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V C G Tjan-Heijnen

Publications and source records attributed to V C G Tjan-Heijnen.

15 recordsLinked to original sources
PubMed2006

Development of quality indicators for diagnosis and treatment of patients with non-small cell lung cancer: a first step toward implementing a multidisciplinary, evidence-based guideline.

BACKGROUND: While developing and distributing clinical practice guidelines are important in optimising clinical healthcare, insight into actual care is necessary to achieve successful implementation. Developing quality indicators may be the first step to becoming aware of actual care. The Dutch national practice guideline Non-small cell lung cancer: staging and treatment is one of the first clinical, multidisciplinary guidelines for oncology in the Netherlands for which quality indicators were developed systematically. We describe indicator development based on this guideline as a practical experience. METHODS: To develop a set of indicators for diagnosis and treatment of patients with non-small cell lung cancer, we systematically achieved consensus on the basis of a national, multidisciplinary, evidence-based guideline and the opinions of professionals and patients. After the researchers extracted the recommendations from the guideline, we carried out a so-called Rand-modified-Delphi procedure. This consisted of three rounds: a national panel of professionals and representatives of the national patient organization scored all recommendations, the professionals had a consensus meeting, and the final set of indicators was e-mailed for a last check. Subsequently, some clinimetric characteristics of this final set were assessed in a practice test. RESULTS: Thirty-two of 83 recommendations were selected in the first round. After the consensus meeting, 8 recommendations met the final criteria and were incorporated into 15 indicators, which were tested in practice. The most successful indicators for quality improvement are indicators that are measurable, have potential for improvement, have a broad range between practices and are applicable to a large part of the population. CONCLUSIONS: For successful implementation of evidence-based guidelines, each new guideline should be developed and tested with a set of indicators based on the guideline. The procedure we describe can serve as an example for other new guidelines.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

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.

Adult↗
PubMed2005

[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.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Timely withdrawal of G-CSF reduces the occurrence of thrombocytopenia during dose-dense chemotherapy.

BACKGROUND: Post chemotherapy Granulocyte colony stimulating factor (G-CSF) reduces leucopenia, while G-CSF priming shortly before chemotherapy increases myelotoxicity. We performed a trial with a two-schedule crossover design to determine the optimal G-CSF schedule for densified 2-weekly chemotherapy. METHODS: During 2-weekly chemotherapy days 1 and 2, G-CSF was given on days 3-10, with a G-CSF-free interval before the next chemotherapy cycle of 5 days, or on days 3-13, with a G-CSF-free interval of 2 days. In schedule A, cycle II was preceded by a 5 days, cycle III and IV by a 2 days and cycle V by a 5 days G-CSF free interval. In schedule B, this was 2, 5, 5, and 2 days, respectively. RESULTS: Intra-patient comparison for cycles II versus III and cycles IV versus V showed that platelet (PLT) nadir count was significantly lower for cycles preceded by a 2-days compared to a 5-days G-CSF free interval: mean difference 45.7 x 10(9)/l (95% CI 33.2-58.2, p = 0.0001). Neutrophil count did not differ significantly (p = 0.85). CONCLUSION: Timely withdrawal of G-CSF in dose-dense chemotherapy reduces chemotherapy-related thrombocytopenia. Leucopenia was not aggravated, reflecting a protective effect of post-chemotherapy G-CSF.

Adult↗
PubMed2004

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.

Adolescent↗
PubMed2004

Vascular endothelial growth factor levels do not predict efficacy of systemic adjuvant treatment as assessed in 1127 breast cancer patients.

The vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and has proven to be of prognostic value in patients with primary breast cancer. In this study we investigated whether VEGF is of predictive value with regard to the efficacy of adjuvant systemic therapy in primary invasive breast cancer. In 1127 tumors of patients with invasive breast cancer the cytosolic levels of VEGF were measured using a quantitative enzyme-linked immunosorbent assay. These patients were followed for a median follow-up time of 59 months (range 2-268 months) after primary surgery. Correlations with well-known prognostic factors, and univariate and multivariate survival analyses were performed. The VEGF levels showed a positive correlation with age, menopausal status and tumor size. In addition, VEGF levels were inversely correlated with estrogen and progesterone receptor levels. A high VEGF level predicted an early relapse in the univariate relapse-free survival (RFS) analysis for all patients (P=0.010), but not in the multivariate analysis. Furthermore, there were no statistically significant interactions between the levels of VEGF and the use of adjuvant endocrine therapy or chemotherapy in the RFS analysis. We conclude that tumor levels of VEGF do not predict the efficacy of adjuvant endocrine therapy or chemotherapy in patients with primary breast cancer.

