The management of patients with biochemical, local, nodal, or oligometastatic relapsed prostate cancer has become more challenging and controversial. Novel imaging modalities designed to detect ...recurrence are increasingly used, particularly PSMA-PET scans in Australia, New Zealand and some European countries. Imaging techniques such as MRI and PET scans using other prostate cancer-specific tracers are also being utilised across the world. The optimal timing for commencing salvage treatment, and the role of local and/or systemic therapies remains controversial. Through surveys of the membership, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified wide variation in the management of recurrent prostate cancer. Following a workshop conducted in April 2017, the FROGG management committee reviewed the literature and developed a set of recommendations based on available evidence and expert opinion, for the appropriate investigation and management of recurrent prostate cancer. These recommendations cover the role and timing of post-prostatectomy radiotherapy, the management of regional nodal metastases and oligometastases, as well as the management of local prostate recurrence after definitive radiotherapy.
AbstractThe management of node-positive prostate cancer is highly variable, with both locoregional and systemic treatment options available. With the increasing use of novel imaging techniques such ...as PSMA-PET and MRI, combined with the increasing use of surgery for high-risk prostate cancer, clinical and pathological regional nodal disease is being detected at a higher rate and at an earlier stage than previously. This creates a window for a potentially curative management approach. The role of radiotherapy including optimal radiation target volumes and dose, as well as the timing and duration of accompanying systemic therapy remains uncertain. At a workshop in 2017, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified variations in the management of node-positive prostate cancer identified on primary staging or on histopathology at radical prostatectomy. FROGG reviewed the literature and developed a set of evidence-based recommendations on the appropriate investigation and management of clinically and pathologically node-positive prostate cancer. These recommendations encompass imaging techniques, radiation treatment target volumes and doses, as well as the use of androgen deprivation therapy.
To test the hypothesis that multileaf collimator (MLC) tracking improves the consistency between the planned and delivered dose compared with the dose without MLC tracking, in the setting of a ...prostate cancer volumetric modulated arc therapy trial.
Multileaf collimator tracking was implemented for 15 patients in a prostate cancer radiation therapy trial; in total, 513 treatment fractions were delivered. During each treatment fraction, the prostate trajectory and treatment MLC positions were collected. These data were used as input for dose reconstruction (multiple isocenter shift method) to calculate the treated dose (with MLC tracking) and the dose that would have been delivered had MLC tracking not been applied (without MLC tracking). The percentage difference from planned for target and normal tissue dose-volume points were calculated. The hypothesis was tested for each dose-volume value via analysis of variance using the F test.
Of the 513 fractions delivered, 475 (93%) were suitable for analysis. The mean difference and standard deviation between the planned and treated MLC tracking doses and the planned and without-MLC tracking doses for all 475 fractions were, respectively, PTV D99% -0.8% ± 1.1% versus -2.1% ± 2.7%; CTV D99% -0.6% ± 0.8% versus -0.6% ± 1.1%; rectum V65% 1.6% ± 7.9% versus -1.2% ± 18%; and bladder V65% 0.5% ± 4.4% versus -0.0% ± 9.2% (P<.001 for all dose-volume results).
This study shows that MLC tracking improves the consistency between the planned and delivered doses compared with the modeled doses without MLC tracking. The implications of this finding are potentially improved patient outcomes, as well as more reliable dose-volume data for radiobiological parameter determination.
To quantify the radiotherapy dose-response of prostate cancer, adjusted for prognostic factors in a mature cohort of men treated relatively uniformly at a single institution.
The study cohort ...consisted of 1,530 men treated with three-dimensional conformal external-beam radiotherapy between 1989 and 2002. Patients were divided into four isocenter dose groups: <70 Gy (n = 43), 70-74.9 Gy (n = 552), 75-79.9 Gy (n = 568), and > or =80 Gy (n = 367). The primary endpoints were freedom from biochemical failure (FFBF), defined by American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2.0 ng/mL) criteria, and freedom from distant metastases (FFDM). Multivariate analyses were performed and adjusted Kaplan-Meier estimates were calculated. Logit regression dose-response functions were determined at 5 and 8 years for FFBF and at 5 and 10 years for FFDM.
