Long-term evaluation of the safety of a rectal-prostate spacer, the ProSpace® balloon, in patients treated with radiotherapy for prostate cancer.

BACKGROUND: Due to the close proximity of the prostate and rectum, rectal toxicity remains a major problem in patient treated by radiotherapy for prostate adenocarcinoma. One method of increasing the distance between the prostate and the rectum is to use a spacer implanted into the rectoprostatic space. This report describes the long-term outcomes obtained with a new ballon spacer. METHODS: Patients treated with curative radiotherapy for low- or intermediate-risk prostate adenocarcinoma, who underwent insertion of the ProSpace® (BioProtect Ltd, Tzur Yigal, Israel) rectal-prostate balloon spacer, were included. The main objective was to evaluate the dosimetric benefit of the spacer for OARs. The secondary objectives were to evaluate the feasibility and tolerability of ProSpace® balloon placement and to evaluate its long-term therapeutic efficacy and tolerance. RESULTS: Between October 2013 and March 2015, 16 patients were enrolled in the Pasteur Clinic, Toulouse, France. The median follow-up was 85.5 months. From top to bottom, the space created was a mean of 16.3 mm (range: 11-20.5 mm) at the base of the prostate, 12.1 mm (range: 4-16 mm) at the middle and 8.9 mm at the apex (range: 5-15 mm). On average, rectal volumes receiving a dose of 70 Gy, 60 Gy and 50 Gy were significantly lower after balloon implantation: -4.81 cc (1.5 vs. 6.3; p < 0.0005), -8.08 cc (6.4 vs. 14.5; p = 0.002) and -9.06 cc (16.7 vs. 25.7; p = 0.003), respectively. There were significant differences in coverage after balloon implantation: Median V95% (p < 0.0005), median Dmin (p = 0.01) and median V98% (p < 0.001) were higher after balloon implantation. At 5 years, cumulative gastrointestinal toxicity was grade 1 in 6% (1/16 patients). No toxicity of grade 2 or higher was found. At 5 years, no urinary toxicity grade 3 or 4 toxicity was found. The QoL was not deteriorated. CONCLUSIONS: The use of the ProSpace® balloon seems to be well accepted by patients, allowing a double dosimetric gain: a decrease in doses received by the rectum and an improvement in the coverage of the high-risk PTV. The long-term gastrointestinal toxicity remains low and QoL is preserved in all treated patients.

Cone beam CT doses in radiotherapy patient positioning in Finland-prostate treatments.

Imaging parameters, frequencies and resulting patient organ doses in treatments of prostate cancer were assessed in Finnish radiotherapy centres. Based on a questionnaire to the clinics, Monte Carlo method was used to estimate organ doses in International Commission on Radiological Protection standard phantom for prostate, bladder, rectum and femoral head. The results show that doses from cone beam computed tomography imaging have reduced compared to earlier studies and are between 3.6 and 34.5 mGy per image for the above-mentioned organs and for normal sized patients. There still is room for further optimization of the patient exposure, as many centres use the default imaging parameters, and the length of the imaged region may not be optimal for the purpose.

The use of dose surface maps as a tool to investigate spatial dose delivery accuracy for the rectum during prostate radiotherapy.

PURPOSE: This study aims to address the lack of spatial dose comparisons of planned and delivered rectal doses during prostate radiotherapy by using dose-surface maps (DSMs) to analyze dose delivery accuracy and comparing these results to those derived using DVHs. METHODS: Two independent cohorts were used in this study: twenty patients treated with 36.25 Gy in five fractions (SBRT) and 20 treated with 60 Gy in 20 fractions (IMRT). Daily delivered rectum doses for each patient were retrospectively calculated using daily CBCT images. For each cohort, planned and average-delivered DVHs were generated and compared, as were planned and accumulated DSMs. Permutation testing was used to identify DVH metrics and DSM regions where significant dose differences occurred. Changes in rectal volume and position between planning and delivery were also evaluated to determine possible correlation to dosimetric changes. RESULTS: For both cohorts, DVHs and DSMs reported conflicting findings on how planned and delivered rectum doses differed from each other. DVH analysis determined average-delivered DVHs were on average 7.1% ± 7.6% (p ≤ 0.002) and 5.0 ± 7.4% (p ≤ 0.021) higher than planned for the IMRT and SBRT cohorts, respectively. Meanwhile, DSM analysis found average delivered posterior rectal wall dose was 3.8 ± 0.6 Gy (p = 0.014) lower than planned in the IMRT cohort and no significant dose differences in the SBRT cohort. Observed dose differences were moderately correlated with anterior-posterior rectal wall motion, as well as PTV superior-inferior motion in the IMRT cohort. Evidence of both these relationships were discernable in DSMs. CONCLUSION: DSMs enabled spatial investigations of planned and delivered doses can uncover associations with interfraction motion that are otherwise masked in DVHs. Investigations of dose delivery accuracy in radiotherapy may benefit from using DSMs over DVHs for certain organs such as the rectum.