Adult↗
PubMed2003

Carboplatin and paclitaxol (Taxol) as an induction regimen for patients with biopsy-proven stage IIIA N2 non-small cell lung cancer. an EORTC phase II study (EORTC 08958).

The aim of this study was to document the activity and toxicity of paclitaxel (Taxol)/carboplatin when used as induction chemotherapy in patients with stage IIIA N2 non-small cell lung cancer (NSCLC) prior to definitive local treatment within a large, ongoing comparative study (EORTC 08941). 52 eligible, consenting, chemotherapy-naïve patients with NSCLC, median age of 60 years, stage IIIA N2 disease and the ability to tolerate a pneumonectomy received paclitaxel 200 mg/m2 as a 3-h infusion followed by carboplatin at an area under the concentration curve (AUC) of 6 every 3 weeks for three courses. Most patients received three courses. No grade 3/4 anaemia or thrombocytopenia was documented. Over all of the cycles, 6% (3 patients) experienced grade 3 leucopenia while 63% (32/51 patients) experienced grade 3-4 neutropenia. There was 1 patient (2%) with febrile neutropenia, no early or toxic deaths and no hypersensitivity reactions. Severe non-haematological toxicity was uncommon, with the exception of grade 3 alopecia in 39%, lethargy in 8% and myalgia in 6%. Of the eligible patients (n=52), there was one complete response (CR) and 32 partial responses (PR), resulting in a response rate of 64% (95% Confidence Interval (CI) 49%-76%). Of the 15 eligible patients randomised to surgery after induction chemotherapy, 3 patients did not receive surgery and 2 patients (n=12) had no tumour in the mediastinal nodes (17%). Resections were considered complete in 2 of the 12. Median survival for all eligible patients (n=52) was 20.5 months (95% CI 16.1-31.2), with an estimated 1-year survival rate of 68.5% (95% CI 55.2-81.7). In patients with N2 stage IIIA NSCLC, paclitaxel/carboplatin is an active and very well-tolerated induction regimen.

Adult↗
PubMed2003

EORTC Cancer in the Elderly Task Force guidelines for the use of colony-stimulating factors in elderly patients with cancer.

Increasing age is not, in itself, a contraindication to cancer chemotherapy. Myelosuppression, however, a common adverse consequence of the administration of many standard-dose chemotherapy regimens to both young and elderly patients with cancer, increases with age. The risk of development of febrile neutropenia may contribute to a reluctance to administer chemotherapy in the elderly patient population. We conducted a detailed literature search (1992-2002) to derive evidence-based conclusions on the value of prophylactic colony-stimulating factor (CSF) administration in elderly patients receiving chemotherapy. Sufficient evidence allows us to affirm that prophylactic granulocyte colony-stimulating factor (G-CSF) reduces the incidence of chemotherapy-induced neutropenia, febrile neutropenia and infections in elderly patients receiving myelotoxic chemotherapy for non-Hodgkin's lymphoma (NHL), small-cell lung cancer (SCLC) or urothelial tumours. Lack of available trial data does not allow similar conclusions to be drawn for other cancers studied, but it is likely that similar benefits would accrue from the use of prophylactic G-CSF. There is insufficient evidence to extend this recommendation to include the use of granulocyte-macrophage colony-stimulating factor (GM-CSF). There are insufficient data available to allow the evaluation of the impact of prophylactic CSF on the incidence of toxic deaths in elderly patients with cancer and this is a crucial question for geriatric oncology practice. There is no evidence in elderly patients that the delivery of standard-dose chemotherapy on schedule improves efficacy measures. The data show that febrile neutropenic events are more likely to occur during the first and second cycles of chemotherapy, thus prophylactic measures should be considered early in the course of treatment. Furthermore, since systematic dose reduction can impact on outcome, primary prophylactic use of G-CSF for all elderly patients receiving curative myelotoxic chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP-like) is indicated and we suggest a risk-adapted strategy with primary prophylactic G-CSF administration in high-risk patients. Dose intensification, through dose interval reduction, facilitated by prophylactic G-CSF, improved survival in elderly patients with some specific diseases. There is a need for further well-designed studies to identify the elderly patients who will benefit most from prophylactic G-CSF. To achieve this, we strongly urge the design of and participation in further trials.

