Magnetic Resonance Imaging-Guided Adaptive Brachytherapy for the Treatment of Cervical Cancer and its Impact on Clinical Outcome.

We implemented magnetic resonance imaging-based image-guided adaptive brachytherapy (IGABT) for the management of cervical cancer at the Northern Centre for Cancer Care in January 2015. The Royal College of Radiologists recommended IGABT as the new standard of care for the management of cervical cancer in the UK in 2009, following earlier publication of recommendations of Groupe European de Curietherapie of the European Society for Radiotherapy and Oncology for three-dimensional magnetic resonance imaging-based IGABT. The purpose of this study was to investigate if the introduction of IGABT in the management of cervical cancer at our institute indeed improved the treatment outcomes with a better toxicity profile as compared with conventional brachytherapy (CBT). A retrospective analysis of 213 patients with International Federation of Gynecology and Obstetrics stage IB-IVA cervical cancer treated with curative radiotherapy ± chemotherapy at the Northern Centre for Cancer Care was carried out for the period January 2010 to December 2019. Patients were categorised into three groups based on their brachytherapy planning process. Fifty-eight patients were treated with CBT, 35 patients were treated with retrospective brachytherapy (RBT) planning and 120 patients were treated with IGABT. Eighty-six per cent received concomitant chemotherapy with cisplatin. Outcome measures were local control rates, overall and progression-free survival, and impact on treatment-related toxicities. The median follow-up was 36, 32 and 25 months for CBT, RBT and IGABT, respectively. Three-year local control achieved was 70.4, 77.8 and 86.9%, respectively. Three-year overall survival was 53.8, 61.1 and 86.2%, respectively. Grade 2 or 3 bladder and bowel toxicity was 8% and 10% in IGABT group versus 20% and 27% in the CBT group. Our analysis indicated that IGABT proved to be very effective in not only improving locoregional control, but also offered quality survivorship to these women, with a significant drop in radiation-related bladder and bowel toxicities.

Singhal S ，Veeratterapillay J ，Locks S ，Morgan D ，Patil R ，Chamberlain HM ... -  《-》

MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study.

The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1-L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5-6 cycles, 1 day per cycle, plus 45-50 Gy external-beam radiotherapy delivered in 1·8-2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20-40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85-94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20-64), actuarial overall 5-year local control was 92% (95% CI 90-93). Actuarial cumulative 5-year incidence of grade 3-5 morbidity was 6·8% (95% CI 5·4-8·6) for genitourinary events, 8·5% (6·9-10·6) for gastrointestinal events, 5·7% (4·3-7·6) for vaginal events, and 3·2% (2·2-4·5) for fistulae. Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies. Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems.

Pötter R ，Tanderup K ，Schmid MP ，Jürgenliemk-Schulz I ，Haie-Meder C ，Fokdal LU ，Sturdza AE ，Hoskin P ，Mahantshetty U ，Segedin B ，Bruheim K ，Huang F ，Rai B ，Cooper R ，van der Steen-Banasik E ，Van Limbergen E ，Pieters BR ，Tan LT ，Nout RA ，De Leeuw AAC ，Ristl R ，Petric P ，Nesvacil N ，Kirchheiner K ，Kirisits C ，Lindegaard JC ，EMBRACE Collaborative Group ... -  《-》

MRI-guided adaptive brachytherapy for locally advanced cervix cancer: Treatment outcomes from a single institution in Hong Kong.

Paradigm has shifted from 2D to image-guided adaptive brachytherapy (IGABT) for locally advanced cervix cancer (LACC). Increasing reports from pioneering institutions and large retrospective multicenter series have demonstrated improvements in outcome and reduction in toxicity with IGABT. However, there is scarcity of data on magnetic resonance (MR)-IGABT in Chinese patients. To evaluate the clinical outcome of MR-IGABT for LACC in a single institution in Hong Kong. Patients with FIGO stage IB-IVA LACC treated with definitive external beam radiotherapy +/- concurrent cisplatin followed by MR-IGABT from January 2015 to January 2018 were included. Brachytherapy planning and dose reporting followed the GEC-ESTRO recommendations. Dosimetric and clinical outcomes including local control (LC), pelvic control (PC), cancer-specific survival, overall survival (OS), and toxicity were analyzed. Forty-two consecutive patients were included. 71% were FIGO stage IIB or above; 52% had pelvic node involvement. Median high-risk clinical target volume (HRCTV) was 34.7 cm3 (12.3-155.1 cm3). Median dose to HRCTV D90 was 88.5 Gy (63.4-113.4 Gy) (EQD210). Median doses to the D2cc of bladder, rectum, sigmoid, and small bowel were 83.1 Gy, 67.5 Gy, 69.0 Gy, and 68.9 Gy (EQD23), respectively. Median followup was 20.3 months (4.0-35.1 months). 24-month actuarial LC, PC, cancer-specific survival, and OS were 90%, 84%, 90%, and 90%, respectively. Stratification by clinical variables showed that FIGO stage had significant impact on LC and dose to HRCTV on both LC and PC. Treatment was well tolerated without any severe late toxicity. Intermediate-term results from systematic MR-IGABT for LACC demonstrate very promising outcomes with minimal toxicity. This fills the gap in evidence for MR-IGABT in Chinese patients.

