Table 1.
Summary of studies included in review
| Focus | Title | Authors | Year of publication | Study type | Number of patients/subjects | Main conclusions |
|---|---|---|---|---|---|---|
| Feasibility | Prostate motion during standard radiotherapy as assessed by FMs | Crook et al6 | 1995 | Retrospective cohort | 55 | Significant prostate motion during radiotherapy. Recommend using markers and EPIDs to verify position of target |
| Technical aspects of daily online positioning of the prostate for 3D conformal radiotherapy using an EPI device | Herman et al7 | 2003 | Prospective feasibility | 20 | EPID and intraprostatic markers can be used to precisely localize and correct variations in target position following setup to external reference marks | |
| Feasibility of insertion/implantation of 2.0-mm-diameter gold internal FMs for precise setup and real-time tumour tracking in radiotherapy | Shirato et al8 | 2003 | Prospective feasibility | 93 (31 prostate) | Internal FMs can be safely inserted into various organs. Three-marker method has been shown to be useful for spinal/paraspinal and prostate setup | |
| Prostate position relative to pelvic bony anatomy based on intraprostatic gold markers and EPI | Schallenkamp et al9 | 2005 | Prospective feasibility | 20 | Independent prostate motion is significant. FMs within the prostate are stable and facilitate margin reduction | |
| A comparison of the use of bony anatomy and internal markers for offline verification and an evaluation of the potential benefit of online and offline verification protocols for prostate radiotherapy | McNair et al10 | 2008 | Retrospective analysis | 30 | FMs and an offline imaging protocol are effective in reducing systematic errors | |
| Utilization of CBCT for reconstruction of dose distribution delivered in IGRT of prostate carcinoma—bony landmark setup compared with FM setup | Paluska et al11 | 2013 | Retrospective analysis | 59 | PTV margin reduction is feasible using FMs for image guidance | |
| Analysis of FM-based position verification in EBRT of patients with PCa | Van der Heide et al12 | 2007 | Retrospective analysis | 453 | FMs are stable. Identified time trends in prostate motion | |
| Prostate motion | Intrafraction motion of the prostate during EBRT: analysis of 427 patients with implanted FMs | Kotte et al13 | 2007 | Retrospective analysis | 427 | Frequent prostate motion observed during EBRT, which can be encompassed with a 2-mm margin |
| IMRT using implanted FMs with daily portal imaging: assessment of prostate organ motion | Chen et al14 | 2007 | Retrospective analysis | 33 | Prostate motion is significant. Daily imaging with FMs is necessary for the reduction of margins | |
| Intrafraction prostate displacement in radiotherapy estimated from pre- and post-treatment imaging of patients with implanted FMs | Kron et al15 | 2010 | Retrospective analysis | 184 | Prostate motion is a limiting factor when considering margins for radiotherapy | |
| Intrafraction motion during extreme hypofractionated radiotherapy of the prostate using pre- and post-treatment imaging | Quon et al16 | 2012 | Phase I/II trial | 53 | Prostate displacements during hypofractionated radiotherapy are comparable with intrafraction conventionally fractionated treatments | |
| Intrafractional motion of the prostate during hypofractionated radiotherapy | Xie et al17 | 2008 | Retrospective analysis | 21 | With monitoring and intervention prostate motion within the range of the Cyberknife tracking range; however, there is significant variation between patients | |
| Deformation of prostate and SVs relative to intraprostatic FMs | Van der Weilen et al18 | 2008 | Prospective clinical study | 21 | With respect to FMs, prostate deformation is small, SV deformation considerable | |
| An MRI study of prostate deformation relative to implanted gold FMs | Nichol et al21 | 2007 | Prospective clinical study | 25 | During radiotherapy, FMs in-migrated and prostate volume decreased. Patients undergoing TURP demonstrated greater deformation than those not undergoing TURP | |
| Hybrid registration of prostate and SVs for IGRT | De Boer et al19 | 2013 | Retrospective analysis | 20 | Substantial differences observed between SV and prostate orientations | |
| Margin evaluation in the presence of deformation, rotation and translation in prostate and entire SV irradiation with daily marker-based setup corrections | Mutanga et al20 | 2011 | Retrospective study | 21 | PTV margins based on FM, prostate 5 mm and >8 mm for SVs. Correction of rotational errors of little benefit | |
| Implantation | Technique for implantation of FMs in the prostate | Shinohara and Roach22 | 2008 | Retrospective study | 705 | TRUS-guided FM implantation is well tolerated. Experience provides a guide for clinicians |
| Technique of outpatient placement of intraprostatic FMs before EBRT | Linden et al23 | 2009 | Retrospective study | 98 | TRUS-guided FM implantation is safe and efficacious | |
| Implantation of FMs for image guidance in prostate radiotherapy: patient-reported toxicity | Igdem et al24 | 2009 | Prospective clinical study | 177 | TRUS-guided FM implantation is safe and well tolerated | |
