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 ... -  《-》

Clinical efficacy and toxicity of radio-chemotherapy and magnetic resonance imaging-guided brachytherapy for locally advanced cervical cancer patients: A mono-institutional experience.

Lakosi F ，de Cuypere M ，Viet Nguyen P ，Jansen N ，Warlimont B ，Gulyban A ，Gennigens C ，Seidel L ，Delbecque K ，Coucke P ，Hermesse J ，Kridelka F ... -  《-》

Safety and efficacy of single insertion accelerated MR-image guided brachytherapy following chemo-radiation in locally advanced cervix cancer: modifying our EMBRACE during the COVID pandemic.

Utero-vaginal brachytherapy (BT) is an irreplaceable care component for the curative treatment of locally advanced cervix cancer (LACC). Magnetic Resonance Imaging (MRI)-image guided adaptive BT (IGABT) using the GYN-GEC-ESTRO EMBRACE guidelines is the international care standard. Usually following chemo-radiation therapy (CRT), IGABT has high proven utility in LACC but requires significant health system resources. Timely access was disrupted by the COVID-19 pandemic which challenged us to re-design our established IGABT care pathway. From April 2020 consecutive patients with LACC were enrolled after CRT in a single arm exploratory non-inferiority study of a modified IGABT (mIGABT) protocol. This delivered an iso-effective IGABT dose (39.3 Gy: EQD2: α/β10Gy concept) over a 24-h period during a single overnight hospitalisation. Fourteen LACC patients received mIGABT from April 2020 to March 2022. Median age was 62.5 years (37-82 years). LACC histology was primary squamous (9/14) or adeno-carcinoma (5/14). International Federation of Gynaecology and Obstetrics (FIGO) 2018 stages ranged from IB1/2 (N = 3), IIA1/IIB (5), IIIB (2), IIIC1/2 (4) with mean ± standard deviation (SD) gross tumour volume-at-diagnosis (GTV_D) of 37.7 cc ± 71.6 cc. All patients achieved complete metabolic, clinical, and cytologic cancer response with CRT and IGABT. High-risk HPV was cleared by 6-months. Complete MRI-defined cancer response before mIGABT (GTV_Fx1) was seen in 77% of cases (10/13). Only two women developed metastatic disease and one died at 12-months; 13 patients were alive without cancer at mean 20.3 ± 7.2 months follow-up. Actuarial 2-year overall survival was 93%. Compared with our pre-COVID IGABT program, overall mIGABT cost-saving in this cohort was USD 22,866. Prescribed dose covered at least 90% (D90) of the entire cervix and any residual cancer at time of BT (HRCTV_D90: high-risk clinical target volume) with 3-fractions of 8.5 Gy delivered over 24-h (22.8 ± 1.7 h). Total treatment time including CRT was 38 days. The mIGABT schedule was well tolerated and the entire cohort met EMBRACE recommended (EQD2: α/β10Gy) combined HRCTV_D90 coverage of 87.5 ± 3.7 Gy. Similarly, organ-at-risk (OAR) median: interquartile range D2cc constraints (EQD2: α/β3Gy) were EMBRACE compliant: bladder (65.9 Gy: 58.4-72.5 Gy), rectum (59.1 Gy: 55.7-61.8 Gy), and sigmoid colon (54.6 Gy: 50.3-58.9 Gy). ICRU recto-vaginal point dose was significantly higher (75.7 Gy) in our only case of severe (G4) pelvic toxicity. This study demonstrated the utility of mIGABT and VMAT CRT in a small cohort with LACC. Loco-regional control was achieved in all cases with minimal emergent toxicity. Single insertion mIGABT was logistically efficient, cost-saving, and patient-centric during the COVID-19 pandemic.

Stevens MJ ，Ko F ，Martland J ，Brown R ，Bell L ，Atyeo J ，Yim J ... -  《Radiation Oncology》

Feasibility study of toxicity outcomes using GEC-ESTRO contouring guidelines on CT based instead of MRI-based planning in locally advanced cervical cancer patients.

To report late rectal and bladder toxicity outcomes of a CT-based image-guided brachytherapy (IGBT) technique for treatment of cervical cancer. Between 2008 and 2014, 95 women with International Federation of Gynecology and Obstetrics stage IB to IVA cervical carcinoma treated with definitive concurrent cisplatin-based chemotherapy and external beam radiation therapy 50.4 Gy in 28 fractions followed by planned prescription dose of 7 Gy × 4 fractions of high-dose-rate IGBT was retrospectively reviewed. At each implantation, all patients had a urinary catheter in situ and received bowel enema before undergoing planning CT simulation. A high-risk clinical target volume (HRCTV) as per GEC-ESTRO guidelines and the entire cervix, rectum, and bladder was contoured on the simulation CT according to Radiation Therapy Oncology Group Gynaecology Contouring Atlas. Reported doses to HRCTV and organs at risk were recorded. Toxicities were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events version 3. The median followup time was 29 months. The mean HRCTV equivalent dose in 2 Gy fractions (EQD2) of external beam radiation therapy combined with brachytherapy was 80 Gy (standard deviation [SD], 11), and the rectal doses to 2 cm3 (D2cc) EQD2 and bladder D2cc EQD2 were 74 Gy (SD, 6) and 79 Gy (SD, 15), respectively. Twenty-two patients (23%) had grade 2 proctitis and 10 patients (11%) had grade 3 proctitis. Four patients (4%) had grade 2 cystitis and two patients (2%) had grade 3 cystitis. No patients had ≥ grade 4 toxicity. Despite CT-based brachytherapy planning, reported organ at risk toxicity was still significant compared with reported MRI-based planning series. Coimplementation of interstitial IGBT using the European Study on MRI-guided Brachytherapy in Locally Advanced Cervical Cancer (EMBRACE) protocol or using intensity-modulated radiation therapy during the external beam phase treatment might help to limit these late toxicities.

Koh V ，Choo BA ，Lee KM ，Tan TH ，Low JH ，Ng SY ，Ilancheran A ，Shen L ，Tang J ... -  《-》

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 ... -  《-》