Pimasertib-associated ophthalmological adverse events.

Purpose: To analyse ophthalmological adverse events associated with mitogen-activated protein kinase kinase (MEK) inhibition with pimasertib treatment for metastatic cutaneous melanoma (CM).

Methods: In this prospective observational, cohort-based, cross-sectional study, eight patients treated with the MEK inhibitor pimasertib received a complete ophthalmic examination. This included Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, visual field testing, colour vision testing, slit-lamp examination, applanation tonometry, indirect ophthalmoscopy, digital colour fundus photography and optical coherence tomography (OCT).

Baseline comprehensive geriatric assessment is associated with toxicity and survival in elderly metastatic breast cancer patients receiving single-agent chemotherapy: results from the OMEGA study of the Dutch breast cancer trialists' group.

Aim: To evaluate the association between baseline comprehensive geriatric assessment (CGA) or the Groningen Frailty Indicator (GFI) and toxicity in elderly metastatic breast cancer (MBC) patients treated with first-line palliative chemotherapy.

Patients And Methods: MBC patients (≥65 years) were randomized between pegylated liposomal doxorubicine or capecitabine. CGA included instrumental activities of daily living (IADL), cognition using the mini-mental state examination (MMSE), mood using the geriatric depression scale (GDS), comorbidity using the Charlson index, polypharmacy and nutritional status using the body mass index.

High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study.

Purpose: Half the patients with acute myeloid leukemia (AML) who achieve complete remission (CR), ultimately relapse. Residual treatment-surviving leukemia is considered responsible for the outgrowth of AML. In many retrospective studies, detection of minimal residual disease (MRD) has been shown to enable identification of these poor-outcome patients by showing its independent prognostic impact.

Effector memory and late memory T cells accumulate in the blood of CMV-carrying individuals but not in their cerebrospinal fluid.

Cytomegalovirus (CMV)-carrying individuals have significantly higher levels of effector memory and late memory T lymphocytes in their blood than non-carriers. To date, it is well recognized that the central nervous system is subjected to active immunosurveillance, as evidenced by the presence of central memory T cells in cerebrospinal fluid (CSF) of healthy individuals. In order to investigate whether levels of effector memory and late memory T cells were also increased in the CSF of CMV-carrying individuals, we characterized CD4⁺ and CD8⁺ T-cell subsets in CSF and blood of both groups.

Prognosis in patients with sentinel node-positive melanoma without immediate completion lymph node dissection.

Background: The therapeutic value of immediate completion lymph node dissection (CLND) for sentinel node (SN)-positive melanoma is unknown. The aim of this study was to evaluate the impact of immediate CLND on the outcome of patients with SN-positive melanoma.

Methods: Patients with SN metastases treated between 1993 and 2008 at ten cancer centres from the European Organization for Research and Treatment of Cancer Melanoma Group were included in this retrospective study.

Expert opinion in melanoma: the sentinel node; EORTC Melanoma Group recommendations on practical methodology of the measurement of the microanatomic location of metastases and metastatic tumour burden.

The sentinel node (SN) status has been recognised to be the most important prognostic factor in melanoma. Many studies have investigated additional factors to further predict survival/lymph node involvement. The EORTC Melanoma Group (MG) has formulated the following question: How should we report the microanatomic location and SN tumour burden? The EORTC MG recommends the following: the EORTC MG SN pathology protocol or a similarly extensive protocol, which has also been proven to be accurate, should be used.

Impact of anthracycline dose on quality of life and rehabilitation in breast cancer treatment.

Background: In 2005 the Dutch national guidelines for treatment of breast cancer were updated. From then onwards, patients with operable breast cancer, who formerly received four cycles of adjuvant chemotherapy with doxorubicin/cyclophosphamide (AC), were treated with five cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC), based on data suggesting survival benefit.

Primary Objective: evaluation of the effect on quality-of-life and trainability after four AC versus five FEC cycles of polychemotherapy.

Isolated hypoxic hepatic perfusion with melphalan in patients with irresectable ocular melanoma metastases.

Aim: Ocular melanoma prefers to metastasize to the liver and the liver is the sole site of metastatic disease in 80% of patients. Until now there has been no standard treatment available and these patients have a very poor prognosis (median survival 2-5 months). Isolated hepatic perfusion may be an option in patients with irresectable hepatic ocular melanoma metastases.

Isolated hepatic perfusion for the treatment of liver tumors: sunset or sunrise?

