Bladder Dose Research Articles

Reduction of Intra-Dosimetrist Variation, and Improvement of Overall Plan Quality as Assessed by Dose-Volume Histograms, Through Training and Implementation of Advanced Optimization Tools

Our Cancer Center network comprises a research Cancer Center as well as 10 independent community practices, with 18 total Dosimetrists. Many steps have been taken to increase treatment planning standardization, while dosimetry techniques and practices across the system have remained independent, with limited use of advanced optimization tools, knowledge-based planning (KBP) and multi-criteria optimization (MCO). With the objective to improve standardization of techniques, identify best practices, and improve overall quality, we implemented an in-house dosimetry plan challenge and solicited participation from 18 dosimetrists within the network.We anonymized an existing intermediate risk prostate adenocarcinoma clinical T1c N0 M0 patient dataset with physician drawn target contours (prostate plus proximal 1cm seminal vesicles) and normal structures, to create an identical test case for each dosimetrist. Clinically relevant planning objectives were provided in addition to instructions to produce a plan of clinical quality, committing typical clinical time/effort, using only standard optimization tools. Following submission of all plans, the results were discussed with the dosimetry team, including evaluations of dose-volume histograms (DVH). Instruction was provided on the advanced optimization tools KBP and MCO. Dosimetrists were instructed to repeat the challenge with the explicit instruction to use KBP and MCO. KBP/MCO plan results were compared to the plan results without KBP/MCO use to show the overall impact of advanced tools on achieved plan quality and intra-dosimetrist variation. All plans were explicitly normalized to the PTV D100% = 95% to allow direct comparison of DVHs.All initial plans submitted by 16 dosimetrists met the prescribed objectives outlined for clinical practice. However, plans demonstrated a wide range of acceptable dose-volume histograms. In addition to visual evaluation of the DVHs, multiple dose points for the Target (PTV), Rectum and Bladder, were exported for comparison between groups of plans. The group average achieved bladder doses were reduced from 52.8%Rx to 41.9%Rx, 23.9%Rx to 15.5%Rx, and 6.3%Rx to 5.5%Rx at D15%, D30%, and D60% respectively. The group average achieved rectal doses were reduced from 62.3%Rx to 45.8%Rx, 49.3%Rx to 32.7%Rx, and 33.9%Rx to 19.9%Rx at D10%, D20%, and D40% respectively. Similarly, the standard deviations also showed marked decrease with those for the bladder reduced from 0.084 to 0.044, 0.067 to 0.02, and 0.014 to 0.010 for D15%, D30%, and D60% respectively, and those for rectum reduced from 0.106 to 0.0690, 0.109 to 0.066, 0.086 to 0.038 at D10%, D20%, and D40% respectively.Standardization of clinical treatment planning objectives and consistent use of advanced optimization tools can improve overall planning quality and reduce intra-dosimetrist variation of treatment planning results based on clinical DVH metrics.

Predicting the Optimal Bladder Volume to Minimize the Dose to the Organs at Risk in Carcinoma Cervix Treated With Modern Radiotherapy.

Whilst planning external beam radiotherapy (EBRT) for carcinoma cervix, bladder volume is an important consideration in deciding dose to other organs at risk (OARs). Though conformal techniques like volumetric-modulated radiotherapy (VMAT) have reduced the dose received by the OARs, there is still scope for improvement by utilizing other techniques. Planning with a full bladder is one such strategy that pushes a part of the bladder wall and the bowel away from the planning target volume (PTV). This is complicated by the fact that holding urine becomes increasingly more difficult along the course of pelvic radiotherapy. This makes the bladder volume threshold important to reduce the doses received by the OARs. We aim to assess the optimal bladder volume to spare OARs in patients with carcinoma cervix treated with VMAT.The data of 81 patients of carcinoma cervix stage IB2-IVB treated with EBRT using VMAT followed by brachytherapy was prospectively collected in this study. The patients were advised to void and drink 500 ml of water, 30 minutes following which, a simulation scan was acquired. The target was contoured according to the Japanese Clinical Oncology Group guidelines and OARs in line with Radiation Therapy Oncology Group guidelines. Constraints to the bowel, bladder, rectum, and sigmoid were V45 < 195cc, V45 < 35%, V45 < 45% and V45 < 45% respectively. A dose of 50.4 Gy in 28 fractions was prescribed to the PTV using VMAT. The generated plans were analyzed and acceptable plans were finalized for treatment with higher priority to PTV coverage while minimizing the OAR doses. The bladder volumes at simulation and the doses received by the OARS were correlated using Pearson's correlation. A receiver operating characteristic (ROC) curve was constructed to find the cut-off value of the bladder volume which facilitated achieving the dose constraints to the significantly correlated OARs with acceptable specificity and sensitivity.A correlational analysis of the bladder volume with the OAR dose constraints revealed that there was a significant negative weak correlation with the V45 Gy of the bladder and the bowel. A ROC curve was constructed assessing bladder volume against the achievability of the bladder dose constraint. The area under the curve was 0.78 showing a fairly accurate relationship between the variables. A bladder volume of 270cc is noted to be the best cut-off to achieve the bladder dose constraint with a sensitivity and specificity of approximately 75% and 80% respectively. The curve for bladder volume and achievability of bowel constraints yielded a curve with poor accuracy and an area under the curve of 0.64 and so further analysis for the same was abandoned given the low sensitivity and specificity of the attained cut-off (approximately 65%).Increasing bladder volume has reduced the doses received by bowel and bladder. A volume of 270cc is to be aimed at to achieve the V45 Gy of the bladder in patients of carcinoma cervix being treated with VMAT.S. Kombathula: None. J. Pandjatcharam: None. D. Kannikanti: None. A. Menon: None. J.M. Mathew: None. T. Elumalai: None. M. Sinnatamby: None.

