A 'SMART' way to determine treatment goals in pharmacotherapy education.

Aim: Determining treatment goals is an important part of the treatment decision-making process, but medical students are not trained in a structural way on how to define these goals. 'SMART' criteria are widely used in non-medical professions for determining goals and may improve treatment goal setting. The aim of this study was to assess the effect of implementation of SMART criteria on medical students' ability to set treatment goals and to analyze the effects on treatment choice and monitoring.

Excision Repair Cross-Complementation group 1 (ERCC1) C118T SNP does not affect cellular response to oxaliplatin.

Aims: ERCC1 is involved in the repair of oxaliplatin-induced DNA damage. Studies for the association of the C118T SNP with clinical response to treatment with platinum drugs have rendered inconsistent results. We investigated the ERCC1 C118T SNP with respect to overall and progression-free survival in patients with advanced colorectal cancer (ACC) treated with oxaliplatin and in vitro DNA repair capacity after oxaliplatin exposure.

Correlation of FCGR3A and EGFR germline polymorphisms with the efficacy of cetuximab in KRAS wild-type metastatic colorectal cancer.

Background: Next to KRAS mutation status, additional predictive markers are needed for the response to cetuximab in patients with metastatic colorectal cancer (mCRC). Previous studies indicated that germline polymorphisms in specific genes may predict efficacy and toxicity of cetuximab in mCRC patients.

Methods: Germline DNA was isolated from 246 KRAS wild-type mCRC patients who were treated in the phase III CAIRO2 study with chemotherapy and bevacizumab alone or with the addition of cetuximab.

The relevance of breast cancer subtypes in the outcome of neoadjuvant chemotherapy.

Background: Breast cancer is increasingly considered a heterogeneous disease. The aim of this study was to assess the differences between histological and receptor-based subtypes in breast-conserving surgery and pathological complete response (pCR) after neoadjuvant chemotherapy.

Method: A consecutive series of 254 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed.

Do medical students copy the drug treatment choices of their teachers or do they think for themselves?

Purpose: Although the importance of rational prescribing is generally accepted, the teaching of pharmacotherapy to undergraduate medical students is still unsatisfactory. Because clinical teachers are an important role model for medical students, it is of interest to know whether this extends to therapeutic decision-making. The aim of this study was to find out which factors contribute to the drug choices made by medical students and their teachers (general practitioners and clinical specialists).

Impact of pathological characteristics on local relapse after breast-conserving therapy: a subgroup analysis of the EORTC boost versus no boost trial.

Purpose: To investigate the long-term impact of pathologic characteristics and an extra boost dose of 16 Gy on local relapse, for stage I and II invasive breast cancer patients treated with breast conserving therapy (BCT).

Patients And Methods: In the European Organisation for Research and Treatment of Cancer boost versus no boost trial, after whole breast irradiation, patients with microscopically complete excision of invasive tumor, were randomly assigned to receive or not an extra boost dose of 16 Gy. For a subset of 1,616 patients central pathology review was performed.

Comparison of three micromorphometric pathology classifications of melanoma metastases in the sentinel node.

Objective: The purposes of this study were to determine which classification best predicts additional lymph node disease and survival, and to suggest a threshold below which a completion dissection may be omitted.

Summary Background Data: Three micromorphometric parameters of melanoma sentinel node metastases were compared: invasion depth from the capsule (Starz-classification), maximum diameter (Rotterdam-criteria), and location within the node (Dewar-classification).

Methods: The pathology slides of 116 patients with tumor-positive sentinel nodes were reviewed.

Explorative study to identify novel candidate genes related to oxaliplatin efficacy and toxicity using a DNA repair array.

Purpose: To identify new polymorphisms (single nucleotide polymorphisms, SNPs) in DNA repair pathways that are associated with efficacy and toxicity in patients receiving oxaliplatin and capecitabine for advanced colorectal cancer (ACC).

Methods: We studied progression-free survival (PFS) in 91 ACC patients, of whom germ-line DNA was isolated and genotyped using an Asper Biotech array. Overall survival (OS) and toxicity were studied as secondary end points.

