1p/19q loss within oligodendroglioma is predictive for response to first line temozolomide but not to salvage treatment.

Background: Combined loss of 1p/19q predicts an almost 100% response rate to first line procarbazine, CCNU and vincristine chemotherapy (PCV) chemotherapy in oligodendroglial tumours. We assessed the impact of 1p and 19q loss on the outcome to first line temozolomide (TMZ) chemotherapy and to second line PCV or TMZ in progressive oligodendroglial tumours.

Materials And Methods: Tumour samples from patients included in two prospective EORTC studies on first line and second line TMZ chemotherapy in recurrent oligodendroglioma were used for this study.

Value of intraoperative radiotherapy in locally advanced rectal cancer.

Purpose: This study was designed to analyze the results of a multimodality treatment using preoperative radiotherapy, followed by surgery and intraoperative radiotherapy in patients with primary locally advanced rectal cancer.

Methods: Between 1987 and 2002, 123 patients with initial unresectable and locally advanced rectal cancer were identified in our prospective database, containing patient characteristics, radiotherapy plans, operation notes, histopathologic reports, and follow-up details. An evaluation of prognostic factors for local recurrence, distant metastases, and overall survival was performed.

CD38 as a prognostic factor in B cell chronic lymphocytic leukaemia (B-CLL): comparison of three approaches to analyze its expression.

Background: Increased CD38 expression by leukemic cells has been suggested as an adverse prognostic factor in B-CLL. Several approaches have been proposed to quantify its level of expression by flow cytometry.

Methods: We compared the use of (i) the percentage of CD38 positive cells, (ii) CD38 antibodies bound per cell (ABC), and (iii) a semi-quantitative method based on the shape of the CD38 histogram, within a cohort of 78 B-CLL patients.

Outcome and prognostic factor analysis of 217 consecutive isolated limb perfusions with tumor necrosis factor-alpha and melphalan for limb-threatening soft tissue sarcoma.

Background: Extensive and mutilating surgery is often required for locally advanced soft tissue sarcoma (STS) of the limb. As it has become apparent that amputation for STS does not improve survival rates, the interest in limb-preserving approaches has increased. Isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF) and melphalan is successful in providing local tumor control and enables limb-preserving surgery in a majority of cases.

The predictive value of lipoprotein lipase for survival in chronic lymphocytic leukemia.

Background And Objectives: The mutational status of the immunoglobulin heavy chain variable region genes (IGVH) is a strong indicator of prognosis in B-cell chronic lymphocytic leukaemia (CLL). Since the determination of the IGVH mutation status is very labor-intensive, alternative prognostically relevant markers would facilitate CLL diagnostics.

Design And Methods: Ten genes were selected from previously published gene expression profiling studies based on their differential expression in IGVH mutated versus unmutated cases of CLL, and tested with real-time quantitative polymerase chain reaction (RQ-PCR) in unpurified samples from 130 CLL patients.

High positive sentinel node identification rate by EORTC melanoma group protocol. Prognostic indicators of metastatic patterns after sentinel node biopsy in melanoma.

Methods to work-up sentinel nodes (SN) vary considerably between institutes. This single institution study evaluated the positive SN-identification rate of the EORTC Melanoma Group (MG) protocol and investigated the prognostic value of the SN status regarding disease-free survival (DFS) and overall survival (OS) and evaluated the locoregional control after the SN procedure. Multivariate and univariate analyses using Cox's proportional hazard regression model was employed to assess the prognostic value of covariates regarding DFS and OS.

The palliative value of tumor necrosis factor alpha-based isolated limb perfusion in patients with metastatic sarcoma and melanoma.

Background: Both patients with soft tissue sarcoma (STS) and patients with melanoma have limited treatment possibilities once the tumor has metastasized systemically. In patients with extremity STS or bulky melanoma in-transit metastases, the local tumor burden may be so problematic that, even in patients with systemically metastasized disease, an amputation may be inevitable. Isolated limb perfusion (ILP) has proven to be an excellent, local, limb-saving treatment option in patients with locally advanced extremity tumors.

TNF dose reduction in isolated limb perfusion.

Aims: Isolated limb perfusion with TNF and melphalan (TM-ILP) is highly effective in the local treatment of advanced sarcoma and melanoma of the limb. The optimal dose of TNF for this procedure is not well established. The aim of this study was to assess the efficacy and toxicity of TM-ILPs with reduced TNF dose.

Efficacy of repeat isolated limb perfusions with tumor necrosis factor alpha and melphalan for multiple in-transit metastases in patients with prior isolated limb perfusion failure.

