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Purpose: Stereotactic body radiotherapy (SBRT) boost is a promising treatment for cervical cancer patients who are ineligible for intracavitary brachytherapy (ICBT). The aim of this multicenter, single-arm, phase I/II study was to prospectively evaluate the efficacy and toxicity of SBRT boost., Materials and Methods: ICBT-ineligible patients with untreated cervical cancer were enrolled. Patients underwent whole-pelvic radiotherapy (45 Gy in 25 fractions) with SBRT boost to the primary lesion. In the phase I dose-escalation cohort (3 + 3 design), patients were treated with SBRT boost of 21 or 22.5 Gy in three fractions. Although dose-limiting toxicity was not confirmed, a dose of 21 Gy was selected for the phase II cohort because it was difficult to reproduce the pelvic organs position in two patients during the phase I trial. The primary endpoint was 2-year progression-free survival., Results: Twenty-one patients (phase I, n = 3; phase II, n = 18) were enrolled between April 2016 and October 2020; 17 (81%) had clinical stage III-IV (with para-aortic lymph node metastases) disease. The median (range) follow-up was 40 (10-84) months. The initial response was complete response in 20 patients and partial response in one patient. The 2-year locoregional control, progression-free survival, and overall survival rates were 84%, 67%, and 81%, respectively. Grade ≥ 3 toxicity was confirmed in one patient each in the acute (diarrhea) and late (urinary tract obstruction) phases., Conclusion: These findings suggested that a SBRT boost is more effective than the conventional EBRT boost and can be an important treatment option for ICBT-ineligible patients with cervical cancer., Study Registration: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036845)., (© 2024. The Author(s).)

We quantified intra-fractional dose variation and organ movement during CT-based 3D-image guided brachytherapy (3D-IGBT) in cervical cancer patients. Fifteen patients who underwent CT-based 3D-IGBT were studied. For all patients, pre-delivery CT for treatment planning after applicator insertion and post-delivery CT after dose delivery without changing the applicator position were acquired. Pre- and post-delivery CT were rigidly fused by matching the inserted applicator and planned dose on pre-delivery CT (pre-delivery dose) was mapped on post-delivery CT (post-delivery dose). D2, D1, and D0.1 cm 3 of the rectum and bladder were compared between pre- and post-delivery doses with contours on each CT image. Organ movement and deformation was evaluated using deformation vector fields calculated by deformable image registration between pre- and post-delivery CT. We also evaluated dose variation and DVF between with and without a catheter to control filling. Differences in all DVH parameters were <±3% in physical dose and ± 5% in EQD2. However, a > 15% dose difference was found in 13.8% of the fractions in rectum D2 cm 3 and in 11.1% of those in bladder D2 cm 3 . The mean value of DVF for bladder was larger than that of rectum, especially for the superior-inferior (S-I) direction. Insertion catheters in bladder reduced mean dose and DVF variation compared with that of without catheters. In fraction groups with large dose increasing, DVF in the S-I direction was significantly larger than that of other fraction groups. Our results indicated that preparation is needed to reduce changes in the S-I direction affect dose variation., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: We determined correction factors for absorbed dose energy dependence and intrinsic energy dependence for measurements of absorbed dose to water around an 192 Ir source using a radiophotoluminescent glass dosimeter (RPLD) calibrated with a 4-MV photon beam., Methods: The ratio of the absorbed dose to the water and the average absorbed dose to RPLD for the 192 Ir beam relative to the same ratio in a 4 MV photon beam defines the absorbed dose energy dependence and was determined at distances of 2-10 cm (at intervals of 1 cm) from the 192 Ir source in a water phantom using the egs&#95;chamber user code. The RPLD was calibrated to measure absorbed dose to water, D w , in a 4 MV photon beam using an ionization chamber, which was also used to measure absorbed dose to water, D w , in a water phantom using the 192 Ir source. The detector response radiophotoluminescence (RPL signal per average absorbed dose in the detector) in the 192 Ir beam relative to that in the 4 MV photon beam (the relative intrinsic efficiency) was determined experimentally. Finally, the beam quality correction factor was obtained as the quotient between the absorbed dose energy dependence and the relative intrinsic efficiency and corrects for the difference between the beam quality Q 0 used at calibration and the beam quality Q used in the measurements., Results: The relative dose ratio of the average absorbed dose to water relative to RPLD ranged from 0.930 to 0.746, and the beam quality correction factor ranged from 0.999 to 0.794 for distances of 2-10 cm from the 192 Ir source. The relative detector response to an 192 Ir source and a 4-MV photon beam was 0.930, and it did not vary significantly with distance., Conclusions: These results demonstrate that corrections for absorbed dose energy dependence and intrinsic energy dependence are required when using an RPLD to measure with sources different from the reference source providing the primary calibration., (© 2018 American Association of Physicists in Medicine.)