The influence of the use of CT-planning on the irradiated boost volume in breast conserving treatment.

Background And Purpose: The purpose of this study was to investigate the effect of CT-based delineation and planning on the irradiated boost volume. For this specific purpose we used the data as derived from 2 prospective phase III randomised trials.

Patients And Methods: Data from 1331 patients ( View Article and Find Full Text PDF

Is completion lymph node dissection needed in case of minimal melanoma metastasis in the sentinel node?

Objective: The purpose of this study was to evaluate the micromorphometric Starz-classification in melanoma patients.

Summary Background Data: The micromorphometric Starz-classification suggests that melanoma patients with a sentinel node metastasis invading no more than 0.3 mm (S-I) or 0.

Quantitative intra-operative assessment of peritoneal carcinomatosis - a comparison of three prognostic tools.

Aims: Selecting patients for cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (HIPEC) remains challenging. We compared the predictive power of three intra-operative assessment tools of peritoneal involvement of colorectal cancer.

Methods: Ninety-two procedures (1999-2005) were prospectively scored using the Simplified Peritoneal Cancer Index (SPCI) and 7 Region Count.

Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer.

Background: Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer.

Methods: We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients).

Deficient mismatch repair system in patients with sporadic advanced colorectal cancer.

A deficient mismatch repair system (dMMR) is present in 10-20% of patients with sporadic colorectal cancer (CRC) and is associated with a favourable prognosis in early stage disease. Data on patients with advanced disease are scarce. Our aim was to investigate the incidence and outcome of sporadic dMMR in advanced CRC.

Glutathione-S-transferase pi (GSTP1) codon 105 polymorphism is not associated with oxaliplatin efficacy or toxicity in advanced colorectal cancer patients.

Purpose: Oxaliplatin is detoxified by conjugation to glutathione via the enzyme Glutathione-S-transferase pi (GSTP1). The aim of this study is to investigate the association of GSTP1 Ile105Val genetic polymorphism with oxaliplatin efficacy and toxicity in advanced colorectal cancer (ACC) patients.

Experimental Design: A total of 91 ACC patients received capecitabine and oxaliplatin (CAPOX) as a part of a multicentre phase-III study of the Dutch Colorectal Cancer Group.

[Neoadjuvant systemic therapy in patients with operable primary breast cancer: more benefits than breast-conserving therapy].

Objective: To analyse the extent to which primary systemic therapy (PST) achieves the main goals in patients with operable primary breast cancer, these goals being breast-conserving therapy and pathological complete remission (pCR), and to evaluate the response.

Design: Retrospective.

Method: In a retrospective analysis of 254 patients treated with PST in 2000-2007 in the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, patients with inoperable disease (T4 and/or N3) were excluded.

GSTP1 Ile105Val polymorphism correlates with progression-free survival in MCRC patients treated with or without irinotecan: a study of the Dutch Colorectal Cancer Group.

A Valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity. As nuclear GSTP1 activity decreases irinotecan cytotoxicity, Val-allele carriers may benefit more from irinotecan chemotherapy. Our aim was to investigate the association of GSTP1 genotype with treatment outcome of irinotecan.

Evaluation of current TNM classification of penile carcinoma.

Purpose: The TNM classification is the most common tool for staging malignancies. The current classification for penile carcinoma has been unchanged since 1987. There are several shortcomings to this classification.

UGT1A1*28 genotype and irinotecan dosage in patients with metastatic colorectal cancer: a Dutch Colorectal Cancer Group study.

The aim of the study was to investigate the associations between UGT1A1(*)28 genotype and (1) response rates, (2) febrile neutropenia and (3) dose intensity in patients with metastatic colorectal cancer treated with irinotecan. UGT1A1(*)28 genotype was determined in 218 patients receiving irinotecan (either first-line therapy with capecitabine or second-line as monotherapy) for metastatic colorectal cancer. TA(7) homozygotes receiving irinotecan combination therapy had a higher incidence of febrile neutropenia (18.