Intrarectal formalin treatment for haemorrhagic radiation-induced proctopathy: efficacy and safety.

AIM: Pelvic radiotherapy is limited by dose-dependent toxicity to surrounding organs. The aim of this prospective study was to evaluate the efficacy and safety of intrarectal formalin treatment for radiotherapy-induced haemorrhagic proctopathy (RHP) at the Royal Marsden Hospital. METHOD: Adult patients were enrolled. Haemoglobin was evaluated before and after formalin treatment. Antiplatelet and/or anticoagulation treatment and administration of transfusion were recorded. The interval between completion of radiotherapy and the first intrarectal 5% formalin treatment was assessed and the dose of radiotherapy was evaluated. Clinical assessment of the frequency and amount of rectal bleeding (rectal bleeding score 1-6) and endoscopic appearance (grade 0-3) were classified. Complications were recorded. RESULTS: Nineteen patients were enrolled, comprising 13 men (68%) and 6 women. The mean age was 75 ± 9 years. The median time between completion of radiotherapy and the first treatment was 20 months [interquartile range (IQR) 15 months] and the median dose of radiotherapy was 68 Gy (IQR 14 Gy). Thirty-two procedures were performed (average 1.7 per patient). In total, 9/19 (47%) patients were receiving anticoagulation and/or antiplatelet medication and 5/19 (26%) received transfusion prior to treatment. The mean value of serum haemoglobin before the first treatment was 110 ± 18 g/L and afterwards it was 123 ± 16 g/L (p = 0.022). The median rectal bleeding score before the first treatment was 6 (IQR 0) and afterwards 2 (IQR 1-4; p < 0.001), while the median endoscopy score on the day of first treatment was 3 (IQR 0) compared with 1 (IQR 1-2) on the day of the last treatment 1 (p < 0.001). One female patient with a persistent rectal ulcer that eventually healed (18 months of healing) subsequently developed rectovaginal fistula (complication rate 1/19, 5%). CONCLUSIONS: Treatment with intrarectal formalin in RHP is effective and safe.

Transrectal ultrasound for intraoperative interstitial needle guidance in cervical cancer brachytherapy.

OBJECTIVE: This study aimed to prospectively assess the visibility of interstitial needles on transrectal ultrasound (TRUS) in cervical cancer brachytherapy patients and evaluate its impact on implant and treatment plan quality. MATERIAL AND METHODS: TRUS was utilized during and after applicator insertion, with each needle's visibility documented through axial images at the high-risk clinical target volume's largest diameter. Needle visibility on TRUS was scored from 0 (no visibility) to 3 (excellent discrimination, margins distinct). Quantitative assessment involved measuring the distance between tandem and each needle on TRUS and comparing it to respective magnetic resonance imaging (MRI) measurements. Expected treatment plan quality based on TRUS images was rated from 1 (meeting all planning objectives) to 4 (violation of High-risk clinical target volume (CTVHR) and/or organ at risk (OAR) hard constraints) and compared to the final MRI-based plan. RESULTS: Analysis included 23 patients with local FIGO stage IB2-IVA, comprising 41 applications with a total of 230 needles. A high visibility rate of 99.1% (228/230 needles) was observed, with a mean visibility score of 2.5 ±â€¯0.7 for visible needles. The maximum and mean difference between MRI and TRUS measurements were 8 mm and -0.1 ±â€¯1.6 mm, respectively, with > 3 mm discrepancies in 3.5% of needles. Expected treatment plan quality after TRUS assessment exactly aligned with the final MRI plan in 28 out of 41 applications with only minor deviations in all other cases. CONCLUSION: Real-time TRUS-guided interstitial needle placement yielded high-quality implants, thanks to excellent needle visibility during insertion. This supports the potential of TRUS-guided brachytherapy as a promising modality for gynecological indications.

