Gert De Meerleer - Academia.edu (original) (raw)

Papers by Gert De Meerleer

International Journal of Radiation Oncology*Biology*Physics, 2012

To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (&am... more To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

Clinical genitourinary cancer, 2013

We investigated whether repeated stereotactic body radiotherapy (SBRT) of oligometastatic disease... more We investigated whether repeated stereotactic body radiotherapy (SBRT) of oligometastatic disease is able to defer the initiation of palliative androgen deprivation therapy (ADT) in patients with low-volume bone and lymph node metastases. Patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary end point. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic or in case of a prostate specific antigen elevation above 50 ng/mL in the absence of metastases. Secondary end points were local control, clinical progression-free survival, and toxicity. Toxicity was scored using the Common Te...

Acta Clinica Belgica, Mar 27, 2015

Men diagnosed with localised prostate cancer (PC) have to make a well-informed treatment choice b... more Men diagnosed with localised prostate cancer (PC) have to make a well-informed treatment choice between (robot-assisted) radical prostatectomy (RARP), external beam radiotherapy (EBRT) and, in selected cases, brachytherapy and active surveillance. We developed and validated a questionnaire to determine the cognitive reasons why patients choose their treatment. The Prostate Cancer Decision-Making Questionnaire (PC-DMQ) was designed in-house and validated through the Delphi method by seven external experts. Finally, we tested this questionnaire in a cohort of 24 men, recently diagnosed with localised PC, before undergoing RARP (n = 16), EBRT (n = 6), brachytherapy (n = 1) or active surveillance (n = 1). The experts reached consensus after three discussion rounds. In the patient cohort, 75% of men undergoing RARP chose this treatment because 'it provides the best chance of cure'. Reasons to choose EBRT were not as explicit: 33.3% chose this treatment because 'it provides the best chance of cure' and 33.3% because 'the maintenance of potency is important to them'. The PC-DMQ is a comprehensive and standardised tool that allows further research into cognitive factors that influence treatment decision-making in patients with localised PC.

European urology, Jan 17, 2014

The introduction of novel imaging modalities has increased the detection of oligometastatic prost... more The introduction of novel imaging modalities has increased the detection of oligometastatic prostate cancer (PCa) recurrence, potentially justifying the use of a metastasis-directed therapy (MDT) with surgery or radiotherapy (RT) rather than a systemic approach. To perform a systematic review of MDT for oligometastatic PCa recurrence. This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We searched the Medline and Embase databases from 1946 to February 2014 for studies reporting on biochemical or clinical progression and/or toxicity or complications of MDT (RT or surgery). Reports were excluded if these end points could not be ascertained or separately analysed, or if insufficient details were provided. Methodological quality was assessed using an 18-item validated quality appraisal tool for case series. Fifteen single-arm case series reporting on a total of 450 patients met the inclusion criteria. Seven stu...

BioMed Research International, 2015

Methodology. Seventeen patients with prostate-specific antigen (PSA) rise following local treatme... more Methodology. Seventeen patients with prostate-specific antigen (PSA) rise following local treatment for prostate cancer with curative intent underwent open or minimally invasive salvage pelvic lymph node dissection (SLND) for oligometastatic disease (<4 synchronous metastases) or as staging prior to salvage radiotherapy. Biochemical recurrence after complete biochemical response (cBR) was defined as 2 consecutive PSA increases >0,2 ng/mL; and after incomplete biochemical response as 2 consecutive PSA rises. Newly found metastasis on imaging defined clinical progression (CP). Palliative androgen deprivation therapy (ADT) was initiated if >3 metastases were detected or if patients became symptomatic. Kaplan-Meier statistics were applied. Results. Clavien-Dindo grade 1, 2, 3a, and 3b complications were seen in 6, 1, 1, and 2 patients, respectively. Median follow-up time was 22 months. Among 13 patients treated for oligometastatic disease, 8 (67%) had a PSA decline, with 3 patients showing cBR. Median PSA progression-free survival (FS) was 4.1 months and median CP-FS 7 months. Three patients started ADT, resulting in a 2-year ADT-FS rate of 79.5%. Conclusion. SLND is feasible, but postoperative complication rate seems higher than that for primary LND. Biochemical and clinical response duration is limited, but as part of an oligometastatic treatment regime it can defer palliative ADT.

International Journal of Gynecological Cancer, 2012

To report on the value of magnetic resonance imaging (MRI) and 2-deoxy-2-[18] fluoro-D-glucose po... more To report on the value of magnetic resonance imaging (MRI) and 2-deoxy-2-[18] fluoro-D-glucose positron emission tomography computed tomography (¹⁸FDG PET-CT) in predicting resectability and pathological response of primary locally advanced cervical cancer after neoadjuvant intensity-modulated arc therapy (IMAT) with or without cisplatin (C). Twenty-seven patients with International Federation of Gynecology and Obstetrics stages IB2 to IVA cervical cancer were treated with IMAT-C followed by extrafascial hysterectomy (EH). All patients received MRI and ¹⁸FDG PET-CT after IMAT-C. The end points of this study were to: 1. Assess the ability of MRI to predict negative surgical margins (R0). 2. Assess the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI in predicting the following situation at the EH specimen: "no residual disease or minimal microscopically visible residual tumor." 3. Assess the sensitivity, specificity, PPV, and NPV value of ¹⁸FDG PET-CT in predicting "no residual viable tumor cells" at the EH specimen. An R0 resection was obtained in all patients. None of the EH specimens contained macroscopically visible tumor. In 13 patients, no viable tumor cells were found and only 14 had residual microscopic disease. Twenty-four of 27 MRIs were able to correctly predict R0 resection. A negative MRI was 100% predictive for the end point "R0 resection." The specificity and NPV of MRI (end point 2) were 74% and 100%, respectively. No sensitivity or PPV could be calculated. The sensitivity, specificity, PPV, and NPV of ¹⁸FDG PET-CT were 29%, 62%, 44%, and 44%, respectively (end point 3). A negative MRI after IMAT-C predicts 100% correctly for R0 resection. The role of FDG PET-CT in predicting viable tumor cells at EH specimen is at least debatable.

Radiotherapy and Oncology, 2008

The aim was to prospectively evaluate both acute and late toxicity and biochemical non-evidence o... more The aim was to prospectively evaluate both acute and late toxicity and biochemical non-evidence of disease (bNED) in patients treated with salvage intensity-modulated radiotherapy (IMRT) ± androgen deprivation (AD) for biochemical relapse after radical prostatectomy (RP).

