Longer time to testosterone recovery impacts favorably on outcomes for prostate cancer following androgen deprivation and radiotherapy.

PURPOSE: To evaluate the impact of sustained hypogonadism after androgen deprivation therapy (ADT) associated with radiotherapy in prostate cancer (PCa) patients with biochemical relapse-free survival (bRFS). METHODS: A retrospective cohort analysis of 213 consecutive PCa patients referred for radiotherapy plus ADT was carried out. Follow-up times including time to testosterone recovery (TTR) and bRFS were calculated from the end of ADT. Univariate and multivariate Cox regression analyses predicting bRFS were used. The optimal cutoffs for TTR and duration of ADT were determined using the maximally selected rank statistics (MSRS). RESULTS: After a median follow-up of 104 months, 18 patients relapsed among those who had recovered testosterone levels and 9 among those who did not. Median ADT duration was 36 months. The optimal cutoff for TTR was determined using MSRS. TTR >48 months was significantly associated with better bRFS (logrank, p < 0.0027). Five-year bRFS was 100% for >48 months vs. 85% for <48 months. TTR was the only significant variable for bRFS in multivariate Cox analysis. CONCLUSION: Our data show an association between longer TTR and bRFS values among PCa patients treated with ADT.

Pilot Study for the Assessment of the Best Radiomic Features for Bosniak Cyst Classification Using Phantom and Radiologist Inter-Observer Selection.

Since the Bosniak cysts classification is highly reader-dependent, automated tools based on radiomics could help in the diagnosis of the lesion. This study is an initial step in the search for radiomic features that may be good classifiers of benign-malignant Bosniak cysts in machine learning models. A CCR phantom was used through five CT scanners. Registration was performed with ARIA software, while Quibim Precision was used for feature extraction. R software was used for the statistical analysis. Robust radiomic features based on repeatability and reproducibility criteria were chosen. Excellent correlation criteria between different radiologists during lesion segmentation were imposed. With the selected features, their classification ability in benignity-malignity terms was assessed. From the phantom study, 25.3% of the features were robust. For the study of inter-observer correlation (ICC) in the segmentation of cystic masses, 82 subjects were prospectively selected, finding 48.4% of the features as excellent regarding concordance. Comparing both datasets, 12 features were established as repeatable, reproducible, and useful for the classification of Bosniak cysts and could serve as initial candidates for the elaboration of a classification model. With those features, the Linear Discriminant Analysis model classified the Bosniak cysts in terms of benignity or malignancy with 88.2% accuracy.

Does postoperative irradiation improve survival in early-stage endometrial cancer?

Endometrial cancer is the most common gynecological cancer in developed countries. Postoperative irradiation has been shown to lower locoregional relapses among high-intermediate risk endometrial cancer patients. In addition, vaginal cuff brachytherapy has demonstrated similar control to external beam radiotherapy but with lower toxicity. Although randomized trials have failed to translate that into better overall survival, reports from large databases, such as the National Cancer Database and the Surveillance, Epidemiology, and End Results database, have shown evidence of a statistical relationship between postoperative irradiation and survival in the intermediate- and high-risk groups. This review will address the risk groups that have led the therapeutic decisions and then we will review the clinical results accordingly. Special attention will be paid to the survival results based on the data presented through an analysis of the large databases that suggest a possible survival benefit.

Radiomics of CT Features May Be Nonreproducible and Redundant: Influence of CT Acquisition Parameters.

Purpose To identify the reproducible and nonredundant radiomics features (RFs) for computed tomography (CT). Materials and Methods Two phantoms were used to test RF reproducibility by using test-retest analysis, by changing the CT acquisition parameters (hereafter, intra-CT analysis), and by comparing five different scanners with the same CT parameters (hereafter, inter-CT analysis). Reproducible RFs were selected by using the concordance correlation coefficient (as a measure of the agreement between variables) and the coefficient of variation (defined as the ratio of the standard deviation to the mean). Redundant features were grouped by using hierarchical cluster analysis. Results A total of 177 RFs including intensity, shape, and texture features were evaluated. The test-retest analysis showed that 91% (161 of 177) of the RFs were reproducible according to concordance correlation coefficient. Reproducibility of intra-CT RFs, based on coefficient of variation, ranged from 89.3% (151 of 177) to 43.1% (76 of 177) where the pitch factor and the reconstruction kernel were modified, respectively. Reproducibility of inter-CT RFs, based on coefficient of variation, also showed large material differences, from 85.3% (151 of 177; wood) to only 15.8% (28 of 177; polyurethane). Ten clusters were identified after the hierarchical cluster analysis and one RF per cluster was chosen as representative. Conclusion Many RFs were redundant and nonreproducible. If all the CT parameters are fixed except field of view, tube voltage, and milliamperage, then the information provided by the analyzed RFs can be summarized in only 10 RFs (each representing a cluster) because of redundancy.

