Future technological developments in proton therapy - A predicted technological breakthrough.

In the current spectrum of cancer treatments, despite high costs, a lack of robust evidence based on clinical outcomes or technical and radiobiological uncertainties, particle therapy and in particular proton therapy (PT) is rapidly growing. Despite proton therapy being more than fifty years old (first proposed by Wilson in 1946) and more than 220,000 patients having been treated with in 2020, many technological challenges remain and numerous new technical developments that must be integrated into existing systems. This article presents an overview of on-going technical developments and innovations that we felt were most important today, as well as those that have the potential to significantly shape the future of proton therapy. Indeed, efforts have been done continuously to improve the efficiency of a PT system, in terms of cost, technology and delivery technics, and a number of different developments pursued in the accelerator field will first be presented. Significant developments are also underway in terms of transport and spatial resolution achievable with pencil beam scanning, or conformation of the dose to the target: we will therefore discuss beam focusing and collimation issues which are important parameters for the development of these techniques, as well as proton arc therapy. State of the art and alternative approaches to adaptive PT and the future of adaptive PT will finally be reviewed. Through these overviews, we will finally see how advances in these different areas will allow the potential for robust dose shaping in proton therapy to be maximised, probably foreshadowing a future era of maturity for the PT technique.

Contact X-ray brachytherapy for rectal cancer: Past, present, and future.

The Papillon experience and the Lyon R96-02 trial have shown that contact X-ray brachytherapy of 50kV is efficient and safe to achieve long term local control and organ preservation for cT1 and early cT2-3 rectal cancers. The OPERA trial, using the Papillon 50™ machine, brings further support to this preservation strategy for selected T2T3ab lesions. Future trials using a contact X-ray boost will try to consolidate and enlarge its place in organ preservation for rectal cancers.

An Option for Shaft-Only Gender-Affirming Phalloplasty: Vaginal Preservation and Vulvoscrotoplasty. A Technical Description.

SUMMARY: Genital masculinizing gender-affirming surgery is a growing field. Because of a spectrum of gender identity, gender expression, sexual expression, patient desires, and patient tolerance for complications, options for surgery vary accordingly. Shaft-only phalloplasty avoids urethral lengthening, but may still be accompanied by hysterectomy, vaginectomy, scrotoplasty, clitoroplasty (burying of the clitoris), glansplasty, and placement of erectile devices and testicular implants. Patients who desire retention of vaginal canal patency are candidates for vaginal preservation vulvoscrotoplasty; however, there is a paucity of literature describing the procedure and its outcomes. In this article, the authors review the technique used by the senior author at Oregon Health and Science University and report surgical outcomes for four patients. Future studies regarding patient-recorded outcome measures, aesthetics, sexual function, urologic function, patient satisfaction, and conversion to other options will help surgeons better understand patients pursuing gender-affirming surgery through shaft-only phalloplasty.

Efficacy of Spacers in Radiation Therapy for Locally Advanced Pancreatic Cancer: A Planning Study.

BACKGROUND/AIM: We aimed to investigate the dosimetric effects of a spacer placed between the pancreas and surrounding gastrointestinal structures in intensity-modulated radiation therapy (IMRT) planning to provide more effective radiation therapy for locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Treatment planning was performed for six patients with LAPC based on computed tomography images without spacers and with 5-mm or 10-mm spacers virtually inserted under the supervision of a hepatobiliary pancreatic surgeon. The prescription dose was 63 Gy in 28 fractions. RESULTS: With the exception of one case of pancreatic head cancer, planning target volume receiving ≥95% of the prescribed dose (PTV V95) was achieved by 90% or more by inserting a spacer, and by 95% or more in all 3 cases of pancreatic body and tail cancer by inserting a 10-mm spacer. CONCLUSION: IMRT with appropriate spacer placement may help provide high-dose treatment for LAPC and improve associated patient outcomes.

Pilot study of neurologic toxicity in mice after proton minibeam therapy.

Proton minibeams (MBs) comprised of parallel planar beamlets were evaluated for their ability to spare healthy brain compared to proton broad beams (BBs). Juvenile mice were given partial brain irradiation of 10 or 30 Gy integral dose using 100 MeV protons configured either as BBs or arrays of 0.3-mm planar MBs spaced 1.0 mm apart on center. Neurologic toxicity was evaluated during an 8-month surveillance: no overt constitutional or neurologic dysfunction was noted for any study animals. Less acute epilation was observed in MB than BB mice. Persistent chronic inflammation was noted along the entire BB path in BB mice whereas inflammation was confined to just within the MB peak regions in MB mice. The potential neurologic sparing, possibly via reduced volume of chronic inflammation, offers a compelling rationale for clinical advancement of this proton technique.