International Journal of Radiation Oncology*Biology*Physics, 2011

The present study aims to assess the interobserver agreement of prostate bed delineation after ra... more The present study aims to assess the interobserver agreement of prostate bed delineation after radical prostatectomy using CT alone as proposed by the European Organization for Research and Treatment of Cancer (EORTC) guidelines. Six observers delineated the postoperative prostate bed (PB) and the original seminal vesicle position or remnants (SV) of 10 patients according to the EORTC guidelines. Contours were then compared for agreement between observers (the apparent volume overlap and generalized kappa statistics). Standard deviations were also calculated to measure the variability of the position of the outer margins. The mean volume of 100% agreement (±1 standard deviation, SD) was only 5.0 (±3.3) ml for the PB and 0.9 (±1.5) ml for the SV, whereas the mean union of all contours (±1 SD) was 41.1 (±11.8) ml and 25.3 (±13.4) ml, respectively. The mean overall agreement corrected for chance was moderate for both the PB (mean kappa, 0.49; range, 0.35-0.62) and SV (mean kappa, 0.42; range, 0.22-0.59). The overall SD of the outer margins of the PB ranged from 4.6 to 7.0 mm The delineation of the postprostatectomy bed using CT shows only a moderate observer agreement when following the EORTC guidelines.

International Journal of Radiation Oncology*Biology*Physics, 2009

To determine the planning results and acute toxicity after hypofractionated intensity-modulated a... more To determine the planning results and acute toxicity after hypofractionated intensity-modulated arc radiotherapy and androgen deprivation for lymph node metastasized (Stage N1) prostate cancer. A total of 31 patients with Stage T1-T4N1M0 prostate cancer were treated with intensity-modulated arc radiotherapy and 3 years of androgen deprivation as primary treatment. The clinical target volume (CTV(p)) was the prostate and seminal vesicles. Elective lymph node areas ((e)) were delineated and expanded by 2 mm to create the CTV(e). The planning target volumes (PTV(p) and PTV(e)) were created using a three-dimensional expansion of the CTV(p) and CTV(e), respectively, of 7 mm. A median dose of 69.3 Gy and 50 Gy was prescribed to the PTV(p) and PTV(e) respectively, to be delivered in 25 fractions. Upper and lower gastrointestinal toxicity was scored using the Radiation Therapy Oncology Group toxicity and radiotherapy-induced lower intestinal toxicity scoring system. Genitourinary toxicity was scored using a combined Radiation Therapy Oncology Group, LENT-SOMA (late effects normal tissue-subjective, objective, management, analytic), and Common Toxicity Criteria toxicity scoring system. The median follow-up time was 3 months. The mean prescription dose to the CTV(p) and PTV(p) was 70.4 Gy and 68.6 Gy, respectively. The minimal dose to the CTV(e) and PTV(e) was 49.0 Gy and 47.0 Gy, respectively. No acute Grade 2 or greater gastrointestinal toxicity occurred. Fourteen patients developed acute Grade 2 lower gastrointestinal toxicity. Acute Grade 3 and 2 genitourinary toxicity developed in 2 and 14 patients, respectively. The results of our study have shown that hypofractionated intensity-modulated arc radiotherapy as primary therapy for N1 prostate cancer is feasible with low toxicity.

International Journal of Gynecological Cancer, 2013

Since the addition of chemotherapy to radiotherapy, the survival rates of locally advanced cervic... more Since the addition of chemotherapy to radiotherapy, the survival rates of locally advanced cervical cancer (LACC) have improved but are still disappointing. Therefore, the idea of surgery after chemoradiation in case of LACC or bulky disease was adopted. One of the concerns regarding surgery following chemoradiotherapy is surgery-related morbidity. The objectives of this study were to investigate the feasibility of surgery after advanced radiotherapy techniques such as intensity-modulated arc therapy (IMAT) and to describe the morbidity. This was a prospective study of primary inoperable LACC patients primary treated with IMAT, in most cases combined with weekly cisplatin. Then the resectability was reevaluated. If resectable patients were treated with Wertheim type 2 surgery ± pelvic lymphadenectomy (on positron emission tomography-computed tomography indication). If tumor is not resectable, patients were treated with brachytherapy. Since 2006, 41 consecutive patients were included. After neoadjuvant IMAT, 34 were considered resectable and underwent surgery, whereas 7 proceeded with brachytherapy. The operative mortality rate was nil. There were no major perioperative complications. No ureter, bladder, or bowel injuries occurred. No postoperative urinary/digestive fistulae or stenoses were noted. Eleven patients had postoperatively urinary retention problems. At the time of discharge, 5 patients still needed self-catheterization. All problems resolved within 3 months. In 4 cases, we saw significant lymphoceles. In all patients intended to treat, overall survival and disease-free survival at 3 years were 63% and 74%. In the Wertheim group, overall survival and disease-free survival at 3 years were 81% and 91%. Completing surgery after chemoradiation therapy (with IMAT) for LACC or bulky disease is feasible, and complication rates are comparable with those of primary surgery for cervical cancer.

International Journal of Radiation Oncology*Biology*Physics, 2012

This is a prospective report on toxicity in cervical (n Z 25) and endometrial (n Z 41) cancer pat... more This is a prospective report on toxicity in cervical (n Z 25) and endometrial (n Z 41) cancer patients treated with postoperative radiotherapy using intensitymodulated arc therapy. Apart from 12% Grade 3 hematologic toxicity, Grade 3 acute toxicity was very low (2% genitourinary and no gastrointestinal). No severe (Grade 3) late toxicity was noted. Para-aortic lymph node irradiation is feasible when intensity-modulated arc therapy is used. Concomitant chemotherapy and para-aortic lymph node irradiation significantly Purpose: To report on toxicity after postoperative intensity-modulated arc therapy (IMAT) for cervical (CC) and endometrial cancer (EC). Methods and Materials: Twenty-four CC and 41 EC patients were treated with postoperative IMAT. If indicated, para-aortic lymph node irradiation (preventive or when affected, PALN) and/or concomitant cisplatin (40 mg/m 2 , weekly) was administered. The prescribed dose for IMAT was 45 Gy (CC, 25 fractions) and 46 Gy (EC, 23 fractions), followed by a brachytherapeutic boost if possible. Radiation-related toxicity was assessed prospectively. The effect of concomitant cisplatin and PALN irradiation was evaluated. Results: Regarding acute toxicity (n Z 65), Grade 3 and 2 acute gastrointestinal toxicity was observed in zero and 63% of patients (79% CC, 54% EC), respectively. Grade 3 and 2 acute genitourinary toxicity was observed in 1% and 18% of patients, respectively. Grade 2 (21%) and 3 (12%) hematologic toxicity (n Z 41) occurred only in CC patients. Seventeen percent of CC patients and 2% of EC patients experienced Grade 2 fatigue and skin toxicity, respectively. Adding cisplatin led to an increase in Grade >2 nausea (57% vs. 9%; p Z 0.01), Grade 2 nocturia (24% vs. 4%; p Z 0.03), Grade 2 hematologic toxicity (38% vs. nil, p Z 0.003), Grade 2 leukopenia (33% vs. nil, p Z 0.009), and a strong trend toward more fatigue (14% vs. 2%; p Z 0.05). Para-aortic lymph node irradiation led to an increase of Grade 2 nocturia (31% vs. 4%, p Z 0.008) and a strong trend toward more Grade >2 nausea (44% vs. 18%; p Z 0.052). Regarding late toxicity (n Z 45), no Grade 3 or 4 late toxicity occurred. Grade 2 gastrointestinal toxicity, genitourinary toxicity, and fatigue occurred in 4%, 9%, and 1% of patients. Neither concomitant cisplatin nor PALN irradiation increased late toxicity rates. Conclusions: Postoperative IMAT for EC or CC is associated with low acute and late toxicity. Concomitant chemotherapy and PALN irradiation influences acute but not late toxicity.

