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M J Bolster,
M J Pepels,
C A P Wauters,
R F M Schapers,
J W R Meijer,
L J A Strobbe,
C L H van Berlo,
J H G Klinkenbijl,
T Wobbes,
A C Voogd,
P Bult, V C G Tjan-Heijnen
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ABSTRACT: BACKGROUND: Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN) in breast cancer patients. Previously, we reported that ultra-staging led to more axillary lymph node dissections (ALND). The question was, whether ultra-staging is effective in reducing the risk of regional relapse. METHODS: From January 2002 to July 2003, 541 patients from 4 hospitals were prospectively registered when they underwent a SN biopsy. In hospitals A, B, and C, 3 levels of the SN were examined pathologically, whereas in hospital D at least 7 additional levels were examined. Patients with a positive SN, including isolated tumor cells, underwent an ALND. This analysis focuses on the 341 patients with a negative SN. Primary endpoint was 5-year regional recurrence rate. RESULTS: In hospital D 34% of the patients had a negative SN as compared to 71% in hospitals A, B, and C combined (p < 0.001). At 5 years follow-up, 9 (2.6%) patients had developed a regional lymph node relapse. In hospital D none of the patients had a regional recurrence, as compared to 9 (2.9%) cases of recurrence in hospitals A, B, and C. CONCLUSION: The less intensified SN pathology protocol appeared to be associated with a slightly increased risk of regional recurrence. The absolute risk was still less than 3%, and does not seem to justify the intensified SN pathology protocol of hospital D.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 02/2013; · 2.56 Impact Factor
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ABSTRACT: OBJECTIVES: This systematic review aimed to assess the role of magnetic resonance imaging (MRI) in evaluating residual disease extent and the ability to detect pathologic complete response (pCR) after neoadjuvant chemotherapy for invasive breast cancer. METHODS: PubMed, the Cochrane Library, MEDLINE, and Embase databases were searched for relevant studies published until 1 July 2012. After primary selection, two reviewers independently assessed the content of each eligible study using a standardised extraction form and pre-defined inclusion and exclusion criteria. RESULTS: A total of 35 eligible studies were selected. Correlation coefficients of residual tumour size assessed by MRI and pathology were good, with a median value of 0.698. Reported sensitivity, specificity, positive predictive value and negative predictive value for predicting pCR with MRI ranged from 25 to 100 %, 50-97 %, 47-73 % and 71-100 %, respectively. Both overestimation and underestimation were observed. MRI proved more accurate in determining residual disease than physical examination, mammography and ultrasound. Diagnostic accuracy of MRI after neoadjuvant chemotherapy could be influenced by treatment regimen and breast cancer subtype. CONCLUSIONS: Breast MRI accuracy for assessing residual disease after neoadjuvant chemotherapy is good and surpasses other diagnostic means. However, both overestimation and underestimation of residual disease extent could be observed. MAIN MESSAGES : • Breast MRI accuracy for assessing residual disease is good and surpasses other diagnostic means. • Correlation coefficients of residual tumour size assessed by MRI and pathology were considered good. • However, both overestimation and underestimation of residual disease were observed. • Diagnostic accuracy of MRI seems to be affected by treatment regimen and breast cancer subtype.
Insights into imaging. 01/2013;
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ABSTRACT: We compared the breast core needle biopsy and the resection specimen with respect to estrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (HER2) status to identify predictors for discordant findings. We retrospectively collected data from 526 newly diagnosed breast cancer patients. ER, PR and HER2 status had been assessed in both the core needle biopsy and resection specimen. The assessment of ER by immunohistochemistry (IHC) in core needle biopsy was false negative in 26.5% and false positive in 6.8% of patients. For the PR status the false negative and false positive results of core needle biopsy were 29.6% and 10.3%, respectively. The results of the HER2 status, as determined by IHC and silver in situ hybridization (SISH), were false negative in 5.4% and false positive in 50.0%. We need to be aware of the problem of false negative and false positive test results in ER, PR and HER2 assessment in core needle biopsy and the potential impact on adjuvant systemic treatment. With current techniques, we recommend using the resection specimen to measure these receptors in patients without neoadjuvant treatment. A better alternative might be the use of tissue microarray, combining both core needle biopsy and resection specimen.