Factors Contributing to Bladder Filling Variability in Patients Receiving Radiotherapy for Prostate Cancer

Prostate cancer patients receiving radiotherapy (RT) are treated with full bladders to minimize bladder dose and displace bowel from the treatment field. While limitations in controlling bladder filling reproducibility during RT have been shown to affect bladder and bowel dosimetry, the factors affecting bladder volume variability have not been elucidated. We herein evaluate the impact of prostate cancer risk group, bladder volume (BV) at the beginning of treatment, and pre-treatment International Prostate Symptom Score (IPSS) on metrics quantifying BV changes during RT.We retrospectively reviewed 78 prostate cancer patients treated from 2016-19 with definitive RT 8,100 cGy in 45 fractions (n = 32), definitive stereotactic body RT 3625 cGy in 5 fractions over 2.5 weeks (n = 24), and adjuvant or salvage RT 7020 cGy in 39 fractions (n = 22). Thirty-six patients with high or unfavorable intermediate risk disease received androgen deprivation therapy (ADT) prior to RT, while 29 patients with high risk disease received pelvic nodal RT in addition to prostate or prostate bed RT. Each patient completed a pre-treatment IPSS survey and received daily cone-beam CT (CBCT) scans for positioning during treatment. The BV at beginning of treatment was defined as the patient's first attempt to fully fill his bladder without assistance. BVs were contoured on the CT simulation scan and CBCT images from the first and last days of radiotherapy. Age, risk group, IPSS and initial BV were compared with change in BV (ΔBV), change in BV relative to initial BV (%Δ) and absolute change in BV (|ΔBV|) between first and last day of RT.Median age and IPSS were 69 (range 50-84) years and 8 (0-30), respectively. Mean and standard deviation initial BV, ΔBV, %ΔBV and |ΔBV| were 314 ± 152 cc, -59 ± 123 cc, -8 ± 40%, 106 ± 85 cc, respectively. On multivariable analysis, initial BV was negatively correlated with ΔBV and %ΔBV independent of age, prostate cancer risk group, ADT, pelvic nodal RT, and duration of treatment (P < 0.05). Initial BV and prostate cancer risk group were positively, while IPSS was negatively, correlated with |ΔBV| (P < 0.05).Prostate cancer patients with large initial BV experienced larger total and relative declines in BV during RT. High initial BV, increasing prostate cancer risk group, and low IPSS correlated with greater absolute changes in BV (|ΔBV|) over the course of treatment. Hence, maximizing bladder volume during simulation appears to negatively impact reproducibility, which must be taken into consideration when optimizing bladder volume reproducibility using a non-invasive approach during prostate radiotherapy. We have already implemented these findings into our simulation and treatment protocols and look forward to reporting our clinical outcomes in the near future.

Effect of bladder volume on radiation doses to organs at risk and tumor in cervical cancer during image-guided adaptive brachytherapy and treatment outcome analysis.

