Erectile dysfunction after radiotherapy for prostate cancer and radiation dose to the penile structures: a critical review.

Erectile dysfunction (ED) is a common sequela after external beam radiotherapy and brachytherapy for prostate cancer. There are several structures in the vicinity of the prostate that are critical to erectile function and that receive a substantial radiation dose: neurovascular bundles (NVBs), internal pudendal arteries (IPAs), accessory pudendal arteries, corpora cavernosa and the penile bulb. Most reports analyzing the correlation between radiation dose to these structures and radiation-induced ED are limited by the small number of patients analyzed in each study.

Management of locally advanced primary and recurrent rectal cancer.

Treatment for patients with locally advanced and recurrent rectal cancer differs significantly from patients with rectal cancer restricted to the mesorectum. Adequate preoperative imaging of the pelvis is therefore important to identify those patients who are candidates for multimodality treatment, including preoperative chemoradiation protocols, intraoperative radiotherapy, and extended surgical resections. Much effort should be made to select patients with these advanced tumors for treatment in specialized referral centers.

Prophylactic mastectomy in BRCA1/2 mutation carriers and women at risk of hereditary breast cancer: long-term experiences at the Rotterdam Family Cancer Clinic.

Background: BRCA1/2 mutation carriers and women from a hereditary breast(/ovarian) cancer family have a highly increased risk of developing breast cancer (BC). Prophylactic mastectomy (PM) results in the greatest BC risk reduction. Long-term data on the efficacy and sequels of PM are scarce.

Quantitative validation of the 3D SAR profile of hyperthermia applicators using the gamma method.

For quality assurance of hyperthermia treatment planning systems, quantitative validation of the electromagnetic model of an applicator is essential. The objective of this study was to validate a finite-difference time-domain (FDTD) model implementation of the Lucite cone applicator (LCA) for superficial hyperthermia. The validation involved (i) the assessment of the match between the predicted and measured 3D specific absorption rate (SAR) distribution, and (ii) the assessment of the ratio between model power and real-world power.

CSF flow cytometry greatly improves diagnostic accuracy in CNS hematologic malignancies.

Objective: To assess the diagnostic accuracy of flow cytometric immunophenotyping in comparison with classic cytomorphology for diagnosing CNS localizations of hematologic malignancies, and to evaluate the implications of CSF pleocytosis and protein content in this context.

Methods: We reviewed the results of diagnostic evaluations of all CSF samples analyzed for localization of a hematologic malignancy between 2001 and 2004 at our center.

Results: A total of 1,054 samples from 219 patients were available for analysis.

eNAL: an extension of the NAL setup correction protocol for effective use of weekly follow-up measurements.

Purpose: The no action level (NAL) protocol reduces systematic displacements relative to the planning CT scan by using the mean displacement of the first few treatment fractions as a setup correction in all subsequent fractions. This approach may become nonoptimal in case of time trends or transitions in the systematic displacement of a patient. Here, the extended NAL (eNAL) protocol is introduced to cope with this problem.

Sexual function after three-dimensional conformal radiotherapy for prostate cancer: results from a dose-escalation trial.

Purpose: The purpose of this study is to provide information about sexual function (SF) after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer while taking important factors into account that influence SF.

Methods And Materials: Between June 1997 and February 2003, a total of 268 patients from a randomized dose-escalation trial comparing 68 Gy and 78 Gy agreed to participate in an additional part of the trial that evaluated SF.

Results: At baseline 28% of patients had erectile dysfunction (ED).

HOXB13-to-IL17BR expression ratio is related with tumor aggressiveness and response to tamoxifen of recurrent breast cancer: a retrospective study.

Purpose: A HOXB13-to-IL17BR expression ratio was previously identified to predict clinical outcome of breast cancer patients treated with adjuvant tamoxifen. However, this ratio may predict a tumor's response to tamoxifen, its intrinsic aggressiveness, or both.

Patients And Methods: We have measured the HOXB13 and IL17BR expression levels by real-time polymerase chain reaction in 1,252 primary breast tumor specimens.

Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases.

Aim Of The Study: Results on tumour characteristics and survival of hereditary breast cancer (BC), especially on BRCA2-associated BC, are inconclusive. The prognostic impact of the classical tumour and treatment factors in hereditary BC is insufficiently known.

Methods: We selected 103 BRCA2-, 223 BRCA1- and 311 non-BRCA1/2 BC patients (diagnosis 1980-2004) from the Rotterdam Family Cancer Clinic.

3D dose reconstruction for clinical evaluation of IMRT pretreatment verification with an EPID.

Background And Purpose: Pretreatment verification with an electronic portal imaging device is an important part of our patient-specific quality assurance program for advanced treatment techniques. Up to now, this verification has been performed for over 400 IMRT patient plans. For every treatment field, a 2D portal dose image (PDI) is measured and compared with a predicted PDI.

Influence of ketoconazole on the fecal and urinary disposition of docetaxel.

Objective: The anticancer drug docetaxel is extensively metabolized by cytochrome P450 (CYP) 3A isozymes. Furthermore, docetaxel is also a substrate for the transmembrane ATP-binding cassette efflux transporter protein ABCB1. CYP3A-inhibition significantly reduces docetaxel total systemic clearance, on average by 50%.

ABCB1 gene polymorphisms are not associated with treatment outcome in elderly acute myeloid leukemia patients.

Objectives: The classical multidrug resistance (MDR) gene MDR1 (ABCB1) encodes for the drug efflux pump P-glycoprotein (P-gp). P-gp expression is an adverse prognostic factor for treatment outcome in acute myeloid leukemia (AML) and is more frequently observed in older patients. Single-nucleotide polymorphisms of the ABCB1 gene, C1236T, G2677T, and C3435T, have been associated with altered drug metabolism and treatment outcome.