A Novel Framework for Thermoradiotherapy Treatment Planning.

PURPOSE: Thermoradiotherapy combines radiation therapy with hyperthermia to increase therapeutic effectiveness. Currently, both modalities are optimized separately and in state-of-the-art research the enhanced therapeutic effect is evaluated using equivalent radiation dose in 2-Gy fractions (EQD2). This study proposes a novel thermoradiotherapy treatment planning framework with voxelwise EQD2 radiation therapy optimizing including thermal radiosensitization and direct thermal cytotoxicity. METHODS AND MATERIALS: To demonstrate proof-of-concept of the planning framework, 3 strategies consisting of 20 radiation therapy fractions were planned for 4 prostate cancer cases with substantially different temperature distributions: (1) Conventional radiation therapy plan of 60 Gy combined with 4 hyperthermia sessions (RT60 + HT), (2) standalone uniform dose escalation to 68 Gy without hyperthermia (RT68), and (3) uniform target EQD2 that maximizes the tumor control probability (TCP) accounting for voxelwise thermal effects of 4 hyperthermia sessions without increasing normal tissue doses (RTHT + HT). Assessment included dose, EQD2, TCP, and rectal normal tissue complication probability (NTCP), alongside robustness analyses for TCP and NTCP against parameter uncertainties. RESULTS: The estimated TCP of around 76% for RT60 without hyperthermia was increased to an average of 85.9% (range, 81.3%-90.5%) for RT60 + HT, 92.5% (92.4%-92.5%) for RT68, and 94.4% (91.7%-96.6%) for RTHT + HT. The corresponding averaged rectal NTCPs were 8.7% (7.9%-10.0%), 14.9% (13.8%-17.1%), and 8.4% (7.5%-9.7%), respectively. RT68 and RTHT + HT exhibited slightly enhanced TCP robustness against parameter uncertainties compared with RT60 + HT, and RT68 presented higher and less robust rectal NTCP values compared with the other planning strategies. CONCLUSIONS: This study introduces an innovative thermoradiotherapy planning approach, integrating thermal effects into EQD2-based radiation therapy optimization. Results demonstrate an ability to achieve enhanced and uniform target EQD2 and TCP across various temperature distributions without elevating normal tissue EQD2 or NTCP compared with conventional methods. Although promising for improving clinical outcomes, realizable enhancements depend on accurate tumor- and tissue-specific data and precise quantification of hyperthermic effects, which are seamlessly integrable in the planning framework as they emerge.

Understanding Relative Biological Effectiveness and Clinical Outcome of Prostate Cancer Therapy Using Particle Irradiation: Analysis of Tumor Control Probability With the Modified Microdosimetric Kinetic Model.

PURPOSE: Recent experimental studies and clinical trial results might indicate that-at least for some indications-continued use of the mechanistic model for relative biological effectiveness (RBE) applied at carbon ion therapy facilities in Europe for several decades (LEM-I) may be unwarranted. We present a novel clinical framework for prostate cancer treatment planning and tumor control probability (TCP) prediction based on the modified microdosimetric kinetic model (mMKM) for particle therapy. METHODS AND MATERIALS: Treatment plans of 91 patients with prostate tumors (proton: 46, carbon ions: 45) applying 66 GyRBE [RBE = 1.1 for protons and LEM-I, (α/ß)x = 2.0 Gy, for carbon ions] in 20 fractions were recalculated using mMKM [(α/ß)x = 3.1 Gy]). Based solely on the response data of photon-irradiated patient groups stratified according to risk and usage of androgen deprivation therapy, we derived parameters for an mMKM-based Poisson-TCP model. Subsequently, new carbon and helium ion plans, adhering to prescribed biological dose criteria, were generated. These were systematically compared with the clinical experience of Japanese centers employing an analogous fractionation scheme and existing proton plans. RESULTS: mMKM predictions suggested significant biological dose deviation between the proton and carbon ion arms. Patients irradiated with protons received (3.25 ± 0.08) GyRBEmMKM/Fx, whereas patients treated with carbon ions received(2.51 ± 0.05) GyRBEmMKM/Fx. TCP predictions were (86 ± 3)% for protons and (52 ± 4)% for carbon ions, matching the clinical outcome of 85% and 50%. Newly optimized carbon ion plans, guided by the mMKM/TCP model, effectively replicated clinical data from Japanese centers. Using mMKM, helium ions exhibited similar target coverage as proton and carbon ions and improved rectum and bladder sparing compared with proton. CONCLUSIONS: Our mMKM-based model for prostate cancer treatment planning and TCP prediction was validated against clinical data for proton and carbon ion therapy, and its application was extended to helium ion therapy. Based on the data presented in this work, mMKM seems to be a good candidate for clinical biological calculations in carbon ion therapy for prostate cancer.