The influence of the image registration method on the adaptive radiotherapy. A proof of the principle in a selected case of prostate IMRT.

PURPOSE: To analyse the influence of the image registration method on the adaptive radiotherapy of an IMRT prostate treatment, and to compare the dose accumulation according to 3 different image registration methods with the planned dose. MATERIAL AND METHODS: The IMRT prostate patient was CT imaged 3 times throughout his treatment. The prostate, PTV, rectum and bladder were segmented on each CT. A Rigid, a deformable (DIR) B-spline and a DIR with landmarks registration algorithms were employed. The difference between the accumulated doses and planned doses were evaluated by the gamma index. The Dice coefficient and Hausdorff distance was used to evaluate the overlap between volumes, to quantify the quality of the registration. RESULTS: When comparing adaptive vs no adaptive RT, the gamma index calculation showed large differences depending on the image registration method (as much as 87.6% in the case of DIR B-spline). The quality of the registration was evaluated using an index such as the Dice coefficient. This showed that the best result was obtained with DIR with landmarks compared with the rest and it was always above 0.77, reported as a recommended minimum value for prostate studies in a multi-centre review. CONCLUSIONS: Apart from showing the importance of the application of an adaptive RT protocol in a particular treatment, this work shows that the election of the registration method is decisive in the result of the adaptive radiotherapy and dose accumulation.

Influence of body habitus on dose parameters of nodal levels III to IV irradiation for breast cancer: comparison of 3 techniques.

This study aimed to investigate the effect of body habitus on supraclavicular (SC) dose-volume histogram (DVH) parameters among breast cancer patients according to 3 different techniques. Three SC irradiation plans were generated for 24 postoperative breast cancer patients: (1) direct antero-posterior field only (1fieldP), with dose prescribed to a 3-cm depth; (2) 3-cm depth plan (3cmP) using an antero-posterior field plus a posterior boost with the dose prescription defined to 3 cm; and (3) optimized plan (OptP) similar to 3cmP, with dose prescribed depending on the anatomy. The OptP plans had the least variation in DVH parameters with body habitus; 3cmP plans were the most varied. Conformity index among normal weight patients were 0.73, 0.78, and 0.87 (p = 0.02) and 0.61, 0.6, and 0.82 among overweight-obese patients for 1fieldP, 3cmP, and OptP, respectively (p < 0.001). V95% of the planning target volume among normal weight patients were 72.63%, 78.03%, and 87.18% for 1fieldP, 3cmP, and OptP, respectively (p = 0.02). The corresponding values among overweight-obese patients were 60.5%, 59.62%, and 81.62%, respectively (p = 0.001). Fixed depth dose prescriptions caused greater SC under dose than plans optimized according to patient's anatomy.

Vaginal cuff brachytherapy in endometrial cancer - a technically easy treatment?

Endometrial cancer (EC) is one of the most common gynecological cancers among women in the developed countries. Vaginal cuff is the main location of relapses after a curative surgical procedure and postoperative radiation therapy have proven to diminish it. Nevertheless, these results have not translated into better survival results. The preeminent place of vaginal cuff brachytherapy (VCB) in the postoperative treatment of high- to intermediate-risk EC was given by the PORTEC-2 trial, which demonstrated a similar reduction in relapses with VCB than with external beam radiotherapy (EBRT), but VCB induced less late toxicity. As a result of this trial, the use of VCB has increased in clinical practice at the expense of EBRT. A majority of the clinical reviews of VCB usually address the risk categories and patient selection but pay little attention to technical aspects of the VCB procedure. Our review aimed to address both aspects. First of all, we described the risk groups, which guide patient selection for VCB in clinical practice. Then, we depicted several technical aspects that might influence dose deposition and toxicity. Bladder distension and rectal distension as well as applicator position or patient position are some of those variables that we reviewed.

The usefulness of fleet rectal enemas on high-dose-rate intracavitary cervical cancer brachytherapy. A prospective trial.