Aged↗
PubMed2003

The prognostic value of the mitotic activity index in patients with primary breast cancer who were not treated with adjuvant systemic therapy.

BACKGROUND: At the St Gallen meeting of 2001 it was agreed to select high-risk patients for adjuvant systemic therapy by lymph node status, tumor size, age, hormone receptor status, and histological grade. In The Netherlands it was chosen to use either the histological grade or the mitotic activity index (MAI). The aim of this study was to retrospectively evaluate the independent prognostic value of the MAI in primary breast cancer patients, who were not treated with adjuvant systemic therapy, on relapse-free survival (RFS) and overall survival (OS). PATIENTS AND METHODS: The data of 137 systemically untreated patients with primary breast cancer diagnosed between 1992 and 1996, of whom MAI was assessed, were retrospectively collected. The MAI was correlated to classical prognostic factors and we determined the prognostic value of the MAI, the histological grade and other prognostic factors. RESULTS: The median observation time was 4.2 years. The MAI showed a positive correlation to lymph node status (P < 0.001) and a negative correlation to age (P = 0.005), menopausal status (P < 0.001) and the ER and PgR status (r(s) = -0.390 [ER], r(s) = -0.440 [PgR], both P < 0.001). A high MAI (> or = 15) predicted a reduced RFS and OS in the Kaplan-Meier analysis (P = 0.0070 and P = 0.0017, respectively). Also in the multivariate analysis, the MAI showed to be an independent predictor of poor RFS (P = 0.035), in addition to lymph node status. However, the MAI did not predict for OS, in contrast to tumor size and lymph node status. CONCLUSION: The present study confirms that the MAI is an independent prognostic factor for RFS, but not for OS and may be useful for daily clinical practice.

Adult↗
PubMed2003

Economic evaluation of antibiotic prophylaxis in small-cell lung cancer patients receiving chemotherapy: an EORTC double-blind placebo-controlled phase III study (08923).

BACKGROUND: To determine whether the cost of prophylactic antibiotics during chemotherapy is offset by cost savings due to a decreased incidence of febrile leukopenia (FL). PATIENTS AND METHODS: Small-cell lung cancer (SCLC) patients were randomised to standard or intensified chemotherapy with granulocyte colony-stimulating factor to assess the impact on survival (n = 244). In addition, patients were randomised to prophylactic ciprofloxacin and roxithromycin or placebo to assess the impact on FL (n = 161). The economic evaluation examined the costs and effects of patients taking antibiotics versus placebo. Medical resource utilisation was documented prospectively, including 33 patients from one centre in The Netherlands (NL) and 49 patients from one centre in Germany (GE). The evaluation takes the perspective of the health insurance systems and of the hospitals. Sensitivity analyses were performed. RESULTS: In the main trial, prophylactic antibiotics reduced the incidence of FL, hospitalisation due to FL and use of therapeutic antibiotics by 50%. In GE, the incidence of FL was not reduced by prophylaxis. This resulted in an average cost difference of only 35 Euros [95% confidence interval (CI) (-)1.713-2.263] in favour of prophylaxis (not significant). In NL, prophylaxis reduced the incidence of FL by nearly 50%, comparable with the results of the main trial, resulting in a cost difference of 2706 Euros [95% CI 810-5948], demonstrating savings in favour of prophylactic antibiotics of nearly 45%. Sensitivity analyses indicate that with an efficacy of prophylaxis of 50%, and with expected costs of antibiotic prophylaxis of 500 Euros or less, cost savings will incur over a broad range of baseline risks for FL; that is, a risk >10-20% for FL per cycle. CONCLUSIONS: Giving oral prophylactic antibiotics to SCLC patients undergoing chemotherapy is the dominant strategy in both GE and NL, demonstrating both cost-savings and superior efficacy. The sensitivity analyses demonstrate that, due to the efficacy of prophylactic antibiotics and their low unit cost, cost savings will incur over a broad range of baseline risks for FL. We recommend the use of prophylactic antibiotics in patients at risk for FL during chemotherapy.