Worsening of 2-year patient-reported intestinal functionality after radiotherapy for prostate cancer including pelvic node irradiation.

BACKGROUND AND PURPOSE: To quantify patient-reported 2-year intestinal toxicity (IT) from pelvic nodal irradiation (PNI) for prostate cancer. The association between baseline/acute symptoms and 2-year worsening was investigated. MATERIALS AND METHODS: Patient-reported IT was prospectively assessed through the Inflammatory Bowel Disease Questionnaire (IBDQ), filled in at baseline, radiotherapy mid-point and end, at 3 and 6 months and every 6 months until 5 years. Two-year deterioration of IBDQ scores relative to the Bowel Domain was investigated for 400 patients with no severe baseline symptoms and with questionnaires available at baseline, 2 years, RT mid-point and/or end and at least three follow-ups between 3 and 18 months. The significance of the 2-year differences from baseline was tested. The association between baseline values and ΔAcute (the worst decline between baseline and RT mid-point/end) was investigated. RESULTS: In the IBDQ lower scores indicate worse symptoms. A significant (p < 0.0001) 2-year mean worsening, mostly in the range of -0.2/-0.4 points on a 1-7 scale, emerged excepting one question (IBDQ29, "nausea/feeling sick"). This decline was independent of treatment intent while baseline values were associated with 2-year absolute scores. The ΔAcute largely modulated 2-year worsening: patients with ΔAcute greater than the first quartile (Q1) and ΔAcute less or equal than Q1 showed no/minimal and highly significant (p < 0.0001) deterioration, respectively. Rectal incontinence, urgency, frequency and abdominal pain showed the largest mean changes (-0.5/-1): risk of severe worsening (deemed to be of clinical significance if ≤ 2) was 3-5 fold higher in the ΔAcute ≤ Q1 vs ΔAcute > Q1 group (p < 0.0001). CONCLUSION: A modest but significant deterioration of two-year patient-reported intestinal symptoms from PNI compared to baseline was found. Patients experiencing more severe acute symptoms are at higher risk of symptom persistence at 2 years, with a much larger prevalence of clinically significant symptoms.

Predictive Factors for Toxicity After Primary Chemoradiation for Locally Advanced Cervical Cancer: A Systematic Review.

PURPOSE: Women with locally advanced cervical cancer (LACC) undergoing primary platinum-based chemoradiotherapy and brachytherapy often experience toxicities. Normal-tissue complication probability (NTCP) models quantify toxicity risk and aid in optimizing radiation therapy to minimize side effects. However, it is unclear which predictors to include in an NTCP model. The aim of this systematic review was to provide an overview of the identified predictors contributing to gastrointestinal (GI), genitourinary (GU), and vaginal toxicities and insufficiency fractures for LACC. METHODS AND MATERIALS: A systematic search was performed and articles evaluating the relationship between predictors and toxicities in women with LACC treated with primary chemoradiation were included. The Quality In Prognosis Studies tool was used to assess risk of bias, with high-risk studies being excluded from further analysis. Relationships between dose-volume parameters, patient and treatment characteristics, and toxicity endpoints were analyzed. RESULTS: Seventy-three studies were identified. Twenty-six had a low or moderate risk of bias and were therefore included. Brachytherapy-related dose-volume parameters of the GI tract, including rectum and bowel equivalent dose in 2 Gy fractions (EQD2) D2 cm3, were frequently related to toxicities, unlike GU dose-volume parameters. Furthermore, (recto)vaginal point doses predicted toxicities. Few studies evaluated external beam radiation therapy dose-volume parameters and identified rectum EQD2 V30 Gy, V40 Gy, and V55 Gy, bowel and bladder EQD2 V40 Gy as toxicity predictors. Also, total reference air kerma and vaginal reference length were associated with toxicities. Relationships between patient characteristics and GI toxicity were inconsistent. The extent of vaginal involvement at diagnosis, baseline symptoms, and obesity predicted GU or vaginal toxicities. Only 1 study evaluated insufficiency fractures and demonstrated lower pretreatment bone densities to be associated. CONCLUSIONS: This review detected multiple candidate predictors of toxicity. Larger studies should consider insufficiency fractures, assess dose levels from external beam radiation therapy, and quantify the relationship between the predictors and treatment-related toxicities in women with LACC to further facilitate NTCP model development for clinical use.