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2014

To define rectal dose volume constraints (DVC) to prevent ⩾grade2 late rectal toxicity (LRT) afte... more To define rectal dose volume constraints (DVC) to prevent ⩾grade2 late rectal toxicity (LRT) after intensity modulated radiotherapy (IMRT) for prostate cancer (PC). Six hundred thirty-seven PC patients were treated with primary (prostate median dose: 78Gy) or postoperative (prostatic bed median dose: 74Gy (adjuvant)-76Gy (salvage)) IMRTwhile restricting the rectal dose to 76Gy, 72Gy and 74Gy respectively. The impact of patient characteristics and rectal volume parameters on ⩾grade2 LRT was determined. DVC were defined to estimate the 5% and 10% risk of developing ⩾grade2 LRT. The 5-year probability of being free from ⩾grade2 LRT, non-rectal blood loss and persisting symptoms is 88.8% (95% CI: 85.8-91.1%), 93.4% (95% CI: 91.0-95.1%) and 94.3% (95% CI: 92.0-95.9%) respectively. There was no correlation with patient characteristics. All volume parameters, except rectal volume receiving ⩾70Gy (R70), were significantly correlated with ⩾grade2 LRT. To avoid 10% and 5% risk of ⩾grade2 LRT ...

Radiotherapy and Oncology, 2005

Local relapse after radiotherapy for prostate cancer mostly originates at the original tumor loca... more Local relapse after radiotherapy for prostate cancer mostly originates at the original tumor location. Dose escalation reduces local relapse rates. It may be of benefit to focus the highest dose to the intraprostatic lesion (GTVMRI) using intensity-modulated radiotherapy (IMRT). Therefore, the visualization of the GTVMRI and its inclusion into computer optimization is mandatory. Fifteen patients with prostatic adenocarcinoma were referred for IMRT. All these patients had a palpable lesion on digital rectal examination (DRE) and/or a PSA >10.0 ng/ml. A T2-weighted MR examination of the prostate was performed in order to detect a GTV(MRI) and correlate the location of the GTV(MRI) with the site of the tumour-containing cylinder (biopsy). Two IMRT plans were compared: a plan without the inclusion of the GTV(MRI) (IMRT-CONV) versus a plan including the GTV(MRI) into the plan optimization (IMRT-GTV(MRI)). For comparison, both physical and biological endpoints of the GTV(MRI), CTV, PTV and rectum were taken into account. After the finalization of the planning study, the IMRT-GTV(MRI) plans were clinically delivered using step-and-shoot IMRT. Acute gastro-intestinal (GI) and genito-urinary (GU) toxicity were recorded. In all cases, the location of the GTV(MRI) corresponded with the site of the tumor containing biopsy cylinder. The mean and median distance of the GTV(MRI) to the anterior rectal wall was 3 and 2mm, respectively (range: 0-12 mm). For the GTV(MRI), its inclusion in the optimization led to a significant increase of all physical endpoints (P<0.01), without compromising the dose to the CTV, PTV and rectum. Mean GTV(MRI) dose was 78.3 Gy (IMRT-GTV(MRI)) versus 76.9 Gy (IMRT-CONV) (P<0.00001). All IMRT treatments were successfully delivered within 6 min. We did not observe grade 3 acute GI toxicity. One patient developed grade 3 GU toxicity (nocturia), that disappeared after administration of medication. Grade 2 GI and GU toxicity was observed in, respectively, four and six patients. Using T2-weighted MR, the visualization of an intraprostatic lesion is feasible. The inclusion of the GTV(MRI) into planning optimization leads to a modest increase in dose, without compromising the dose to the CTV, PTV and organs at risk. The clinical delivery of these plans runs without problems. Acute toxicity is mild.

European urology, Jan 17, 2014

The introduction of novel imaging modalities has increased the detection of oligometastatic prost... more The introduction of novel imaging modalities has increased the detection of oligometastatic prostate cancer (PCa) recurrence, potentially justifying the use of a metastasis-directed therapy (MDT) with surgery or radiotherapy (RT) rather than a systemic approach. To perform a systematic review of MDT for oligometastatic PCa recurrence. This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We searched the Medline and Embase databases from 1946 to February 2014 for studies reporting on biochemical or clinical progression and/or toxicity or complications of MDT (RT or surgery). Reports were excluded if these end points could not be ascertained or separately analysed, or if insufficient details were provided. Methodological quality was assessed using an 18-item validated quality appraisal tool for case series. Fifteen single-arm case series reporting on a total of 450 patients met the inclusion criteria. Seven stu...

BioMed Research International, 2015

Methodology. Seventeen patients with prostate-specific antigen (PSA) rise following local treatme... more Methodology. Seventeen patients with prostate-specific antigen (PSA) rise following local treatment for prostate cancer with curative intent underwent open or minimally invasive salvage pelvic lymph node dissection (SLND) for oligometastatic disease (<4 synchronous metastases) or as staging prior to salvage radiotherapy. Biochemical recurrence after complete biochemical response (cBR) was defined as 2 consecutive PSA increases >0,2 ng/mL; and after incomplete biochemical response as 2 consecutive PSA rises. Newly found metastasis on imaging defined clinical progression (CP). Palliative androgen deprivation therapy (ADT) was initiated if >3 metastases were detected or if patients became symptomatic. Kaplan-Meier statistics were applied. Results. Clavien-Dindo grade 1, 2, 3a, and 3b complications were seen in 6, 1, 1, and 2 patients, respectively. Median follow-up time was 22 months. Among 13 patients treated for oligometastatic disease, 8 (67%) had a PSA decline, with 3 patients showing cBR. Median PSA progression-free survival (FS) was 4.1 months and median CP-FS 7 months. Three patients started ADT, resulting in a 2-year ADT-FS rate of 79.5%. Conclusion. SLND is feasible, but postoperative complication rate seems higher than that for primary LND. Biochemical and clinical response duration is limited, but as part of an oligometastatic treatment regime it can defer palliative ADT.