Nerve Segmentation with Deep Learning from Label-Free Endoscopic Images Obtained Using Coherent Anti-Stokes Raman Scattering.

Semantic segmentation with deep learning to extract nerves from label-free endoscopic images obtained using coherent anti-Stokes Raman scattering (CARS) for nerve-sparing surgery is described. We developed a CARS rigid endoscope in order to identify the exact location of peripheral nerves in surgery. Myelinated nerves are visualized with a CARS lipid signal in a label-free manner. Because the lipid distribution includes other tissues as well as nerves, nerve segmentation is required to achieve nerve-sparing surgery. We propose using U-Net with a VGG16 encoder as a deep learning model and pre-training with fluorescence images, which visualize the lipid distribution similar to CARS images, before fine-tuning with a small dataset of CARS endoscopy images. For nerve segmentation, we used 24 CARS and 1,818 fluorescence nerve images of three rabbit prostates. We achieved label-free nerve segmentation with a mean accuracy of 0.962 and an F 1 value of 0.860. Pre-training on fluorescence images significantly improved the performance of nerve segmentation in terms of the mean accuracy and F 1 value ( p < 0 . 05 ). Nerve segmentation of label-free endoscopic images will allow for safer endoscopic surgery, while reducing dysfunction and improving prognosis after surgery.

Greater increase in femoral offset with use of collum femoris-preserving stem than Tri-Lock stem in primary total hip arthroplasty.

OBJECTIVE: This study was performed to compare the clinical outcomes and performance of the collum femoris-preserving (CFP) stem (Waldemar Link GmbH & Co., Hamburg, Germany) and the Tri-Lock stem (DePuy Orthopaedics, Warsaw, IN, USA) in terms of femoral offset (FO) and leg length reconstruction. METHODS: Clinical and radiographic data of patients who underwent total hip arthroplasty with either a CFP stem or Tri-Lock stem from January 2016 to March 2017 were compared (65 and 57 patients, respectively). The Harris hip score and Western Ontario and McMaster Universities Osteoarthritis Index were recorded. The FO, femoral vertical offset, and neck-shaft angle were measured at the last follow-up. The occurrence of dislocation and periprosthetic fracture during the follow-up period was recorded. RESULTS: The CFP stem induced significantly more FO than did the Tri-Lock stem on the operated side than contralateral side (3.63 ± 4.28 vs. 0.83 ± 5.46 mm). Significantly fewer patients had a >5-mm decrease in FO on the unaffected side in the CFP stem group (n = 1) than Tri-Lock stem group (n = 10). CONCLUSION: Both stems similarly improved hip function and reconstructed the leg length, but the CFP stem was superior to the Tri-Lock stem in reconstructing FO.

Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System.

PURPOSE: Recent studies suggest that ultrahigh-dose-rate, "FLASH," electron radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Here, we describe a novel RT apparatus that delivers FLASH proton RT (PRT) using double scattered protons with computed tomography guidance and provide the first report of proton FLASH RT-mediated normal tissue radioprotection. METHODS AND MATERIALS: Absolute dose was measured at multiple depths in solid water and validated against an absolute integral charge measurement using a Faraday cup. Real-time dose rate was obtained using a NaI detector to measure prompt gamma rays. The effect of FLASH versus standard dose rate PRT on tumors and normal tissues was measured using pancreatic flank tumors (MH641905) derived from the KPC autochthonous PanCa model in syngeneic C57BL/6J mice with analysis of fibrosis and stem cell repopulation in small intestine after abdominal irradiation. RESULTS: The double scattering and collimation apparatus was dosimetrically validated with dose rates of 78 ± 9 Gy per second and 0.9 ± 0.08 Gy per second for the FLASH and standard PRT. Whole abdominal FLASH PRT at 15 Gy significantly reduced the loss of proliferating cells in intestinal crypts compared with standard PRT. Studies with local intestinal irradiation at 18 Gy revealed a reduction to near baseline levels of intestinal fibrosis for FLASH-PRT compared with standard PRT. Despite this difference, FLASH-PRT did not demonstrate tumor radioprotection in MH641905 pancreatic cancer flank tumors after 12 or 18 Gy irradiation. CONCLUSIONS: We have designed and dosimetrically validated a FLASH-PRT system with accurate control of beam flux on a millisecond time scale and online monitoring of the integral and dose delivery time structure. Using this system, we found that FLASH-PRT decreases acute cell loss and late fibrosis after whole-abdomen and focal intestinal RT, whereas tumor growth inhibition is preserved between the 2 modalities.