Prostate cancer invading rectal serosa and anal sphincter treated with definitive radiation therapy: Case report and review of the literature.

ABSTRACT: Despite anatomical proximity, prostatic adenocarcinoma with rectal invasion is rare. We describe a case of prostate cancer invading the anal sphincter, treated with radiation therapy (RT). A 78-year-old patient underwent definitive radiotherapy in 2018 because of poorly differentiated adenocarcinoma, Gleason 4 + 3 (7). The initial stage was mrT4N0 on magnetic resonance imaging (MRI) images. The pre-treatment prostate-specific antigen level was 142 ng/mL, and the patient was subjected to androgen deprivation therapy. RT was performed using volumetric modulated arc therapy (VMAT) and a dose of 76 Gy in 38 fractions. After 2 months, MRI showed a complete response. During RT, toxicity was limited to mild gastro-intestinal and urologic symptoms. This report is the first to describe prostate cancer invasion of the anal sphincter and to extend to that condition the use of RT - already regarded as a useful treatment option for inoperable locally advanced high-risk prostate cancer (PC). This study suggests that VMAT can be a safe and effective treatment option for locally advanced high-risk PC patients.

The Current Trend of Radiation Therapy for Patients with Localized Prostate Cancer.

A recent approach to radiotherapy for prostate cancer is the administration of high doses of radiation to the prostate while minimizing the risk of side effects. Thus, image-guided radiotherapy utilizes advanced imaging techniques and is a feasible strategy for increasing the radiation dose. New radioactive particles are another approach to achieving high doses and safe procedures. Prostate brachytherapy is currently considered as a combination therapy. Spacers are useful to protect adjacent organs, specifically the rectum, from excessive radiation exposure.

Achievable Dosimetric Constraints in Stereotactic Reirradiation for Recurrent Prostate Cancer.

PURPOSE: Stereotactic body radiation therapy has been proposed as a salvage treatment for recurrent prostate cancer after irradiation. One crucial issue is choosing appropriate dose-volume constraints (DVCs) during planning. The objectives of this study were to (1) quantify the proportion of patients respecting the DVCs according to the Urogenital Tumor Study Group GETUG-31 trial, testing 36 Gy in six fractions, (2) explain geometrically why the DVCs could not be respected, and (3) propose the most suitable DVCs. METHODS AND MATERIALS: This retrospective dosimetric analysis included 141 patients treated for recurrent prostate cancer with Cyberknife (Accuray), according to GETUG-31 DVCs: V95% ≥ 95% for the planning target volume (PTV), V12Gy < 20% and V27Gy < 2 cc for the rectum, and V12Gy < 15% and V27Gy < 5 cc for the bladder. The percentage of patients not respecting the DVCs was quantified. Correlations between the DVCs and anatomic structures were examined. New DVCs were proposed. RESULTS: Only 19% of patients respected all DVCs, with a mean PTV of 18.5 cc (range, 3-48 cc), although the mean PTV was 40.5 cc (range, 3-174 cc) in the whole series. A total of 98% of the patients with a clinical target volume (CTV)/prostate ratio >0.5 could not respect the DVCs in the organs at risk. The target coverage and organ-at-risk sparing decreased significantly with increase in the values of PTV, CTV, CTV/prostate ratio, the overlapping volume between the PTV and bladder wall and between the PTV and rectal wall. Threshold values of PTV, >20 cc and 40 cc, allowed for the PTV and bladder DVCs, respectively. To improve DVC respect in case of large target volume, we proposed the following new DVCs: V12Gy < 25% and 25% and V27Gy < 2 cc and 5 cc for the rectum and bladder, respectively. CONCLUSIONS: GETUG-31 DVCs are achievable only for small target volumes (CTV more than half of the prostate). For a larger target volume, new DVCs have been proposed.