There is no consensus in clinical practice on the optimal bladder volume during brachytherapy. The present study aimed to assess the effect of bladder volume on radiation dose to organs at risk and tumor in cervical cancer during image-guided adaptive brachytherapy and clinical outcome. The retrospective study included patients treated at University of Hong Kong-Shenzhen Hospital between January 2015 and July 2019. Patients with International Federation of Gynecology and Obstetrics (2009) stage IB1-IVB (retroperitoneal lymph nodes metastasis only) cervical cancer treated by external beam radiotherapy with concurrent cisplatin followed by brachytherapy were assessed. A total of 421 brachytherapy insertions were analyzed. Every 83 and 90 cm3 (cc) increase in bladder volume led to an incremental raise of 1 Gy in bladder wall minimum dose received by the most irradiated 1 and 2 cc volumes (D1 and D2cc) of the bladder wall, respectively. An increase in bladder volume was associated with increased D1 and D2cc of bladder (both P<0.001, respectively) and rectal wall (P=0.150 and P=0.084, respectively), and decreased D1cc (P=0.003) and D2cc (P=0.001) of sigmoid wall, the maximum doses to the most minimally exposed 90 (D90) and 95% (D95) of the high risk-clinical target volume (HR-CTV; D90, P=0.010; D95, P=0.006). Patients with cumulative HR-CTV D90≤89.6 Gy had shorter median overall survival (OS) than those with cumulative HR-CTV D90>89.6 Gy (42.1 months vs. not reached, P=0.001). Patients with grade 2 acute urinary toxicity had significantly higher cumulative bladder wall D2cc than those with acute urinary toxicity<grade 2 (86.7±3.7 vs. 78.5±7.9 Gy; P=0.001). As the bladder volume increased, the dose to the bladder and rectal wall increase and dose to the sigmoid colon wall and HR-CTV decrease based on intracavitary brachytherapy. The higher dose of HR-CTV predicted better OS and the higher dose received by the bladder wall was associated with more grade 2 acute urinary toxicity.

Biologically Targeted Radiation Therapy: Incorporating Patient-Specific Hypoxia Data Derived from Quantitative Magnetic Resonance Imaging.

Simple SummaryRecent clinical trials have demonstrated the capability of safely delivering prostate radiotherapy with a simultaneous focal boost. These studies have also indicated limitations to achieving focal boosts whilst trying to limit normal tissue toxicity. More guidance in the location and level of the required boost could alleviate such limitations. Tumour hypoxia is one of the causes of clinically observed radioresistance and hypoxic volumes represent prime candidates for a focal boost. Multiparametric magnetic resonance imaging (mpMRI) has the potential to quantitatively describe the extent and spatial distribution of hypoxia in prostate cancer. In this article we demonstrate a biologically targeted radiotherapy approach that can utilise this information to target hypoxia for favourable treatment outcomes.Purpose: Hypoxia has been linked to radioresistance. Strategies to safely dose escalate dominant intraprostatic lesions have shown promising results, but further dose escalation to overcome the effects of hypoxia require a novel approach to constrain the dose in normal tissue.to safe levels. In this study, we demonstrate a biologically targeted radiotherapy (BiRT) approach that can utilise multiparametric magnetic resonance imaging (mpMRI) to target hypoxia for favourable treatment outcomes. Methods: mpMRI-derived tumour biology maps, developed via a radiogenomics study, were used to generate individualised, hypoxia-targeting prostate IMRT plans using an ultra- hypofractionation schedule. The spatial distribution of mpMRI textural features associated with hypoxia-related genetic profiles was used as a surrogate of tumour hypoxia. The effectiveness of the proposed approach was assessed by quantifying the potential benefit of a general focal boost approach on tumour control probability, and also by comparing the dose to organs at risk (OARs) with hypoxia-guided focal dose escalation (DE) plans generated for five patients. Results: Applying an appropriately guided focal boost can greatly mitigate the impact of hypoxia. Statistically significant reductions in rectal and bladder dose were observed for hypoxia-targeting, biologically optimised plans compared to isoeffective focal DE plans. Conclusion: Results of this study suggest the use of mpMRI for voxel-level targeting of hypoxia, along with biological optimisation, can provide a mechanism for guiding focal DE that is considerably more efficient than application of a general, dose-based optimisation, focal boost.

Hybrid Tomo-Helical and Tomo-Direct radiotherapy for localized prostate cancer.

