G. De Meerleer

A comparison of the acute toxicity profile between two-dimensional and three-dimensional image-guided radiotherapy for postoperative prostate cancer

AIMS To compare acute gastrointestinal and genitourinary toxicity for patients positioned with an electronic portal imaging device (EPID) and patients positioned with kilovoltage cone beam computed tomography (CBCT) during postoperative prostate radiotherapy. MATERIALS AND METHODS Between 1999 and April 2010, 196 prostate cancer patients were referred for postoperative salvage radiotherapy. Patient position was corrected using EPID (1999 to December 2006, n=116) or CBCT (January 2007 to present, n=80). The treatment technique, number of beams, dose prescription, dose computation algorithm and planning target volume margins were not altered over time. Grade 1-3 acute gastrointestinal and genitourinary toxicity were compared between the EPID group and the CBCT group. RESULTS The incidence of grade 1 and 2 genitourinary toxicity was significantly reduced by 17 and 14%, respectively, in the CBCT group compared with the EPID group (P<0.05). This was mainly attributed to a decrease in the following grade 1 symptoms: frequency (P<0.05), nocturia (P=0.06) and urgency (P=0.07). Grade 2 incontinence (P=0.06) and frequency (P=0.06) were lower in the CBCT group. Grade 3 genitourinary toxicity was comparably low (EPID 3% versus CBCT 1%). There was no significant difference in gastrointestinal grade 1-2 toxicity between both groups. No grade 3 gastrointestinal toxicity was observed. CONCLUSIONS Patient positioning with CBCT significantly reduces acute genitourinary toxicity compared with positioning with EPID.

Screening and early diagnoSiS of proState cancer: an update

Abstract Screening for prostate cancer has become a main controversial topic. First the currently used screening tools, PSA (Prostate Specific Antigen) and DRE (Digital Rectal Examination) have a low accuracy in the prediction of prostate cancer. Second, the benefit of screening in reducing the prostate cancer related mortality was not uniformly shown in older screening studies and there was concern about the risk of overdiagnosis and overtreatment of insignificant prostate cancers. Very recently, 3 major prospective, randomized screening studies have been published. This paper aims to provide an overview how the performance of the current screening tools can be ameliorated and evaluates the recently published screening studies with practical considerations for future screening protocols.

Imaging treated prostate cancer

In patients with a clinical suspicion of recurrence after treatment for prostate cancer, imaging can be used to distinguish between local recurrence and metastatic disease. Multiparametric magnetic resonance imaging (mpMRI) of the prostate may be a valuable imaging modality for the detection and localization of local recurrence in patients treated for prostate cancer. In mpMRI, morphological T2-weighted images are combined with functional MRI techniques including diffusion-weighted imaging, dynamic contrast-enhanced imaging, and magnetic resonance spectroscopic imaging to improve accuracy. In this paper, the current status of imaging techniques used to detect and to localize tumor recurrence in patients treated for prostate cancer will be reviewed, with emphasis on mpMRI for local prostate cancer recurrence.

The single-isocentre treatment of head and neck cancer: time gain using MLC and automatic set-up

PURPOSE In this manuscript, we studied the difference in the treatment time required to execute a single-isocentre three-field irradiation of the head and neck, using either tray-mounted cerrobend blocks or a multileaf collimator (MLC) for field shaping and automatic set-up. MATERIALS AND METHODS A total of twenty consecutive, unselected patients (16 males, four females), were eligible for this study because the dose they were to received was 44 Gy (2 Gy/fraction) to the head, neck and supraclavicular regions. Patients were randomly allocated to one of two treatment groups. The first group (n = 11) was treated on a Philips SL-75 linear accelerator (SL-75), using 5 MV photons and tray-mounted cerrobend blocks. The second group (n = 9) was treated on a Philips SL-25 linear accelerator (SL-25-MLC), using 6 MV photons and a MLC. Patients of the second group were treated using the automatic set-up facility of the SL-25-MLC, without entering the treatment room between consecutive fields. RESULTS Overall treatment time was significantly shorter on the SL-25-MLC than on the SL-75 (P < 0.0001). The difference in total treatment-execution time was in the range of 157 s per treatment session. The largest difference was observed in the set-up time. There was an average of a 125 s time gain per treatment day (P < 0.0001) in favour of the SL-25-MLC. CONCLUSIONS Compared to tray-mounted cerrobend blocks, a MLC and automatic set-up results in a significant time advantage when a single isocentre technique is used to treat head and neck cancer.