Tumor Biology 12/2012; · 1.94 Impact Factor
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ABSTRACT: OBJECTIVES: To assess whether magnetic resonance imaging (MRI) can identify pre-treatment differences or monitor early response in breast cancer patients receiving neoadjuvant chemotherapy. METHODS: PubMed, Cochrane library, Medline and Embase databases were searched for publications until January 1, 2012. After primary selection, studies were selected based on predefined inclusion/exclusion criteria. Two reviewers assessed study contents using an extraction form. RESULTS: In 15 studies, which were mainly underpowered and of heterogeneous study design, 31 different parameters were studied. Most frequently studied parameters were tumour diameter or volume, K(trans), K(ep), V(e), and apparent diffusion coefficient (ADC). Other parameters were analysed in only two or less studies. Tumour diameter, volume, and kinetic parameters did not show any pre-treatment differences between responders and non-responders. In two studies, pre-treatment differences in ADC were observed between study groups. At early response monitoring significant and non-significant changes for all parameters were observed for most of the imaging parameters. CONCLUSIONS: Evidence on distinguishing responders and non-responders to neoadjuvant chemotherapy using pre-treatment MRI, as well as using MRI for early response monitoring, is weak and based on underpowered study results and heterogeneous study design. Thus, the value of breast MRI for response evaluation has not yet been established. KEY POINTS: • Few well-validated pre-treatment MR parameters exist that identify responders and non-responders. • Eligible studies showed heterogeneous study designs which hampered pooling of data. • Confounders and technical variations of MRI accuracy are not studied adequately. • Value of MRI for response evaluation needs to be established further.
European Radiology 09/2012; · 3.22 Impact Factor
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J H M J Vestjens,
M J Pepels,
M de Boer,
G F Borm,
C H M van Deurzen,
P J van Diest,
J A A M van Dijck,
E M M Adang,
J W R Nortier,
E J Th Rutgers,
C Seynaeve,
M B E Menke-Pluymers,
P Bult, V C G Tjan-Heijnen
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ABSTRACT: Background In the MIRROR study, pN0(i + ) and pN1mi were associated with reduced 5-year disease-free survival (DFS) compared with pN0. Nodal status (N-status) was assessed after central pathology review and restaging according to the sixth AJCC classification. We addressed the impact of pathology review. Patients and methods Early favorable primary breast cancer patients, classified pN0, pN0(i + ), or pN1(mi) by local pathologists after sentinel node procedure, were included. We assessed the impact of pathology review on N-status (n = 2842) and 5-year DFS for those without adjuvant therapy (n = 1712). Results In all, 22% of the 1082 original pN0 patients was upstaged. Of the 623 original pN0(i + ) patients, 1% was downstaged, 26% was upstaged. Of 1137 patients staged pN1mi, 15% was downstaged, 11% upstaged. Originally, 5-year DFS was 85% for pN0, 74% for pN0(i + ), and 73% for pN1mi; HR 1.70 [95% confidence interval (CI) 1.27-2.27] and HR 1.57 (95% CI 1.16-2.13), respectively, compared with pN0. By review staging, 5-year DFS was 86% for pN0, 77% for pN0(i + ), 77% for pN1mi, and 74% for pN1 + . Conclusion Pathology review changed the N-classification in 24%, mainly upstaging, with potentially clinical relevance for individual patients. The association of isolated tumor cells and micrometastases with outcome remained unchanged. Quality control should include nodal breast cancer staging.
