Determination of docetaxel in dried blood spots by LC-MS/MS: Method development, validation and clinical application.

In this study, a LC-MS/MS method for the measurement of docetaxel in Dried Blood Spots (DBS) samples was developed and validated. Docetaxel was extracted from 8 mm DBS punch with a mixture of methanol and acetonitrile (9:1, v/v). The chromatographic separation occurred in an Acquity® C18 column (150 × 2.1 mm, 1.7 µm) eluted with a mixture of water and acetonitrile plus 0.1% formic acid (45:55, v/v). Total analytical run time was 7 min. The method was linear from 50 to 3000 ng ml-1. Precision assays showed CV% < 9.8% and accuracy between 99 and 103%, mean recovery was 81%. The method was applied in the determination of the docetaxel in 31 patients, after collection of two paired venous blood and DBS samples, following a limited sampling strategy protocol. The analyte was stable in DBS for 18 days at 25 °C and 9 days at 45 °C. The interval of docetaxel concentrations measured in DBS collected before the end of the infusion was 756-3047 ng ml-1 and 60 ±â€¯10 min after the end of the infusion was 57-331 ng ml-1. AUC values calculated from DBS-derived estimated plasma concentrations (EPC) represented on average 100% of those obtained in plasma samples of 3.1 mgh/l (2.4-4.9 mg h/l). There was a 93% agreement between the classification of patients as within or without the therapeutic range by plasma and EPC AUC. These findings support the clinical use of DBS sampling for routine therapeutic drug monitoring of docetaxel.

Comparison of breast-conserving therapy with mastectomy for treatment of early breast cancer in community hospitals.

Although the results of clinical trials support breast-conserving therapy as a replacement for mastectomy in early breast cancer, the question remains whether these results apply in routine clinical practice. In the present analysis the breast cancer-specific survival and recurrence-free survival of 464 consecutive patients with breast tumors < or = 3 cm across undergoing breast-conserving therapy were compared with a group of 459 patients with similar extent of disease and period of diagnosis undergoing mastectomy. All patients were treated in community hospitals in the south-eastern Netherlands. Median follow-up of both treatment groups was 6.2 years. After adjustment for the prognostic effects of age, tumour size, axillary nodal status and adjuvant systemic therapy, neither breast cancer-specific survival nor recurrence-free survival differed significantly between the breast-conserving therapy group and the mastectomy group. This finding indicates that in routine clinical practice breast-conserving therapy may be as effective as mastectomy.

Long-term prognosis of breast cancer: an analysis of 462 patients in a general hospital in south east Netherlands.

In this study the long-term prognosis was analysed of all 462 consecutive female breast cancer patients who were diagnosed and carefully staged between 1970 and 1980 in a 600-bed community hospital in Eindhoven, south east Netherlands. Follow-up of recurrence and causes of death was obtained until 1 January 1993. Observed survival rates at 5, 10 and 20 years were 66%, 45% and 32%, respectively, and the corresponding breast cancer-specific survival rates were 71%, 54% and 44%. The yearly risk for a recurrence of breast cancer after treatment steadily decreased from 10% the first year to 1% after 10 years. In a multivariate survival analysis both tumour size and nodal status appeared to be equally important prognostic factors in the first 5 years after diagnosis. After 5 years only tumour size had independent prognostic value, which was not significant any more after 10 years. In patients with a tumour size < or = 2 cm and without lymph node involvement at diagnosis, the risk for a recurrence was found to be negligible after 10 years. Those patients may be considered cured, although a search for early diagnosis of a second primary breast cancer in this group is still advisable.

Improved prognosis of breast cancer since 1970 in south-eastern Netherlands.

Despite many new advances in breast cancer therapy since the 1970s, there are only few reports on improved prognosis in a general population. A follow-up of more than 10 years is rarely reported, and a differentiation according to stage of the disease or between follow-up intervals is seldom made. Our purpose was to assess whether prognosis of primary breast cancer improved in patients diagnosed between 1970 and 1984 in south-eastern Netherlands, and to distinguish between different stages and follow-up intervals. Data from 4,467 breast cancer patients diagnosed between 1970 and 1984 were derived from the population-based Eindhoven Cancer Registry. Follow-up was attained up to 1 July 1991. Relative survival rates, as the ratio of the observed to the expected rates, were calculated. In a multivariate analysis a change in prognosis over time was computed with adjustment for age and stage; this was done separately for 5 year follow-up intervals. The relative survival rates were 69% after 5 years, 55% after 10 years and 50% after 20 years. Relative survival, after adjustment for age, was strongly related to the stage of the disease in the first 5 years of follow-up, less markedly between 5 and 10 years, and to a small, borderline significant, extent after 10 years of follow-up. Relative survival rates increased markedly over time, during the whole interval of follow-up. This increase was apparent in all age groups and in all stages, except for those with distant disease at diagnosis. The observed improvement in survival is unlikely to be explained by the increased use of adjuvant chemo- and hormonal therapy. Other factors, such as a change in the natural history of the disease in this period, cannot be ruled out.