PURPOSE: To evaluate the effects of rectal enemas on rectal doses during radical high-dose-rate (HDR) intracavitary cervical brachytherapy (BT). MATERIAL AND METHODS: Twenty patients suffering from cervical cancer and treated with external beam radiotherapy and HDR-BT were included in a prospective trial. The first brachytherapy fraction was considered the basal status, and patients were instructed to self-administer two rectal cleansing enemas before the second fraction. Dose-volume histogram (DVH) values were generated for the rectum and correlated with rectal volume variation. Brachytherapy was carried out with a Fletcher or Utrecht applicator. RESULTS: No significant rectal volume differences were observed between fractions with or without rectal enemas (without, 52.64 ± 15.92 cc; with, 53.16 ± 19.28 cc). There was a significant correlation between both rectal volumes (r = 0.722, p = 0.001). No significant differences were observed in analyzed DVH parameters (median values: ΔD0.1cc, 4.17 vs. 3.61 Gy; ΔD1cc, 3.23 vs. 2.87 Gy; ΔD2cc, 2.9 vs. 2.54 Gy; ΔD5cc, 2.35 vs. 2.05 Gy, for no enema and enema fraction, respectively). No significant rectal volume differences nor DVH parameter differences were observed according the applicator type. CONCLUSIONS: Our rectal enemas protocol prior to HDR-BT was ineffective in significantly modifying rectal DVH parameters. No differences were observed according to the type of applicator used.

Analysing the integration of MR images acquired in a non-radiotherapy treatment position into the radiotherapy workflow using deformable and rigid registration.

AIM: Our aim was to analyse the feasibility of integrating an MRI acquired in a non-radiotherapy set-up into the prostate cancer radiotherapy workflow. MATERIAL AND METHODS: The MRIs of 15 prostate cancer patients, acquired with a flat table-top (MRI-flat), and with a curved tabletop (MRI-curve) were analysed. MRIs were rigidly (RIR) and non-rigidly registered (DIR) with CT images. The prostate and rectum were contoured in each image set and translated to the CT, and IMRT plans were computed taking into account structural changes after RIR and DIR (P-flatRIR, P-curveRIR and P-curveDIR). In addition the P-curveDIR was overlaid with RIR structures. Spatial overlap parameters and dose-volume histogram metrics were generated. RESULTS: No significant differences were observed among P-flatRIR and P-curveRIR or P-flatRIR and P-curveDIR. Median gamma-values: P-curveRIR, 95.3%; P-curveDIR, 96%, translated-P-curveDIR, 95%. DVH metrics for translated-P-curveDIR were: Dmin, 64.5Gy; Dmean, 70.06Gy; V95%, 100%. No statistically significant differences were found in the dosimetric MRI-flatDIR values. CONCLUSIONS: The dosimetric reproduction of treatment position image following image registration of non-radiotherapy set-up images suggests that it is feasible to integrate these images into the radiotherapy workflow.

Effect of rectal enemas on rectal dosimetric parameters during high-dose-rate vaginal cuff brachytherapy: A prospective trial.

PURPOSE: To evaluate the effects of rectal enemas on rectal doses during postoperative high-dose-rate (HDR) vaginal cuff brachytherapy (VCB). PATIENTS AND METHODS: This prospective trial included 59 patients. Two rectal cleansing enemas were self-administered before the second fraction, and fraction 1 was considered the basal status. Dose-volume histogram (DVH) values were generated for the rectum and correlated with rectal volume variation. Statistical analyses used paired and unpaired t-tests. RESULTS: Despite a significant 15 % reduction in mean rectal volume (44.07 vs. 52.15 cc, p = 0.0018), 35.6 % of patients had larger rectums after rectal enemas. No significant rectal enema-related DVH differences were observed compared to the basal data. Although not statistically significant, rectal cleansing-associated increases in mean rectal DVH values were observed: D0.1 cc: 6.6 vs. 7.21 Gy; D1 cc: 5.35 vs. 5.52 Gy; D2 cc: 4.67 vs. 4.72 Gy, before and after rectal cleaning, respectively (where Dx cc is the dose to the most exposed x cm(3)). No differences were observed in DVH parameters according to rectal volume increase or decrease after the enema. Patients whose rectal volume increased also had significantly larger DVH parameters, except for D5 %, D25 %, and D50 %. In contrast, in patients whose rectal volume decreased, significance was only seen for D25 % and D50 % (Dx % dose covering x % of the volume). In the latter patients, nonsignificant reductions in D2 cc, D5 cc and V5 Gy (volume receiving at least 5 Gy) were observed. CONCLUSION: The current rectal enemas protocol was ineffective in significantly modifying rectal DVH parameters for HDR-VCB.