Background: Isolated limb perfusion (ILP) is an effective treatment modality for multiple in-transit melanoma metastases confined to the limb. Recurrences after ILP, however, occur in approximately 50% of patients and are a challenge for further treatment. The efficacy of repeat ILPs to prolong local control in this patient category is evaluated in this article.

Prognostic factors after cervical lymph node dissection for cutaneous melanoma metastases.

Cervical lymph node dissection (CLND) is the surgical therapy used for the local control of regionally metastasized cutaneous head and neck melanoma. This study evaluated the outcome of patients undergoing CLND at our institution in order to determine the prognostic factors for recurrence-free survival and overall survival after this procedure. The hospital records of 66 patients with histologically proven lymph node metastases who underwent curative or palliative CLND between 1982 and 2004 were analysed.

Isolated limb perfusion with tumor necrosis factor and melphalan prevents amputation in patients with multiple sarcomas in arm or leg.

Background: Treatment for extremity soft tissue sarcoma (STS) has shifted in recent years from amputation to local wide excision combined with irradiation. For multiple sarcomas, this limb-sparing approach is often not possible. To avoid amputations, isolated limb perfusion (ILP) with tumor necrosis factor and melphalan is an attractive treatment option for patients with multiple extremity sarcomas.

Preoperative radiotherapy improves outcome in recurrent rectal cancer.

Purpose: When local recurrent rectal cancer is diagnosed without signs of metastases, a potentially curative resection can be performed. This study was designed to compare the results of preoperative radiotherapy followed by surgery with surgery only.

Methods: Between 1985 and 2003, 117 patients with recurrent rectal cancer were prospectively entered in our database.

Leg coverage with towels during regional deep hyperthermia treatment and its effect on pelvic temperature and temperature distribution.

Introduction: The feasibility and its effects on pelvic temperature distribution of covering the legs with towels during the second half of the deep hyperthermia treatment (DHT) is evaluated.

Patients And Methods: Patients treated with DHT and radiotherapy were randomized to an alternating treatment schedule: 2nd and 4th treatment or 3rd and 5th treatment with the legs covered with towels in the second half of the treatment. Intra-luminal temperatures (vesical, vaginal and rectal) classified as tumour indicative (TI) or tumour contact (TC), oral temperature, applied maximum power and power at the end of the treatment were measured and compared between the two treatment schedules.

Prospective evaluation of the pharmacokinetics and toxicity profile of docetaxel in the elderly.

Purpose: To prospectively study the pharmacokinetics and toxicity profile of docetaxel in elderly patients with cancer.

Patients And Methods: Docetaxel was administered at a dose 75 mg/m(2) once every 3 weeks to 25 elderly cancer patients aged >/= 65 years and 26 cancer patients aged younger than 65 years. Pharmacokinetic studies and toxicity assessments were performed during the first cycle of therapy.

Measurement of hypoxia-related parameters in bronchial mucosa by use of optical spectroscopy.

Rationale: Tumor hypoxia has both prognostic and therapeutic consequences for solid tumors. We developed a novel noninvasive technique, differential path-length spectroscopy (DPS), which allows the measurement of hypoxia-related parameters in the superficial microvasculature of tissue.

Objectives: The aim of this study was to measure the microvascular oxygenation of histologically normal endobronchial mucosa and of neoplastic lesions during bronchoscopy using DPS.

Relationship of systemic exposure to unbound docetaxel and neutropenia.

Objective: Our objective was to evaluate the association between exposure to unbound docetaxel and neutropenia in patients with cancer and to identify factors influencing unbound docetaxel clearance.

Methods: Docetaxel was administered once every 3 weeks at a dose of 75 mg/m 2 to 49 patients with normal liver function (n = 40, group 1) or mild elevations in liver function test results (n = 9, group 2) or at a dose of 50 mg/m2 to patients with moderate elevations in liver function test results (n = 6, group 3). Pharmacokinetic studies and toxicity assessments were performed during the first cycle of therapy.

Factors affecting cytochrome P-450 3A activity in cancer patients.

Purpose: The purpose is to identify the demographic, physiologic, and inheritable factors that influence CYP3A activity in cancer patients.

Experimental Design: A total of 134 patients (62 females; age range, 26 to 83 years) underwent the erythromycin breath test as a phenotyping probe of CYP3A. Genomic DNA was screened for six variants of suspected functional relevance in CYP3A4 (CYP3A4*1B, CYP3A4*6, CYP3A4*17, and CYP3A4*18) and CYP3A5 (CYP3A5*3C and CYP3A5*6).