PurposeThe aim of the study is to present a new planning approach to provide better planning target volume (PTV) coverage and reduce bladder and rectum dose with hybrid Tomo‐Helical (TH)/Tomo‐Direct (TD) radiotherapy (RT) for localized prostate cancer (LPC).MethodsTwenty‐five LPC patients were included in this retrospective study. TH plans, TD plans, and hybrid TH/TD plans were created. Lateral beams were used for the hybrid TD plan and the prescribed dose was 70 Gy in 28 fractions (hybrid plans were combined 45 Gy/ 18 fxs for TH and 25 Gy/10 fxs for TD). Doses of PTV (D2%, D98%, D50%, homogeneity index (HI), conformity index (CI), coverage) and organs at risk (OARs) (V50%, V35%, V25%, V5%, and V95%) were analyzed. The Wilcoxon signed‐rank test was used to analyze the difference in dosimetric parameters. p‐Value < 0.05 was considered statistically significant.ResultsTH plans showed better CI, and target coverage (p < 0.01) than TD and hybrid plans in all patient plan evaluations. However, TD plans D2%, D98%, and D50% doses were better than TH and hybrid plans. The HI values were similar between the three plans. Significant reductions in bladder and rectum V50%, V35%, and V25% doses (p < 0.001) were observed with hybrid plans compared to TH and TD. Penile bulb V95% and bowel V5% doses were better in the hybrid plans. Left and right femoral head V5% doses were higher in the hybrid plan compared to others (p < 0.001).ConclusionConcurrently hybrid TH/TD RT plan can be a good option to reduce the doses of the rectum and bladder in the RT of LPC.

Dosimetric Impact of Bladder Volumetric Changes During Helical Radiotherapy for Rectal Cancer

Purpose: This study aims to investigate the dosimetric impact of bladder volumetric changes during helical radiotherapy (RT) for rectal cancer (RC).Methods: A total of 42 RC patients' helical RT treatment plans were analyzed. The bladder volumes were divided into 3 groups (Group1: V 200ml). Planning target volume(PTV), PTVboost, bladder, bowel, right, and left femoral head dose values were analyzed and compared between groups. Statistical analysis was done with a one-way ANOVA test in SPSS18.0 program. A value of p <0.05 was considered statistically significant.Results: The median age of the patients was 59 (range:22-87) and bladder volume ranged from 41.44ml-620.82ml. In the dosimetric data comparison of the patient groups with different bladder volumes, the D50 dose values of PTV and PTV boost volume was highest in Group 3 (p=0.039). No statistical significance was found between PTV and PTVboost’ doses of D98 and D2 and groups. The optimum PTV dose value was in Group2. Bowel doses were highest in Group 1. As the bladder volume increased, the Dmax, Dmean, V15%, and V30% values of the bowel doses decreased. There was a statistical significant relationship between bladder Dmax doses and groups (p = 0.024). Femoral heads doses increased in proportion to increasing bladder volume groups and these results were statistical significant for V5% and V30% (p <0.05).Conclusion: In our study, as the bladder volume increased, there was an inversely proportional decrease in the bowel doses and a directly proportional increase in the femoral head and bladder doses. Bladder volume values significantly affected values of the target and critical organs dose during helical RT for RC.

Quantifying the impact of SpaceOAR hydrogel on inter-fractional rectal and bladder dose during 0.35T MR-guided prostate adaptive radiotherapy.

PurposeTo investigate the impact of rectal spacing on inter‐fractional rectal and bladder dose and the need for adaptive planning in prostate cancer patients undergoing SBRT with a 0.35 T MRI‐Linac.Materials and MethodsWe evaluated and compared SBRT plans from prostate cancer patients with and without rectal spacer who underwent treatment on a 0.35 T MRI‐Linac. Each group consisted of 10 randomly selected patients that received prostate SBRT to a total dose of 36.25 Gy in five fractions. Dosimetric differences in planned and delivered rectal and bladder dose and the number of fractions violating OAR constraints were quantified. We also assessed whether adaptive planning was needed to meet constraints for each fraction.ResultsOn average, rectal spacing reduced the maximum dose delivered to the rectum by more than 8 Gy (p < 0.001). We also found that D3cc received by the rectum could be 12 Gy higher in patients who did not have rectal spacer (p < 9E‐7). In addition, the results show that a rectal spacer can reduce the maximum dose and D15cc to the bladder wall by more than 1 (p < 0.004) and 8 (p < 0.009) Gy, respectively. Our study also shows that using a rectal spacer could reduce the necessity for adaptive planning. The incidence of dose constraint violation was observed in almost 91% of the fractions in patients without the rectal spacer and 52% in patients with implanted spacer.ConclusionInter‐fractional changes in rectal and bladder dose were quantified in patients who underwent SBRT with/without rectal SpaceOAR hydrogel. Rectal spacer does not eliminate the need for adaptive planning but reduces its necessity.

Equivalent Dose and Risk of Exposure Induced Cancer Death of Different Organs due to Various Image Techniques of EOS Imaging System.