Annals of Oncology 04/2012; 23(10):2561-6. · 6.43 Impact Factor
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M de Boer,
E M M Adang,
K C G Van Dycke,
J A A M van Dijck,
G F Borm,
S C Seferina,
C H M van Deurzen,
P J van Diest,
P Bult,
A R T Donders, V C G Tjan-Heijnen
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ABSTRACT: Background The cost-effectiveness of adjuvant systemic therapy in patients with low-risk breast cancer and nodal isolated tumor cells or micrometastases is unknown. Patients and methods A cost-effectiveness analysis of adjuvant systemic therapy was carried out using the costs per 1% event prevented after 5 years of follow-up as incremental cost-effectiveness ratio (ICER). Secondary objective was to establish when adjuvant systemic therapy becomes cost saving. Patients included in the MIRROR study with isolated tumor cells or micrometastases who had a complete 5-year follow-up and who either did or did not receive systemic therapy were eligible. Sensitivity analyses were carried out. Results In the no adjuvant therapy cohort (N = 366), 24.9% of patients had an event within 5 years versus 16.8% of patients in the adjuvant therapy cohort (N = 483) (P < 0.01). The ICER was €363 per 1% event prevented. Beyond 18 years after diagnosis, the extrapolated mean cumulative costs per patient in the no adjuvant therapy cohort exceeded those of the adjuvant therapy cohort. Conclusions In this population of breast cancer patients with isolated tumor cells or micrometastases, €36 300 had to be invested to prevent one event in 5 years of follow-up. Adjuvant systemic therapy was cost saving beyond 18 years after diagnosis.
Annals of Oncology 03/2012; 23(10):2585-91. · 6.43 Impact Factor
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ABSTRACT: To evaluate the trend in the use of primary endocrine treatment (PET) for elderly patients with operable breast cancer and to study mean time to response (TTR), local control, time to progression (TTP), and overall survival.
Data of 184 patients aged≥75 years, diagnosed with breast cancer in the south of the Netherlands between 2001 and 2008 and receiving PET, were analyzed.
The percentage of women≥75 years with breast cancer receiving PET in the south of the Netherlands decreased from 23% in the period 1988-1992 to 12% in 1997-2000, and increased to 29% in 2005-2008. Mean age at diagnosis of 184 patients treated with PET in the period 2001-2008 was 84 years (range 75-89 years). Mean length of follow-up was 2.6 years. In 107 patients (58%), an initial response was achieved (mean TTR 7 months), 21 patients (12%) showed stable disease. A total of 64 patients (35%), with or without prior response, eventually displayed progression (mean TTP 20 months). No differences in TTR and TTP were observed between the patients starting with tamoxifen or an aromatase inhibitor. One hundred nineteen (65%) of 184 patients had died by January 1, 2010. In 17 patients (14%), breast cancer was the cause of death.
Tumor progression was observed in a substantial proportion of the cohort, but only a small number of patients died of breast cancer. Further research is needed on the safety and effectiveness of PET for elderly women with breast cancer to justify the current widespread use.
Annals of Surgical Oncology 10/2011; 19(4):1185-91. · 4.17 Impact Factor
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ABSTRACT: Though most studies on surgical resection of the breast tumor in patients with primary distant metastatic breast cancer (MBC) indicated that surgery is associated with prolonged overall survival, some state that this effect has been confounded by indication and timing of surgery. In this study we analyzed these possible confounders and their relation to overall survival.
To determine the impact of potential confounders, individual charts of 279 patients with primary MBC were reviewed.
The median survival in patients treated with surgery of the breast tumor was 39 months, compared to 15 months for those without surgery (p < 0.0001). The median survival of patients with symptomatic metastatic disease (n = 112) was 19 months, compared to 22 months for those without symptomatic disease (n = 167) (p = 0.15). Patients who received surgery and whose metastases were detected before surgery of the breast tumor had taken place (n = 40) had a median survival of 38 months, compared to 40 months for patients in whom the metastatic disease was diagnosed after surgery (n = 43) (p = 0.81).