Long-term results of the iBP elbow prosthesis: beware of destructive metallosis!

BACKGROUND: The aim of this study was to review the long-term results of the instrumented Bone Preserving (iBP) elbow prosthesis. METHODS: Thirty-one patients (10 M, 21F, 28-77 year) were retrospectively evaluated using the Oxford Elbow Score (OES), Disabilities of Arm, Shoulder and Hand Outcome Measure (DASH), Mayo Elbow Performance (MEPS), physical examination and standard radiographs. Kaplan-Meier survival analysis was used. RESULTS: Thirty-seven primary iBPs have been placed in 31 patients between 2000 and 2007. Six patients (8 prostheses) had died, 10 elbows had been revised and three patients (4 prostheses) were lost to follow-up. Fourteen patients (15 prostheses) were available for follow-up. The main indication for surgery was rheumatoid arthritis. Mean follow-up was 11 years (8-15). Kaplan-Meier survival analysis showed a survival of 81% at 10 years after surgery. Main reason for revision was particle disease and loosening due to instability and malalignment. Eleven of 14 patients were satisfied, although radiographs showed radiolucencies in 11 patients. CONCLUSION: The iBP elbow prosthesis gives a survival rate of 81% 10 years after surgery with a progressive decline beyond 10 years. However, many patients have radiolucencies. Discrepancy between clinical signs and radiological results warrants structural follow-up, to assure quality of bone stock in case revision surgery is indicated. The study was reviewed and approved by the Medical Ethical Committee of University Medical Center Groningen (METc2016/038). LEVEL OF EVIDENCE: Level IV, Case series.

Dynamic Modulated Brachytherapy (DMBT) Balloon Applicator for Accelerated Partial Breast Irradiation.

PURPOSE: To propose a novel high-dose-rate brachytherapy applicator for balloon-based dynamic modulated brachytherapy (DMBT) for accelerated partial breast irradiation (APBI) and to demonstrate its dosimetric advantage compared to the widely used Contura applicator. METHODS AND MATERIALS: The DMBT balloon device consists of a fixed central channel enabling real-time, in vivo dosimetry and an outer motion-dynamic, adjustable-radius channel capable of moving to any angular position within the balloon. This design allows placement of dwell positions anywhere within the balloon volume, guaranteeing optimal placement and generation of the applicator and treatment plan, respectively. Thirteen clinical treatment plans for patients with early-stage breast cancer receiving APBI after lumpectomy using Contura were retrospectively obtained under institutional review board approval. New treatment plans were created by replacing the Contura with the DMBT device. DMBT plans were limited to 4 angular positions and an outer channel radius of 1.5 cm. The new plans were optimized to limit dose to ribs and skin while maintaining target coverage similar to that of the clinical plan. RESULTS: Similar target coverage was obtained for the DMBT plans compared with clinical Contura plans. Across all patients the mean (standard deviation) reductions in D0.1 cc to the ribs and skin were 6.70% (6.28%) and 5.13% (6.54%), respectively. A threshold separation distance between the balloon surface and the organ at risk (OAR), below which dosimetric changes of greater than 5% were obtained, was observed to be 12 mm for ribs and skin. When both OARs were far from the balloon, DMBT plans were of similar quality to Contura plans, as expected. CONCLUSIONS: This study demonstrates the superior ability of the APBI DMBT applicator to spare OARs while achieving target coverage comparable to current treatment plans, especially when in close proximity. The DMBT balloon may enable new modes of dynamic high-dose-rate treatment delivery and allow for ultrahypofractionated dose regimens to be safely used.

Breast cancer robotic nipple sparing mastectomy: evaluation of several surgical procedures and learning curve.