Background: Euronext Paris Advanced Orthopedic Solutions (EOS) system is a new radiography system, capable of obtaining two-dimensional and three-dimensional images from bony structures in the body. Objective: The aim of this study is to estimate equivalent dose and the risk of exposure induced cancer death (REID) in different organs of body due to EOS imaging system.Material and Methods: In this experimental study, totally 120 patients were evaluated for various imaging techniques of lower limb, full spine and whole body. Equivalent dose and REID for colon, liver, lung, stomach, breast, bladder, ovary, blood cells (leukemia) and other organs were calculated using PCXMC software (version 2.0.1.2) based on Monte Carlo simulation of X-ray and human phantoms. The data on imaging technique, including age, sex, kVp, dose area product (DAP), mA, focal to detector distance were introduced as the input of PCXMC.Results: The maximum equivalent dose (mSv) due to EOS imaging system, was estimated for the bladder 0.240±0.066 for the full body technique and 0.240±0.093 for the lower limb technique, respectively, in both males and females. The maximum organ REID (incidence per million) due to EOS imaging system was estimated for lungs as 2.59±1.0 and 2.53±0.9, for the full body technique in both males and females, respectively. Conclusion: Generally, the equivalent dose and REID by EOS imaging system in different organs of body is low due to the low radiation dose received by the body in different techniques and views.

Magnetic Resonance–Guided Reirradiation for Local Recurrence Within the Prostate or in the Prostate Bed: Preliminary Results of a Prospective Registry Study

PurposeThis prospective registry study evaluated the feasibility of stereotactic magnetic resonance imaging (MRI)–guided radiation therapy for the local treatment of isolated prostate cancer recurrence within the gland or prostate bed after primary radiation therapy. Methods and MaterialsPatients with isolated recurrence without any regional or distant extension after treatment by external radiation therapy of the prostate gland/bed or by prostate brachytherapy were included. A 173-second Fast Imaging with Steady state Precession (TrueFISP) sequence was used for MRI simulation, and the gross tumor volume was delineated using multimodal images. The initial treatment plan varied from 27.5 Gy in 5 fractions to 38.7 Gy in 9 fractions and was adapted at each session, if necessary. The primary endpoint was acute toxicities (according to the Common Terminology Criteria for Adverse Events v5.0 criteria). Secondary endpoints were the effects of the adaptive treatment on target volume coverage, late toxicities, and oncologic events. ResultsTwenty patients were included. After a minimum follow-up of 6 months, grade 2 dysuria (from grade 1 at baseline; n = 1), grade 2 polyuria (n = 1), grade 1 urinary incontinence (n = 1), grade 1 urinary pain (n = 2), and grade 1 diarrhea (n = 1) were reported.All initial treatment plans met the tumor coverage objectives, with a mean 95% planning target volume value of 95.7%. No plan exceeded the bladder and rectum dose constraints, but 8 exceeded the urethra dose constraints because of urethra proximity to the planning target volume. The initial plan was adapted in 7 patients (35%). The tumor coverage improved by 3.7% compared with the predicted plan (P = .0001) without increase in the dose to organs at risk. The biochemical control rate for the whole cohort was 75% (15/20 patients) including the 4 patients who received androgen-deprivation therapy. ConclusionsMRI-guided reirradiation for isolated recurrence within the prostate or in the prostate bed appears to be safe with excellent dosimetric results.

Organs dosimetry in targeted radionuclide therapy

The objective of this study is to assess the patients' effective and organ dose during theranostic applications in Kuwait. In total, eighteen adults' patients were conducted nuclear medicine procedures with 177Lu Dotatate for theranostic purpose in Kuwait Cancer control center (KCCC), Kuwait. Medium energy collimator (MEC) (208 keV Scatter 26% better than 113 keV Scatter 60%) was utilized to obtain scans in definite time intervals ranged from one to 2 h (before voiding), 6:00, 24:00, 48:00, 72:00 h. Patients, tissue and organ radiation doses were computed utilizing OLINDA/EXM Software. The average radiation effective dose (in mSv/MBq) for bladder, liver, and both kidneys (left & right), were 0.36, 0.08, 0.61 & 0.60. The range of the effective dose was from 0.55 mSv to 7.7 mSv. The acquired scans using 177Lu were delivered diagnostic findings. The patients’ effective dose is lower compared to the previous studies. Variation is attributed to the departmental protocol and administered activity. The values of the mean organ dose were comparable and lower than previously published studies. Different organs have different level of doses, which may affected by the presence of the metastatic tumors in the entire organ.

Tree-based exploration of the optimization objectives for automatic cervical cancer IMRT treatment planning.