Cognitive factors influencing treatment decision-making in patients with localised prostate cancer: development of a standardised questionnaire.

Abstract Background: Men diagnosed with localised prostate cancer have to make a well-informed treatment choice between (robot-assisted) radical prostatectomy, external beam radiotherapy and, in selected cases, brachytherapy and active surveillance. We developed and validated a questionnaire to determine the cognitive reasons motivating this choice. Materials and methods: The Prostate Cancer Decision-Making Questionnaire (PC-DMQ) was designed in-house and validated through the Delphi method. Finally, we tested the 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). Results: The experts reached consensus after three 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’. Conclusions: 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.

MAGNETIC RESONANCE IMAGING IN DIAGNOSIS, STAGING AND RADIOTHERAPY PLANNING FOR PROSTATE CANCER

Abstract T2-weighted magnetic resonance imaging (MRI), preferably using an endorectal coil, is able to clearly depict the normal prostatic anatomy and to identify prostate cancer with fair diagnostic accuracy. The latter can be further increased by using functional techniques such as spectroscopy (assessment of prostatic metabolism), dynamic contrast-enhanced MRI (assessment of angiogenesis) and diffusion-weighted imaging (assessment of cellular density). T2-weighted MRI is an important tool for local staging of prostate cancer in patients clinically staged as cT1 or cT2, because of its high specifi city for macroscopic capsular extension or seminal vesicle invasion. Compared to CT-imaging, MRI depicts the internal prostatic anatomy, prostatic margins and the extent of prostatic tumours much more clearly. This benefi t can be exploited to improve the accuracy of target delineations in radiotherapy planning.

O12 Salvage stereotactic body radiotherapy for patients with limited prostate cancer metastases: Deferring androgen deprivation therapy

Patients with metastatic prostate cancer are uniformly treated with castration (surgically or medically), which is associated with numerous side effects such as sexual dysfunction, fatigue, osteoporosis, metabolic syndrome, and others. This single-arm study including 24 patients with limited bone or lymph node prostate cancer (PCa) metastases shows that repeated salvage stereotactic body radiotherapy is well tolerated and defers the necessity to start castration treatment. Background: 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 and Methods: 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 Terminology Criteria for Adverse Events. Results: We treated 24 patients with a median follow-up of 24 months. Ten patients started with ADT resulting in a median ADT-FS of 38 months. The 2-year local control and clinical progression-free survival was 100% and 42%, respectively. Eleven and 3 patients, respectively, required a second and third salvage treatment for metachronous low-volume metastatic disease. No grade 3 toxicity was observed. Conclusion: Repeated salvage SBRT is feasible, well tolerated and defers palliative ADT with a median of 38 months in patients with limited bone or lymph node PCa metastases.