Radiation Oncology, 2014

Purpose: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic d... more Purpose: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic disease at recurrence and treated with stereotactic body radiotherapy (SBRT).

Strahlentherapie und Onkologie, 2009

To report on the planning procedure, quality control, and clinical implementation of intensity-mo... more To report on the planning procedure, quality control, and clinical implementation of intensity-modulated arc therapy (IMAT) delivering a simultaneous integrated boost (SIB) in patients with primary irresectable cervix carcinoma. Patients and Methods: Six patients underwent PET-CT (positron emission tomography-computed tomography) and MRI (magnetic resonance imaging) before treatment planning. Prescription (25 fractions) was

World Journal of Urology, 2012

The first publication of the European Association of Urology (EAU) guidelines on Pain Management ... more The first publication of the European Association of Urology (EAU) guidelines on Pain Management in Urology dates back to 2003. Since then, these guidelines have been revised several times with the most recent update achieved in 2010. Given the scope of the full text guidelines, condensing the entire document was no option in this context. This paper presents a summary of the section of pain management in prostate cancer, a topic considered of direct relevance for the practicing urologist. A multidisciplinary expert panel (urologists, anaesthesiologists, radio-oncologists) compiled this document based on a comprehensive consultation of the literature. Data were identified through a structured search, covering the time frame 2000 through 2010, using Medline and Embase as well as the Cochrane Library of systematic reviews. The scientific papers were weighed by the expert panel and a level of evidence (LE) assigned. Recommendations have been graded as a means to provide transparency between the underlying evidence and the guidance provided. Pain can occur in each stage of prostate cancer. It could be caused by the cancer itself (77%), be related to the cancer treatment (19%) or be unrelated to either (3%). The incidence of pain rises to 90% as patients enter the terminal phase of their illness. The physician's task is to discover and treat the cause of pain and the pain itself, to determine whether or not the underlying cause is treatable, to provide pain relief and palliative care. These tasks more often than not require a multidisciplinary team. Pain management involves mainly pharmacotherapy, including direct anticancer therapy such as androgen deprivation and chemotherapy, as well as analgetics, for instance non-steroidal anti-inflammatory drugs (NSAIDs) or opioids. In case of local impairment due to the cancer or its metastases, primary treatments like surgery, radiotherapy or radionuclides can provide adequate pain relief. In addition, in palliative care, functional, psychosocial and spiritual support are essential components. The EAU guidelines on Pain Management in Urology are available in a number of different formats through the EAU Central Office and the EAU website ( http://www.uroweb.org/guidelines/online-guidelines/ ). The mainstay of pain management in prostate cancer is involvement of and collaboration between experts from a number of disciplines to be able to achieve a complete pain evaluation and to offer the full range of treatment options. Prostate cancer-related pain can, in most cases, be managed effectively, but it requires careful monitoring where a balance should be found between pain relief and potential side effects of treatment and quality of life (QoL).

Strahlentherapie und Onkologie, 2004

To describe the implementation and to evaluate the results of direct segment aperture optimizatio... more To describe the implementation and to evaluate the results of direct segment aperture optimization using the segment outline and weight adapting tool (SOWAT) in intensity-modulated radiotherapy (IMRT) for prostate cancer. Patients and Methods: 14 consecutive, unselected patients with localized prostate cancer were entered in a planning study comparing IMRT without and with the use of SOWAT. The clinical target volume (CTV) consisted of the prostate and seminal vesicles in all cases. To create the planning target volume (PTV), a three-dimensional anisotropic margin (10 mm in craniocaudal direction, 7 mm in both other directions) was used. To compare both plans, physical as well as biological endpoints were considered. Results: Considering the CTV, SOWAT resulted in a significantly higher minimal dose together with a higher dose to 95% (D 95 ) and 90% (D 90 ) of the CTV volume (p < 0.05; ). Target dose homogeneity was significantly improved (p < 0.001). Tumor control probability (TCP) was significantly increased (p < 0.05). Considering the PTV, D 90 was significantly increased (p < 0.05). Target dose homogeneity was significantly improved (p < 0.05; ). For rectum, the volumes receiving 50 Gy (R vol50 ), 60 Gy (R vol60 ), or 65 Gy (R vol65 ) as well as the mean dose were significantly lowered after SOWAT (p = 0.0001; ). Rectal normal tissue complication probability (NTCP) was significantly lower after SOWAT (p = 0.005). Probability of uncomplicated local control (P+) was significantly higher after SOWAT (p < 0.0001). Conclusion: SOWAT is a powerful planning tool to increase the therapeutic ratio of IMRT for prostate cancer. It leaves the delivery time unchanged, so that treatments can still be delivered within a time slot of 8 min.

Radiotherapy and Oncology, 2006

To evaluate the early side effects of a short course hypofractionated radiotherapy regimen in pro... more To evaluate the early side effects of a short course hypofractionated radiotherapy regimen in prostate cancer. Three institutions (IRE, AZ VUB, GUH) included 36 patients with T1-T3N0M0 prostate cancer in a phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Early side effects were scored using the RTOG/EORTC criteria and the international prostate symptom index (IPSI) weekly during treatment and 1 and 2 months afterwards. The results were compared with two control groups of patients previously treated with conventional fractionation at AZ VUB (238 patients) and GUH (114 patients). None of the patients experienced grade 3-4 toxicity. Grade 1-2 Gastro-intestinal (GI), grade 2 GI, grade 1-2 Genito-urinary (GU) and grade 2 GU toxicity occurred in 75%, 36%, 75% and 44% for the hypofractionation schedule. The corresponding figures were 25-44%, 6-29%, 47-53% and 16-44% for the control groups (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01 for grade 1-2 GI and GU toxicity). Two months after treatment all GU and the majority of GI symptoms had resolved. The IPSI increased from (average +/-1 SD) 5.6+/-4 pre-treatment to 10.0+/-6 during week 2-4 and had normalized (5.2+/-4) two months after treatment. Though no grade 3-4 side effects were observed, the investigated schedule results in a marked increase of grade 1-2 early side effects as compared to a conventional regimen. Side effects resolved within two months post-treatment.