Objective: We investigated whether the pretreatment albumin to globulin ratio, serum albumin level, and serum globulin level can be used to predict survival among cervical cancer patients treated with radiation based therapy and assessed globulin fractions., Methods: We retrospectively enrolled 128 patients with cervical cancer treated with radiation based therapy at our institution between 2010 and 2015. The associations of the pretreatment albumin to globulin ratio, and serum albumin and globulin levels with overall survival were assessed. Additionally, the associations of the globulin fractions with the serum globulin levels and overall survival were evaluated., Results: Median follow-up duration was 30 months (IQR 16-44 months). A low albumin to globulin ratio (< 1.53) was found to be an independent prognostic factor for overall survival (HR= 3.07; 95% CI, 1.03 to 13.3; P=0.044). On evaluating serum globulin and albumin separately, a high serum globulin level was significantly associated with overall survival (cut-off value 2.9 g/dL; HR=3.74; 95% CI 1.08 to 23.6; P=0.036) whereas a low serum albumin level was not associated with overall survival (cut-off value 3.6 g/dL; HR=1.77; 95% CI 0.57 to 4.54; P=0.29). Electrophoresis data of the serum proteins revealed that the γ-globulin fraction was most strongly correlated with the globulin levels (P<0.001). Furthermore, a high γ-globulin level (≥1.28 g/dL) was significantly associated with poor overall survival (log rank test, P=0.034)., Conclusions: A pretreatment low albumin to globulin ratio, which might be attributable to a high serum globulin level, can be used to predict poor prognosis in cervical cancer patients treated with radiation based therapy., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

We evaluated the impact of model-based dose calculation algorithms (MBDCAs) on high-dose-rate brachytherapy (HDR-BT) treatment planning for patients with cervical cancer. Seven patients with cervical cancer treated using HDR-BT were studied. Tandem and ovoid applicators were used in four patients, a vaginal cylinder in one, and interstitial needles in the remaining two patients. MBDCAs were applied to the Advanced Collapsed cone Engine (ACE; Elekta, Stockholm, Sweden). All plans, which were originally calculated using TG-43, were re-calculated using both ACE and Monte Carlo (MC) simulations. Air was used as the rectal material. The mean difference in the rectum D2cm3 between ACErec-air and MCrec-air was 8.60 ± 4.64%, whereas that in the bladder D2cm3 was -2.80 ± 1.21%. Conversely, in the small group analysis (n = 4) using water instead of air as the rectal material, the mean difference in the rectum D2cm3 between TG-43 and ACErec-air was 11.87 ± 2.65%, whereas that between TG-43 and ACErec-water was 0.81 ± 2.04%, indicating that the use of water as the rectal material reduced the difference in D2cm3 between TG-43 and ACE. Our results suggested that the differences in the dose-volume histogram (DVH) parameters of TG-43 and ACE were large for the rectum when considerable air (gas) volume was present in it, and that this difference was reduced when the air (gas) volume was reduced. Also, ACE exhibited better dose calculation accuracy than that of TG-43 in this situation. Thus, ACE may be able to calculate the dose more accurately than TG-43 for HDR-BT in treating cervical cancers, particularly for patients with considerable air (gas) volume in the rectum.

