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Apeldoorn, Netherlands

Incrocci L.,Erasmus Daniel Den Hoed Cancer Center | Jensen P.T.,University of Southern Denmark
Journal of Sexual Medicine | Year: 2013

Introduction. Despite the decrease in overall cancer incidence and mortality rates in developed countries since the early 1990s, cancer remains a major public health problem. Sexual dysfunction is one of the more common consequences of cancer treatment. Aim. To shortly review the literature and level of evidence on sexual dysfunction in men and women following pelvic radiotherapy. Main Outcome Measures. Male and female sexual dysfunction. Methods. Literature review. Results. Sexual dysfunction in cancer patients is multidimensional and may result from biological, psychological, and social factors. Anatomic changes caused by surgery and/or radiotherapy, physiological changes following hormonal manipulation, and the secondary effect of medical intervention may impede or preclude sexual functioning, even when sexual desire is intact. Pelvic irradiation constitutes the primary or adjuvant treatment for a large number of both female and male cancers. No randomized controlled trials could be identified regarding the effect of radiotherapy on sexual dysfunction. However, prospective and clinical controlled trials all demonstrated a severe negative effect on sexual functioning in men and women following radiotherapy for a pelvic cancer. Following pelvic radiotherapy for prostate cancer, a positive effect of phosphodiesterase type 5 inhibitors on erectile dysfunction has been demonstrated, whereas no significant effect on female sexuality was found. Few studies evaluated treatment of female sexual dysfunction following radiotherapy; hormone replacement therapy and the use of vaginal dilator in combination with psycho-educational support is recommended. Conclusion. Pelvic radiotherapy plays a significant negative role in the complex scenario of male and female sexual dysfunction. The literature has focused on sexual dysfunction and intervention in prostate and cervical cancer patients. Sexual dysfunction following pelvic radiotherapy for cancer in other pelvic organs, e.g., bladder, rectum, and anus, requires more attention in future studies. Health care providers should pay attention to and provide psychological and medical support regarding sexual dysfunction to all patients who have received pelvic radiotherapy. Incrocci L and Jensen PT. Pelvic radiotherapy and sexual function in men and women. © 2013 International Society for Sexual Medicine. Source

Romero A.M.,Erasmus Daniel Den Hoed Cancer Center | Hoyer M.,Aarhus University Hospital
Current Opinion in Supportive and Palliative Care | Year: 2012

Purpose of review The liver is a common site of metastatic disease. Systemic therapy is most frequently the preferred therapy for patients with liver metastases, but surgical excision or tumor ablation strategies are often considered for patients with limited disease and favorable histology. Advances in radiation therapy technology made it possible to deliver potent biological doses to limited volumes of the liver with high precision in a few fractions. This method is known as stereotactic body radiation therapy (SBRT). Low-dose radiation therapy administered to the whole-liver radiation therapy (WLRT) is not regularly used for palliation of patients with massive liver metastases. The purpose of this review is to present an update of the most recent literature on SBRT and WLRT. Recent findings Recently published studies confirm the role of SBRT as a highly effective treatment for ablation of liver metastases. The toxicity related to the therapy is mild or moderate. This treatment is indicated for patients with limited burden of intrahepatic and extrahepatic disease. Low-dose WLRT is a useful treatment for symptom palliation in patients with end-stage cancer and diffuse metastatic infiltration of the liver which became refractory to systemic treatment. Summary SBRT and WLRT are highly efficient in the treatment of patients with liver metastases. However, prospective randomized trials in radiation therapy for liver metastases are warranted. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Kruit W.H.,Erasmus Daniel Den Hoed Cancer Center
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

Active immunization against the tumor-specific MAGE-A3 antigen is followed by a few but impressive and durable clinical responses. This randomized phase II trial evaluated two different immunostimulants combined with the MAGE-A3 protein to investigate whether a more robust and persistent immune response could be associated with increased clinical benefit. Patients with MAGE-A3-positive stage III or IV M1a melanoma were randomly assigned to receive the MAGE-A3 protein combined either with AS02B or with AS15 immunostimulant. Clinical end points were toxicity and rates of objective clinical responses, progression-free survival (PFS), and overall survival (OS). Seventy-five patients were treated, with 36 eligible patients per arm. Both treatments were well tolerated. In the AS15 arm, four objective responses were observed (three complete responses and one partial response) versus one partial response in the AS02B arm. In the AS15 and AS02B arms, the PFS rates after 6 months were 25% and 14%, respectively; and the median OS times were 33 months and 19.9 months, respectively, with a median observation period of 48 months. Antibodies against MAGE-A3, found in all patients, showed three-fold higher titers in the AS15 arm. The anti-MAGE-A3 cellular response was also more pronounced in the AS15 arm. In the MAGE-A3+AS15 arm, clinical activity was higher and the immune response more robust. Therefore, the AS15 immunostimulant was selected for combination with the MAGE-A3 protein in phase III trials. Source