| Patient-reported complications from FM implantation for prostate IGRT | Gill et al26 | 2012 | Retrospective study (questionnaires) | 234 | TRUS-guided FM insertion for IGRT is well tolerated in the majority of patients with PCa | |
| Is periprostatic nerve block a gold standard in case of TRUS-guided prostate biopsy? | Kumar et al27 | 2013 | Prospective randomized double-blinded placebo-controlled study | 150 | Periprostatic nerve block provides better pain control in TRUS-guided prostate biopsy, but still there is need of additional analgesic in the form of tramadol or INB. Tramadol has advantage of oral intake and analgesic effect at time of probe insertion and at nerve block. Both tramadol and INB may be used in combination along with PNB | |
| Ultrasound-guided TR implantation of gold markers for prostate localization during EBRT: complication rate and risk factors | Langenhuijsen et al28 | 2007 | Retrospective analysis | 209 | TR gold marker implantation well tolerated. Moderate complication rate influenced by disease stage, ADT and age | |
| Single-centre experience in prostate fiducial placement: technique and mid-term follow-up | Kably et al30 | 2014 | Retrospective analysis | 75 | TR ultrasound guidance of FMs is feasible, well tolerated and safe | |
| Long-term experience with TR and TP implantations of gold FMs in the prostate for position verification in EBRT; feasibility, toxicity and quality of life | Moman et al33 | 2010 | Retrospective analysis | 914 | Clinical use of TP-implanted gold FMs for position verification in EBRT for PCa is a feasible and safe procedure without influencing patient quality of life | |
| Infections after FM implantation for prostate radiotherapy: are we underestimating the risks? | Loh et al31 | 2015 | Retrospective analysis | 285 | Overall rate of symptomatic infection with FM implantation is higher than other FM series at 7.7%. This is in keeping with prostate biopsy reports of infection | |
| Number and type of FM | Improving positioning in high-dose radiotherapy for PCa: safety and visibility of frequently used gold FMs | Fonteyne et al35 | 2012 | Prospective RCT | 25 | Stability and visibility of five different types of marker was proven. Larger markers facilitate automatic image fusion; however; they generate more scatter than smaller markers |
| Feasibility, detectability and experience with platinum seed internal FMs for CT–MRI fusion and real-time tumour tracking during SABR | Janardanan et al38 | 2012 | Retrospective study | 29 | Platinum seeds provide superior contrast to gold seeds on MR images and a better choice for CT–MRI fusion | |
| Clinical results from first use of prostate stent as FM for radiotherapy of PCa | Carl et al44 | 2011 | Prospective clinical study | 62 | Ni–Ti stents have potential as new prostate FM | |
| Influence of the number of elongated FMs on the localization accuracy of the prostate | De Boer et al42 | 2012 | Retrospective study | 24 | Two elongated markers placed at either side of the prostate can be used to accurately localize the prostate for IGRT | |
| Multi-institutional clinical experience with the Calypso system in localization and continuous, real-time monitoring of the prostate gland during external radiotherapy | Kupelian et al46 | 2007 | Prospective clinical study | 41 | Using three implanted electromagnetic transponders provides clinically efficient, accurate and objective localization of the prostate | |
| Patient positioning based on a radioactive tracer implanted in patients with localized PCa: a performance and safety evaluation | De Kruijf et al48 | 2013 | Prospective single-arm multi-institutional study | 20 | Implantation of the tracer is safe and feasible and patients can be positioned and monitored accurately using RealEye | |
| Migration | (Non)-migration of radiopaque markers used for online localization of the prostate with an EPI device | Pouliot et al29 | 2003 | Retrospective analysis | 10 | None of the markers studied migrated significantly. The use of three markers provides a tool to monitor prostate position and volume changes that can occur over time owing to hormone or radiation therapy |
| Marker seed migration in prostate localization | Poggi et al49 | 2003 | Prospective clinical study | 9 | Negligible seed migration over the course of radiotherapy | |
| Intraprostatic fiducials for localization of the prostate gland: monitoring IMDs during radiation therapy to test for marker stability | Kupelian et al50 | 2005 | Retrospective analysis | 56 | Seed migration within the prostate during a course of radiotherapy is negligible. Prostate deformation rather than true migration results in observed marker position variations | |
| Migration of intraprostatic FMs and its influence on the matching quality in EBRT for PCa | Delouya et al51 | 2010 | Retrospective analysis | 31 | Average daily seed migration is often negligible. Migration >2 mm from planning to first treatment may require adjustment of PTV margin to account for this | |