Presence of symptomatic metastatic disease was no significant prognostic factor for patients with distant metastasis at diagnosis, neither was the timing of surgery. It is unlikely that the prolonged survival after surgery is explained by these potentials confounders.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 08/2011; 37(10):883-9. · 2.56 Impact Factor
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R I Lalisang,
F L G Erdkamp,
C J Rodenburg,
C T A M Knibbeler-van Rossum,
J W R Nortier,
A van Bochove,
P H Th J Slee,
E E Voest,
J A Wils,
J Wals,
O J L Loosveld,
A E M Smals,
G H Blijham, V C G Tjan-Heijnen,
H C Schouten
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ABSTRACT: An increased dose-intensity can be achieved by either higher dose of chemotherapy per cycle (dose-escalation) or by shortening the interval between cycles (dose-dense). This multicenter randomized phase II study assessed the efficacy and safety of two different approaches: epirubicin 110 mg/m(2) combined with paclitaxel 200 mg/m(2) every 21 days and epirubicin 75 mg/m(2) combined with paclitaxel 175 mg/m(2) every 10 days, both supported with G-CSF. Patients with advanced breast cancer and without prior palliative chemotherapy were scheduled for 6 cycles. Evaluable for response were 101 patients and for toxicity 106 patients. Grade ≥ 3 toxicities occurred in 39% of patients in the dose-escalated arm and in 29% of the dose-dense arm, mainly febrile neutropenia, thrombocytopenia, neurotoxicity and (asymptomatic) cardiotoxicity. The median delivered cumulative doses for epirubicin/paclitaxel were 656/1194 and 448/1045 mg/m(2), treatment durations were 126 and 61 days, and delivered dose intensities were 36/67 and 51/120 mg/m(2)/week for the dose-escalated and dose-dense arm, respectively. Response rates were 75 and 70%, the progression-free survival 6 and 7 months, respectively. Dose-dense chemotherapy with a lower cumulative dose, a halved treatment time, but a higher dose-intensity may be as effective and safe as dose-escalated chemotherapy. The value of dose-densification over standard scheduled chemotherapy regimes yet needs to be determined.
Breast Cancer Research and Treatment 07/2011; 128(2):437-45. · 4.43 Impact Factor
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ABSTRACT: Trastuzumab in conjunction with adjuvant chemotherapy markedly improves outcome. In the Netherlands, a national guideline was released in September 2005 stating that trastuzumab should be given in conjunction with adjuvant chemotherapy in women with HER2-positive breast cancer. Aim of this study was to identify the number of women with HER2-positive breast cancer and to evaluate the level of implementation of adjuvant trastuzumab in clinical practice nationwide. Women diagnosed with primary breast cancer between September 2005 and January 2007 were selected from the Netherlands Cancer Registry (NCR). HER2 status, adjuvant treatment and reasons to withhold trastuzumab were registered. 14,934 Breast cancer patients were diagnosed in this period of whom 1,928 (13%) had a HER2-positive tumour. Of all HER2-positive women receiving adjuvant chemotherapy, 66 (6%) did not receive trastuzumab. This percentage decreased from 10% at the time of introduction of the guideline to 4% in the study period September 2005-December 2006. Most common reasons to withhold trastuzumab were cardiovascular disease (29%) and patient refusal (21%). Of all HER2-positive patients who received adjuvant chemotherapy, 94% received trastuzumab. The implementation of trastuzumab in clinical practice was realized within 8 months after introduction of the new guideline.
Breast Cancer Research and Treatment 03/2011; 129(1):229-33. · 4.43 Impact Factor
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ABSTRACT: In this study, changes in prognosis for more than 8,000 patients with primary distant metastatic breast cancer were analyzed, using nation-wide data of the Netherlands Cancer Registry. Besides the roll of systemic treatment, the effect of surgery of the primary tumor was evaluated. Between 1995 and 2008, 160,595 new patients were diagnosed with invasive breast cancer. Of these patients, 8,031 (5.0%) had distant metastases at diagnosis. Patients were divided into three periods, based on the year of diagnosis of their disease. The median survival was 1.42 years for patients diagnosed in the period 1995-1999, 1.61 years in the period 2000-2004 and 1.95 years in the period 2005-2008. The improvement of the median survival was most pronounced for patients younger than 50 years. Patients receiving systemic treatment, loco-regional radiotherapy or breast surgery had a significantly lower risk of death compared to patients not receiving these treatments. An improvement of 6 months is observed in the median survival of patients with primary distant metastatic breast cancer between 1995 and 2008. The increased efficacy of chemotherapy and the introduction of targeted treatments are the most likely explanations for this improvement, which was most marked for younger patients.
