Clinical Outcomes and Toxicity of CT-guided High Dose-rate Brachytherapy in Women With Locally-advanced Cervical Cancer

Background/Aim: To evaluate the outcome and toxicities in patients with locally advanced cervical cancer (LACC) treated with radiochemotherapy and intracavitary brachytherapy. Patients and Methods: This study included 67 patients with LACC treated between 2010 and 2018. The most represented stage was FIGO IIB. The patients were treated with external beam radiotherapy (EBRT) to the pelvis and boost to the cervix and parametrials. Concomitant chemotherapy (CHT) with cisplatin (CDDP) 40 mg/mq was planned. Subsequently, the patients underwent CT-based endouterine brachytherapy (BT). The response was evaluated at 3 months with PET-CT and/or pelvic magnetic resonance imaging (MRI). Since then, the patients have been followed with clinical instrumental controls every 4 months for the first 2 years and every 6 months for the following 3 years. Local response was assessed with pelvic MRI and/or PET-CT scan at the end of intracavitary BT) according to RECIST 1.1 criteria. Results: The median duration of treatment was 55 days (range=40-73 days). The prescription dose to the planning target volume (PTV) was delivered in 25 to 30 (median 28) daily fractions. The EBRT median dose to the pelvis and gross tumor volume were 50.4 Gy (range=45-56.25) and 61.6 Gy (range=45-70.4), respectively. The 1-year, 2-year, 3-year, and 5-year overall survival rates were 92.44%, 80.81%, 78.84%, and 76.45% respectively. The actuarial 1-year, 2-year, 3-year, and 5-year disease-free survival rates were 89.5%, 83.6%, 81%, and 78.2% respectively. Conclusion: This study analyzed acute and chronic toxicity, survival, and local control in cervical cancer patients treated with IMRT followed by CT-planned high dose rate-brachytherapy. Patients demonstrated satisfactory outcomes and incidence of acute and late toxicities

Nasopharyngeal cancer: the impact of guidelines and teaching on radiation target volume delineation

Target volume delineation in the radiation treatment of nasopharyngeal cancer is challenging due to several reasons such as the complex anatomy of the site, the need for the elective coverage of definite anatomical regions, the curative intent of treatment and the rarity of the disease, especially in non-endemic areas. We aimed to analyze the impact of educational interactive teaching courses on target volume delineation accuracy between Italian radiation oncology centers. Only one contour dataset per center was admitted. The educational course consisted in three parts: (1) The completely anonymized image dataset of a T4N1 nasopharyngeal cancer patient was shared between centers before the course with the request of target volume and organs at risk delineation; (2) the course was held online with dedicated multidisciplinary sessions on nasopharyngeal anatomy, nasopharyngeal cancer pattern of diffusion and on the description and explanation of international contouring guidelines. At the end of the course, the participating centers were asked to resubmit the contours with appropriate corrections; (3) the pre- and post-course contours were analyzed and quantitatively and qualitatively compared with the benchmark contours delineated by the panel of experts. The analysis of the 19 pre- and post-contours submitted by the participating centers revealed a significant improvement in the Dice similarity index in all the clinical target volumes (CTV1, CTV2 and CTV3) passing from 0.67, 0.51 and 0.48 to 0.69, 0.65 and 0.52, respectively. The organs at risk delineation was also improved. The qualitative analysis consisted in the evaluation of the inclusion of the proper anatomical regions in the target volumes; it was conducted following internationally validated guidelines of contouring for nasopharyngeal radiation treatment. All the sites were properly included in target volume delineation by >50% of the centers after correction. A significant improvement was registered for the skull base, the sphenoid sinus and the nodal levels. These results demonstrated the important role that educational courses with interactive sessions could have in such a challenging task as target volume delineation in modern radiation oncology

Pretreatment MRI Radiomics Based Response Prediction Model in Locally Advanced Cervical Cancer