| Impact of concurrent androgen deprivation on FM migration in EBRT for PCa | Tiberi et al52 | 2012 | Retrospective analysis | 37 | A delay between the start of ADT and the start of EBRT; prostate involution has little or no effect on FM positioning within the gland. <1% of treatments studied demonstrated significant marker migration | |
| Imaging modality used | IGRT for PCa comparing kV imaging of FMs with CBCT | Barney et al56 | 2011 | Retrospective study | 36 | Target verification for CBCT and kV imaging using FMs are similar; however, over 25% of shifts differed enough to affect target coverage |
| EPI vs kV imaging in FM IGRT for PCa: an analysis of setup uncertainties | Gill et al41 | 2012 | Prospective | 333 | Suggests a larger CTV–PTV margin is used in EPI-based IGRT for PCa | |
| Method comparison of ultrasound and kV X-ray FM imaging for prostate radiotherapy targeting | Fuller et al61 | 2006 | Prospective non-randomized study | 40 | Significant differences in ultrasound and FM IG setup data. Data between ultrasound and FM imaging not interchangeable | |
| Study of ExacTrac X-ray 6D IGRT setup uncertainty for marker-based prostate IMRT treatment | Shi et al60 | 2012 | Retrospective study | 43 | Overall interfraction mean error of 2 mm or less for 3D translations and 0.25° rotation, facilitating margin reduction | |
| Comparison of daily MV EPI or kV imaging with marker seeds with ultrasound imaging or skin marks for prostate localization and treatment positioning in patients with PCa | Serago et al43 | 2006 | Retrospective study | 35 | MV and kV EPI similar in terms of accuracy and superior to ultrasound | |
| Comparison of ultrasound and implanted seed marker prostate localization methods: implications for IGRT | Scarbrough et al62 | 2006 | Retrospective analysis | 40 | Ultrasound and FM setup data differ significantly, resulting in different PTV margins. More variation is seen in ultrasound data | |
| Comparison of TAUS and electromagnetic transponders for prostate localization | Foster et al63 | 2010 | Retrospective analysis | 41 | Ultrasound and electromagnetic transponder setup data differ significantly. Ultrasound-derived PTV margins 3–4 times smaller than Calypso data | |
| Clinical impact | Individualized PTVs for intrafraction motion during hypofractionated IMRT boost for PCa | Cheung et al64 | 2005 | Prospective clinical study | 33 | Acute toxicity using IMRT for hypofractionated boost was acceptable. Grade 3 urinary toxicity may be increased compared with standard fractionation |
| PTV margins for prostate radiotherapy using daily EPI and implanted FMs | Skarsgard et al65 | 2010 | Prospective Phase I/II study | 46 | Daily image guidance with FMs allows significant reduction of PTV margin, facilitating dose escalation which may improve outcomes for patients with PCa | |
| Does IGRT improve toxicity profile in whole pelvic-treated high-risk PCa? | Chung et al68 | 2009 | Prospective study | 25 | Rectal and bladder toxicity consistently lower for FM-guided radiotherapy group than that for non-FM-guided radiotherapy. This is likely attributable to reduced PTV margins in the FM-guided group | |
| Treatment-related morbidity in PCa: a comparison of 3D conformal radiation therapy with and without image guidance using implanted FMs | Singh et al69 | 2013 | Retrospective study | 282 | A significant reduction in bowel dysfunctional symptoms reported by the IGRT group vs the non-IGRT group | |
| Treatment outcome of high-dose IG-IMRT using intraprostate FMs for localized PCa at a single institute in Japan | Takeda et al67 | 2012 | Retrospective study | 141 | High-dose FM-guided IMRT well tolerated | |
| Late toxicity and biochemical control in 554 patients with PCa treated with and without dose-escalated IGRT | Kok et al71 | 2013 | Retrospective study | 186 | FM-guided IGRT associated with a reduction in late urinary toxicity and improved biochemical tumour control. Further studies required | |
| Improvement in toxicity in patients at high risk of PCa treated with IG-IMRT compared with 3D conformal radiotherapy without daily image guidance | Sveistrup et al72 | 2014 | Retrospective study | 311 | FM-IGRT can be an effective method of reducing GI and GU toxicity when treating PCa |
3D, three-dimensional; ADT, androgen deprivation therapy; CBCT, cone-beam CT; CTV, clinical target volume; EBRT, external beam radiotherapy; EPI, electronic portal imaging; EPID, electronic portal imaging device; FM, fiducial marker; GI, gastrointestinal; GU, genitourinary; IG, image-guided; IG-IMRT, image-guided intensity-modulated radiotherapy; IGRT, image-guided radiotherapy; IMD, intermarker distance; IMRT, intensity-modulated radiotherapy; INB, intraprostatic nerve block; kV, kilovoltage; MV, megavoltage; PCa, prostate cancer; PNB, periprostatic nerve block; PTV, planning target volume; RCT, randomized controlled trial; SABR, stereotactic ablative radiotherapy; SV, seminal vesicle; TAUS, transabdominal ultrasound; TP, transperineal; TR, transrectal; TRUS, transrectal ultrasound; TURP, transurethral resection of the prostate.