International Journal of Radiation Oncology*Biology*Physics, 2012

To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (&amp;am... more To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

Clinical genitourinary cancer, 2013

We investigated whether repeated stereotactic body radiotherapy (SBRT) of oligometastatic disease... more We investigated whether repeated stereotactic body radiotherapy (SBRT) of oligometastatic disease is able to defer the initiation of palliative androgen deprivation therapy (ADT) in patients with low-volume bone and lymph node metastases. Patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary end point. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic or in case of a prostate specific antigen elevation above 50 ng/mL in the absence of metastases. Secondary end points were local control, clinical progression-free survival, and toxicity. Toxicity was scored using the Common Te...

Acta Clinica Belgica, Mar 27, 2015

Men diagnosed with localised prostate cancer (PC) have to make a well-informed treatment choice b... more Men diagnosed with localised prostate cancer (PC) have to make a well-informed treatment choice between (robot-assisted) radical prostatectomy (RARP), external beam radiotherapy (EBRT) and, in selected cases, brachytherapy and active surveillance. We developed and validated a questionnaire to determine the cognitive reasons why patients choose their treatment. The Prostate Cancer Decision-Making Questionnaire (PC-DMQ) was designed in-house and validated through the Delphi method by seven external experts. Finally, we tested this questionnaire in a cohort of 24 men, recently diagnosed with localised PC, before undergoing RARP (n = 16), EBRT (n = 6), brachytherapy (n = 1) or active surveillance (n = 1). The experts reached consensus after three discussion rounds. In the patient cohort, 75% of men undergoing RARP chose this treatment because &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;it provides the best chance of cure&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;. Reasons to choose EBRT were not as explicit: 33.3% chose this treatment because &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;it provides the best chance of cure&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; and 33.3% because &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;the maintenance of potency is important to them&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;. The PC-DMQ is a comprehensive and standardised tool that allows further research into cognitive factors that influence treatment decision-making in patients with localised PC.

European urology, Jan 17, 2014

The introduction of novel imaging modalities has increased the detection of oligometastatic prost... more The introduction of novel imaging modalities has increased the detection of oligometastatic prostate cancer (PCa) recurrence, potentially justifying the use of a metastasis-directed therapy (MDT) with surgery or radiotherapy (RT) rather than a systemic approach. To perform a systematic review of MDT for oligometastatic PCa recurrence. This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We searched the Medline and Embase databases from 1946 to February 2014 for studies reporting on biochemical or clinical progression and/or toxicity or complications of MDT (RT or surgery). Reports were excluded if these end points could not be ascertained or separately analysed, or if insufficient details were provided. Methodological quality was assessed using an 18-item validated quality appraisal tool for case series. Fifteen single-arm case series reporting on a total of 450 patients met the inclusion criteria. Seven stu...

BioMed Research International, 2015

Methodology. Seventeen patients with prostate-specific antigen (PSA) rise following local treatme... more Methodology. Seventeen patients with prostate-specific antigen (PSA) rise following local treatment for prostate cancer with curative intent underwent open or minimally invasive salvage pelvic lymph node dissection (SLND) for oligometastatic disease (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;4 synchronous metastases) or as staging prior to salvage radiotherapy. Biochemical recurrence after complete biochemical response (cBR) was defined as 2 consecutive PSA increases &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0,2 ng/mL; and after incomplete biochemical response as 2 consecutive PSA rises. Newly found metastasis on imaging defined clinical progression (CP). Palliative androgen deprivation therapy (ADT) was initiated if &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;3 metastases were detected or if patients became symptomatic. Kaplan-Meier statistics were applied. Results. Clavien-Dindo grade 1, 2, 3a, and 3b complications were seen in 6, 1, 1, and 2 patients, respectively. Median follow-up time was 22 months. Among 13 patients treated for oligometastatic disease, 8 (67%) had a PSA decline, with 3 patients showing cBR. Median PSA progression-free survival (FS) was 4.1 months and median CP-FS 7 months. Three patients started ADT, resulting in a 2-year ADT-FS rate of 79.5%. Conclusion. SLND is feasible, but postoperative complication rate seems higher than that for primary LND. Biochemical and clinical response duration is limited, but as part of an oligometastatic treatment regime it can defer palliative ADT.

International Journal of Gynecological Cancer, 2012

To report on the value of magnetic resonance imaging (MRI) and 2-deoxy-2-[18] fluoro-D-glucose po... more To report on the value of magnetic resonance imaging (MRI) and 2-deoxy-2-[18] fluoro-D-glucose positron emission tomography computed tomography (¹⁸FDG PET-CT) in predicting resectability and pathological response of primary locally advanced cervical cancer after neoadjuvant intensity-modulated arc therapy (IMAT) with or without cisplatin (C). Twenty-seven patients with International Federation of Gynecology and Obstetrics stages IB2 to IVA cervical cancer were treated with IMAT-C followed by extrafascial hysterectomy (EH). All patients received MRI and ¹⁸FDG PET-CT after IMAT-C. The end points of this study were to: 1. Assess the ability of MRI to predict negative surgical margins (R0). 2. Assess the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI in predicting the following situation at the EH specimen: &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;no residual disease or minimal microscopically visible residual tumor.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; 3. Assess the sensitivity, specificity, PPV, and NPV value of ¹⁸FDG PET-CT in predicting &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;no residual viable tumor cells&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; at the EH specimen. An R0 resection was obtained in all patients. None of the EH specimens contained macroscopically visible tumor. In 13 patients, no viable tumor cells were found and only 14 had residual microscopic disease. Twenty-four of 27 MRIs were able to correctly predict R0 resection. A negative MRI was 100% predictive for the end point &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;R0 resection.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; The specificity and NPV of MRI (end point 2) were 74% and 100%, respectively. No sensitivity or PPV could be calculated. The sensitivity, specificity, PPV, and NPV of ¹⁸FDG PET-CT were 29%, 62%, 44%, and 44%, respectively (end point 3). A negative MRI after IMAT-C predicts 100% correctly for R0 resection. The role of FDG PET-CT in predicting viable tumor cells at EH specimen is at least debatable.

Radiotherapy and Oncology, 2008

The aim was to prospectively evaluate both acute and late toxicity and biochemical non-evidence o... more The aim was to prospectively evaluate both acute and late toxicity and biochemical non-evidence of disease (bNED) in patients treated with salvage intensity-modulated radiotherapy (IMRT) ± androgen deprivation (AD) for biochemical relapse after radical prostatectomy (RP).

