications as proposed in the protocol appears to be one of the most important prognostic factors (p < 0.0001) on multivariate analysis. Other prognostic factors, most of which are known, have now been quantified and confirmed in this prospective study. CONCLUSION: The EORTC trial 22844 has not revealed the presence of radiotherapeutic dose-response for patients with LGG for the two dose levels investigated with this conventional setup, but objective prognostic parameters are recognized. The tumor size or T parameter as used in this study appears to be a very important factor.

Age-specific differences in the diagnostics and treatment of cancer patients aged 50 years and older in the province of Limburg, The Netherlands.

BACKGROUND: In the Netherlands, 45% of all cancer cases occur in men and women aged 70 years and older. Since the population is ageing and cancer incidence rises with age, the number of new malignancies in the elderly is increasing. It has become apparent that there is a relationship between age at diagnosis and the treatment received. Therefore, age-specific variations in patterns of care for six common forms of cancer in the elderly, are examined. PATIENTS AND METHODS: Patients aged 50 years and older, diagnosed in the period 1988-1992 in Middle and South Limburg with breast, colorectal, lung, ovarian, head and neck cancer and non-Hodgkin lymphoma were included (n = 6911). Data were obtained from the population-based Regional Cancer Registry of the Comprehensive Cancer Centre Limburg. Age-specific differences in diagnostics and treatment were analysed using chi-square analysis (age categories: 50-59, 60-69, 70+). Logistic regression analyses were used to examine the extent to which age increased the chance of not being treated or of receiving less intensive treatment, while controlling for the stage of the disease and the sex of the patient. RESULTS: For all malignancies the stage was unknown in a larger proportion of the patients aged 70 years and older than in the younger patient groups. Compared to their younger counterparts, the diagnosis of elderly breast, colorectal and lung cancer patients was more often based solely on clinical grounds. In the total study population, 16% were not treated. Per age category 50-59 years, 60-69 years and 70+ these percentages were 7%, 12% and 22%, respectively, (P-trend = 0.001). For all malignancies the chance of not receiving treatment increased with increasing age. However, the size and nature of the differences varied with the localisation of the tumour. The proportion of untreated patients was particularly high in the patients with lung cancer and metastatic colorectal and ovarian cancer, and there was an increase with increasing age (P-trend = 0.001). The vast majority of patients with NHL, breast, head and neck and non-metastatic colorectal cancer received treatment, 90%, 94%, 91%, and 99%, respectively. However, elderly patients less often received a combination of treatment modalities. CONCLUSIONS: The diagnostics and choice of treatment for several common types of cancer were dependent on age. This study could not take into account the major problem of co-morbidity which can be a reason to choose for lesser therapy in the elderly. More research is necessary to determine which factors determine the diagnostics and choice of treatment and whether these factors differ between young and elderly patients.

Prognostic significance of radial margins of clearance in rectal cancer.

A retrospective review of 325 patients was undertaken to analyse whether involvement of the radial resection margin (RRM) could predict locally recurrent disease or distant metastases in patients who had curative surgery for rectal or rectosigmoid cancer. Information on the RRM was available in 253 patients. The RRM was involved in 31 (12 per cent). Nine of these 31 patients developed local recurrence (29 per cent), while only 17 local recurrences were diagnosed in 217 patients (8 per cent) without involvement of the RRM (P < 0.01). At 2 years the overall local recurrence rate was 10 per cent. Distant metastases were diagnosed in 46 patients (18 per cent) and RRM involvement was identified as a prognostic factor depending on lymph node involvement (N stage) (P = 0.02). Local recurrence and some distant metastases result from microscopically incomplete resection. Assessment of the radial depth of tumour invasion by careful histological examination of x791p4ecimen may be used for selection of patients for adjuvant radiotherapy and/or chemotherapy.

Mammography in the follow-up after breast-conserving treatment in cancer of the breast: suitability for mammographic interpretation, validity and interobserver variation.

The aims of this study were to determine the suitability for radiographic interpretation, interobserver variability and validity of mammography after breast-conserving treatment. Initial and post-treatment mammograms of 100 consecutive patients treated between 1982 and 1987, with a minimal follow-up of 5 years, were independently selected for review by two radiologists. Mammograms were classified according to suitability for interpretation and radiological diagnosis based on the presence of characteristics of malignancy. The interobserver variability was expressed in kappa values, the validity in a receiver operating characteristic (ROC) plot. 534 post-treatment and 86 initial mammograms of 92 patients were obtained. Suitability for interpretation was not different from pre-treatment mammograms and was significantly associated with age, being better in the age group over 50 years. No association was observed between suitability for interpretation and treatment-related factors, even if irradiation was combined with concurrent chemotherapy. Reliability of conclusions regarding sensitivity and specificity in this study are limited due to the small number of events. Interobserver agreement concerning classification was moderate (weighted kappa = 0.49). ROC analysis showed an optimal decision threshold between the "uncertain" and "suspect" categories of malignancy, resulting in a sensitivity of 86% and a specificity of 98%. The appearance of new pathological microcalcifications with or without tumour mass seemed to be the most important characteristics of malignancy predicting local relapse. No clear alteration in suitability for interpretation was observed in the mammograms after breast-conserving treatment, even if irradiation was combined with concurrent chemotherapy. Mammography after breast conserving-treatment may be slightly less sensitive but is equally specific compared with mammography in the screening situation.