Breast Cancer Research and Treatment 01/2011; 128(2):495-503. · 4.43 Impact Factor
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ABSTRACT: To describe variation in staging and primary treatment by hospital characteristics including type and volume and region in patients with early breast cancer (BC) in the Netherlands, 2003-2006 after completion of national guidelines in 2002.
All patients newly diagnosed with invasive BC in 2003-2006 and recorded in the Netherlands Cancer Registry were included (n = 51 354). Multivariable logistic regression analyses examined the influence of patient and hospital characteristics, also by region, on type of breast surgery, axillary lymph node dissection (ALND), sentinel node procedure (SNP), and adjuvant irradiation and/or systemic treatment.
Patients <40 years more often underwent breast conserving surgery (BCS) in general hospitals (OR 1.4 (95%CI 1.1-1.5)) than in teaching and academic hospitals, whereas patients of 40-69 years less often received BCS in an academic hospital (OR 0.9 (95%CI 0.8-1.0)) than in teaching hospitals. Patients with pT1-2N0 cancer more often underwent primary ALND in a general hospital than in a larger teaching or academic hospital. Type of hospital did not seem to affect utilization of adjuvant systemic therapy, but patient age and tumour size and grade did. Over time, patients more often received SNP, BCS, and adjuvant systemic therapy, primary ALND being on the decline, but with substantial regional variation between geographic regions.
With detailed evidence-based national guidelines since 2002 the considerable regional and hospital variation in staging procedures and primary treatment among newly diagnosed patients with early breast cancer in the Netherlands decreased markedly, suggesting the presence of late adaptors rather than specific hospital characteristics.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 09/2010; 36 Suppl 1:S36-43. · 2.56 Impact Factor
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ABSTRACT: The prognostic relevance of isolated tumor cells and micrometastases in lymph nodes from patients with breast cancer has become a major issue since the introduction of the sentinel lymph node procedure. We conducted a systematic review of this issue.
Studies published from January 1, 1977, until August 11, 2008, were identified by use of MEDLINE, EMBASE, and the Cochrane Library. A total of 58 studies (total number of patients = 297,533) were included and divided into three categories according to the method for pathological assessment of the lymph nodes: cohort studies with single-section pathological examination of axillary lymph nodes (n = 285,638 patients), occult metastases studies with retrospective examination of negative lymph nodes by step sectioning and/or immunohistochemistry (n = 7740 patients), and sentinel lymph node biopsy studies with intensified work-up of the sentinel but not of the nonsentinel lymph nodes (n = 4155 patients). We used random-effects meta-analyses to calculate pooled estimates of the relative risks (RRs) of 5- and 10-year disease recurrence and death and the multivariably corrected pooled hazard ratio (HR) of overall survival of the cohort studies.
In the cohort studies, the presence (vs the absence) of metastases of 2 mm or less in diameter in axillary lymph nodes was associated with poorer overall survival (pooled HR of death = 1.44, 95% confidence interval [CI] = 1.29 to 1.62). In the occult metastases studies, the presence (vs the absence) of occult metastases was associated with poorer 5-year disease-free survival (pooled RR = 1.55, 95% CI = 1.32 to 1.82) and overall survival (pooled RR = 1.45, 95% CI = 1.11 to 1.88), although these endpoints were not consistently assessed in multivariable analyses. Sentinel lymph node biopsy studies were limited by small patient groups and short follow-up.
