3D image guided adaptive brachytherapy in patients with locally advanced cervical cancer: experience and clinical results from a minimum of six years of follow-up

In 2005, individualized 3D image guided brachytherapy was implemented for cervical cancer patients, in accordance with the (GYN) GEC ESTRO recommendation, at St. Olav's Hospital, Trondheim, Norway. This study reports the clinical results of sixty-five consecutive patients treated from 2005 to 2010. The patients were treated with curative intent using external beam radiotherapy, brachytherapy and cisplatin. Results of this treatment are presented, including Kaplan-Meier estimates for overall survival (OS) and cancer specific survival (CSS), as well as biological effective dose normalized to equivalent 2 Gy fractions to tumor, defined as high-risk clinical target volume (CTVHR ), and to organs at risk (OARs, here bladder and rectum). Morbidity was prospectively assessed and scored in accordance with the CTCAE 3.0. 92% of the patients achieved treatment response. Local control (LC) remained in all but one patient during follow-up. Five-year OS and CSS were 71% and 80%, respectively. The mean minimum dose to CTVHR for all patients was 80.2 ± 7.3 Gy; 16% and 23% of the patients developed bladder and GI symptoms respectively, 14% of all symptoms were categorized as serious (CTCAE score ≥ 3). A dose-effect relationship was observed for adverse effects of the bladder, and the findings support the more recently recommended lower total dose limit for this OAR.publishedVersion©2021 The Authors. Published by IMR Press. This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/)

3D image guided adaptive brachytherapy in patients with locally advanced cervical cancer: experience and clinical results from a minimum of six years of follow-up

In 2005, individualized 3D image guided brachytherapy was implemented for cervical cancer patients, in accordance with the (GYN) GEC ESTRO recommendation, at St. Olav's Hospital, Trondheim, Norway. This study reports the clinical results of sixty-five consecutive patients treated from 2005 to 2010. The patients were treated with curative intent using external beam radiotherapy, brachytherapy and cisplatin. Results of this treatment are presented, including Kaplan-Meier estimates for overall survival (OS) and cancer specific survival (CSS), as well as biological effective dose normalized to equivalent 2 Gy fractions to tumor, defined as high-risk clinical target volume (CTVHR ), and to organs at risk (OARs, here bladder and rectum). Morbidity was prospectively assessed and scored in accordance with the CTCAE 3.0. 92% of the patients achieved treatment response. Local control (LC) remained in all but one patient during follow-up. Five-year OS and CSS were 71% and 80%, respectively. The mean minimum dose to CTVHR for all patients was 80.2 ± 7.3 Gy; 16% and 23% of the patients developed bladder and GI symptoms respectively, 14% of all symptoms were categorized as serious (CTCAE score ≥ 3). A dose-effect relationship was observed for adverse effects of the bladder, and the findings support the more recently recommended lower total dose limit for this OAR

Radiobiological treatment planning evaluation of inverse planning simulated annealing for cervical cancer high-dose-rate brachytherapy

Aim: To compare five inverse treatment plans with one conventional manually optimized plan for cervical cancer brachytherapy (BT) using radiobiological parameters combined with dosimetric and volumetric parameters.Materials and Methods: Five inverse treatment plans were calculated using an inverse planning simulated annealing (IPSA) algorithm for each of four fractions for 12 cervical cancer patients treated with high-dose-rate (HDR) brachytherapy. The inverse treatment plans were compared with a manually optimized plan used for the actual treatment of the patients. The comparison of the plans was performed with respect to the probability of cure without complication.Results: Overall, the manually optimized plan scored the best results; however, the probability of cure without complication is within an acceptable clinical range for all the plans.Conclusion: Although there are still considerable uncertainties in the radiobiological parameters, the radiobiological plan evaluation method presents itself as a potential complement to physical dosimetric methods.</p

Dosimetric evaluation of manually and inversely optimized treatment planning for high dose rate brachytherapy of cervical cancer