Litiere S.,European Organisation for Research and Treatment of Cancer EORTC | Werutsky G.,European Organisation for Research and Treatment of Cancer EORTC | Fentiman I.S.,Guys and St Thomas NHS Foundation Trust | Rutgers E.,Netherlands Cancer Institute | And 5 more authors.
The Lancet Oncology | Year: 2012

Background: The EORTC 10801 trial compared breast-conserving therapy (BCT) with modified radical mastectomy (MRM) in patients with tumours 5 cm or smaller and axillary node negative or positive disease. Compared with BCT, MRM resulted in better local control, but did not affect overall survival or time to distant metastases. We report 20-year follow-up results. Methods: The EORTC 10801 . trial was open for accrual between 1980 and 1986 in eight centres in the UK, the Netherlands, Belgium, and South Africa. 448 patients were randomised to BCT and 420 to MRM. Randomisation was done centrally, stratifying patients by institute, carcinoma stage (I or II), and menopausal status. BCT comprised of lumpectomy and complete axillary clearance, followed by breast radiotherapy and a tumour-bed boost. The primary endpoint was time to distant metastasis. This analysis was done on all eligible patients, as they were randomised. Findings: After a median follow-up of 22·1 years (IQR 18·5-23·8), 175 patients (42%) had distant metastases in the MRM group versus 207 (46%) in the BCT group. Furthermore, 506 patients (58%) died (232 [55%] in the MRM group and 274 [61%] in the BCT group). No significant difference was observed between BCT and MRM for time to distant metastases (hazard ratio 1·13, 95% CI 0·92-1·38; p=0·23) or for time to death (1·11, 0·94-1·33; 0·23). Cumulative incidence of distant metastases at 20 years was 42·6% (95% CI 37·8-47·5) in the MRM group and 46·9% (42·2-51·6) in the BCT group. 20-year overall survival was estimated to be 44·5% (95% CI 39·3-49·5) in the MRM group and 39·1% (34·4-43·9) in the BCT group. There was no difference between the groups in time to distant metastases or overall survival by age (time to distant metastases: <50 years 1·09 [95% CI 0·79-1·51] . vs ≥50 years 1·16 [0·90-1·50]; overall survival <50 years 1·17 [0·86-1·59] . vs ≥50 years 1·10 [0·89-1·37]). Interpretation: BCT, including radiotherapy, offered as standard care to patients with early breast cancer seems to be justified, since long-term follow-up in this trial showed similar survival to that after mastectomy. Funding: European Organisation for Research and Treatment of Cancer (EORTC). © 2012 Elsevier Ltd. Source

Al-Mamgani A.,Erasmus Daniel Den Hoed Cancer Center | Heemsbergen W.D.,Netherlands Cancer Institute | Levendag P.C.,Erasmus Daniel Den Hoed Cancer Center | Lebesque J.V.,Netherlands Cancer Institute
Radiotherapy and Oncology | Year: 2010

Purpose: To investigate the effect of dose escalation within prognostic risk groups in prostate cancer. Patients and methods: Between 1997 and 2003, 664 patients with localized prostate cancer were randomly assigned to receive 68- or 78-Gy of radiotherapy. Two prognostic models were examined: a risk group model (low-, intermediate-, and high-risk) and PSA-level groupings. High-risk patients with hormonal therapy (HT) were analyzed separately. Outcome variable was freedom from failure (FFF) (clinical failure or PSA nadir + 2 μg/L). Results: In relation to the advantage of high-dose radiotherapy, intermediate-risk patients benefited most from dose escalation. However no significant heterogeneity could be demonstrated between the risk groups. For two types of PSA-level groupings: PSA < 10 and ≥10 μg/L, and <8, 8-18 and >8 μg/L, the test for heterogeneity was significant (p = 0.03 and 0.05, respectively). Patients with PSA 8-18 μg/L (n = 297, HR = 0.59) derived the greatest benefit from dose escalation. No heterogeneity could be demonstrated for high-risk patients with and without HT. Conclusion: Intermediate-risk group derived the greatest benefit for dose escalation. However, from this trial no indication was found to exclude low-risk or high-risk patients from high-dose radiotherapy. Patients could be selected for high-dose radiotherapy based on PSA-level groupings: for patients with a PSA < 8 μg/L high-dose radiotherapy is probably not indicated, but should be confirmed in other randomized studies. © 2010 Elsevier Ireland Ltd. All rights reserved. Source

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