The presence (vs the absence) of metastases of 2 mm or less in diameter in axillary lymph nodes detected on single-section examination was associated with poorer disease-free and overall survival.
CancerSpectrum Knowledge Environment 02/2010; 102(6):410-25. · 14.07 Impact Factor
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ABSTRACT: Recent studies indicate that removal of the primary tumour may have a beneficial effect on mortality risk of patients with primary distant metastatic breast cancer (stage IV), although most of them did not rule out confounding by the presence of co-morbidity. In this retrospective study the impact of surgical resection of the primary tumour on the survival of patients with primary distant metastatic disease is investigated, taking into account the presence of co-morbidity and other potential confounders.
Between 1993 and 2004, 15 769 patients with breast cancer were diagnosed in the south of the Netherlands. This study included the 728 patients with distant metastatic disease at initial presentation, which was 5% of all patients. Of them, 40% had surgery of the primary tumour. Follow-up was carried out until 1 July 2006.
Median survival of the patients who had surgery of their primary tumour was significantly longer than for the patients who did not have surgery (31 vs. 14 months). The 5-year survival rates were 24.5% and 13.1%, respectively (p < 0.0001). In a multivariable Cox regression analysis, adjusting for age, period of diagnosis, T-classification, number of metastatic sites, co-morbidity, use of loco-regional radiotherapy and use of systemic therapy, surgery appeared to be an independent prognostic factor for overall survival (HR = 0.62; 95% CI 0.51-0.76).
Removal of the primary tumour in patients with primary distant metastatic disease was associated with a reduction of the mortality risk of around 40%. The association was independent of age, presence of co-morbidity and other potential confounders, but a randomized controlled trial will be needed to rule out residual confounding.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 04/2009; 35(11):1146-51. · 2.56 Impact Factor
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ABSTRACT: HER2 positive breast cancers are characterized by their aggressive course of disease. Treatment with trastuzumab has significantly improved survival of patients with these cancers. Trastuzumab has few side effects, although in 10-15% of cases it is necessary to interrupt therapy because of cardiotoxicity, in most cases temporarily. It has become clear that patients receiving trastuzumab more frequently develop brain metastases than patients with a HER2 negative tumor. It is important to realize that patients with brain metastases from a HER2 positive breast tumor have a more favorable prognosis than patients with brain metastases from a HER2 negative tumor. Continuation of treatment with trastuzumab should be considered, next to the surgical intervention and/ or radiotherapy. Recently, lapatinib, a tyrosine kinase inhibitor, was registered by EMEA for patients with a HER2 positive tumor after previous treatment with anthracyclines, taxanes and trastuzumab. In combination with capacitabine, this agent leads to partial responses of cerebral metastases. More HER2 targeting drugs are expected to be introduced.
Nederlands tijdschrift voor geneeskunde 01/2009; 152(50):2701-6.
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ABSTRACT: The incidence of breast cancer in the Netherlands in women under 40 years has been more or less stable for the last 2 decades, while the mortality rate has decreased in the same period. Breast cancer in young women generally has a worse prognosis than in older women. Systemic therapy reduces the risk oflocoregional relapse after breast-conserving therapy from approximately 2% to less than 1% on an annual basis. Breast-conserving therapy therefore seems to be a safe option in young women who have consented beforehand to receive adjuvant systemic therapy. According to current treatment guidelines, adjuvant systemic therapy will be offered to approximately 80% of young breast cancer patients. The risk of premature postmenopausal symptoms, osteoporosis and unwanted infertility are, however, disadvantages of adjuvant chemotherapy and hormonal therapy. This specific treatment-related toxicity in young breast cancer patients requires support by experts with endowments for these specific issues.
Nederlands tijdschrift voor geneeskunde 12/2008; 152(46):2495-500.