8 Surgical outcome of robot-assisted radical prostatectomy after a training program in a high-volume robotic centre

Objectives : Robot-assisted radical prostatectomy (RARP) is an excellent technique in the treatment of prostate cancer but requires substantial surgical skills. A training program that allows the robot-surgeon to obtain these skills can overcome the problem of a learning curve. This report aims to evaluate the value of such a training program. Material and Methods : Before starting RARP, a young urologist followed a 6-month training program at a high-volume robotic centre. The surgical outcome of the first 50 RARPs are evaluated and compared with a cohort of 50 open radical prostatectomies (ORP) performed by an experienced senior urologist during the same period. An independent t-test was performed for continuous variables and a chi-square test for categorical variables. Values were presented as mean (± standard deviation). Tumor stage and grade were similar in both groups. Nerve-sparing (uni-or bilateral) was significantly more performed with RARP. Follow-up duration was significantly longer in ORP. Results : Operation time was similar in both groups. Hospital stay was on average almost one day shorter with RARP. Catheterization duration was significantly shorter (8,6 days (± 6,9) vs. 15,2 (± 5,2); p<0.0001) and decline in Hb was significantly less in RARP (2,10 g/dl (± 1,09) vs. 4,03 (± 1,17); p<0.0001). Complication rate was not significantly different among groups but tended to be more severe in ORP. Positive surgical margin rate was 6% and 24% for respectively RARP and ORP (p=0.022). At 12 months, urinary continence was 81 and 82,9% for respectively RARP and ORP (p=1). Conclusions : These data indicate that a training program in a high volume robotic centre can reduce the learning curve. RARP was associated with significantly less positive surgical margins, shorter catheterization duration and less blood loss compared to ORP.

Clinical Implementation of IMRT by MLC Technology

The case in favour of IMRT is made as IMRT allows to shape the dose distribution in such a way that at least three challenges in clinical radiotherapy can be addressed. These are i) conforming dose to concave PTV shapes (i.e. head and neck (HN ii) reducing the volume of surrounding tissues irradiated to intermediate dose levels by using beam combinations with restricted hinge angles (lung, mediastinal tumours) and iii) generating controlled 3D-inhomogeneous dose distributions (i.e. prostate, paranasal sinus tumours). The two largest groups of patients that we treat with IMRT are H&N and prostate cancer patients.

Adjuvant high-dose intensity-modulated radiotherapy following radical prostatectomy: Updated 5-year results.

69 Background: Approximately 25% of patients treated with immediate post-prostatectomy (adjuvant) radiotherapy will develop a biochemical failure within 5 years after radiotherapy when doses of 60-64 Gy are used. We wanted to report on the safety and biochemical outcome of adjuvant intensity-modulated radiotherapy (AIMRT) with a median dose of 74 Gy. METHODS Between 1999 and 2008, 104 patients underwent a radical prostatectomy followed by AIMRT +/- androgen deprivation (AD). Indications for AIMRT were capsule perforation, seminal vesicle invasion and/or positive surgical margins at prostatectomy specimen. All patients were irradiated at a single tertiary academic centre. AD was initiated in 65% of the patients on the basis of seminal vesicles invasion, pre-prostatectomy PSA > 20ng/mL, Gleason score ≥ 4+3 or personal preference of the referring urologist. A median dose of 74 Gy was prescribed to the planning target volume using IMRT in all patients. AD consisted out of a LHRH analogue for 6 months. The Kaplan-Meier method was used to estimate biochemical relapse-free survival (bRFS). Univariate and multivariate analysis were used to examine the influence of patient- and treatment-related factors on bRFS. RESULTS The median follow-up was 5 years. Late toxicity: no patients developed grade 3 gastrointestinal (GI) toxicity. Grade 2 GI toxicity was seen in 8%. Seven patients (7%) and 24 (23%) developed grade 3 and 2 genitourinary (GU) toxicity, respectively. An urethral stricture was observed in 8 patients (8%). The 3- and 5-year actuarial bRFS was 91% and 85%, respectively. On univariate analysis bRFS rates was reduced with seminal vesicle invasion (p < 0.04) or Gleason score ≥ 4+3 (p < 0.02) or negative margins (p < 0.001). AD and preoperative PSA levels did not influence bRFS. None of the variables remained significant on multivariate analysis.Eight patients had a distant clinical relapse (pelvic lymph nodes: 3, bone metastases: 3 and 2 patients had both). Seven patients died (3 prostate cancer related deaths). CONCLUSIONS Adjuvant high-dose IMRT after prostatectomy is safe. Five-year bRFS is excellent. No significant financial relationships to disclose.