Radiotherapy dose was significant in multivariate analyses for FFBF (ASTRO and Phoenix) and FFDM. Adjusted 5-year estimates of ASTRO FFBF for the four dose groups were 60%, 68%, 76%, and 84%. Adjusted 5-year Phoenix FFBFs for the four dose groups were 70%, 81%, 83%, and 89%. Adjusted 5-year and 10-year estimates of FFDM for the four dose groups were 96% and 93%, 97% and 93%, 99% and 95%, and 98% and 96%. Dose-response functions showed an increasing benefit for doses > or =80 Gy.
Doses of > or =80 Gy are recommended for most men with prostate cancer. The ASTRO definition of biochemical failure does not accurately estimate the effects of radiotherapy at 5 years because of backdating, compared to the Phoenix definition, which is less sensitive to follow-up and more reproducible over time.
•4DCT and 4DCBCT under-predict treatment lung target motion ranges.•4DCT under-predicts target motion by factors of 1.7–1.9 and 4DCBCT by factors of 1.5–1.6.•4DCBCT shows higher correlations with ...target motion than 4DCT.•4DCT and 4DCBCT motion measurements should be interpreted carefully.
To test the hypothesis that 4DCT and 4DCBCT-measured target motion ranges predict target motion ranges during lung cancer SABR.
Ten lung SABR patients were implanted with Calypso beacons. 4DCBCT was reconstructed for 29 fractions (1–4fx/patient) from a 1 min CBCT scan. The beacon centroid motion segmented for all 4DCT and 4DCBCT bins was compared with the real-time imaging and treatment beacon centroid (“target”) motion range (4SDs) for each fraction. We tested the hypotheses that (1) 4DCT and 4CBCT predict treatment motion range and (2) there is no difference between 4DCT and 4DCBCT for predicting treatment motion range. Phase-wise root-mean-square errors (RMSEs) between imaging and treatment motion and reconstructed motion (4DCT, 4DCBCT) were calculated. Relationships between motion ranges in 4DCT and 4DCBCT and imaging and treatment motion ranges were investigated for the superior–inferior (SI), left–right (LR) and anterior–posterior (AP) directions. Baseline drifts and amplitude variability were investigated as potential factors leading to motion misrepresentation.
SI 4DCT, 4DCBCT, imaging and treatment motion ranges were 6.3 ± 3.6 mm, 7.1 ± 4.5 mm, 11.1 ± 7.5 mm and 10.9 ± 6.9 mm, respectively. Similar 4DCT and 4DCBCT under-predictions were observed in the LR and AP directions. Hypothesis (1) was rejected (p < 0.0001). Treatment target motion range was under-predicted in 4DCT by factors of 1.7, 1.9 and 1.7 and in 4DCBCT by factors of 1.5, 1.6 and 1.6 in the SI, LR, and AP directions, respectively. RMSEs were generally lower for end-exhale than inhale. 4DCBCT showed higher correlations with the imaging and treatment target motion than 4DCT and testing hypothesis (2) a statistically significant difference between 4DCT and 4DCBCT was shown in the SI direction (p = 0.03).
For lung SABR patients both 4DCT and 4DCBCT significantly under-predict treatment target motion ranges.
Purpose:
We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which ...occurred on 28 November 2013 at the Northern Sydney Cancer Centre.
Methods:
An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used.
Results:
The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion.
Conclusions:
The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy.
Most linear accelerators purchased today are equipped with a gantry-mounted kilovoltage X-ray imager which is typically used for patient imaging prior to therapy. A novel application of the X-ray ...system is kilovoltage intrafraction monitoring (KIM), in which the 3-dimensional (3D) tumor position is determined during treatment. In this paper, we report on the first use of KIM in a prospective clinical study of prostate cancer patients undergoing intensity modulated arc therapy (IMAT).