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H Struikmans,
J W R Nortier,
E J Th Rutgers,
H M Zonderland,
M Bontenbal,
P H M Elkhuizen,
G van Tienhoven, V C G Tjan-Heijnen,
T van Vegchel,
M K Tuut,
J Benraadt
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ABSTRACT: The Dutch evidence-based guideline 'Treatment of breast cancer' has been revised, and integrated with the guideline 'Screening for and diagnosis of breast cancer'. The guideline can be found on www. oncoline.nl and on www.cbo.nl. The Internet programme 'Adjuvant!' (www.adjuvantonline.com) can be used to predict both the prognosis and the efficacy of systemic adjuvant therapy for each patient. The indications for adjuvant chemotherapy and endocrine therapy have been widened. The aim is to reduce the absolute probability of death by at least 4-5% within 10 years. The goal of neoadjuvant chemotherapy in operable breast cancer is to enable breast-conserving therapy for large tumours in relatively small breasts. One could consider transferring responsibility for follow-up after 5 years from the hospital to the screening organisation following mastectomy, to the family doctor following breast-conserving therapy, and to an outpatient clinic for hereditary tumours in carriers of gene mutation. Cessation of follow-up above the age of 75 could also be considered.
Nederlands tijdschrift voor geneeskunde 12/2008; 152(46):2507-11.
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ABSTRACT: In advanced non-small cell lung cancer (NSCLC) the clinical benefit of a platinum-based doublet is only modest, therefore, attenuated dosed three-drug combinations are investigated. We hypothesized that with adequate support a full dosed chemotherapy triplet is feasible. The study was designed as a dose finding study of paclitaxel in chemotherapy-naive patients. Paclitaxel was given as a 3-h infusion on day 1, followed by fixed doses of teniposide (or etoposide) 100mg/m(2) days 1, 3, 5 and cisplatin 80 mg/m(2) day 1 every 3 weeks. As myelotoxicity was expected to be the dose-limiting toxicity, prophylactic G-CSF and antibiotic support was evaluated. Indeed, paclitaxel 120 mg/m(2) resulted in dose-limiting neutropenia, despite G-CSF support. Teniposide/etoposide day 1, 3, 5 was less myelotoxic compared to day 1, 2, 3. G-CSF support allowed paclitaxel dose-escalation to 250 mg/m(2). The addition of prophylactic antibiotics enabled dose-escalation to 275 mg/m(2) without reaching MTD. In conclusion, G-CSF and antibiotics prophylaxis enables the delivery of a full dosed chemotherapy triplet in previously untreated NSCLC patients.
Lung Cancer 06/2008; 60(2):222-30. · 3.43 Impact Factor
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ABSTRACT: Two women, aged 57 and 55 years, with metastatic breast cancer were admitted for uncontrolled pain due to bone metastases. Despite the fact that progressive disease was evident, a change in antitumour therapy had not been recommended. The pain control was optimised in both patients. In one patient, palliative chemotherapy was installed, combined with trastuzumab because of HER2/neu overexpression. She was still alive after one and a half year of treatment. The other patient could not adjust mentally to the fact that her palliative therapy was changed to antitumour therapy; she died one month later. It is important to be aware of the various kinds of therapy in metastatic breast cancer because palliative treatment is more than just symptomatic treatment. Systemic antitumour therapy includes hormone therapy, chemotherapy and targeted therapy. Furthermore, in patients with bone metastases, radiotherapy combined with bisphosphonates results in pain relief and can reduce skeletal complications. Because of the ensuing complexity of the treatment of metastatic breast cancer, these patients should be regularly managed by a breast-cancer care team in order to improve the quality of care.
Nederlands tijdschrift voor geneeskunde 04/2007; 151(12):673-8.
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R P M G Hermens,
M M T J Ouwens,
S Y Vonk-Okhuijsen,
Y van der Wel, V C G Tjan-Heijnen,
L D van den Broek,
V K Y Ho,
M L G Janssen-Heijnen,
H J M Groen,
R P T M Grol,
H C H Wollersheim
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ABSTRACT: 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.
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.
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.
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.
Lung Cancer 11/2006; 54(1):117-24. · 3.43 Impact Factor
