Stage migration in breast cancer: surgical decisions concerning isolated tumour cells and micro-metastases in the sentinel lymph node.

AIMS: Sentinel lymph node biopsy has replaced the axillary lymph node dissection (ALND) in primary surgery for breast cancer in many hospitals and is expected to become the standard of care in due time. Since the sentinel lymph node is subjected to more extensive pathologic examination than the lymph nodes in the axillary dissection specimen, more patients are found to be node positive (N+); however many of them contain micro-metastases (相似文献   

Cost-effectiveness of new guidelines for adjuvant systemic therapy for patients with primary breast cancer.

BACKGROUND: In this study, the potential impact of a new national guideline for adjuvant systemic therapy in breast cancer (introduced in The Netherlands in 1998) was assessed, as well as the modifications of this guideline, issued in 2001. Both the change in total number of patients eligible for adjuvant therapy, as well as the cost-effectiveness of the changed clinical management of these patients were analysed. PATIENTS AND METHODS: Percentages of patients who would be eligible for adjuvant therapy in 1994, 1998 and 2001 were estimated, based on clinical data from 127 patients, who were operated on in 1994. Ten-year overall survival rates were used as a measure of effectiveness, based on the two most recent EBCTCG meta-analyses. Actual resource costs were calculated. With a decision analytic model, the incremental cost-effectiveness ratios (1998 versus 1994, and 2001 versus 1998) were calculated. RESULTS: The introduction of the 1998 guideline resulted in a relative increase of 80% in the total number of patients eligible for adjuvant therapy, compared with 1994 (from 40% to 72% of all patients with primary breast cancer). With an estimated absolute increase of 10-year overall survival of 2%, the 1998 guideline was found to have an expected incremental cost-effectiveness ratio of about 4837 per life-year gained. CONCLUSIONS: Introduction of the new guideline considerably affected the number of patients eligible for adjuvant systemic therapy for breast cancer. The associated incremental cost-effectiveness ratio is well within the range of values that are generally considered acceptable.     

Standard versus intensified chemotherapy with granulocyte colony-stimulating factor support in small-cell lung cancer: a prospective European Organization for Research and Treatment of Cancer-Lung Cancer Group Phase III Trial-08923.

PURPOSE: To assess the impact on survival of increasing dose-intensity (DI) of cyclophosphamide, doxorubicin, and etoposide (CDE) in small-cell lung cancer (SCLC). PATIENTS AND METHODS: Previously untreated SCLC patients were randomized to standard CDE (cyclophosphamide 1,000 mg/m(2) and doxorubicin 45 mg/m(2) on day 1, and etoposide 100 mg/m(2) on days 1 to 3 every 3 weeks, for five cycles) or intensified CDE (cyclophosphamide 1,250 mg/m(2) and doxorubicin 55 mg/m(2) on day 1, and etoposide 125 mg/m(2) on days 1 to 3 with granulocyte colony-stimulating factor [G-CSF] 5 micro g/kg/d on days 4 to 13 every 2 weeks, for four cycles). Projected cumulative dose was almost identical on the two arms, whereas projected DI was nearly 90% higher on the intensified arm. Two hundred forty-four patients were enrolled. The first 163 patients were also randomized (2 x 2 factorial design) to prophylactic antibiotics or placebo to assess their impact on preventing febrile leukopenia (FL). This report focuses on chemotherapy DI results. RESULTS: With a median follow-up of 54 months, 216 deaths have occurred. Actually delivered DI on the intensified arm was 70% higher than on the standard arm. Intensified CDE was associated with more grade 4 leukopenia (79% v 50%), grade 4 thrombocytopenia (44% v 11%), anorexia, nausea, and mucositis. FL and number of toxic deaths were similar on the two arms. The objective response rate was 79% for the standard arm and 84% for the intensified arm (P =.315). Median survival was 54 weeks and 52 weeks, and the 2-year survival rates were 15% and 18%, respectively (P =.885). CONCLUSION: A 70% increase of CDE actual DI does not translate into an improved outcome in SCLC patients.     

