Geert Villeirs

Interobserver Delineation Variation Using CT versus Combined CT + MRI in Intensity–Modulated Radiotherapy for Prostate Cancer

Purpose:To quantify interobserver variation of prostate and seminal vesicle delineations using CT only versus CT + MRI in consensus reading with a radiologist.Material and Methods:The prostate and seminal vesicles of 13 patients treated with intensity–modulated radiotherapy for prostatic adenocarcinoma were retrospectively delineated by three radiation oncologists on CT only and on CT + MRI in consensus reading with a radiologist. The volumes and margin positions were calculated and intermodality and interobserver variations were assessed for the clinical target volume (CTV), seminal vesicles, prostate and three prostatic subdivisions (apical, middle and basal third).Results:Using CT + MRI as compared to CT alone, the mean CTV, prostate and seminal vesicle volumes significantly decreased by 6.54%, 5.21% and 10.47%, respectively. More importantly, their standard deviations significantly decreased by 63.06%, 62.65% and 44.83%, respectively. The highest level of variation was found at the prostatic apex, followed by the prostatic base and seminal vesicles.Conclusion: Addition of MRI to CT in consensus reading with a radiologist results in a moderate decrease of the CTV, but an important decrease of the interobserver delineation variation, especially at the prostatic apex.Ziel:Quantifizierung der Interobserver–Variation bei der Abgrenzung von Prostata und Samenblasen im CT im Vergleich zur Kombination CT und MRT nach einer Konsensusbefundung mit einem Radiologen.Material und Methodik: Die Prostata und die Samenblasen von 13 Patienten, die für eine intensitätsmodulierte Strahlentherapie wegen Adenokarzinoms der Prostata vorgesehen waren, wurden retrospektiv im CT und mit der Kombination CT und MRT durch drei Strahlentherapeuten nach einer Konsensusbefundung mit einem Radiologen abgegrenzt. Volumen und Randpositionen wurden berechnet und die Intermodalitäts- bzw. Interobservervariationen für das klinische Zielvolumen (CTV), die Samenblasen, die Prostata und drei Prostatasegmente (apikales, mittleres und basales Drittel) beurteilt.Ergebnisse:Mit der Kombination von CT und MRT verringerte sich im Vergleich zur alleinigen CT der Mittelwert für das CTV, Prostata– und Samenblasenvolumen signifikant um 6,54%, 5,21% und 10,47%. Von größerer Bedeutung war die signifikante Abnahme der Standardabweichungen um 63,06%, 62,65% und 44,83%. Die höchste Variation wurde im Apex der Prostata festgestellt, gefolgt von der Basis der Prostata und den Samenblasen.Schlussfolgerung:Die Kombination von CT und MRT nach Konsensus mit einem Radiologen resultiert in einer bedeutenden Abnahme der Interobservervariation bei der anatomischen Abgrenzung, insbesondere im Bereich des Apex der Prostata, und zusätzlich in einer moderaten Verringerung des CTV.

Intensity-Modulated Radiotherapy as Primary Therapy for Prostate Cancer: Report on Acute Toxicity After Dose Escalation With Simultaneous Integrated Boost to Intraprostatic Lesion

PURPOSE To report on the acute toxicity of a third escalation level using intensity-modulated radiotherapy for prostate cancer (PCa) and the acute toxicity resulting from delivery of a simultaneous integrated boost (SIB) to an intraprostatic lesion (IPL) detected on magnetic resonance imaging (MRI), with or without spectroscopy. METHODS AND MATERIALS Between January 2002 and March 2007, we treated 230 patients with intensity-modulated radiotherapy to a third escalation level as primary therapy for prostate cancer. If an IPL (defined by MRI or MRI plus spectroscopy) was present, a SIB was delivered to the IPL. To report on acute toxicity, patients were seen weekly during treatment and 1 and 3 months after treatment. Toxicity was scored using the Radiation Therapy Oncology Group toxicity scale, supplemented by an in-house-developed scoring system. RESULTS The median dose to the planning target volume was 78 Gy. An IPL was found in 118 patients. The median dose to the MRI-detected IPL and MRI plus spectroscopy-detected IPL was 81 Gy and 82 Gy, respectively. No Grade 3 or 4 acute gastrointestinal toxicity developed. Grade 2 acute gastrointestinal toxicity was present in 26 patients (11%). Grade 3 genitourinary toxicity was present in 15 patients (7%), and 95 patients developed Grade 2 acute genitourinary toxicity (41%). No statistically significant increase was found in Grade 2-3 acute gastrointestinal or genitourinary toxicity after a SIB to an IPL. CONCLUSION The results of our study have shown that treatment-induced acute toxicity remains low when intensity-modulated radiotherapy to 80 Gy as primary therapy for prostate cancer is used. In addition, a SIB to an IPL did not increase the severity or incidence of acute toxicity.