(Potential) Mishaps of High-Dose-Rate Vaginal Cuff Brachytherapy.

Considering how commonly vaginal cuff brachytherapy is used, there is relatively little literature regarding the potential, albeit low, risk for complications. We present 3 potentially serious mishaps involving cylinder misplacement, dehiscence, and excessive normal tissue irradiation due to unique anatomy. Three patients with potentially serious treatment errors were encountered in the authors' usual clinical practice. Each patient's records were reviewed for this report. For patient 1, computed tomography (CT) simulation revealed grossly inadequate cylinder insertion, which was most obvious on the sagittal view. For patient 2, CT simulation revealed that the cylinder extended beyond the perforated vaginal cuff and was surrounded by bowel. For patient 3, CT images were used only to verify cylinder depth. A standard library plan based on cylinder diameter and active length was used. In retrospect, the images revealed an unusually thin rectovaginal septum, with the lateral and posterior vaginal wall thickness estimated to be <2 mm. This patient's fractional normal tissue doses were calculated for this report, revealing a rectal maximum dose (per fraction) of 10.8 Gy, maximum dose that 2 cc of the organ receives of 7.4 Gy, and volume of the organ that receives the prescription dose or higher of 2.8 cc. All doses were far in excess of those anticipated for a minimal 0.5-cm vaginal wall depth. Vaginal cuff high-dose-rate brachytherapy is a high-volume, routine procedure. Even in experienced hands, however, it carries a risk of improper cylinder placement, cuff dehiscence, and excessive normal tissue dose, all of which could seriously affect outcomes. These potential mishaps would be better appreciated and avoided with more extensive use of CT-based quality assurance measures.

Circulating microvesicles correlate with radiation proctitis complication after radiotherapy.

In a large retrospective study, we assessed the putative use of circulating microvesicles (MVs), as innovative biomarkers of radiation toxicity in a cohort of 208 patients with prostate adenocarcinoma overexposed to radiation. The level of platelet (P)-, monocyte (M)- and endothelial (E)-derived MVs were assessed by flow cytometry. Rectal bleeding toxicity scores were collected at the time of blood sampling and during the routine follow-up and were tested for association with MVs using a multivariate logistic regression. MVs dosimetric correlation was investigated using dose volume histograms information available for a subset of 36 patients. The number of PMVs was significantly increased in patients with highest toxicity grades compared to lower grades. Risk prediction analysis revealed that increased numbers of PMVs, and an increased amount of MMVs relative to EMVs, were associated with worst rectal bleeding grade compared to the time of blood sampling. Moreover, a significant correlation was found between PMV and MMV numbers, with the range of doses up to the median exposure (40 Gy) of bladder/rectum and anterior rectal wall, respectively. MVs could be considered as new biomarkers to improve the identification of patients with high toxicity grade and may be instrumental for the prognosis of radiation therapy complications.

Parameters of the Lyman Model for Calculation of Normal-Tissue Complication Probability: A Systematic Literature Review.

PURPOSE: The Lyman model is one of the most used radiobiological models for calculation of normal-tissue complication probability (NTCP). Since its introduction in 1985, many authors have published parameter values for the model based on clinical data of different radiotherapeutic situations. This study attempted to collect the entirety of radiobiological parameter sets published to date and provide an overview of the data basis for different variations of the model. Furthermore, it sought to compare the parameter values and calculated NTCPs for selected endpoints with sufficient data available. METHODS AND MATERIALS: A systematic literature analysis was performed, searching for publications that provided parameters for the different variations of the Lyman model in the Medline database using PubMed. Parameter sets were grouped into 13 toxicity-related endpoint groups. For 3 selected endpoint groups (≤25% reduction of saliva 12 months after irradiation of the parotid, symptomatic pneumonitis after irradiation of the lung, and bleeding of grade 2 or less after irradiation of the rectum), parameter values were compared and differences in calculated NTCP values were analyzed. RESULTS: A total of 509 parameter sets from 130 publications were identified. Considerable heterogeneities were detected regarding the number of parameters available for different radio-oncological situations. Furthermore, for the 3 selected endpoints, large differences in published parameter values were found. These translated into great variations of calculated NTCPs, with maximum ranges of 35.2% to 93.4% for the saliva endpoint, of 39.4% to 90.4% for the pneumonitis endpoint, and of 5.4% to 99.3% for the rectal bleeding endpoint. CONCLUSIONS: The detected heterogeneity of the data as well as the large variations of published radiobiological parameters underline the necessity for careful interpretation when using such parameters for NTCP calculations. Appropriate selection of parameters and validation of values are essential when using the Lyman model.