Rectal contrast increases rectal dose during vaginal cuff brachytherapy.

PURPOSE: To evaluate the impact of rectal dose on rectal contrast use during vaginal cuff brachytherapy (VCB). METHODS AND MATERIALS: A retrospective review of gynecology patients who received some brachytherapy fractions with and without rectal contrast was carried out. Rectal contrast was instilled at the clinician's discretion to increase rectal visibility. Thirty-six pairs of CT scans in preparation for brachytherapy were analyzed. Pairs of CTs were segmented and planned using the same parameters. The rectum was always defined from 1 cm above the cylinder tip up to 1.5 cm below the last activated dwell source position. An individual plan was computed at every VCB fraction. A set of values (Dmax, D(0.1cc), D(1cc), and D(2cc)) derived from dose-volume histograms were extracted and compared according to the rectal status. RESULTS: Rectal volume was 26.7% larger in the fractions with rectal contrast. Such an increase in volume represented a significant increase from 7.7% to 10.4% in all parameters analyzed except Dmax dose-volume histogram. CONCLUSIONS: Avoiding rectal contrast is a simple way of decreasing the rectal dose parameters of VCB, which would mean a better therapeutic ratio. Results also suggest that action directed at maintaining the rectum empty might have the same effect.

Dosimetric analysis of rectal filling on rectal doses during vaginal cuff brachytherapy.

PURPOSE: Several studies have analyzed the effect of bladder filling during vaginal cuff brachytherapy (VCB), but the effect of rectum filling has not been studied. We sought to evaluate the effects of rectal volume on rectal doses during postoperative VCB. METHODS AND MATERIALS: Brachytherapy planning CT scans (334 sets) obtained from 92 consecutive patients treated with VCB were resegmented (bladder and rectum) and replanned retrospectively using the same parameters to homogenize data and improve analysis. Rectal volume and a set of values derived from dose-volume histograms (DVHs) were extracted (maximal dose [Dmax], D0.1cc, D1cc, and D2cc). Univariate and multivariate analyses were carried out to evaluate the association between rectal volume and DVH metrics after adjusting for other clinical factors. RESULTS: A positive significant correlation was observed between rectal volume correlated and Dmax, D0.1cc, D1cc, and D2cc. Multiple linear regression models found that rectal volume, cylinder angle position, and cylinder diameter variables correlated significantly with the different DVH parameters analyzed. These variables explained the 14.5% and 18% of variance on regression models. CONCLUSIONS: Larger rectal volumes are associated with higher rectal dose parameters during VCB fractions. Prospective studies are needed to investigate whether these data are linked to differences in rectal toxicity.

Body Mass Index and Doses at Organs at Risk in a Mediterranean Population Treated with Postoperative Vaginal Cuff Brachytherapy.

PURPOSE: Association between body mass index (BMI) and doses in organs at risk during postoperative vaginal cuff brachytherapy (VCB) treatment has not been evaluated. The aim of this study was to analyse the impact of BMI on the dose delivered to bladder and rectum during high-dose-rate VCB using computed tomography (CT) scans at every fraction. MATERIALS AND METHODS: A retrospective analysis of 220 planning CT sets derived from 59 patients was conducted. Every planning CT was re-segmented and re-planned under the same parameters. Rectum and bladder dose-volume histogram values (D0.1cc, D1cc, and D2cc) were extracted and evaluated. The mean values for all applications per patient were calculated and correlated with BMI, as well as other factors influencing rectal and bladder doses. Multiple regression analysis performed to model organ at risk dose-volume parameters. RESULTS: According to World Health Organization (WHO), 6.8% of patients were normal, 35.6% were overweight, and 57.6% were class I obese. Median rectal doses were 133.5%, 110.9%, and 99.3% for D0.1cc, D1cc, and D2cc, respectively. The corresponding median bladder doses were 96.2%, 80.6%, and 73.3%, respectively. BMI did not show significant association with rectal doses. However, BMI did show a significant association with evaluated bladder dose metrics (D0.1cc, r=-0.366, p=0.004; D1cc, r=-0.454, p < 0.001; D2cc, r=-0.451, p < 0.001). BMI was retained in the multivariate regression models (D0.1cc, p=0.004; D1cc, p < 0.001; D2cc, p=0.001). CONCLUSION: In this group of Mediterranean, overweight, and moderately obese patients, BMI showed association with lower bladder dose values, but not with rectal doses.