Salvage Stereotactic Body Radiotherapy for Patients With Limited Prostate Cancer Metastases: Deferring Androgen Deprivation Therapy

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.

Volumetric Arc Therapy and Intensity-Modulated Radiotherapy for Primary Prostate Radiotherapy With Simultaneous Integrated Boost to Intraprostatic Lesion With 6 and 18 MV: A Planning Comparison Study

PURPOSE The aim of the present study was to compare intensity-modulated radiotherapy (IMRT) with volumetric arc therapy (VMAT), in the treatment of prostate cancer with maximal dose escalation to the intraprostatic lesion (IPL), without violating the organ-at-risk constraints. Additionally, the use of 6-MV photons was compared with 18-MV photons for all techniques. METHODS AND MATERIALS A total of 12 consecutive prostate cancer patients with an IPL on magnetic resonance imaging were selected for the present study. Plans were made for three IMRT field setups (three, five, and seven fields) and one VMAT field setup (single arc). First, optimal plans were created for every technique using biologic and physical planning aims. Next, an additional escalation to the IPL was planned as high as possible without violating the planning aims of the first step. RESULTS No interaction between the technique and photon energy (p=.928) occurred. No differences were found between the 6- and 18-MV photon beams, except for a reduction in the number of monitor units needed for 18 MV (p<.05). All techniques, except for three-field IMRT, allowed for dose escalation to a median dose of ≥93±6 Gy (mean±standard deviation) to the IPL. VMAT was superior to IMRT for rectal volumes receiving 20-50 Gy (p<.05). CONCLUSION VMAT allowed for dose escalation to the IPL with better sparing of the rectum than static three-, five-, and seven-field IMRT setups. High-energy photons had no advantage over low-energy photons.

Salvage intensity-modulated radiotherapy for rising PSA after radical prostatectomy

INTRODUCTION 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). MATERIALS AND METHODS IMRT was prescribed to a mean prescription dose to the planning target volume (PTV) of 75 Gy to be delivered in 37 fractions of 2 Gy. In total, 135 patients were treated with IMRT. Median age was 64 years. Median PSA level was 0.8 ng/ml. AD was initiated in 94 patients. Indications were perineural invasion, seminal vesicle invasion or Gleason score > or = 8 at RP. (1) Acute toxicity (n = 135). All patients were available for this analysis. Acute toxicity was scored using an in-house developed scoring system. (2) Late toxicity (n = 68). Only patients with a follow-up of at least 18 months were considered for late toxicity analysis. The RILIT score was used to register gastro-intestinal (GI) toxicity. An in-house developed scale was used to register genito-urinary (GU) toxicity. (3) bNED (n = 87). For bNED, all AD-naive patients (n = 38) together with the AD-positive patients with a follow-up > or = 18 months (n = 49) were considered. Factors influencing the results of salvage treatment were analyzed. RESULTS (1) Acute toxicity (n = 135). No patient developed grade 3 GI toxicity. We observed grade 2 toxicity in 20 patients. Four patients developed grade 3 GU toxicity. (2) Late toxicity (n = 68). One patient developed grade 3 rectal blood loss. One patient developed grade 3 anal pain (anal fissure). We observed grade 2 GI toxicity in 9 patients. Two patients developed grade 3GU toxicity. Twenty-one patients developed grade 2 GU toxicity. We observed an urethral stricture in 5 patients. (3) bNED (n = 87). The 3- and 5-year bNED was 67%. Gleason score at RP, perineural invasion and capsular perforation were significant predictors for bNED. PSA before IMRT (<1.0 vs. 1.0 ng/ml) showed a trend in predicting bNED (p = 0.08). CONCLUSION IMRT to 75Gy+/-AD can be delivered with low levels of acute and late toxicity. In patients without perineural invasion and capsular invasion and with a Gleason score > or = 7 (3 + 4), IMRT offers very good 5-years bNED.