International Journal of Radiation Oncology*Biology*Physics, 2011

The present study aims to assess the interobserver agreement of prostate bed delineation after ra... more The present study aims to assess the interobserver agreement of prostate bed delineation after radical prostatectomy using CT alone as proposed by the European Organization for Research and Treatment of Cancer (EORTC) guidelines. Six observers delineated the postoperative prostate bed (PB) and the original seminal vesicle position or remnants (SV) of 10 patients according to the EORTC guidelines. Contours were then compared for agreement between observers (the apparent volume overlap and generalized kappa statistics). Standard deviations were also calculated to measure the variability of the position of the outer margins. The mean volume of 100% agreement (±1 standard deviation, SD) was only 5.0 (±3.3) ml for the PB and 0.9 (±1.5) ml for the SV, whereas the mean union of all contours (±1 SD) was 41.1 (±11.8) ml and 25.3 (±13.4) ml, respectively. The mean overall agreement corrected for chance was moderate for both the PB (mean kappa, 0.49; range, 0.35-0.62) and SV (mean kappa, 0.42; range, 0.22-0.59). The overall SD of the outer margins of the PB ranged from 4.6 to 7.0 mm The delineation of the postprostatectomy bed using CT shows only a moderate observer agreement when following the EORTC guidelines.

International Journal of Radiation Oncology*Biology*Physics, 2009

To determine the planning results and acute toxicity after hypofractionated intensity-modulated a... more To determine the planning results and acute toxicity after hypofractionated intensity-modulated arc radiotherapy and androgen deprivation for lymph node metastasized (Stage N1) prostate cancer. A total of 31 patients with Stage T1-T4N1M0 prostate cancer were treated with intensity-modulated arc radiotherapy and 3 years of androgen deprivation as primary treatment. The clinical target volume (CTV(p)) was the prostate and seminal vesicles. Elective lymph node areas ((e)) were delineated and expanded by 2 mm to create the CTV(e). The planning target volumes (PTV(p) and PTV(e)) were created using a three-dimensional expansion of the CTV(p) and CTV(e), respectively, of 7 mm. A median dose of 69.3 Gy and 50 Gy was prescribed to the PTV(p) and PTV(e) respectively, to be delivered in 25 fractions. Upper and lower gastrointestinal toxicity was scored using the Radiation Therapy Oncology Group toxicity and radiotherapy-induced lower intestinal toxicity scoring system. Genitourinary toxicity was scored using a combined Radiation Therapy Oncology Group, LENT-SOMA (late effects normal tissue-subjective, objective, management, analytic), and Common Toxicity Criteria toxicity scoring system. The median follow-up time was 3 months. The mean prescription dose to the CTV(p) and PTV(p) was 70.4 Gy and 68.6 Gy, respectively. The minimal dose to the CTV(e) and PTV(e) was 49.0 Gy and 47.0 Gy, respectively. No acute Grade 2 or greater gastrointestinal toxicity occurred. Fourteen patients developed acute Grade 2 lower gastrointestinal toxicity. Acute Grade 3 and 2 genitourinary toxicity developed in 2 and 14 patients, respectively. The results of our study have shown that hypofractionated intensity-modulated arc radiotherapy as primary therapy for N1 prostate cancer is feasible with low toxicity.

International Journal of Gynecological Cancer, 2013

Since the addition of chemotherapy to radiotherapy, the survival rates of locally advanced cervic... more Since the addition of chemotherapy to radiotherapy, the survival rates of locally advanced cervical cancer (LACC) have improved but are still disappointing. Therefore, the idea of surgery after chemoradiation in case of LACC or bulky disease was adopted. One of the concerns regarding surgery following chemoradiotherapy is surgery-related morbidity. The objectives of this study were to investigate the feasibility of surgery after advanced radiotherapy techniques such as intensity-modulated arc therapy (IMAT) and to describe the morbidity. This was a prospective study of primary inoperable LACC patients primary treated with IMAT, in most cases combined with weekly cisplatin. Then the resectability was reevaluated. If resectable patients were treated with Wertheim type 2 surgery ± pelvic lymphadenectomy (on positron emission tomography-computed tomography indication). If tumor is not resectable, patients were treated with brachytherapy. Since 2006, 41 consecutive patients were included. After neoadjuvant IMAT, 34 were considered resectable and underwent surgery, whereas 7 proceeded with brachytherapy. The operative mortality rate was nil. There were no major perioperative complications. No ureter, bladder, or bowel injuries occurred. No postoperative urinary/digestive fistulae or stenoses were noted. Eleven patients had postoperatively urinary retention problems. At the time of discharge, 5 patients still needed self-catheterization. All problems resolved within 3 months. In 4 cases, we saw significant lymphoceles. In all patients intended to treat, overall survival and disease-free survival at 3 years were 63% and 74%. In the Wertheim group, overall survival and disease-free survival at 3 years were 81% and 91%. Completing surgery after chemoradiation therapy (with IMAT) for LACC or bulky disease is feasible, and complication rates are comparable with those of primary surgery for cervical cancer.

International Journal of Radiation Oncology*Biology*Physics, 2012

This is a prospective report on toxicity in cervical (n Z 25) and endometrial (n Z 41) cancer pat... more This is a prospective report on toxicity in cervical (n Z 25) and endometrial (n Z 41) cancer patients treated with postoperative radiotherapy using intensitymodulated arc therapy. Apart from 12% Grade 3 hematologic toxicity, Grade 3 acute toxicity was very low (2% genitourinary and no gastrointestinal). No severe (Grade 3) late toxicity was noted. Para-aortic lymph node irradiation is feasible when intensity-modulated arc therapy is used. Concomitant chemotherapy and para-aortic lymph node irradiation significantly Purpose: To report on toxicity after postoperative intensity-modulated arc therapy (IMAT) for cervical (CC) and endometrial cancer (EC). Methods and Materials: Twenty-four CC and 41 EC patients were treated with postoperative IMAT. If indicated, para-aortic lymph node irradiation (preventive or when affected, PALN) and/or concomitant cisplatin (40 mg/m 2 , weekly) was administered. The prescribed dose for IMAT was 45 Gy (CC, 25 fractions) and 46 Gy (EC, 23 fractions), followed by a brachytherapeutic boost if possible. Radiation-related toxicity was assessed prospectively. The effect of concomitant cisplatin and PALN irradiation was evaluated. Results: Regarding acute toxicity (n Z 65), Grade 3 and 2 acute gastrointestinal toxicity was observed in zero and 63% of patients (79% CC, 54% EC), respectively. Grade 3 and 2 acute genitourinary toxicity was observed in 1% and 18% of patients, respectively. Grade 2 (21%) and 3 (12%) hematologic toxicity (n Z 41) occurred only in CC patients. Seventeen percent of CC patients and 2% of EC patients experienced Grade 2 fatigue and skin toxicity, respectively. Adding cisplatin led to an increase in Grade >2 nausea (57% vs. 9%; p Z 0.01), Grade 2 nocturia (24% vs. 4%; p Z 0.03), Grade 2 hematologic toxicity (38% vs. nil, p Z 0.003), Grade 2 leukopenia (33% vs. nil, p Z 0.009), and a strong trend toward more fatigue (14% vs. 2%; p Z 0.05). Para-aortic lymph node irradiation led to an increase of Grade 2 nocturia (31% vs. 4%, p Z 0.008) and a strong trend toward more Grade >2 nausea (44% vs. 18%; p Z 0.052). Regarding late toxicity (n Z 45), no Grade 3 or 4 late toxicity occurred. Grade 2 gastrointestinal toxicity, genitourinary toxicity, and fatigue occurred in 4%, 9%, and 1% of patients. Neither concomitant cisplatin nor PALN irradiation increased late toxicity rates. Conclusions: Postoperative IMAT for EC or CC is associated with low acute and late toxicity. Concomitant chemotherapy and PALN irradiation influences acute but not late toxicity.