Wu PY ，Wong TPW ，Yip YYC ，Chang TYA ，Chan LKL ，Lee MCH ，Law LYA ，Yeung MWR ，Soong SI ... -  《-》

Improved survival of patients with cervical cancer treated with image-guided brachytherapy compared with conventional brachytherapy.

Since the Group Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO) published recommendations for 3D MRI-based image-guided adaptive brachytherapy (IGBT) in the treatment of cervical cancer, many institutions have implemented this technique and favourable results were documented. We investigated if introduction of IGBT in our centre indeed improved treatment outcomes and reduced toxicity compared to conventional brachytherapy (CBT). A retrospective analysis was done of outcomes of patients with stage IB-IVA cervical cancer treated with primary radiation therapy with curative intent between 2000 and 2012. Outcome measures were overall and disease-free survival, pelvic control, distant metastasis and treatment related adverse events (AE). 126 patients were analysed; 43 had been treated with CBT between 2000-2007, and 83 with IGBT between 2007-2012. External beam radiation (mean; 46.6Gy) was combined with concurrent weekly cisplatin (51.6%), or hyperthermia (24.6%); radiation alone was used in 23.8%. Median follow-up was 121.8months for CBT patients, vs. 42.3months for IGBT. Complete remission was achieved in 83.7% of patients in the CBT group and in 98.8% of IGBT patients (p<0.01). Overall survival at 3years was 51% and 86%, respectively (p=0.001). Pelvic recurrence was found in 32% vs. 7% (p<0.001). Most patients had low grade adverse events. High grade (3-4) AE occurred in 15.4% vs. 8.4% at 3years (p=0.06). Introduction of IGBT for cervical cancer has led to significantly increased 3-year locoregional control and survival rates, whilst reducing late morbidity.

Rijkmans EC ，Nout RA ，Rutten IH ，Ketelaars M ，Neelis KJ ，Laman MS ，Coen VL ，Gaarenstroom KN ，Kroep JR ，Creutzberg CL ... -  《-》

Long term experience with 3D image guided brachytherapy and clinical outcome in cervical cancer patients.

To report our 10years' experience and learning curve of the treatment of cervical cancer patients with chemo radiotherapy and MRI (or CT in 9 selected patients) guided brachytherapy using pulsed dose rate (PDR) brachytherapy (BT). Hundred and seventy consecutive patients with cervical cancer FIGO stage IB-IVB (without metastases beyond the para-aortic nodal region) were treated in our institute between 2002 and 2012. Patients received external beam radiotherapy (nodal boost to the lymph nodes positive at diagnosis)±chemotherapy followed by a pulsed or low dose rate brachytherapy boost. MRI (or CT) images were taken with the applicator in situ. The first 16 patients were treated according to X-ray-based plans, optimized on MRI. High-risk CTV, intermediate-risk CTV, bladder, rectum and sigmoid were retrospectively contoured according to the GEC-ESTRO recommendations. In all other patients, treatment plans were optimized after delineation of the target volumes and organs at risk at MRI (or CT). Doses were converted to the equivalent dose in 2Gy (EQD2) by applying the linear quadratic model. The median age of the patients was 55years (range 16-88). 41% had stage III or IV disease. Of the 170 patients, 91 patients had on imaging metastatic lymph nodes at diagnosis (62 patients pelvic lymph node involvement and 29 para-aortic). In 27 (16%) patients the intracavitary technique was combined with interstitial brachytherapy. The mean D90 and D100 for the high-risk CTV were 84.8±8.36Gy and 67.5±6.29Gy for the entire patient group. Mean D90 and D100 values for the IR CTV were 68.7±5.5Gy and 56.5±6.25Gy. There was an important learning curve between both patient groups, with an increase in mean D90 of 75.8Gy for the first 16 patients compared to 85.8Gy for the second group. At the same time, the mean dose to 2cm3 of bladder and sigmoid decreased from 86.1Gy to 82.7Gy and from 70Gy to 61.7Gy, respectively. At a median follow-up of 37months (range 2-136months), local control rate for all patients was 96%, the regional control (pelvic and para-aortic) rate 81% and crude disease free survival rate 55%. The overall survival at 5years is 65%. The higher dose to the target volume resulted in an increase in local control from 88% in the first 16 patients compared to 97% in the second patient group. Regarding late toxicity, 21 patients (12%) presented grade 3-4 late morbidity. Rectal, urinary, sigmoid and vaginal morbidity was 5%, 6%, 2% and 5%, respectively. A correlation between rectal D2cm3 >65Gy and grade >3 late morbidity was found (p=0.006). Although the majority of the patients presented with locally advanced carcinoma, excellent local and regional control rates were achieved. Rectal, urinary, sigmoid and vaginal grade 3-4 morbidity was 5%, 6%, 2% and 5%, respectively. A correlation between rectal D2cm3 >65Gy and grade >3 late morbidity was found (p=0.006).

Ribeiro I ，Janssen H ，De Brabandere M ，Nulens A ，De Bal D ，Vergote I ，Van Limbergen E ... -  《-》