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• W3135499119 abstract "We would like to thank Yuce Sari et al. [ [1] Yuce Sari S. Yigit E. Gultekin M. Yildi F. In regard to Spampinato et al.. Radiother Oncol. 2021; Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ] for the opportunity to further explain the reasons behind our article focusing on the importance of the ICRU Bladder Point (ICRU-BP) dose for urinary frequency and incontinence after radio(chemo)therapy and image-guided adaptive brachytherapy in locally advanced cervical cancer [ [2] Spampinato S. et al. Importance of the ICRU bladder point dose on incidence and persistence of urinary frequency and incontinence in locally advanced cervical cancer: An EMBRACE analysis. Radiother Oncol. 2021; 158: 300-308 Abstract Full Text Full Text PDF Scopus (12) Google Scholar ]. Our analysis was carried out within the international, prospective and multi-institutional EMBRACE I study [ [3] www.embracestudy.dk. Google Scholar ], which collected information on several physician-assessed (CTCAE v.3) and patient-reported (EORTC C30 and CX24) symptoms. Having enrolled 1416 patients from 2008 to 2015 and with a median follow-up of 4 years, EMBRACE I allowed to analyse individual late urinary side effects. We agree that a single article on risk factors and dose-effects for the complex spectrum of radiation-induced urinary dysfunctions would have been more comprehensive than publishing more studies on different urinary symptoms. Nonetheless, our analysis on urinary morbidity in EMBRACE I showed that different endpoints have different risk factors and dose-effects in agreement with clinical radiobiological findings [ [4] ICRU report 89: prescribing, recording, and reporting brachytherapy for cancer of the cervix (Chapter 6: Organs at Risk and Morbidity-Related Concepts and Volumes), J Int Comm Radiat Units Meas, 13, 2016, 79–87. Google Scholar ]. Another study on urinary morbidity within EMBRACE I recently published has indeed shown that bladder fistula, bleeding and cystitis, and to a lesser extent also patient-reported pain and difficulty in urination, correlate with bladder D2cm3 [ [5] Spampinato S. et al. Risk factors and dose-effects for bladder fistula, bleeding and cystitis after radiotherapy with imaged-guided adaptive brachytherapy for cervical cancer: an EMBRACE analysis. Radiother Oncol. 2021; 158: 312-320 Abstract Full Text Full Text PDF Scopus (11) Google Scholar ]. Therefore, we believe that a single article could not have effectively summarized the analysis of several physician-assessed and patient-reported symptoms/endpoints that showed different risk factors and dose-effects. Based on different underlying pathomechanisms, we decided to group symptoms as either involving functional subunits of the bladder [ [2] Spampinato S. et al. Importance of the ICRU bladder point dose on incidence and persistence of urinary frequency and incontinence in locally advanced cervical cancer: An EMBRACE analysis. Radiother Oncol. 2021; 158: 300-308 Abstract Full Text Full Text PDF Scopus (12) Google Scholar ] or a defined bladder volume receiving a high dose regardless of its location. The choice to focus this study only on two symptoms arose also from the possibility to match physician-assessed and patient-reported urinary frequency and incontinence reported in EMBRACE I. We also considered appropriate to dedicate an article to the importance of the ICRU-BP dose that until now could had not be systematically associated with overall urinary morbidity [ [6] ICRU report 89: prescribing, recording, and reporting brachytherapy for cancer of the cervix (Chapter 8: Dose and Volume Parameters for Prescribing, Recording and Reporting Brachytherapy, Alone and Combined with External-Beam Radiotherapy), J Int Comm Radiat Units Meas, 13, 2016, 105–121. Google Scholar ]. ICRU-BP dose and bladder D2cm3 showed only a moderate correlation in the EMBRACE I cohort, with the ICRU-BP placed in a definite position (most posterior extent of the Foley catheter balloon) while D2cm3 does not contain spatial information. This was also highlighted by a study on an EMBRACE I sub-cohort [ [7] Spampinato S. Fokdal L. Marinovskij E. Axelsen S. Pedersen E.M. Pötter R. Assessment of dose to functional sub-structures in the lower urinary tract in locally advanced cervical cancer radiotherapy. Phys Medica. 2019; 59: 127-132 Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar ], where ICRU-BP and trigone dose showed a good correlation, while D2cm3 did not. However, the combination of both dosimetric parameters allows to estimate the high dose region in the bladder wall (D2cm3) and the trigone (ICRU-BP). The reason for the lack of correlation with morbidity can be assumed as due to the fact that most of the studies conducted so far have mainly focused on an overall score obtained by combining different urinary symptoms [ 8 Mazeron R. et al. Pulsed-dose rate image-guided adaptive brachytherapy in cervical cancer: Dose-volume effect relationships for the rectum and bladder. Radiother Oncol. 2015; 116: 226-232 Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar , 9 Mazeron R. et al. D2cm3/DICRU ratio as a surrogate of bladder hotspots localizations during image-guided adaptive brachytherapy for cervical cancer: Assessment and implications in late urinary morbidity analysis. Brachytherapy. 2015; 14: 300-307 Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar , 10 Georg P. et al. Dose effect relationship for late side effects of the rectum and urinary bladder in magnetic resonance image-guided adaptive cervix cancer brachytherapy. Int J Radiat Oncol Biol Phys. 2012; 82: 653-657 Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar , 11 Manea E. et al. Risk of late urinary complications following image guided adaptive brachytherapy for locally advanced cervical cancer: refining bladder dose-volume parameters. Int. J. Radiat Oncol Biol Phys. 2018; 101: 411-420 Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar ]. Our new findings underline the importance of analysing individual symptoms and the need to monitor ICRU-BP dose in combination with volume parameters (e.g. bladder D2cm3) during treatment planning. Based on these findings new planning aims should include dose constraints for different morbidity endpoints of one single organ like the bladder, assessed via a combination of multiple dosimetric parameters. In regard to Spampinato et alRadiotherapy and OncologyVol. 158PreviewWe read the article by Spampinato et al. [1] focusing on the importance of ICRU bladder point (BP) dose on the incidence and persistence of urinary frequency and incontinence with great interest. The authors aimed to determine the patient- and treatment-related risk factors that may be associated with urinary frequency and incontinence by analyzing the patients with locally advanced cervical cancer (LACC) in the EMBRACE-I trial who underwent intracavitary brachytherapy (ICB) following chemoradiotherapy (CRT). 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• W3135499119 title "Response to Yuce Sari et al." @default.
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