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2014

To define rectal dose volume constraints (DVC) to prevent ⩾grade2 late rectal toxicity (LRT) afte... more To define rectal dose volume constraints (DVC) to prevent ⩾grade2 late rectal toxicity (LRT) after intensity modulated radiotherapy (IMRT) for prostate cancer (PC). Six hundred thirty-seven PC patients were treated with primary (prostate median dose: 78Gy) or postoperative (prostatic bed median dose: 74Gy (adjuvant)-76Gy (salvage)) IMRTwhile restricting the rectal dose to 76Gy, 72Gy and 74Gy respectively. The impact of patient characteristics and rectal volume parameters on ⩾grade2 LRT was determined. DVC were defined to estimate the 5% and 10% risk of developing ⩾grade2 LRT. The 5-year probability of being free from ⩾grade2 LRT, non-rectal blood loss and persisting symptoms is 88.8% (95% CI: 85.8-91.1%), 93.4% (95% CI: 91.0-95.1%) and 94.3% (95% CI: 92.0-95.9%) respectively. There was no correlation with patient characteristics. All volume parameters, except rectal volume receiving ⩾70Gy (R70), were significantly correlated with ⩾grade2 LRT. To avoid 10% and 5% risk of ⩾grade2 LRT ...

Radiotherapy and Oncology, 2005

Local relapse after radiotherapy for prostate cancer mostly originates at the original tumor loca... more Local relapse after radiotherapy for prostate cancer mostly originates at the original tumor location. Dose escalation reduces local relapse rates. It may be of benefit to focus the highest dose to the intraprostatic lesion (GTVMRI) using intensity-modulated radiotherapy (IMRT). Therefore, the visualization of the GTVMRI and its inclusion into computer optimization is mandatory. Fifteen patients with prostatic adenocarcinoma were referred for IMRT. All these patients had a palpable lesion on digital rectal examination (DRE) and/or a PSA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10.0 ng/ml. A T2-weighted MR examination of the prostate was performed in order to detect a GTV(MRI) and correlate the location of the GTV(MRI) with the site of the tumour-containing cylinder (biopsy). Two IMRT plans were compared: a plan without the inclusion of the GTV(MRI) (IMRT-CONV) versus a plan including the GTV(MRI) into the plan optimization (IMRT-GTV(MRI)). For comparison, both physical and biological endpoints of the GTV(MRI), CTV, PTV and rectum were taken into account. After the finalization of the planning study, the IMRT-GTV(MRI) plans were clinically delivered using step-and-shoot IMRT. Acute gastro-intestinal (GI) and genito-urinary (GU) toxicity were recorded. In all cases, the location of the GTV(MRI) corresponded with the site of the tumor containing biopsy cylinder. The mean and median distance of the GTV(MRI) to the anterior rectal wall was 3 and 2mm, respectively (range: 0-12 mm). For the GTV(MRI), its inclusion in the optimization led to a significant increase of all physical endpoints (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), without compromising the dose to the CTV, PTV and rectum. Mean GTV(MRI) dose was 78.3 Gy (IMRT-GTV(MRI)) versus 76.9 Gy (IMRT-CONV) (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.00001). All IMRT treatments were successfully delivered within 6 min. We did not observe grade 3 acute GI toxicity. One patient developed grade 3 GU toxicity (nocturia), that disappeared after administration of medication. Grade 2 GI and GU toxicity was observed in, respectively, four and six patients. Using T2-weighted MR, the visualization of an intraprostatic lesion is feasible. The inclusion of the GTV(MRI) into planning optimization leads to a modest increase in dose, without compromising the dose to the CTV, PTV and organs at risk. The clinical delivery of these plans runs without problems. Acute toxicity is mild.

European urology, Jan 17, 2014

The introduction of novel imaging modalities has increased the detection of oligometastatic prost... more The introduction of novel imaging modalities has increased the detection of oligometastatic prostate cancer (PCa) recurrence, potentially justifying the use of a metastasis-directed therapy (MDT) with surgery or radiotherapy (RT) rather than a systemic approach. To perform a systematic review of MDT for oligometastatic PCa recurrence. This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We searched the Medline and Embase databases from 1946 to February 2014 for studies reporting on biochemical or clinical progression and/or toxicity or complications of MDT (RT or surgery). Reports were excluded if these end points could not be ascertained or separately analysed, or if insufficient details were provided. Methodological quality was assessed using an 18-item validated quality appraisal tool for case series. Fifteen single-arm case series reporting on a total of 450 patients met the inclusion criteria. Seven stu...

BioMed Research International, 2015

Methodology. Seventeen patients with prostate-specific antigen (PSA) rise following local treatme... more Methodology. Seventeen patients with prostate-specific antigen (PSA) rise following local treatment for prostate cancer with curative intent underwent open or minimally invasive salvage pelvic lymph node dissection (SLND) for oligometastatic disease (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;4 synchronous metastases) or as staging prior to salvage radiotherapy. Biochemical recurrence after complete biochemical response (cBR) was defined as 2 consecutive PSA increases &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0,2 ng/mL; and after incomplete biochemical response as 2 consecutive PSA rises. Newly found metastasis on imaging defined clinical progression (CP). Palliative androgen deprivation therapy (ADT) was initiated if &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;3 metastases were detected or if patients became symptomatic. Kaplan-Meier statistics were applied. Results. Clavien-Dindo grade 1, 2, 3a, and 3b complications were seen in 6, 1, 1, and 2 patients, respectively. Median follow-up time was 22 months. Among 13 patients treated for oligometastatic disease, 8 (67%) had a PSA decline, with 3 patients showing cBR. Median PSA progression-free survival (FS) was 4.1 months and median CP-FS 7 months. Three patients started ADT, resulting in a 2-year ADT-FS rate of 79.5%. Conclusion. SLND is feasible, but postoperative complication rate seems higher than that for primary LND. Biochemical and clinical response duration is limited, but as part of an oligometastatic treatment regime it can defer palliative ADT.