Ten prostate cancer patients with implanted fiducial markers undergoing conventionally fractionated IMAT (RapidArc) were enrolled in an ethics-approved study of KIM. KIM involves acquiring kV images as the gantry rotates around the patient during treatment. Post-treatment, markers in these images were segmented to obtain 2D positions. From the 2D positions, a maximum likelihood estimation of a probability density function was used to obtain 3D prostate trajectories. The trajectories were analyzed to determine the motion type and the percentage of time the prostate was displaced ≥ 3, 5, 7, and 10 mm. Independent verification of KIM positional accuracy was performed using kV/MV triangulation.
KIM was performed for 268 fractions. Various prostate trajectories were observed (ie, continuous target drift, transient excursion, stable target position, persistent excursion, high-frequency excursions, and erratic behavior). For all patients, 3D displacements of ≥ 3, 5, 7, and 10 mm were observed 5.6%, 2.2%, 0.7% and 0.4% of the time, respectively. The average systematic accuracy of KIM was measured at 0.46 mm.
KIM for prostate IMAT was successfully implemented clinically for the first time. Key advantages of this method are (1) submillimeter accuracy, (2) widespread applicability, and (3) a low barrier to clinical implementation. A disadvantage is that KIM delivers additional imaging dose to the patient.
Kilovoltage intrafraction monitoring (KIM) is a new real-time 3-dimensional image guidance method. Unlike previous real-time image guidance methods, KIM uses a standard linear accelerator without any ...additional equipment needed. The first prospective clinical trial of KIM is underway for prostate cancer radiation therapy. In this paper we report on the measured motion accuracy and precision using real-time KIM-guided gating.
Imaging and motion information from the first 200 fractions from 6 patient prostate cancer radiation therapy volumetric modulated arc therapy treatments were analyzed. A 3-mm/5-second action threshold was used to trigger a gating event where the beam is paused and the couch position adjusted to realign the prostate to the treatment isocenter. To quantify the in vivo accuracy and precision, KIM was compared with simultaneously acquired kV/MV triangulation for 187 fractions.
KIM was successfully used in 197 of 200 fractions. Gating events occurred in 29 fractions (14.5%). In these 29 fractions, the percentage of beam-on time, the prostate displacement was >3 mm from the isocenter position, reduced from 73% without KIM to 24% with KIM-guided gating. Displacements >5 mm were reduced from 16% without KIM to 0% with KIM. The KIM accuracy was measured at <0.3 mm in all 3 dimensions. The KIM precision was <0.6 mm in all 3 dimensions.
Clinical implementation of real-time KIM image guidance combined with gating for prostate cancer eliminates large prostate displacements during treatment delivery. Both in vivo KIM accuracy and precision are well below 1 mm.
To measure intra-fraction displacement (IFD) in post-prostatectomy patients treated with anisotropic margins and daily soft tissue matching.
Pre-treatment cone beam computed tomography (CBCT) scans ...were acquired daily and post-treatment CBCTs for the first week then weekly on 46 patients. The displacement between the scans was calculated retrospectively to measure IFD of the prostate bed (PB). The marginal miss (MM) rate, and the effect of time between imaging was assessed.
A total of 392 post-treatment CBCT's were reviewed from 46 patients. The absolute mean (95% CI) IFD was 1.5 mm (1.3-1.7 mm) in the AP direction, 1.0 mm (0.9-1.2 mm) SI, 0.8 mm (0.7-0.9 mm) LR, and 2.4 mm (2.2-2.5 mm) 3D displacement. IFD ≥ ± 3 mm and ≥ ± 5 mm was 24.7% and 5.4% respectively. MM of the PB was detected in 33 of 392 post-treatment CBCT (8.4%) and lymph nodes in 6 of 211 post-treatment CBCT images (2.8%). Causes of MM due to IFD included changes in the bladder (87.9%), rectum (66.7%) and buttock muscles (6%). A time ≥ 9 min between the pre and post-treatment CBCT demonstrated that movement ≥ 3 mm and 5 mm increased from 19.2 to 40.5% and 5 to 8.1% respectively.
IFD during PB irradiation was typically small, but was a major contributor to an 8.4% MM rate when using daily soft tissue match and tight anisotropic margins.
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