Guideline on 'non-small cell lung carcinoma; staging and treatment'

A national, evidence-based guideline on the staging and treatment of patients with non-small cell lung carcinoma (NSCLC) has been compiled by the various disciplines involved. The initial diagnostic measures in patients with suspected lung cancer include history taking, physical examination and chest x-ray. Additional examinations include CT scan of the chest and upper abdomen, bronchoscopy, and 18F-fluorodeoxyglucose-positron-emission-tomography(FDG-PET)-scintigraphy, if curative therapy is planned. Cervical mediastinoscopy or endoscopic echography with fine needle aspiration can be performed for mediastinal tissue staging. The preferred treatment in stage I, II or limited III is radical resection. Postoperative radiotherapy is recommended in cases of incomplete resection and can be considered in patients in whom mediastinal lymph-node metastases are unexpectedly encountered. Chemoradiotherapy is recommended in locally advanced NSCLC. In patients with NSCLC stage I-III and poor performance status, palliative radiotherapy may be the only feasible treatment. Some patients with NSCLC stage III and stage IV can be offered palliative chemotherapy and supportive care. In cases of doubt about operability, resectability, significant pulmonary or cardiac comorbidity or combined treatment, a specialist centre should be consulted. Diagnostics should be completed within 3-5 weeks. Ensuing surgery or radiotherapy should be carried out within 2 weeks. Follow-up of patients with NSCLC includes history taking, physical examination and an optional chest x-ray. In the first year after treatment patient visits are planned quarterly, in the second year half-yearly and then yearly for at least five years.     

FDG-PET in staging lung cancer: how does it change the algorithm?

BACKGROUND: In patients with lung cancer, positron emission tomography (PET) using fluor-18-fluorodesoxyglucose (FDG) may be used both to detect extrathoracic metastases (ETM) and for mediastinal lymph node staging (MLS), potentially reducing the need for mediastinoscopy. We assessed the added value of FDG-PET in detecting ETM and focused on the reliability of FDG-PET and mediastinoscopy for MLS. PATIENTS AND METHODS: In 72 consecutive patients with non-small cell lung cancer, the impact of adding FDG-PET to full conventional clinical staging was prospectively analyzed. The predictive value of FDG-PET findings and tumor location for pathologic mediastinal lymph node status were assessed in a logistic regression analysis. RESULTS: Unexpected extrathoracic metastases were detected by FDG-PET in 15% of patients. In MLS overall negative and positive predictive values were 71 and 83% for FDG-PET, and 92 and 100% for mediastinoscopy. However, the negative predictive value of FDG-PET was only 17% in case of FDG-PET positive N1 nodes and/or a centrally located primary tumor, whereas it was 96% in case of FDG-PET negative N1 nodes and a non-centrally located primary tumor. CONCLUSION: By incorporating FDG-PET in clinical staging, 15% of patients with lung cancer are upstaged due to unexpected extrathoracic metastases. In case of a negative mediastinal FDG-PET, mediastinoscopy can only be omitted in the presence of a non-centrally located primary tumor and without FDG-PET positive N1 nodes.     

The complex between urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-I) independently predicts response to first-line endocrine therapy in advanced breast cancer

It has been shown that urokinase-type plasminogen activator (uPA) and its main inhibitor (PAI-I) have predictive value for therapy success in advanced breast cancer. Levels of the complex between uPA and PAI-I, formed when both molecules are in their active form, might have superior predictive power. Here, we investigate the association between levels of uPA:PAI-I complex and rate of response to first-line systemic therapy for advanced breast cancer. Tumor tissues of 170 patients with advanced breast cancer were analyzed for uPA:PAI-I complex concentrations using a quantitative enzyme-linked immunosorbent assay. The patients received either endocrine therapy (n=96) or chemotherapy (n=74) as first-line treatment after diagnosis of advanced disease. Of the endocrine treated patients, those with high levels of uPA:PAI-I complex showed a shorter progression-free survival (PFS) compared to patients with lower uPA:PAI-I complex levels (P=0.035). Furthermore, in the multivariate regression analysis a significant lower rate of response to first-line endocrine therapy was found in patients with high uPA:PAI-I complex levels compared to patients with low uPA:PAI-I complex levels (odds ratio (OR)=0.27, 95% CI, 0.09-0.59, P=0.018), in addition to the predictive impact of the steroid hormone receptor (ER/PgR) status (OR=2.68, 95% CI, 1.08-6.63, P=0.033). Complex levels did not predict efficacy of chemotherapy in patients with advanced breast cancer. The results show that the plasminogen activation system affects the response to endocrine therapy independent of steroid hormone receptor status and may be of help to further refine the indication for this treatment in individual patients. Further studies are warranted to explain this underlying resistance to endocrine therapy when uPA:PAI-I levels are high.     