We evaluated dose-volume histogram (DVH) parameters based on deformable image registration (DIR) between brachytherapy (BT) and external beam radiotherapy (EBRT) that included a center-shielded (CS) plan. Eleven cervical cancer patients were treated with BT, and their pelvic and CS EBRT were studied. Planning CT images for EBRT and BT (except for the first BT, used as the reference image) were deformed with DIR to reference image. We used two DIR parameter settings: intensity-based and hybrid. Mean Dice similarity coefficients (DSCs) comparing EBRT with the reference for the uterus, rectum and bladder were 0.81, 0.77 and 0.83, respectively, for hybrid DIR and 0.47, 0.37 and 0.42, respectively, for intensity-based DIR (P < 0.05). D1 cm3 for hybrid DIR, intensity-based DIR and DVH addition were 75.1, 81.2 and 78.2 Gy, respectively, for the rectum, whereas they were 93.5, 92.3 and 94.3 Gy, respectively, for the bladder. D2 cm3 for hybrid DIR, intensity-based DIR and DVH addition were 70.1, 74.0 and 71.4 Gy, respectively, for the rectum, whereas they were 85.4, 82.8 and 85.4 Gy, respectively, for the bladder. Overall, hybrid DIR obtained higher DSCs than intensity-based DIR, and there were moderate differences in DVH parameters between the two DIR methods, although the results varied among patients. DIR is only experimental, and extra care should be taken when comparing DIR-based dose values with dose-effect curves established using DVH addition. Also, a true evaluation of DIR-based dose accumulation would require ground truth data (e.g. measurement with physical phantom)., (© The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: In this study, we developed a 3D-printed deformable pelvis phantom for evaluating spatial DIR accuracy. We then evaluated the spatial DIR accuracies of various DIR settings for cervical cancer., Methods: A deformable female pelvis phantom was created based on patient CT data using 3D printing. To create the deformable uterus phantom, we first 3D printed both a model of uterus and a model of the internal cavities of the vagina and uterus. We then made a mold using the 3D printed uterus phantom. Finally, urethane was poured into the mold with the model of the internal cavities in place, creating the deformable uterus phantom with a cavity into which an applicator could be inserted. To create the deformable bladder phantom, we first 3D printed models of the bladder and of the same bladder scaled down by 2 mm. We then made a mold using the larger bladder model. Finally, silicone was poured into the mold with the smaller bladder model in place to create the deformable bladder phantom with a wall thickness of 2 mm. To emulate the anatomical bladder, water was poured into the created bladder. We acquired phantom image without applicator for EBRT. Then, we inserted the applicator into the phantom to simulate BT. In this situation, we scanned the phantom again to obtain the phantom image for BT. We performed DIR using the two phantom images in two cases: Case A, with full bladder (170 ml) in both EBRT and BT images; and Case B with full bladder in the BT image and half-full bladder (100 ml) in the EBRT image. DIR was evaluated using Dice similarity coefficients (DSCs) and 31 landmarks for the uterus and 25 landmarks for the bladder. A hybrid intensity and structure DIR algorithm implemented in RayStation with four DIR settings was evaluated., Results: On visual inspection, reasonable agreement in shape of the uterus between the phantom and patient CT images was observed for both EBRT and BT, although some regional disagreements in shape of the bladder and rectum were apparent. The created phantom could reproduce the actual patient's uterus deformation by the applicator. For both Case A and B, large variation was seen in landmark error among the four DIR parameters. In addition, although DSCs were comparable, moderate differences in landmark error existed between the two different DIR parameters selected from the four DIR parameters (i.e., DSC = 0.96, landmark error = 13.2 ± 5.7 mm vs. DSC = 0.97, landmark error = 9.7 ± 4.0 mm). This result suggests that landmark error evaluation might thus be more effective than DSC for evaluating DIR accuracy., Conclusions: Our developed phantom enabled the evaluation of spatial DIR accuracy for the female pelvic region for the first time. Although the DSCs are high, the spatial errors can still be significant and our developed phantom facilitates their quantification. Our results showed that optimization is needed to identify suitable DIR settings. For determining suitable DIR settings, our method of evaluating spatial DIR accuracy using the 3D-printed phantom may prove helpful., (© 2017 American Association of Physicists in Medicine.)