Radiation Oncology, 2014

Purpose: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic d... more Purpose: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic disease at recurrence and treated with stereotactic body radiotherapy (SBRT).

Strahlentherapie und Onkologie, 2009

To report on the planning procedure, quality control, and clinical implementation of intensity-mo... more To report on the planning procedure, quality control, and clinical implementation of intensity-modulated arc therapy (IMAT) delivering a simultaneous integrated boost (SIB) in patients with primary irresectable cervix carcinoma. Patients and Methods: Six patients underwent PET-CT (positron emission tomography-computed tomography) and MRI (magnetic resonance imaging) before treatment planning. Prescription (25 fractions) was

World Journal of Urology, 2012

The first publication of the European Association of Urology (EAU) guidelines on Pain Management ... more The first publication of the European Association of Urology (EAU) guidelines on Pain Management in Urology dates back to 2003. Since then, these guidelines have been revised several times with the most recent update achieved in 2010. Given the scope of the full text guidelines, condensing the entire document was no option in this context. This paper presents a summary of the section of pain management in prostate cancer, a topic considered of direct relevance for the practicing urologist. A multidisciplinary expert panel (urologists, anaesthesiologists, radio-oncologists) compiled this document based on a comprehensive consultation of the literature. Data were identified through a structured search, covering the time frame 2000 through 2010, using Medline and Embase as well as the Cochrane Library of systematic reviews. The scientific papers were weighed by the expert panel and a level of evidence (LE) assigned. Recommendations have been graded as a means to provide transparency between the underlying evidence and the guidance provided. Pain can occur in each stage of prostate cancer. It could be caused by the cancer itself (77%), be related to the cancer treatment (19%) or be unrelated to either (3%). The incidence of pain rises to 90% as patients enter the terminal phase of their illness. The physician&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s task is to discover and treat the cause of pain and the pain itself, to determine whether or not the underlying cause is treatable, to provide pain relief and palliative care. These tasks more often than not require a multidisciplinary team. Pain management involves mainly pharmacotherapy, including direct anticancer therapy such as androgen deprivation and chemotherapy, as well as analgetics, for instance non-steroidal anti-inflammatory drugs (NSAIDs) or opioids. In case of local impairment due to the cancer or its metastases, primary treatments like surgery, radiotherapy or radionuclides can provide adequate pain relief. In addition, in palliative care, functional, psychosocial and spiritual support are essential components. The EAU guidelines on Pain Management in Urology are available in a number of different formats through the EAU Central Office and the EAU website ( http://www.uroweb.org/guidelines/online-guidelines/ ). The mainstay of pain management in prostate cancer is involvement of and collaboration between experts from a number of disciplines to be able to achieve a complete pain evaluation and to offer the full range of treatment options. Prostate cancer-related pain can, in most cases, be managed effectively, but it requires careful monitoring where a balance should be found between pain relief and potential side effects of treatment and quality of life (QoL).

Strahlentherapie und Onkologie, 2004

To describe the implementation and to evaluate the results of direct segment aperture optimizatio... more To describe the implementation and to evaluate the results of direct segment aperture optimization using the segment outline and weight adapting tool (SOWAT) in intensity-modulated radiotherapy (IMRT) for prostate cancer. Patients and Methods: 14 consecutive, unselected patients with localized prostate cancer were entered in a planning study comparing IMRT without and with the use of SOWAT. The clinical target volume (CTV) consisted of the prostate and seminal vesicles in all cases. To create the planning target volume (PTV), a three-dimensional anisotropic margin (10 mm in craniocaudal direction, 7 mm in both other directions) was used. To compare both plans, physical as well as biological endpoints were considered. Results: Considering the CTV, SOWAT resulted in a significantly higher minimal dose together with a higher dose to 95% (D 95 ) and 90% (D 90 ) of the CTV volume (p < 0.05; ). Target dose homogeneity was significantly improved (p < 0.001). Tumor control probability (TCP) was significantly increased (p < 0.05). Considering the PTV, D 90 was significantly increased (p < 0.05). Target dose homogeneity was significantly improved (p < 0.05; ). For rectum, the volumes receiving 50 Gy (R vol50 ), 60 Gy (R vol60 ), or 65 Gy (R vol65 ) as well as the mean dose were significantly lowered after SOWAT (p = 0.0001; ). Rectal normal tissue complication probability (NTCP) was significantly lower after SOWAT (p = 0.005). Probability of uncomplicated local control (P+) was significantly higher after SOWAT (p < 0.0001). Conclusion: SOWAT is a powerful planning tool to increase the therapeutic ratio of IMRT for prostate cancer. It leaves the delivery time unchanged, so that treatments can still be delivered within a time slot of 8 min.

Radiotherapy and Oncology, 2006

To evaluate the early side effects of a short course hypofractionated radiotherapy regimen in pro... more To evaluate the early side effects of a short course hypofractionated radiotherapy regimen in prostate cancer. Three institutions (IRE, AZ VUB, GUH) included 36 patients with T1-T3N0M0 prostate cancer in a phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Early side effects were scored using the RTOG/EORTC criteria and the international prostate symptom index (IPSI) weekly during treatment and 1 and 2 months afterwards. The results were compared with two control groups of patients previously treated with conventional fractionation at AZ VUB (238 patients) and GUH (114 patients). None of the patients experienced grade 3-4 toxicity. Grade 1-2 Gastro-intestinal (GI), grade 2 GI, grade 1-2 Genito-urinary (GU) and grade 2 GU toxicity occurred in 75%, 36%, 75% and 44% for the hypofractionation schedule. The corresponding figures were 25-44%, 6-29%, 47-53% and 16-44% for the control groups (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01 for grade 1-2 GI and GU toxicity). Two months after treatment all GU and the majority of GI symptoms had resolved. The IPSI increased from (average +/-1 SD) 5.6+/-4 pre-treatment to 10.0+/-6 during week 2-4 and had normalized (5.2+/-4) two months after treatment. Though no grade 3-4 side effects were observed, the investigated schedule results in a marked increase of grade 1-2 early side effects as compared to a conventional regimen. Side effects resolved within two months post-treatment.