Focal injection of a radiopaque viscous spacer before focal brachytherapy as re-irradiation for locally recurrent prostate cancer.

PURPOSE: Close vicinity of the target volume and a sensitive organ may prevent an effective radiotherapy/brachytherapy. A liquid hydrogel spacer cannot be placed well focally in specific small areas or fatty tissue. The purpose of this study was to report the injection technique and results of a radiopaque viscous hydrogel spacer. METHODS: The radiopaque viscous spacer was applied focally using transrectal ultrasound guidance before focal brachytherapy in re-irradiated areas in two patients. The technical feasibility of the injection between the recurrence and the rectum / bladder, the resulting distance, visibility in different imaging modalities, stability within several months, dose distribution, toxicity and tumor control up to 18 months after treatment was analyzed. RESULTS: After hydrodissection, the needle was moved from the base towards the apex during injection of each syringe, respectively. The viscous spacer could be successfully injected focally and resulted in a planned distancing of the target volume (right lobe and seminal vesicle area) and the rectum of at least 1 cm and additional distancing to the bladder of at least 5 mm. Both brachytherapy treatments were performed without relevant toxicities. The PSA nadirs indicated a satisfactory short-term response to the treatment. CONCLUSIONS: The viscous hydrogel spacer can be injected focally at a specific prostate lobe or seminal vesicles. A viscous spacer remains stable within fatty tissue in any areas that are accessible by an ultrasound guided needle injection to create a distance between the high brachytherapy dose within the target and the organ at risk.

The dynamic cellular and molecular features during the development of radiation proctitis revealed by transcriptomic profiling in mice.

BACKGROUND: Radiation proctitis (RP) is the most common complication of radiotherapy for pelvic tumor. Currently there is a lack of effective clinical treatment and its underlying mechanism is poorly understood. In this study, we aimed to dynamically reveal the mechanism of RP progression from the perspective of RNomics using a mouse model, so as to help develop reasonable therapeutic strategies for RP. RESULTS: Mice were delivered a single dose of 25 Gy rectal irradiation, and the rectal tissues were removed at 4 h, 1 day, 3 days, 2 weeks and 8 weeks post-irradiation (PI) for both histopathological assessment and RNA-seq analysis. According to the histopathological characteristics, we divided the development process of our RP animal model into three stages: acute (4 h, 1 day and 3 days PI), subacute (2 weeks PI) and chronic (8 weeks PI), which could recapitulate the features of different stages of human RP. Bioinformatics analysis of the RNA-seq data showed that in the acute injury period after radiation, the altered genes were mainly enriched in DNA damage response, p53 signaling pathway and metabolic changes; while in the subacute and chronic stages of tissue reconstruction, genes involved in the biological processes of vessel development, extracellular matrix organization, inflammatory and immune responses were dysregulated. We further identified the hub genes in the most significant biological process at each time point using protein-protein interaction analysis and verified the differential expression of these genes by quantitative real-time-PCR analysis. CONCLUSIONS: Our study reveals the molecular events sequentially occurred during the course of RP development and might provide molecular basis for designing drugs targeting different stages of RP development.

Dose Accumulation for Multicourse Gynecological Reirradiation: A Methodological Narrative and Clinical Examples.