BACKGROUND: Few studies of robotic nipple sparing mastectomy (NSM) were reported. We report feasibility of robotic NSM and determine standard surgical procedure and learning curve threefold. METHODS: A cohort of patients with robotic NSM for breast cancer was analyzed. Complications and post-operative hospitalization stay were reported. The same technic was used for all patients except for skin and nipple areolar complex (NAC) dissection. Differences between three surgical procedures of NAC dissection were analyzed: group 1, dissection with robotic scissors using coagulation; group 2, dissection with robotic scissors without coagulation; and group 3, dissection with non-robotic scissors and then robotic dissection. We explored possible effect of learning curve among patients from group 1 with the same surgical procedure. RESULTS: Twenty-seven NSM with immediate breast reconstruction for breast cancers, 22 invasive and 5 in situ, were performed, with robotic latissimus dorsi-flap (RLDF) only in 17 cases, RLDF and breast implant in 6 cases, and implant alone in 4 cases. Repartition according to 3 surgical procedure groups was 16, 5, and 6 patients. Mean time of surgery and anesthesia decrease according to groups 1 to 3. Among 16 patients from group 1, time of surgery and anesthesia decreased with learning curve. Post-operative hospitalization decreased from group 1 to 3. We reported a total of 11 complications, with significant difference between groups (10 for group 1). Skin complications were higher for group 1 in comparison with groups 2-3 (p = 0.02). CONCLUSION: Robotic NSM can be performed with a brief learning. Standardized technique is proposed with non-robotic scissors superficial dissection and then dissection with robot.

Uterine-preserving surgeries for the repair of pelvic organ prolapse: a systematic review with meta-analysis and clinical practice guidelines.

INTRODUCTION AND HYPOTHESIS: We aimed to systematically review the literature on pelvic organ prolapse (POP) surgery with uterine preservation (hysteropexy). We hypothesized that different hysteropexy surgeries would have similar POP outcomes but varying adverse event (AE) rates. METHODS: MEDLINE, Cochrane, and clinicaltrials.gov databases were reviewed from inception to January 2018 for comparative (any size) and single-arm studies (n ≥ 50) involving hysteropexy. Studies were extracted for participant characteristics, interventions, comparators, outcomes, and AEs and assessed for methodological quality. RESULTS: We identified 99 eligible studies: 53 comparing hysteropexy to POP surgery with hysterectomy, 42 single-arm studies on hysteropexy, and four studies comparing stage ≥2 hysteropexy types. Data on POP outcomes were heterogeneous and usually from <3 years of follow-up. Repeat surgery prevalence for POP after hysteropexy varied widely (0-29%) but was similar among hysteropexy types. When comparing sacrohysteropexy routes, the laparoscopic approach had lower recurrent prolapse symptoms [odds ratio (OR) 0.18, 95% confidence interval (CI) 0.07-0.46), urinary retention (OR 0.05, 95% CI 0.003-0.83), and blood loss (difference -104 ml, 95% CI -145 to -63 ml) than open sacrohysteropexy. Laparoscopic sacrohysteropexy had longer operative times than vaginal mesh hysteropexy (difference 119 min, 95% CI 102-136 min). Most commonly reported AEs included mesh exposure (0-39%), urinary retention (0-80%), and sexual dysfunction (0-48%). CONCLUSIONS: Hysteropexies have a wide range of POP recurrence and AEs; little data exist directly comparing different hysteropexy types. Therefore, for women choosing uterine preservation, surgeons should counsel them on outcomes and risks particular to the specific hysteropexy type planned.

Modern Primary Breast Augmentation: Best Recommendations for Best Results.

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Develop a practical method for preoperative implant size selection. 2. List characteristics and examples of fourth- and fifth-generation silicone implants. 3. Recognize the differences in "profile" designations across implant manufacturers. 4. Recall updated statistics on breast implant-associated anaplastic large cell lymphoma and describe current guidelines on disease diagnosis and treatment. 5. Apply atraumatic and aseptic surgical techniques in primary breast augmentation. SUMMARY: Modern primary breast augmentation requires an intimate knowledge of the expanding breast implant market, including characteristics of current generation silicone implants and "profile" types. Optimal implant size selection requires balancing patient desires with tissue qualities. Evidence and awareness of breast implant-associated anaplastic large cell lymphoma continue to grow, and patients and surgeons alike should be informed on the most updated facts of the disease entity. Atraumatic surgical technique and aseptic adjuncts are critical in reducing periprosthetic inflammation and contamination, both of which are known instigators of capsular contracture and potentially breast implant-associated anaplastic large cell lymphoma.

Dosimetric influence of pitch in patient positioning for radiotherapy of long treatment volumes; the usefulness of six degree of freedom couch.