Current questions in the treatment of advanced colorectal cancer: the CAIRO studies of the Dutch Colorectal Cancer Group.

The outcome of patients with advanced colorectal cancer has significantly improved in the past decade because of the development of new treatment strategies. The Dutch Colorectal Cancer Group (DCCG) is a national multidisciplinary clinical research group in The Netherlands. The 3 CAIRO studies of the DCCG address clinically relevant questions in patients with advanced colorectal cancer: the benefit of combination versus sequential therapy, targeting vascular endothelial growth factor and epidermal growth factor receptor, and the role of maintenance therapy.

Recurrence patterns of squamous cell carcinoma of the penis: recommendations for follow-up based on a two-centre analysis of 700 patients.

Background: Current follow-up recommendations for patients with penile carcinoma are based on small numbers of patients.

Objectives: To give further insight into the recurrence patterns of penile carcinoma in different treatment settings and provide recommendations for follow up. DESIGNS, SETTING, AND PARTICIPANTS: In this retrospective study, we analysed 700 patients from two referral centres for penile carcinoma for recurrences.

Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation.

Chemotherapy plus bevacizumab is currently considered as the standard 1st line treatment of advanced colorectal cancer (ACC). Whereas GI perforation is a known side effect of bevacizumab, the development of GI ulcers has not been reported. We identified 18 patients with ACC who participated in a phase III multicentre trial which included chemotherapy and bevacizumab, who developed a GI ulcer (n = 6), perforation (n = 8) or both (n = 4).

A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity.

Background: Targeting the vascular endothelial growth factor or the epidermal growth factor receptor (EGFR) has shown efficacy in advanced colorectal cancer (ACC), but no data are available on the combination of these strategies with chemotherapy in the first-line treatment. The CAIRO2 study evaluates the effect of adding cetuximab, a chimeric mAb against EGFR, to capecitabine, oxaliplatin and bevacizumab in the first-line treatment of ACC.

Patients And Methods: In all, 755 patients were randomly assigned between treatment with capecitabine, oxaliplatin and bevacizumab with or without cetuximab.

Dissemination patterns in non-gastric MALT lymphoma.

Background: In contrast to gastric extranodal marginal zone mucosa associated lymphoid tissue (MALT) lymphomas, there is little consensus on the value and clinical consequences of extensive staging at diagnosis and during follow-up in non-gastric MALT lymphomas.

Design And Methods: Complete clinical information at presentation and during follow-up was collected for 72 patients with non-gastric MALT lymphoma treated at the Netherlands Cancer Institute between 1977 and 2005. Dissemination patterns at presentation were studied for nine primary dominant organ groups in our series of 72 patients and in a similar cohort treated at Vienna University (for a total of 106 patients).

Axillary and extra-axillary lymph node recurrences after a tumor-negative sentinel node biopsy for breast cancer using intralesional tracer administration.

Background: At our institution, tracer fluids are administered in the primary breast cancer and, in addition to the ones in the axilla, sentinel nodes outside the axilla are rigorously pursued. The objective of the present study of sentinel node-negative breast cancer patients was to determine the lymph node recurrence rates in the axilla and elsewhere, the false-negative rates, and the survival.

Methods: Between January 1999 and November 2005, 1,019 breast cancer patients underwent a sentinel node biopsy.

Immunohistochemical categorisation of ductal carcinoma in situ of the breast.

The aim of this study is to analyse whether immunohistochemistry (IHC) applying a broad set of markers could be used to categorise ductal carcinoma in situ (DCIS) of the breast in distinct subgroups corresponding to the recently defined molecular categories of invasive carcinoma. Immunohistochemistry of pure DCIS cases constructed in tissue arrays was performed with 16 markers (oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), Bcl-2, p53, Her2, insulin-like growth factor receptor, E-cadherin, epithelial membrane antigen (EMA), CA125, keratins 5/6, 14, 19, epidermal growth factor receptor, S100, and CD31). Results in 163 cases were analysed by unsupervised hierarchical clustering.