Changes in long term prognosis for breast cancer in a Dutch cancer registry.

OBJECTIVES: To assess whether the long term survival of patients with breast cancer has changed with time. DESIGN: Population based descriptive study. SETTING: Eindhoven Cancer Registry in south east Netherlands. SUBJECTS: 2052 patients with first primary breast cancer diagnosed between 1955 and 1974. MAIN OUTCOME MEASURES: Overall survival and relative survival. RESULTS: Overall survival was 35% (727 patients) after 10 years, 21% (267) after 20 years, and 15% (25) after 30 years. The corresponding relative survival rates were 43%, 34%, and 34%, respectively. Survival improved from 1955 onwards for all ages and all tumour stages. Improvement was observed in both overall and relative survival. Prognosis was strongly related to the stage at diagnosis in the first 10 years of follow up but independent of stage after 10 years. Survival of patients still alive after 19 years became similar to that of the general female population. CONCLUSIONS: Both short and long term survival improved considerably in all age groups. This improvement was most marked for patients who were diagnosed with a localised tumour. Patients who survive for 19 years may be considered cured.

Management of early breast cancer in southeast Netherlands since 1984. A population-based study. Regional Breast Cancer Study Group.

We studied changes in staging and treatment of patients with early breast cancer (TNM stage I and II) in eight community hospitals in southeast Netherlands between 1984 and 1991 and related these changes to the guidelines for the management of breast cancer drawn up by the regional Breast Cancer Study Group. Since 1984, the proportion of patients that underwent breast-conserving therapy (local tumour excision, axillary dissection, and irradiation of the breast) increased from 26% to 53%. Although the mean number of axillary lymph nodes examined by the pathologists increased significantly, the proportion of patients with positive lymph nodes remained unchanged. The proportion of patients with involved axillary nodes receiving any form of adjuvant systemic therapy increased from 49% to 82%. Therapeutic policy initially varied significantly from one hospital to another but gradually became more uniform. We conclude that, except for elderly patients, treatment of early breast cancer corresponded increasingly to the guidelines of the regional Breast Cancer Study Group.

Breast cancer in the southeastern Netherlands, 1960-1989: trends in incidence and mortality.

Temporal trends in incidence and mortality in breast cancer were examined in the southeastern Netherlands using data from the population-based Eindhoven Cancer Registry. In the period 1960-1989 the incidence rate of first primary breast cancer approximately doubled in all age groups. The increase mainly occurred before 1975 and after 1985, when no screening activities were performed. This trend appeared to be a result of an average yearly increase in incidence of localised and distant tumours with both 4.6%, whereas the incidence of regional tumours did not change. Simultaneously, breast cancer mortality remained unchanged in women aged under 60, and only increased by a yearly average of 0.7% in women aged 60-74 and of 0.9% in women aged 75 and over. These differing trends in incidence and mortality, which can only partially be explained by earlier detection, suggest an improved survival of breast cancer.

[Increased incidence of breast cancer in southeast Netherlands between 1960 and 1989]. / Toegenomen incidentie van borstkanker in Zuidoost-Nederland tussen 1960 en 1989.

Trends in incidence, stage distribution and mortality of breast cancer were determined in the Southeastern Netherlands in 1960-1989. First and second primary breast cancers were analyzed separately. The incidence and mortality rates were age-standardised according to the European Standard Population. The incidence rate of first primary invasive breast cancer increased from 50 per 100,000 women per year in 1960-61 to 96 in 1988-89, and of second primary invasive breast cancer from 3.2 in 1965-66 to 7.8 in 1988-89. The incidence rate of first primary ductal carcinoma in situ (DCIS) increased from 0.3 per 100,000 women per year in 1975-76 to 2.8 in 1988-89 and of second primary DCIS from 0.06 in 1975-79 to 0.4 per 100,000 in 1985-89. The increase in first invasive primaries was observed in all age groups, but mostly at age 75 and over. The percentage with stage I tumours of the patients with a first primary invasive breast cancer increased from 7% in the sixties to 27% in the eighties, whereas the percentage of stage III and IV tumours combined, decreased from 39% in the sixties to 26% in the eighties. While age-adjusted incidence of first primaries almost doubled in the past thirty years, breast cancer mortality rose only slightly. However, breast cancer mortality showed a proportionate increase of total mortality from 4.5% in 1970-71 to 6.3% in 1988-89.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of age on treatment choice and survival of elderly breast cancer patients in south-eastern Netherlands: a population-based study.

The influence of age on treatment choice and survival was studied in 2268 breast cancer patients of 55 years and older reported to the Eindhoven Cancer Registry from 1975 to 1987. Among patients of 75 years and older, stage I and II tumours occurred less often, whereas stage IIIb and undefined tumours occurred more often than among younger patients. Physicians were found to be less likely to treat women of 75 years and older with adjuvant radiotherapy after a mastectomy. Instead, these women received either surgery alone or surgery followed by hormonal therapy. Surgical procedures in the oldest age group were also less extensive. The 10-year relative survival for women over 74 years (32%) was significantly worse than that for younger patients (57%). Multivariate analyses showed that this poor outcome for the oldest age group was largely related to their unfavourable stage distribution: stage-specific survival appeared to be similar in all age groups. Age-related differences in treatment did not have an effect on survival.