Total pelvic exenteration for primary locally advanced and locally recurrent rectal cancer.

Aims: To report the role of total pelvic exenteration in a series of locally advanced and recurrent rectal cancers.

Methods: In the period 1994-2004, TPE was performed in 35 of 296 patients with primary locally advanced and recurrent rectal cancer treated in the Daniel den Hoed Cancer Center; 23 of 176 with primary locally advanced and 12 of 120 with recurrent rectal cancer. All but one patient received pre-operative External Beam Radiation Therapy (EBRT).

Lessons to learn from EORTC study 08981: a feasibility study of induction chemoradiotherapy followed by surgical resection for stage IIIB non-small cell lung cancer.

The present EORTC phase II feasibility study in stage IIIB (T4-N3) NSCLC was conducted to investigate whether an induction regimen with concurrent chemoradiotherapy followed by surgery after restaging by re-mediastinoscopy and/or fluorodeoxyglucose-positron emission tomography (FDG-PET) was feasible in a multicenter setting. Unfortunately, the study closed prematurely because of poor accrual. The combination of more stringent selection criteria, the incorrect prevailing view of Ethical Boards that a tri-modality approach is too toxic, competing studies in the participating centers and the fact that patients with N3 disease could only be enrolled if a re-mediastinoscopy could be performed, underlie the low accrual.

Dosimetric pre-treatment verification of IMRT using an EPID; clinical experience.

Background And Purpose: In our clinic a QA program for IMRT verification, fully based on dosimetric measurements with electronic portal imaging devices (EPID), has been running for over 3 years. The program includes a pre-treatment dosimetric check of all IMRT fields. During a complete treatment simulation at the linac, a portal dose image (PDI) is acquired with the EPID for each patient field and compared with a predicted PDI.

Aprepitant when added to a standard antiemetic regimen consisting of ondansetron and dexamethasone does not affect vinorelbine pharmacokinetics in cancer patients.

Purpose: Aprepitant, a selective neurokinin-1 (NK-1) receptor antagonist approved for the treatment and prevention of emesis caused by moderately and highly emetogenic chemotherapy, is an inhibitor, inducer, and substrate of the cytochrome P450 3194 pathway. The CYP3A4 pathway is the major pathway of the metabolism of vinorelbine, a vinca alkaloid frequently used in combination with cisplatin. Therefore, we studied the potential interaction of the aprepitant 3-day antiemetic regimen on the pharmacokinetics of vinorelbine.

Computer optimization of noncoplanar beam setups improves stereotactic treatment of liver tumors.

Purpose: To investigate whether computer-optimized fully noncoplanar beam setups may improve treatment plans for the stereotactic treatment of liver tumors.

Methods: An algorithm for automated beam orientation and weight selection (Cycle) was extended for noncoplanar stereotactic treatments. For 8 liver patients previously treated in our clinic using a prescription isodose of 65%, Cycle was used to generate noncoplanar and coplanar plans with the highest achievable minimum planning target volume (PTV) dose for the clinically delivered isocenter and mean liver doses, while not violating the clinically applied hard planning constraints.

Lung tumor tracking during stereotactic radiotherapy treatment with the CyberKnife: Marker placement and early results.

Lung tumor tracking during stereotactic radiotherapy with the CyberKnife requires the insertion of markers in or close to the tumor. To reduce the risk of pneumothorax, three methods of marker placement were used: 1) intravascular coil placement, 2) percutaneous intrathoracal, and 3) percutaneous extrathoracal placement. We investigated the toxicity of marker placement and the tumor response of the lung tumor tracking treatment.

Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution phase i-ii study.

The feasibility, toxicity and tumor response of stereotactic body radiation therapy (SBRT) for treatment of primary and metastastic liver tumors was investigated. From October 2002 until June 2006, 25 patients not suitable for other local treatments were entered in the study. In total 45 lesions were treated, 34 metastases and 11 hepatocellular carcinoma (HCC).

A randomized, double-blind, placebo-controlled, cross-over study to assess the efficacy of tadalafil (Cialis) in the treatment of erectile dysfunction following three-dimensional conformal external-beam radiotherapy for prostatic carcinoma.

Purpose: Erectile dysfunction after three-dimensional conformal external-beam radiotherapy (3DCRT) for prostatic carcinoma is reported in as many as 64% of those patients. The purpose of this study was to determine the efficacy of the oral drug tadalafil (Cialis) in patients with erectile dysfunction after radiotherapy for prostatic carcinoma.

Methods And Materials: Patients (N=358) who completed radiotherapy at least 12 months before the study were approached by mail.

Pelvic exenteration for primary and recurrent gynaecological malignancies.

Objective: Analyse the outcome of pelvic exenteration for gynaecological malignancies in a tertiary referral center. Post-operative in-hospital morbidity, long-term morbidity, disease free and overall survival rates were studied.

Study Design: Between 1991 and 2004, 42 patients underwent an anterior, total or posterior exenteration for gynaecological malignancies.

Early destruction of tumor vasculature in tumor necrosis factor-alpha-based isolated limb perfusion is responsible for tumor response.

Addition of high-dose tumor necrosis factor-alpha to melphalan-based isolated limb perfusion enhances anti-tumor effects impressively. Unfortunately, the mechanism of action of tumor necrosis factor-alpha is still not fully understood. Here, we investigated the effects of tumor necrosis factor-alpha on the tumor microenvironment and on secondary immunological events during and shortly after isolated limb perfusion in soft-tissue sarcoma-bearing rats.

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.

Mismatch repair and treatment resistance in ovarian cancer.

Background: The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy.

Methods: We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines

Results: MSI was detected in three of the eight cell lines i.