<div><p></p><p><b>Background.</b> To compare five inverse treatment planning methods with the conventional manually optimized planning approach for brachytherapy of cervical cancer with respect to dosimetric parameters.</p><p><b>Material and methods.</b> Eighteen cervical cancer patients treated with magnetic resonance imaging (MRI)-guided high dose rate (HDR) brachytherapy were included in this study. Six plans were created for each of the 4 HDR brachytherapy fractions for each patient: 1 manually optimized and 5 inversely planned. Three of these were based on inverse planning simulated annealing (IPSA) with and without extra constraints on maximum doses of the target volume, and different constraints on doses to the organs at risk (OARs). In addition there were two plans based on dose to target surface points. The resulting dose-volume histograms were analyzed and compared from the dosimetric point of view by quantifying specific dosimetric parameters, such as clinical target volume (CTV) D₉₀, CTV D₁₀₀, conformal index (COIN), and D_2cm3 for rectum, bladder and the sigmoid colon.</p><p><b>Results.</b> Manual optimization led to a mean target coverage of 78.3% compared to 87.5%, 91.7% and 82.5% with the three IPSA approaches (p < 0.001). Similar COIN values for manual and inverse optimization were found. The manual optimization led to better results with respect to the dose to the OARs expressed as D_2cm3. Overall, the best results were obtained with manual optimization and IPSA plans with volumetric constraints including maximum doses to the target volume.</p><p><b>Conclusions.</b> Dosimetric evaluation of manual and inverse optimization approaches is indicating the potential of IPSA for brachytherapy of cervical cancer. IPSA with constraints of maximum doses to the target volume is closer related to manual optimization than plans with constraints only to minimum dose to the target volume and maximum doses to OARs. IPSA plans with proper constraints performed better than those based on dose to target surface points and manually optimized plans.</p></div

Risk Factors for Late Persistent Fatigue After Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer: An Analysis From the EMBRACE-I Study

Purpose: This study aimed to evaluate patient- and treatment-related risk factors for late persistent fatigue within the prospective, multicenter EMBRACE-I study.Methods and Materials: Fatigue was prospectively assessed (Common Terminology Criteria for Adverse Events, version 3) at baseline and during regular follow up in 993 patients with locally advanced cervical cancer after treatment with chemoradio-therapy and magnetic resonance imaging-guided brachytherapy. Risk factors for baseline and late persistent fatigue were evaluated with multivariable logistic regression. Late persistent fatigue was defined when either grade >= 1 or >= 2 was scored in at least half of the follow ups.Results: The median follow-up time was 57 months. Baseline fatigue grade >= 1/>= 2 (35.8%/6.3%, respectively) was associated with preexisting comorbidities, World Health Organization performance status, being underweight, severe pain, and tumor volume. Late persistent grade >= 1/>= 2 fatigue (36.3%/5.8%, respectively) was associated with patient-related factors (baseline fatigue, younger age, obesity) along with the size of irradiated volumes and the level of radiation doses from external beam radiation therapy (EBRT) and brachytherapy (EBRT: V43Gy, V57Gy; EBRT + brachytherapy: V60Gy equivalent dose in 2-Gy fractions). Large-volume lymph node (LN) boost increased the risk for late persistent fatigue grade >= 2 by 18% and 5% in patients with and without baseline fatigue, respectively, compared with no LN boost. The risk for late persistent fatigue grade >= 1 increased by 7% and 4% with V43Gy 3000 cm(3) in patients with and without baseline fatigue, respectively. Late persistent grade >= 1 fatigue occurred in 13% of patients without late persistent organ-related symptoms (gastrointestinal, genitourinary, and vaginal) versus 34% to 43%, 50% to 58%, and 73% in patients suffering from persistent symptoms involving 1, 2, or 3 organs, respectively.Conclusions: Late persistent fatigue occurs in a considerable number of patients after chemoradiotherapy, and is associated with patient-related factors, the size of volumes irradiated to intermediate and high EBRT and brachytherapy doses, and other persistent organ-related morbidity. These findings support the importance of ongoing efforts to better tailor the target dose and reduce irradiation of healthy tissue without compromising target coverage, using highly conformal EBRT and brachytherapy techniques. (C) 2021 Elsevier Inc. All rights reserved