PURPOSE: Reirradiation (re-RT) is a suitable and potentially curative treatment option for in-field locoregional recurrences in gynecological malignancies. Lack of clear guidelines on prescription, dose-response relationship, and clinical outcomes limits its clinical use. This clinical narrative describes the methodology for integration of deformable image registration (DIR) for cumulative dose assessment in the setting of re-RT for gynecologic malignancies, using the tools available within a commercial treatment planning system. METHODS AND MATERIALS: Four patients who received re-RT for locoregional recurrence or second cancer within previously irradiated areas for a gynecologic primary were identified. Patient-specific DIR for deformable dose mapping and accumulation was retrospectively performed using intensity-based algorithm provided by the Varian Medical Systems Velocity AI version 4.1. Cumulative equivalent doses in 2 Gy fractions (EQD2) delivered to overlapping targets and organs at risk were generated and compared with the physically summated doses. For both approaches, brachytherapy (BT) component was physically summated in cases where the BT applicator caused significant anatomic distortion. RESULTS: The mean maximum cumulative overlapping target dose was 119.4 Gy10 (range, 84.7 Gy10-144.9 Gy10). The mean cumulative doses received by 2 cm3 of bladder, rectum, sigmoid, and bowel were 114.6 Gy3 (101.1-133.4 Gy3), 98.7 Gy3 (67-136.2 Gy3), 92.5 Gy3 (70.4-107 Gy3), and 89.9 Gy3 (81.1-102.8 Gy3), respectively. In the setting of in-field nodal recurrence, DIR-based dose summation was associated with lower cumulative organs at risk doses than those estimated with physical summation, except in one case with a higher bowel dose. In cases where re-RT was given for local recurrence/second primary, variation in sigmoid doses was observed between the 2 dose-summation strategies across all 3 cases, but it was inconsistent with bladder, rectum, or the bowel. CONCLUSIONS: DIR-based dose accumulation can be used to guide re-RT planning and can provide clinically relevant information, especially in cases with nodal recurrences. Registration of BT data sets remain challenging and requires an individualized assessment when applying these algorithms to clinical practice.

Acute Side-effects of Different Radiotherapy Treatment Schedules in Early Prostate Cancer.

BACKGROUND: Optimal radiation therapy (RT) fractionation in early prostate cancer in elderly patients is controversial. We compared acute toxicities of fractionation schedules: 78/2 Gy, 60/3 Gy and 36.25/7.25 Gy, in this single-centre study. We also evaluated the effect of the rectal immobilization system Rectafix on quality of life (QoL). PATIENTS AND METHODS: Seventy-three patients with one or two intermediate prostate cancer risk factors according to National Comprehensive Cancer Network criteria were recruited. Twenty-one patients were treated with 78/2 Gy and 60/3 Gy, and 31 patients with 36.25/7.25 Gy. Their QoL data were assessed with regard to genitourinary, gastrointestinal and sexual wellbeing at the beginning and end of RT and at 3 months after treatment. Rectafix was used in the 78/2 Gy and 60/3 Gy groups. RESULTS: There were no statistically significant QoL differences in between the treatment groups 3 months after RT. The 78/2 Gy group had significantly increased bowel movements between baseline and 3 months after RT (p=0.036). At 3 months after RT, this group also had significantly more erectile dysfunction than the 60/3 Gy group (p=0.025). At the end of RT, the 78/2 Gy group had more symptoms than the 36.25/7.25 Gy group. Rectafix did not reduce acute toxicities in the 78/2 Gy or 60/3 Gy groups. CONCLUSION: Treatment with the 78/2 Gy schedule is no longer to be recommended due to its increased acute toxicity compared to treatments of 60/3 Gy and 36.25/7.25 Gy. The shortest schedule of 36.25 Gy in five fractions seems to be a convenient treatment option with tolerable acute toxicity.

Creation of a protective space between the rectum and prostate prior to prostate radiotherapy using a hydrogel spacer.

The placement of a polyethylene glycol (PEG) hydrogel spacer is a recently developed technique employed to reduce the radiation dose administered to the rectum during prostate radiotherapy. This procedure has been adopted by urologists and radiation oncologists involved in transperineal prostate biopsy and brachytherapy, and more recently by radiologists with experience in transperineal prostate procedures. Radiologists should be familiar with the product, which may be encountered on computed tomography (CT) or magnetic resonance imaging (MRI). Radiologists may wish to become involved in the delivery of this increasingly utilised procedure. This review familiarises radiologists with the technique and risks and benefits of the use of transperineal delivery of hydrogel spacers with imaging examples.