To develop and evaluate a practical automatic treatment planning method for intensity-modulated radiation therapy (IMRT) in cervical cancer cases. A novel algorithm named as Optimization Objectives Tree Search Algorithm (OOTSA) was proposed to emulate the planning optimization process and achieve a progressively improving IMRT plan, based on the Eclipse Scripting Application Programming Interface (ESAPI). 30 previously treated cervical cancer cases were selected from the clinical database and comparison was made between the OOTSA-generated plans and clinical treated plans and RapidPlan-based (RP) plans. In clinical evaluation, compared with plan scores of the clinical plans and the RP plans, 22 and 26 of the OOTSA plans were considered as clinically improved in terms of plan quality, respectively. The average conformity index (CI) for the PTV in the OOTSA plans was 0.86 ± 0.01 (mean ± 1 standard deviation), better than those in the RP plans (0.83 ± 0.02) and the clinical plans (0.71 ± 0.11). Compared with the clinical plans, the mean doses of femoral head, rectum, spinal cord and right kidney in the OOTSA plans were reduced by 2.34 ± 2.87 Gy, 1.67 ± 2.10 Gy, 4.12 ± 6.44 Gy and 1.15 ± 2.67 Gy. Compared with the RP plans, the mean doses of femoral head, spinal cord, right kidney and small intestine in the OOTSA plans were reduced by 3.31 ± 1.55 Gy, 4.25 ± 3.69 Gy, 1.54 ± 2.23 Gy and 3.33 ± 1.91 Gy, respectively. In the OOTSA plans, the mean dose of bladder was slightly increased, with 2.33 ± 2.55 Gy (versus clinical plans) and 1.37 ± 1.74 Gy (vs RP plans). The average elapsed time of OOTSA and clinical planning were 59.2 ± 3.47 min and 76.53 ± 5.19 min. The plans created by OOTSA have been shown marginally better than the manual plans, especially in preserving OARs. In addition, the time of automatic treatment planning has shown a reduction compared to a manual planning process, and the variation of plan quality was greatly reduced. Although improvement on the algorithm is warranted, this proof-of-concept study has demonstrated that the proposed approach can be a practical solution for automatic planning. The proposed method is novel in the emulation strategy of the physicists' iterative operation during the planning process. Based on the existing optimizers, this method can be a simple yet effective solution for automated IMRT treatment planning.

Development and characterization of two novel 68 Ga-labelled neuropeptide Y short analogues with potential application in breast cancer imaging.

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε-amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8±0.4) for 68 Ga-L1 and (4.7±0.4) for 68 Ga-L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging.

Radiomics Analysis of 3D Dose Distributions to Predict Toxicity of Radiotherapy for Cervical Cancer.

Standard treatment for locally advanced cervical cancer (LACC) is chemoradiotherapy followed by brachytherapy. Despite radiation therapy advances, the toxicity rate remains significant. In this study, we compared the prediction of toxicity events after radiotherapy for locally advanced cervical cancer (LACC), based on either dose-volume histogram (DVH) parameters or the use of a radiomics approach applied to dose maps at the voxel level. Toxicity scores using the Common Terminology Criteria for Adverse Events (CTCAE v4), spatial dose distributions, and usual clinical predictors for the toxicity of 102 patients treated with chemoradiotherapy followed by brachytherapy for LACC were used in this study. In addition to usual DVH parameters, 91 radiomic features were extracted from rectum, bladder and vaginal 3D dose distributions, after discretization into a fixed bin width of 1 Gy. They were evaluated for predictive modelling of rectal, genitourinary (GU) and vaginal toxicities (grade ≥ 2). Logistic Normal Tissue Complication Probability (NTCP) models were derived using clinical parameters only or combinations of clinical, DVH and radiomics. For rectal acute/late toxicities, the area under the curve (AUC) using clinical parameters was 0.53/0.65, which increased to 0.66/0.63, and 0.76/0.87, with the addition of DVH or radiomics parameters, respectively. For GU acute/late toxicities, the AUC increased from 0.55/0.56 (clinical only) to 0.84/0.90 (+DVH) and 0.83/0.96 (clinical + DVH + radiomics). For vaginal acute/late toxicities, the AUC increased from 0.51/0.57 (clinical only) to 0.58/0.72 (+DVH) and 0.82/0.89 (clinical + DVH + radiomics). The predictive performance of NTCP models based on radiomics features was higher than the commonly used clinical and DVH parameters. Dosimetric radiomics analysis is a promising tool for NTCP modelling in radiotherapy.