How air influences radiation dose deposition in multiwell culture plates: a Monte Carlo simulation of radiation geometry.

Radiation of experimental culture cells on plates with various wells can cause a risk of underdosage as a result of the existence of multiple air-water interfaces. The objective of our study was to quantify this error in culture plates with multiple wells. Radiation conditions were simulated with the GAMOS code, based on the GEANT4 code, and this was compared with a simulation performed with PENELOPE and measured data. We observed a slight underdosage of ∼ 4% on the most superficial half of the culture medium. We believe that this underdosage does not have a significant effect on the dose received by culture cells deposited in a monolayer and adhered to the base of the wells.

Do breast cups improve breast cancer dosimetry? A comparative study for patients with large or pendulous breasts.

PURPOSE: Treating patients with large or pendulous breasts is challenging. Although brassiere cups are currently in use, no study has yet been carried out to assess their dosimetric impact. The aim of the present study was to evaluate the possible dosimetric advantages of the use of breast cups on patients with large or pendulous breasts. MATERIALS AND METHODS: Two CT studies were carried out on 12 breast cancer patients with large or pendulous breasts, with one study involving the use of breast cups. Radiation plans were developed in accordance with each of the CT studies. The following were compared: planning target volume (PTV), volume irradiated by the 95% isodose, conformity index, homogeneity index, mean lung dose, and mean heart dose was also compared for left breast treatment. The plan involving the use of cups was found to be the best option, leading to all patients being treated with cups. The resulting acute toxicity and cosmesis were also recorded. Both scenarios involved the use of film dosimetry to evaluate the skin doses. RESULTS: The use of breast cups resulted in a significant reduction of the PTV volume (from 1640 cm3 to 1283 cm3), of the irradiated volume (from 2154 cm3 to 1477 cm3) and of the conformity index (from 1383 to 1213). Despite slight improvements in the homogeneity index (from 0.12 to 0.10), statistical significance was not attained. The use of breast cups also led to significant dose reductions in V20 for lung (from 13.7% to 1.7%) and V5 for heart (from 9.8% to 2.7%). No differences in acute toxicity or cosmesis were observed compared to patients treated without cups. CONCLUSIONS: Our results show that the use of brassiere cups during breast radiation therapy leads to improvements in the main dosimetric factors analyzed. Furthermore, modifications to standard irradiation protocols are not required. In summary, we consider the technique of using breast cups with radiation therapy highly appropriate when treating breast cancer patients with large or pendulous breasts.

Dose accumulation during vaginal cuff brachytherapy based on rigid/deformable registration vs. single plan addition.

PURPOSE: To compare dose summation using a single plan (SP) approach for vaginal cuff brachytherapy (VBT) against dose summation after a rigid or deformable registration for each VBT fraction, in women with early stage endometrial cancer receiving postoperative VBT. METHODS AND MATERIALS: A retrospective analysis of 19 patients who received VBT as the sole adjuvant treatment was undertaken. For the purposes of the study, every VBT fraction was re-segmented and re-planned under the same conditions. CT-planning images were registered, initially following a rigid method and then using deformable registration. The transformation vectors were reused to warp the dose files, followed by the dose summation. Three dose accumulation scenarios were studied: (1) an SP approach, (2) a rigid dose warping summation (RDWS), (3) a deformable dose warping summation (DDWS). Each scenario was analyzed for 3 and 5 fractions to evaluate the effect of fractionation. D0.1cc, D1cc, D2cc, D5cc, D5%, and Dmean values were compared for organs at risk, such as the rectum and bladder. RESULTS: No statistical significances were observed in rectal parameters between SP and RDWS or between SP and DDWS. Significant SP, RDWS and DDWS Dmean, D0.1cc, and D2cc metric differences for the 5 fractions bladder scenario were observed (p = 0.0242, 0.0196, and 0.0242, respectively). CONCLUSIONS: A multi-image planning procedure for a VBT course leads to limited differences between different summation methods. SP is an effective and acceptable surrogate for absorbed doses in organs at risk.