Experience with isolated hepatic perfusion (IHP) is limited to a few centers in the world because of the technical difficulties, surgery-related morbidity, and unproved efficacy in randomized trials. Experimental animal IHP models have led to exploring new ways of improving efficacy, reducing technical difficulties, and minimizing regional and systemic toxicity. Future research should be directed to the identification of suitable biologic or chemotherapeutic agents, defining clinical indications, and development of technical modifications to make it more generally applicable and even repeatable.

Preoperative chemoradiation with capecitabine in locally advanced rectal cancer.

Background: Preoperative radiation therapy in combination with 5-fluoracil (5-FU) improves local tumour control in locally advanced rectal cancer. The aim of our study was to evaluate the toxicity and efficacy of preoperative chemoradiation using the oral 5-FU prodrug capecitabine in locally advanced rectal cancer.

Methods: Sixty patients with locally advanced rectal cancer were treated with preoperative chemoradiation.

Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion.

Background: Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure.

Medicinal cannabis in oncology.

In The Netherlands, since September 2003, a legal medicinal cannabis product, constituting the whole range of cannabinoids, is available for clinical research, drug development strategies, and on prescription for patients. To date, this policy, initiated by the Dutch Government, has not yet led to the desired outcome; the amount of initiated clinical research is less than expected and only a minority of patients resorts to the legal product. This review aims to discuss the background for the introduction of legal medicinal cannabis in The Netherlands, the past years of Dutch clinical experience in oncology practice, possible reasons underlying the current outcome, and future perspectives.

Multivariable analysis comparing outcome after sentinel node biopsy or therapeutic lymph node dissection in patients with melanoma.

Background: Sentinel node (SN) status is the most important prognostic factor for overall survival in stage I or II melanoma. Yet SN-positive tumours with submicroscopic involvement of the SN (clusters of cells smaller than 0.1 mm) have shown a distant recurrence rate of only 9 per cent at 5 years, as good as that in SN-negative patients.

Reasons for failure to identify positive sentinel nodes in breast cancer patients with significant nodal involvement.

Aim: To analyse causes of failure of sentinel node (SN) procedures in breast cancer patients and assess the role of pre-operative ultrasound examination of the axilla.

Methods: In 138 consecutive clinically node negative breast cancer patients with the primary tumour in situ a SN procedure with radiolabeled colloid and blue dye was performed. Radioactivity in the SN was scored as inadequate or adequate.

Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial.

Background: Individuals affected by melanoma with thick primary tumours or regional node involvement have a poor outlook, with only 30-50% alive at 5 years. High-dose and low-dose interferon alfa have been assessed for the treatment of these patients, with the former having considerable toxicity and a consistent effect on disease free survival, but not on overall survival, and the latter no consistent effect on either. Our aim was, therefore, to assess the effect of two regimens of interferon of intermediate dose versus observation alone on distant metastasis-free interval (DMFI) and overall survival in such patients.

Impaired neutralising antibody formation and high transduction efficacy after isolated hepatic perfusion with adenoviral vectors.

Local adenoviral gene transfer can be performed by means of isolated hepatic perfusion (IHP). This methodology is a very effective and safe way to deliver adenoviral vectors. We studied the immune response after IHP.

Isolated limb perfusion based anti-p21ras gene therapy in a rat rhabdomyosarcoma.

Background: Inhibition of ras oncogene is a promising new strategy. Gene therapy against ras proved successful in human and murine tumour cell lines. Previously we demonstrated effective targeted transfection of tumour in a rat model by using an isolated limb perfusion (ILP) for the delivery of adenoviral vectors.

Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy.

The overall rate of an ipsilateral breast tumour recurrence (IBTR) after breast-conserving therapy (BCT) ranges from 1% to 2% per year. Risk factors include young age but data on the impact of BRCA1/2 mutations or a definite positive family history for breast cancer are scarce. We investigated IBTR after BCT in patients with hereditary breast cancer (HBC).

Current views on the pathogenesis of testicular germ cell tumours and perspectives for future research: highlights of the 5th Copenhagen Workshop on Carcinoma in situ and Cancer of the Testis.

This review article highlights the most important contributions presented at the 5th Copenhagen Workshop on Carcinoma in situ and Cancer of the Testis, which was held in Denmark, August 29-31, 2002. The major themes that emerged at the meeting are critically discussed and perspectives for future research in this field are presented.