Breast-conserving treatment of early breast cancer: survival and recurrence in community hospitals in southeastern Netherlands.

A total of 514 patients with malignant breast tumours (3 cm or less in diameter) and without evidence of distant metastases underwent tumour excision, axillary dissection and radiotherapy in nine community hospitals in southeastern Netherlands and a regional institute for radiotherapy (1981-1987). Follow-up ranged from 16 to 109 months, mean 50 months. The five-year overall survival was 87 per cent and the breast cancer specific survival 90 per cent. The five-year disease-free survival was 78 per cent. The local recurrence rate was 4.4 per cent at five years and the regional recurrence rate 4.5 per cent. Survival and local recurrence rate were in accordance with the early results reported by leading centres. The regional recurrence rate seemed to be somewhat higher. This study indicates that patients with early breast cancer can be treated effectively and safely with breast-conserving therapy in community hospitals.

[Breast cancer in southeast North Brabant and in North Limburg; trends in incidence and earlier diagnosis in an unscreened female population, 1975-1986]. / Borstkanker in Zuidoost-Noord-Brabant en in Noord-Limburg; beloop van incidentie en vervroeging van de diagnose in een niet-gescreende vrouwelijke bevolking, 1975-1986.

Data on incidence, tumour size at diagnosis and mortality from breast cancer in the southeast of the Netherlands, collected by means of the SOOZ-cancer registry were studied in combination with data on patient management, collected through the regional tumour work group. Age-adjusted incidence increased by approx. 1% per year, especially in women less than 50 years and mortality showed a slight decrease in women less than 60 years. The proportion of patients with a tumour greater than 5 cm and with extension to chest wall or skin decreased from more than 40 to 15%. The proportion of tumours of 2.1-5 cm rose from 30 to 35% and that of less than or equal to 2 cm from 20 to almost 45%, in particular in younger women. The process of patient management changed by the shift to smaller tumours and the introduction of mammography, cytology and breast sparing treatment. These 'spontaneous' changes may have implications for the effectiveness of future breast cancer screening programs, which would only cover 35% of women with invasive breast cancer in this population.

Follow-up after treatment of primary breast cancer.

This study evaluates the usefulness of routine follow-up of breast cancer patients. In all, 416 patients who were treated with curative intent for breast cancer were followed according to a fixed follow-up schedule for a minimum of 2.5 years and a maximum of 13.5 years (mean about 5 years). During the 4533 routine out-patient visits, 4116 chest radiographs, 3889 pelvic radiographs and about 17,000 laboratory tests were carried out routinely. In the follow-up period, 148 patients were found to have distant recurrence of whom 34 (23 per cent) had asymptomatic metastases and 114 symptomatic metastases. Of the 8005 routinely performed radiographs, 24 (0.3 per cent) revealed asymptomatic metastases, and the 17,000 laboratory tests led to the discovery of six asymptomatic bone and four asymptomatic liver recurrences. Screening for metastases did not result in a reduction of the lead time to the diagnosis of asymptomatic metastases; the disease-free interval was equal in both symptomatic and asymptomatic patients. Of the 46 locoregional recurrences 42 were found by physical examination during a routine follow-up visit and 37 had not been noticed by the patient. Seventeen second primary breast cancers were diagnosed, six of which were in stage I (less than 2 cm). Mammography was not a part of the routine follow-up scheme. It is concluded that routine follow-up of breast cancer patients by history and physical examination is sufficient to detect local recurrence and a second primary tumour as well as giving the opportunity to track signs and symptoms of distant recurrence at an early stage. Performing annual or biannual mammography is advisable, but the use of other costly routine investigations in the follow-up is not justifiable, as no therapeutic advantages can be expected.

No-touch isolation technique in colon cancer: a controlled prospective trial.

In order to assess the effect of the no-touch isolation technique, in the treatment of large bowel cancers, on the site of first recurrence and disease-free and overall survival, 236 patients were prospectively and randomly assigned to either the no-touch isolation technique (117 patients) or to a conventional resection technique (119 patients). No patient with distant metastases or unresectable disease entered the study. The two treatment groups were comparable with regard to patient characteristics. Pre- and postoperative complications (including mortality within 30 days) were similar in both groups. After a complete follow-up of 5 years, a tendency for reduction in the number of, and time to, occurrences of liver metastases was seen in the no-touch isolation group (P = 0.14). This effect was most obvious in the sigmoid colon with angio-invasive growth. Overall (P = 0.42) and corrected (P = 0.25) survival did not differ significantly among the treatment groups although in every analysis the survival data of the no-touch isolation group were superior. The data do suggest a limited benefit of the no-touch isolation technique. This observation is important since the morbidity and mortality of surgery were equal in both groups.