Vascular endothelial growth factor is associated with the efficacy of endocrine therapy in patients with advanced breast carcinoma

BACKGROUND: Vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and is associated with a poor prognosis in patients with primary breast carcinoma. In the current study, the authors investigated whether there was an association between VEGF levels in tumor tissues and response rates to first-line, systemic therapy in patients with advanced breast carcinoma. METHODS: In 172 tumors from patients with primary breast carcinoma who developed distant metastases during follow-up, cytosolic levels of VEGF were measured using a quantitative enzyme-linked immunosorbent assay. Patients received either endocrine therapy (n = 96) or chemotherapy (n = 76) as first-line treatment after they were diagnosed with advanced disease. RESULTS: In univariate logistic regression analysis for response to endocrine therapy in 96 patients, an increasing level of VEGF, as a log-transformed, continuous variable, was correlated with a poor rate of response (P = 0.043). In multivariate analysis, a significantly lower rate of response to first-line endocrine therapy was found for patients who had high VEGF levels compared with patients who had low VEGF levels (P = 0.025). Similar results were found for the subgroup of 82 patients who received tamoxifen (P = 0.011). An association of VEGF with response to first-line endocrine therapy was found in addition to a predictive impact for estrogen receptor/progesterone receptor status (P = 0.027). VEGF levels did not predict the rate of response to first-line chemotherapy. CONCLUSIONS: The results demonstrated that the level of VEGF affects response to endocrine therapy independent of steroid hormone receptor status and may help to refine further the indication for this treatment in individual patients. Further studies are warranted to explain this underlying resistance to endocrine therapy.     

Treatment and survival of patients with non-small cell lung cancer Stage IIIA diagnosed in 1989-1994: a study in the region of the Comprehensive Cancer Centre East, The Netherlands

The purpose of this study was to gain insight into the treatment policy and survival of patients with non-small cell lung cancer (NSCLC) clinical stage IIIA in daily practice. We selected 212 patients, who had been diagnosed between 1989 and 1994 and registered by the Cancer Registry, Comprehensive Cancer Centre East (CCCE). Diagnostic tests comprised chest X-ray and bronchoscopy in all cases but one, computed tomography in 89%, mediastinoscopy in 55% and conventional tomography of the chest in 16%. NSCLC had been verified histologically in 88% and cytologically in 12%. The initial treatment for the primary tumor had been surgery alone in 13% of the patients, surgery plus radiotherapy in 8%, radiotherapy alone in 56%, chemotherapy in 1% (three patients, one in addition to surgery); 22% received none of these treatments. Median survival of the 212 patients was 9.4 months (95% confidence interval 8.3-11.0 months). Overall survival rates after 1, 2 and 3 years were 41, 17 and 8%, respectively. Three-year survival of the patients who had undergone surgery, surgery plus radiotherapy, radiotherapy alone and no treatment was 18, 19, 6 and 4%, respectively. Treatment was an independent prognostic factor (multivariate Cox's proportional hazards analysis adjusted for sub-stage, age, number of co-morbid diseases and hospital). In the same model, the Hazard rate ratio for one hospital relative to the five others was 1.9 (95% confidence interval 1.2-2.8). Surgery (whether or not in combination with radiotherapy) independently gave the best results. In conclusion, policies varied between hospitals, although the variation in overall survival was small except at one hospital. New regional management guidelines are in preparation. Physicians will be encouraged to follow these guidelines, both with regard to diagnostic tests and to treatment policies, as our study showed that differences in policy might lead to differences in survival.