Dosimetric impact of rectum and bladder anatomy and intrafractional prostate motion on hypofractionated prostate radiation therapy.

The objective of this study was to evaluate the dosimetric impact on hypofractionated prostate radiation therapy of two geometric uncertainty sources: rectum and bladder filling and intrafractional prostate motion. This prospective study included 544 images (375 pre-treatment cone-beam CT [CBCT] and 169 post-treatment CBCT) from 15 prostate adenocarcinoma patients. We recalculated the dose on each pre-treatment CBCT once the positioning errors were corrected. We also recalculated two dose distributions on each post-treatment CBCT, either using or not intrafractional motion correction. A correlation analysis was performed between CBCT-based dose and rectum and bladder filling as well as intrafraction prostate displacements. No significant differences were found between administered and planned rectal doses. However, we observed an increase in bladder dose due to a lower bladder filling in 66% of treatment fractions. These differences were reduced at the end of the fraction since the lower bladder volume was compensated by the filling during the treatment session. A statistically significant reduction in target volume coverage was observed in 27% of treatment sessions and was correlated with intrafractional prostate motion in sagittal plane > 4mm. A better control of bladder filling is recommended to minimize the number of fractions in which the bladder volume is lower than planned. Fiducial mark tracking with a displacement threshold of 5mm in any direction is recommended to ensure that the prescribed dose criteria are met.

Dosimetric impact of dwell time deviation constraint on inverse brachytherapy treatment planning and comparison with conventional optimization method for interstitial brachytherapy implants.

High-dose rate remote afterloading brachytherapy machine and advanced treatment planning system help in getting optimum dose to tumor and low dose to normal structures. Inverse planning simulated annealing (IPSA) optimization technique has a unique feature of dwell time deviation constraint (DTDC). In this study, six IPSA-based plans having different DTDC values with routinely practiced geometric plus graphical optimization (GO + GrO) have been compared using various dosimetric parameters. For this retrospective study, we have generated IPSA-optimized interstitial brachytherapy plans for ten cancer cervix patients. Routinely practiced GO + GrO-based plans were compared with six different IPSA plans having varying DTDC values from 0.0 to 1.0 using different dosimetric indices. Conformity index and homogeneity index (HI) were higher in GO + GrO plans, compared to IPSA-optimized plans. However, HI of IPSA plans was increasing with increasing DTDC values. High-dose volumes were well controllable using DTDC parameter in IPSA-optimized plans. Dose to the rectum and bladder was smaller for IPSA-optimized plans than GO + GrO plans. One of the benefits of applying DTDC in IPSA-optimized plan is that it reduces high-dose volumes. Another advantage is the reduction in rectum and bladder dose.

Assessment of an ultrasound bladder scanner in prostate radiotherapy: A validation study and analysis of bladder filling variability.

During prostate radiotherapy treatment, it is important to ensure the position of the bladder and prostate is consistent between treatments. The aim of this study was to provide a quantitative basis for incorporating ultrasound bladder volume estimates into local practice for prostate radiotherapy. Agreement between bladder volume estimates obtained using computed tomography (CT) and ultrasound was assessed. Analysis of bladder volumes between planning and treatment scans was used to quantify expected variations in bladder volume over the course of radiotherapy. Dose-volume statistics were estimated and compared to planned dose constraints to propose a target bladder volume and tolerance. Bladder volume measurements were obtained from 19 radiotherapy patients using ultrasound and CT. Ultrasound underestimated bladder volume compared to CT with a mean bias of -28 ± 30 ml. Pre-treatment (planning) bladder volumes varied from 71 to 383 ml with a mean of 200 ml. Treatment bladder volumes reduced by more than half in 9% of patients during the course of their treatment, potentially leading to a 30% increase in mean bladder dose. Patients with pre-treatment bladder volumes < 200 ml were most likely to exhibit differences in bladder volume, resulting in 'out of tolerance' increases in dose. A pragmatic individualised drinking protocol, aimed at achieving a minimum ultrasound bladder volume of 200 ml at planning CT, may be beneficial to reproducibility in radiotherapy treatment. Ultrasound measurements prior to treatment should ideally confirm that bladder volume is at least half the volume measured at planning.