One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastases.

Objective: The aim of this study is to describe the experience with 100 TNF-based ILP for locally advanced melanoma and to determine prognostic factors for response, time to local progression, and survival.

Methods: One hundred TNF-based ILPs were performed between 1991 and 2003 in 87 patients for whom local control by surgery of in-transit melanoma metastases was impossible. In total, 62 iliac, 33 femoral, and 5 axillary ILPs were performed in mild hyperthermic conditions with 2 to 4 mg of TNF and 10 to 13 mg of melphalan per liter of limb volume.

Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes.

Background: Irinotecan is a topoisomerase I inhibitor that has been approved for use as a first- and second-line treatment for colorectal cancer. The response to irinotecan is variable, possibly because of interindividual variation in the expression of the enzymes that metabolize irinotecan, including cytochrome P450 3A4 (CYP3A4) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). We prospectively explored the relationships between CYP3A phenotype, as assessed by erythromycin metabolism and midazolam clearance, and the metabolism of irinotecan and its active metabolite SN-38.

The value of fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high-risk myelodysplastic syndromes and AML in elderly patients.

Fludarabine in addition to cytosine-arabinoside (ARA-C) increases the accumulation of ARA-C-5'-triphosphate (ARA-CTP), which is responsible for the cytotoxic effect in leukemic blasts. In a randomized phase 3 trial, patients with high-risk myelodysplastic syndrome (MDS) (n = 91) or elderly patients with acute myeloid leukemia (AML) (n = 43) were randomized to receive 2 induction courses consisting of ARA-C (2 g/m2 days 1 through 5) and granulocyte colony-stimulating factor (G-CSF) (filgrastim, 5 microg/kg) during and after chemotherapy with or without fludarabine (25 mg/m2, days 1 through 5) (FLAG versus AG). Consolidation consisted of daunorubicin (45 mg/m2, days 1 through 3) and ARA-C (200 mg/m2, days 1 through 7).

High-dose-rate intraoperative radiotherapy for close or positive margins in patients with locally advanced or recurrent rectal cancer.

Purpose: A high-dose-rate intraoperative radiotherapy (HDR-IORT) technique for rectum cancer was developed and the technique, local failure, and survival were analyzed.

Methods And Materials: After the exclusion of metastatic patients, 37 patients were treated with external beam RT, surgery, and HDR-IORT between 1997 and 2000. Primary locally advanced rectum cancer was found in 18 patients and recurrent disease in 19.

Tumor location cannot predict the mobility of lung tumors: a 3D analysis of data generated from multiple CT scans.

Purpose: There is limited information available on the three-dimensional (3D) motion of lung tumors. Data derived from multiple planning computed tomographic (CT) scans were used to characterize the 3D movement of small peripheral lung tumors.

Methods And Materials: A total of 29 data sets from patients with Stage I non-small-cell lung cancer (NSCLC), each of which consisted of three "rapid" and three "slow" planning CT scans, were analyzed.

Weekly high-dose cisplatin is a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients.

In the present study we describe the toxicity of weekly high-dose (70-85 mg x m(-2)) cisplatin in 400 patients (203 men, 197 women; median age 54 years) with advanced solid tumours treated in the period 1990-2001 who took part in phase I/II trials, investigating the feasibility and efficacy of weekly cisplatin alone, or in combination with paclitaxel or etoposide. Cisplatin was administered in 250 ml NaCl 3% over 3 h, for six intended administrations. The mean number of administrations was 5.

Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features.

Background: Patients who have oligodendrogliomas (OD) that demonstrate loss of both 1p and 19q appear to have a better prognosis after they receive chemotherapy and radiotherapy compared with patients who have OD without these characteristics. It is unclear whether this improvement in outcome is due only to a better response to treatment. The authors investigated the correlation between genetic and clinical characteristics of OD in 33 patients who received chemotherapy with procarbazine, lomustine, and vincristine for recurrent disease after receiving radiotherapy.

Has 3-D conformal radiotherapy (3D CRT) improved the local tumour control for stage I non-small cell lung cancer?

Aims And Background: The high local failure rates observed after radiotherapy in stage I non-small cell lung cancer (NSCLC) may be improved by the use of 3-dimensional conformal radiotherapy (3D CRT).

Materials And Methods: The case-records of 113 patients who were treated with curative 3D CRT between 1991 and 1999 were analysed. No elective nodal irradiation was performed, and doses of 60Gy or more, in once-daily fractions of between 2 and 3Gy, were prescribed.