OBJECTIVE:: Pitch, the rotation around the transversal axis of the patient during radiotherapy has little impact on the dose distribution of small spherical treatment volumes; however it might affect treatment of long volumes requiring a correction with a six degree of freedom couch. METHODS:: We included 10 patients each with nasopharyngeal carcinoma (NPC) and esophageal cancer, treated with volumetric modulated arc therapy. Pitch was simulated by tilting the planning CT in ventral and dorsal direction by ± 1.5° and ± 3°. Verification plans were calculated on the tilted datasets and were compared to the original plan and the dose constraints of the organs at risk (OAR). RESULTS:: The deviation in dose to the planning target volume is increasing with the degree of pitch with mean changes of up to 2% for NPC and 1% for esophageal cancer. The most affected OAR in NPC patients are brainstem (max. dose +6.0%) and spinal cord (max. dose +10.0%) when tilted by 3° dorsally and lenses (max. dose +3.3%), oral mucosa (mean dose +2.6%) and parotid glands (mean dose +4.3%) when tilted by 3° ventrally. For esophageal cancer patients, there was no significant change in dose to any OAR. Whereas for esophageal cancer, all tilted treatment plans were still clinically acceptable regarding OAR, 5 NPC plans would no longer be acceptable with a pitch of 1.5° ventral (N = 1), 3° ventral (N = 2) and 3° dorsal (N = 2). CONCLUSION:: Planning target volume coverage in both tumor entities was only slightly affected, but pitch errors could be relevant for OAR in NPC patients. ADVANCES IN KNOWLEDGE:: A correction with a six degree of freedom couch is recommended for NPC patients with a pitch mismatch of more than 1.5° to avoid exceeded doses to the OAR.

Stereotactic radiosurgery for benign brain tumors: Results of multicenter benchmark planning studies.

PURPOSE: Stereotactic radiosurgery (SRS) is strongly indicated for treatment of surgically inaccessible benign brain tumors. Various treatment platforms are available, but few comparisons have included multiple centers. As part of a national commissioning program, benchmark planning cases were completed by all clinical centers in the region. METHODS AND MATERIALS: Four benign cases were provided, with images and structures predelineated, including intracanalicular vestibular schwannoma (VS), larger VS, skull base meningioma, and secreting pituitary adenoma. Centers were asked to follow their local practice, and plans were reviewed centrally using metrics for target coverage, selectivity, gradient falloff, and normal tissue sparing. RESULTS: Sixty-eight plans were submitted using 18 different treatment platforms. Fourteen plans were subsequently revised following feedback, and review of 5 plans led to a restriction of service on 2 platforms (2 centers). Prescription doses were consistent for VS and meningioma submissions, but a wide range of doses were used for the pituitary case. All centers prioritized coverage, with the prescription isodose covering ≥95% of 78/82 target volumes. Lower values may be expected next to air cavities when using advanced algorithms, and in general may be acceptable for some benign lesions. Selectivity was much more variable, and in some cases this was combined with high gradient index and/or >1 mm margin, resulting in large volumes of normal tissue being irradiated. Normal tissue doses were more variable across linear accelerator (LINAC)-based plans than with Gamma Knife or CyberKnife, and dose spillage seemed independent of prescription isodose (inhomogeneity). This may reflect the variety of LINAC-based approaches represented or the necessary tradeoff between different objectives. CONCLUSIONS: These benchmarking exercises have highlighted areas of different clinical practice and priorities and potential for improvement. The subsequent sharing of plan data and margin philosophies between the neurosurgery and oncology communities allowed for meaningful comparison between centers and their peers.

Urethra-sparing stereotactic body radiotherapy for prostate cancer: how much can the rectal wall dose be reduced with or without an endorectal balloon?

BACKGROUND: This is a dosimetric comparative study intended to establish appropriate low-to-intermediate dose-constraints for the rectal wall (Rwall) in the context of a randomized phase-II trial on urethra-sparing stereotactic body radiotherapy (SBRT) for prostate cancer. The effect of plan optimization on low-to-intermediate Rwall dose and the potential benefit of an endorectal balloon (ERB) are investigated. METHODS: Ten prostate cancer patients, simulated with and without an ERB, were planned to receive 36.25Gy (7.25Gyx5) to the planning treatment volume (PTV) and 32.5Gy to the urethral planning risk volume (uPRV). Reference plans with and without the ERB, optimized with respect to PTV and uPRV coverage objectives and the organs at risk dose constraints, were further optimized using a standardized stepwise approach to push down dose constraints to the Rwall in the low to intermediate range in five sequential steps to obtain paired plans with and without ERB (Vm1 to Vm5). Homogeneity index for the PTV and the uPRV, and the Dice similarity coefficient (DSC) for the PTV were analyzed. Dosimetric parameters for Rwall including the median dose and the dose received by 10 to 60% of the Rwall, bladder wall (Bwall) and femoral heads (FHeads) were compared. The monitor units (MU) per plan were recorded. RESULTS: Vm4 reduced by half D30%, D40%, D50%, and Dmed for Rwall and decreased by a third D60% while HIPTV, HIuPRV and DSC remained stable with and without ERB compared to Vmref. HIPTV worsened at Vm5 both with and without ERB. No statistical differences were observed between paired plans on Rwall, Bwall except a higher D2% for Fheads with and without an ERB. CONCLUSIONS: Further optimization to the Rwall in the context of urethra sparing prostate SBRT is feasible without compromising the dose homogeneity to the target. Independent of the use or not of an ERB, low-to-intermediate doses to the Rwall can be significantly reduced using a four-step sequential optimization approach.