Impact of CT-based planning and bladder volume changes on the dosimetry of vaginal vault brachytherapy

AbstractAim:To compare dose to target and organs at risk (OARs) in conventional plan (2D) versus computed tomography (CT)-based three-dimensional (3D) plan in vaginal cuff brachytherapy (VBT) and to compare the effect of bladder distension on target and OARs dosimetry.Materials and methods:Post-hysterectomy patients with an indication for VBT were included in the study. All patients underwent planning CT scans with a full bladder and an empty bladder protocol. For each CT, two plans were generated—one library-based 2D plan and another CT-based 3D plan. Dosimetric parameters were recorded for clinical target volume (CTV) and OARs.Results:A total of 92 observations were made from data collected from 46 patients. Difference between CTV dose in terms of 2D and 3D plans were not statistically significant for CTV (p = 0·11). Significant reduction in D0·1cc, D1cc and D2cc dose parameters were observed in bladder, rectum, sigmoid and bowel doses with the 3D plan (p &lt; 0·001). Bladder distension showed a 20% reduction in dose for bowel (p &lt; 0·001). Bladder distension also showed a 6·12% (p = 0·047) increase in D2cc, but there was a significant reduction in the mean dose to the bladder.Conclusion:Our study demonstrates the dosimetric benefits with 3D CT-based planning for VBT over 2D-based conventional planning and benefit of bladder distension in the reduction of bowel dose without compromising dose to the target volume.

Standard versus hypofractionated intensity-modulated radiotherapy for prostate cancer: assessing the impact on dose modulation and normal tissue effects when using patient-specific cancer biology

Hypofractionation of prostate cancer radiotherapy achieves tumour control at lower total radiation doses, however, increased rectal and bladder toxicities have been observed. To realise the radiobiological advantage of hypofractionation whilst minimising harm, the potential reduction in dose to organs at risk was investigated for biofocused radiotherapy. Patient-specific tumour location and cell density information were derived from multiparametric imaging. Uniform-dose plans and biologically-optimised plans were generated for a standard schedule (78 Gy/39 fractions) and hypofractionated schedules (60 Gy/20 fractions and 36.25 Gy/5 fractions). Results showed that biologically-optimised plans yielded statistically lower doses to the rectum and bladder compared to isoeffective uniform-dose plans for all fractionation schedules. A reduction in the number of fractions increased the target dose modulation required to achieve equal tumour control. On average, biologically-optimised, moderately-hypofractionated plans demonstrated 15.3% (p-value: <0.01) and 23.8% (p-value: 0.02) reduction in rectal and bladder dose compared with standard fractionation. The tissue-sparing effect was more pronounced in extreme hypofractionation with mean reduction in rectal and bladder dose of 43.3% (p-value: < 0.01) and 41.8% (p-value: 0.02), respectively. This study suggests that the ability to utilise patient-specific tumour biology information will provide greater incentive to employ hypofractionation in the treatment of localised prostate cancer with radiotherapy. However, to exploit the radiobiological advantages given by hypofractionation, greater attention to geometric accuracy is required due to increased sensitivity to treatment uncertainties.

Dose accumulation for personalized stereotactic MR-guided adaptive radiation therapy in prostate cancer

Background and purposeAdaptive MR-guided radiotherapy (MRgRT) is an innovative approach for delivering stereotactic body radiotherapy (SBRT) in prostate cancer (PC). Despite the increased clinical use of SBRT for PC, there is limited data on the relation between the actual delivered dose and toxicity. We aimed to identify dose parameters based on the total accumulated delivered bladder dose (DOSEACCTX). Furthermore, for future personalization, we studied whether prospective accumulation of the first 3 of 5 fractions (DOSEACC3FR) could be used as a representative of DOSEACCTX. Materials and methodsWe deployed a recently validated deformable image registration-based dose accumulation strategy to reconstruct DOSEACCTX and DOSEACC3FR in 101 PC patients treated with stereotactic MRgRT. IPSS scores at baseline, end of MRgRT, at 6 and 12 weeks after treatment were analyzed to identify a clinically relevant increase of acute urinary symptoms. A receiver operator characteristic curve analysis was used to investigate the correlation of an increase in IPSS and bladder DOSEACCTX (range V5–V36.25 Gy, D1cc, D5cc) and DOSEACC3FR (range V6–V21.8 Gy, D1cc, D5cc) parameters. ResultsA clinically relevant increase in IPSS in the three months following MRgRT was observed in 25 patients. The V20Gy-32Gy from DOSEACCTX and V15Gy-18Gy from DOSEACC3FR showed good correlation with IPSS increase with area under the curve (AUC) values ranging from 0.71 to 0.75. In contrast, baseline dosimetry showed a poor correlation with AUC values between 0.53 and 0.62. ConclusionDOSEACCTX was superior to baseline dosimetry in predicting acute urinary symptoms. Because DOSEACC3FR also showed good correlation, this can potentially be used to optimize MRgRT for the remaining fractions.