Administration, Oral↗
PubMed2002

The prognostic value of vascular endothelial growth factor in 574 node-negative breast cancer patients who did not receive adjuvant systemic therapy.

The growth and metastasising capacity of solid tumours are dependent on angiogenesis. Vascular endothelial growth factor is a mediator of angiogenesis. In this study we investigated whether vascular endothelial growth factor is associated with the natural course of the disease in primary invasive breast cancer. In 574 tumours of patients with node-negative invasive breast cancer the cytosolic levels of vascular endothelial growth factor were measured using a quantitative enzyme-linked immunosorbent assay. These patients did not receive adjuvant systemic therapy and were followed for a median follow-up time of 61 months (range 2-155 months) after the primary diagnosis. Correlations with well-known prognostic factors, and univariate and multivariate survival analyses were performed. Vascular endothelial growth factor level was positively associated with age and tumour size (P=0.042 and P=0.029, respectively). In addition, vascular endothelial growth factor level was inversely, but weakly correlated with progesterone receptor levels (PgR) (r(s)=-0.090, P=0.035). A high vascular endothelial growth factor level (equal or above the median level of 0.53 ng mg(-1) protein) predicted a reduced relapse-free survival and overall survival in the univariate survival rate analysis (for both P=0.005). In the multivariate analysis as well, vascular endothelial growth factor showed to be an independent predictor of poor relapse-free survival and overall survival (P=0.045 and P=0.029, respectively), in addition to age, tumour size and PgR. The results show that cytosolic levels of vascular endothelial growth factor in tumour tissue samples are independently indicative of prognosis for patients with node-negative breast cancer who were not treated with adjuvant systemic therapy. This implies that vascular endothelial growth factor is related with the natural course of breast cancer progression.

Adult↗
PubMed2002

An analysis of chemotherapy dose and dose-intensity in small-cell lung cancer: lessons to be drawn.

BACKGROUND: The survival in untreated small-cell lung cancer (SCLC) is <3 months. Prognosis has improved with chemotherapy, but remains poor. One of the issues concerning current chemotherapy is whether there is any benefit of increasing chemotherapy dose or dose intensity (DI). DESIGN: In the present review, 20 randomised studies, published in the period 1980-2001, in which dose or DI of chemotherapy in SCLC were the only variables tested, are analysed. The studies were categorised as follows: (i) number of cycles (treatment duration); (ii) dose per cycle; (iii) interval between cycles (dose densification); and (iv) a combination of these variables. RESULTS: (i) With treatment duration reduced to three to six cycles, median survival time (MST) was 2 months shorter, most evident in patients showing a (complete) response to initial chemotherapy. (ii) An improved survival was observed in two out of five high-dose studies. (iii) Survival was increased by 0.6 to 6.2 months in all four densification studies. (iv) Survival was not improved in studies that used dose-escalation and/or -densification in combination with a reduced number of cycles. The sample sizes were too small to be conclusive in most of the individual trials. The median of the MSTs in the 20 trials taken together was 9.8 months for the standard arms and 11.5 months for the intensified arms (i.e. more cycles, higher dose per cycle and/or shorter intervals). After omitting the two trials with reduced number of cycles in the so-called 'high-dose' arm, the median of MSTs was 8.7 and 11.5 months, respectively. There was only a slight improvement (1%) in 2-year survival for all trials taken together. However, when only taking high-dose and dose-densified chemotherapy trials into account, the difference in median 2-year survival became 19% (12% versus 31%). CONCLUSIONS: The above classification facilitates our understanding about doses of chemotherapy and it makes us appreciate the relevance of the individual determinants. It appears that the number of cycles, dose level, dose density, cumulative dose and DI are all important factors for improving survival. Intensification of chemotherapy still deserves further research in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