Laparoscopic subtotal gastrectomy with a new marking technique, endoscopic cautery marking: preservation of the stomach in patients with upper early gastric cancer.

BACKGROUND: Laparoscopic subtotal gastrectomy (LsTG) has several advantages, including technical safety and preservation of postoperative function, compared with total or proximal gastrectomy for early gastric cancer. However, LsTG has some technical issues with respect to achieving a safe resection margin and patency in patients with lesions close to the cardia or fornix. When LsTG is performed for lesions located rather close to the cardia or fornix, conventional marking clips can physically hinder transection by an endoscopic linear stapler. Additionally, tracing the tumor boundary to create a precise resection line is difficult. To resolve these issues, we introduced a new marking technique called endoscopic cautery marking (ECM) involving the creation of small cauterized spots. METHODS: Of 791 patients who underwent laparoscopic gastrectomy from 2015 to 2017, 16 underwent LsTG with ECM. Before surgery, ECM was performed and the pathological tumor boundary was traced according to preoperative biopsies. Under intraoperative endoscopic guidance, we divided the stomach with an endoscopic linear stapler on the proximal side of the ECM site and examined the stump by pathological frozen section analysis to confirm the absence of cancer. RESULTS: The median length of the endoscopically measured distance from the esophagogastric junction to the tumor was 30.0 mm (range 15-40 mm), and the median pathological proximal margin was 11.5 mm (range 0-26 mm). Although the ECM site was completely resected in all patients, frozen section analysis showed a positive margin in one lesion, which had an unclear tumor boundary due to gastritis. For this patient, we converted the procedure to laparoscopic completion gastrectomy. No severe complications or recurrences occurred. CONCLUSIONS: LsTG with ECM was technically feasible, and short-term outcomes were acceptable in this preliminary study. Further experience and investigations are imperative to verify the oncological and functional implications of LsTG with ECM.

Development of an isotoxic decision support system integrating genetic markers of toxicity for the implantation of a rectum spacer.

INTRODUCTION: Previous studies revealed that dose escalated radiotherapy for prostate cancer patients leads to higher tumor control probabilities (TCP) but also to higher rectal toxicities. An isotoxic model was developed to maximize the given dose while controlling the toxicity level. This was applied to analyze the effect of an implantable rectum spacer (IRS) and extended with a genetic test of normal tissue radio-sensitivity. A virtual IRS (V-IRS) was tested using this method. We hypothesized that the patients with increased risk of toxicity would benefit more from an IRS. MATERIAL AND METHODS: Sixteen localized prostate cancer patients implanted with an IRS were included in the study. Treatment planning was performed on computed tomography (CT) images before and after the placement of the IRS and with a V-IRS. The normal tissue complication probability (NTCP) was calculated using a QUANTEC reviewed model for Grade > =2 late rectal bleeding and the number of fractions of the plans were adjusted until the NTCP value was under 5%. The resulting treatment plans were used to calculate the TCP before and after placement of an IRS. This was extended by adding the effect of two published genetic single nucleotide polymorphisms (SNP's) for late rectal bleeding. RESULTS: The median TCP resulting from the optimized plans in patients before the IRS was 75.1% [32.6-90.5%]. With IRS, the median TCP is significantly higher: 98.9% [80.8-99.9%] (p < .01). The difference in TCP between the V-IRS and the real IRS was 1.8% [0.0-18.0%]. Placing an IRS in the patients with SNP's improved the TCP from 49.0% [16.1-80.8%] and 48.9% [16.0-72.8%] to 96.3% [67.0-99.5%] and 90.1% [49.0-99.5%] (p < .01) respectively for either SNP. CONCLUSION: This study was a proof-of-concept for an isotoxic model with genetic biomarkers with a V-IRS as a multifactorial decision support system for the decision of a placement of an IRS.