Role of MRI in Follow-Up After Focal Therapy for Prostate Carcinoma

OBJECTIVE In patients with clinically suspected local recurrence of prostate cancer, a lobulated hyperintense mass in the radical prostatectomy fossa can be readily visualized with T2-weighted MRI, but this imaging technique is less successful after treatments such as radiation therapy, high-intensity focused ultrasound, and cryosurgery. We describe the additional value of functional techniques in the assessment of local recurrence. CONCLUSION The use of functional MRI techniques such as MR spectroscopy, diffusion-weighted imaging, and dynamic contrast-enhanced MRI has shown promise in increasing overall imaging performance in the detection of local recurrence.

Adjuvant High-Dose Intensity-Modulated Radiotherapy after Radical Prostatectomy for Prostate Cancer: Clinical Results in 104 Patients

BACKGROUND Approximately 25% of patients treated with adjuvant radiotherapy (RT) will develop a biochemical failure within 5 yr after RT when doses of 60-64 Gray (Gy) are used. OBJECTIVE To report on the safety and biochemical outcome of adjuvant intensity-modulated RT (IMRT) with doses >70 Gy. DESIGN, SETTING, AND PARTICIPANTS Between 1999 and 2008, 104 patients underwent radical prostatectomy (RP) followed by adjuvant IMRT with or without androgen deprivation (AD) with a median follow-up of 36 mo. Indications for adjuvant IMRT were capsule perforation, seminal vesicle invasion (SVI) and/or positive surgical margins at prostatectomy specimen. All patients were irradiated at a single tertiary academic centre. AD was initiated on the basis of SVI, a preprostatectomy prostate-specific antigen level >20 ng/ml, Gleason score > or = 4+3 (n=36), or personal preference of the referring urologist (n=32). INTERVENTION A median dose of 74 Gy was prescribed to the planning target volume using IMRT in all patients. AD consisted out of a luteinising hormone-releasing hormone analogue for 6 mo. MEASUREMENTS We report on acute and late toxicity, biochemical relapse-free survival (bRFS), and clinical progression. The Kaplan-Meier method was used to estimate bRFS. Univariate analysis was used to examine the influence of patient- and treatment-related factors on bRFS. RESULTS AND LIMITATIONS With respect to acute toxicity, no patients developed grade 3 gastrointestinal (GI) toxicity, and eight patients developed grade 3 genitourinary (GU) toxicity (8%). With respect to late toxicity, no patients developed grade 3 GI toxicity, and four patients (4%) developed grade 3 GU toxicity. A urethral stricture was observed in six patients (6%). The 3- and 5-yr actuarial bRFS was 93%. On univariate analysis, bRFS rates were worse when SVI (p<0.02), Gleason score > or = 4+3 (p<0.02), or negative surgical margins (p<0.02) were present. AD did not influence bRFS. Six patients had a clinical relapse. CONCLUSIONS Adjuvant high-dose IMRT after prostatectomy is safe and bRFS is excellent.

Urinary toxicity after high dose intensity modulated radiotherapy as primary therapy for prostate cancer

BACKGROUND AND PURPOSE Urinary toxicity plays a major role in the quality of life (QOL) of patients treated with external beam radiotherapy as primary therapy for prostate cancer. In this study we report on: (1) Incidence of acute and late GU toxicity after intensity modulated radiotherapy (IMRT) for prostate cancer at Ghent University Hospital (GUH). (2) Time evolution of pre-IMRT and IMRT-induced acute and late GU toxicity. MATERIALS AND METHODS At GUH, 260 patients with a follow-up of > or = 12 months were treated with IMRT for prostate cancer. The incidence and evolution of GU toxicity were recorded. RESULTS Acute grades 3, 2 and 1 GU toxicity occurred in 8%, 42% and 42% of the patients, respectively. Late grades 3, 2 and 1 GU toxicity occurred in 3%, 19% and 40% of the patients, respectively. During therapy baseline grade 1 symptoms increased into grade 2 acute GU toxicity in 48%. After 1 and 2 years, 60% and 70% of the patients, respectively, had less GU symptoms when compared to the pre-treatment status. CONCLUSION IMRT induces mild GU toxicity. There is an improvement in pre-IMRT obstructive miction disorders.

Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography-computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)-free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

Intensity-Modulated Arc Therapy with Simultaneous Integrated Boost in the Treatment of Primary Irresectable Cervical Cancer

Purpose: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(1) a median dose (D50) of 62, 58 and 56 Gy to the primary tumor (GTV_cervix), primary clinical target volume (CTV_cervix) and its planning target volume (PTV_cervix), respectively;(2) a D50 of 60 Gy to the PET-positive lymph nodes (GTV_nodes);(3) a minimal dose (D98) of 45 Gy to the planning target volume of the elective lymph nodes (PTV_nodes).IMAT plans were generated using an anatomy-based exclusion tool with the aid of weight and leaf position optimization. The dosimetric delivery of IMAT was validated preclinically using radiochromic film dosimetry.Results:Five to nine arcs were needed to create valid IMAT plans. Dose constraints on D50 were not met in two patients (both GTV_cervix: 1 Gy and 3 Gy less). D98 for PTV_nodes was not met in three patients (1 Gy each). Film dosimetry showed excellent gamma evaluation. There were no treatment interruptions.Conclusion:IMAT allows delivering an SIB to the macroscopic tumor without compromising the dose to the elective lymph nodes or the organs at risk. The clinical implementation is feasible.Ziel:Evaluation einer intensitätsmodulierten Rotationsbestrahlung (IMAT) mit Applikation eines simultanen integrierten Boosts (SIB) zur primären Behandlung des fortgeschrittenen Zervixkarzinoms.Patienten und Methodik:Sechs Patientinnen mit einem fortgeschrittenen Zervixkarzinom wurden einer MRT- (Magnetresonanztomographie) und PET-CT-basierten (Positronenemissionstomographie-Computertomographie) Bestrahlungsplanung für eine IMAT unterzogen und bestrahlt. Das Dosis-Zeit-Muster wurde, bezogen auf die entsprechenden Zielvolumina für 25 Fraktionen, wie folgt festgelegt:1. Eine mediane Dosis (D50) von 62 Gy, 58 Gy und 56 Gy wurde für das makroskopische Zervixkarzinom (GTV), das klinische Zielvolumen (CTV) und das Planungszielvolumen (PTV) verschrieben.2. Eine mediane Dosis von 60 Gy wurde für die PET-positiven regionären Lymphknoten festgelegt.3. Elektiv zu bestrahlende regionäre Lymphknoten sollten eine minimale Dosis (D98) von 45 Gy erhalten.Die IMAT-Pläne wurden mit Hilfe eines anatomiebasierten Ausschlussalgorithmus durch Optimierung und Wichtung von Leafpositionen erzeugt. Die präklinische Dosimetrie erfolgte mittels Filmdosimetrie.Ergebnisse:Insgesamt fünf bis neun Rotationsfelder waren zur Erzeugung geeigneter IMAT-Pläne erforderlich. Bei zwei Patientinnen war die angestrebte Dosis für das makroskopische Zervixkarzinom (GTV) 1 Gy und 3 Gy zu niedrig. In drei Fällen wurde die minimale Dosis (D98) an den elektiv zu behandelnden Lymphknoten um je 1 Gy unterschritten. Die Daten der Filmdosimetrie zeigten eine ausgezeichnete Gammabewertung. Die Bestrahlung konnte in allen Fällen ohne Unterbrechung appliziert werden.Schlussfolgerung:Die klinische Umsetzung der IMAT mit SIB des Zervixkarzinoms ist ohne Dosiskompromisse an elektiven Lymphknotenstationen und Risikoorganen möglich.