The aim of this study was to create a radiomics model for Locally Advanced Cervical Cancer (LACC) patients to predict pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) analysing T2-weighted 1.5 T magnetic resonance imaging (MRI) acquired before treatment start. Patients with LACC and an International Federation of Gynecology and Obstetrics stage from IB2 to IVA at diagnosis were retrospectively enrolled for this study. All patients underwent NACRT, followed by radical surgery; pCR―assessed on surgical specimen―was defined as absence of any residual tumour. Finally, 1889 features were extracted from MR images; features showing statistical significance in predicting pCR at the univariate analysis were selected following an iterative method, which was ad-hoc developed for this study. Based on this method, 15 different classifiers were trained considering the most significant features selected. Model selection was carried out using the area under the receiver operating characteristic curve (AUC) as target metrics. One hundred eighty-three patients from two institutions were analysed. The model, showing the highest performance with an AUC of 0.80, was the random forest method initialised with default parameters. Radiomics appeared to be a reliable tool in pCR prediction for LACC patients undergoing NACRT, supporting the identification of patient risk groups, which paves treatment pathways tailored according to the predicted outcome

Evaluation of an Early Regression Index (ERITCP) as Predictor of Pathological Complete Response in Cervical Cancer: A Pilot-Study

Background: Recent studies have highlighted the potentialities of a radiobiological parameter, the early regression index (ERITCP), in the treatment response prediction for rectal cancer patients treated with chemoradiotherapy followed by surgery. The aim of this study is to evaluate the performance of this parameter in predicting pathological complete response (pCR) in the context of low field MR guided radiotherapy (MRgRT) for cervical cancer (CC). Methods: A total of 16 patients affected by CC were enrolled. All patients underwent a MRgRT treatment, with prescription of 50.6 Gy in 22 fractions. A daily MR acquisition was performed at simulation and on each treatment fraction. Gross tumor volume (GTV) was delineated on the MR images acquired at the following biological effective dose (BED) levels: 14, 28, 42, 54 and 62 Gy. The ERITCP was calculated at the different BED levels and its predictive performance was quantified in terms of receiver operating characteristic (ROC) curve. Results: pCR was observed in 11/16 cases. The highest discriminative power of ERITCP was reported when a BED value of 28 Gy is reached, obtaining an area under curve (AUC) of 0.84. Conclusion: This study confirmed ERITCP as a promising response biomarker also for CC, although further studies with larger cohort of patients are recommended

Neoadjuvant Chemoradiotherapy With Simultaneous Integrated Boost in Locally Advanced Cervical Cancer: Long Term Results of a Single-Center Experience

Aim of this study was to analyze the efficacy and tolerability of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) associated with cisplatin-based chemotherapy in preoperative setting of patients with locally advanced cervical cancer (LACC). From June 2013 to September 2019, we analyzed patients with LACC who had undergone neoadjuvant chemoradiation (CRT). A radiation dose of 39.6 Gy, 1.8 Gy/fraction was delivered to the pelvis plus a radiation dose to the primary tumor delivered with SIB-VMAT strategy for a total of 50.6Gy, 2.3Gy/fraction in 25 fractions. Cisplatin-based chemotherapy was delivered combined with radiotherapy. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 7 to 8 weeks from CRT. One hundred forty-eight patients (median age: 49.5 years; FIGO stage IB2: 7, IIA: 8, IIB: 106, IIIA: 5; IIIB: 16; IVA: 5, IVB: 1; N0: 56, N1: 92) were analyzed. The treatment was well tolerated with good compliance: no grade 3/4 gastrointestinal or genitourinary toxicity was reported; grade 3 neutropenia was described in five cases. Pathological complete response (pCR) was documented in 68 cases (46%) and 32 patients (21.6%) had microscopic residual disease. Pathological nodal involvement was observed in 23 patients (15.5%). At median follow-up of 59 months (range: 27-100), the 3-year local control was 78.5%, whereas the 3-year metastasis-free survival was 70.5%. The 3-year overall survival rate was 89.0%. Neoadjuvant CRT with SIB-VMAT followed by radical surgery results in a high rate of pathologically assessed complete response and a very encouraging local control rate, with acceptable toxicity

Evaluation of early regression index as response predictor in cervical cancer: A retrospective study on T2 and DWI MR images

Background and Purpose: Early Regression Index (ERITCP) is an image-based parameter based on tumor control probability modelling, that reported interesting results in predicting pathological complete response (pCR) after pre-operative chemoradiotherapy (CRT) in rectal cancer. This study aims to evaluate this parameter for Locally Advanced Cervical Cancer (LACC), considering not only T2-weighted but also diffusion-weighted (DW) Magnetic Resonance (MR) images, comparing it with other image-based param-eters such as tumor volumes and apparent coefficient diffusion (ADC).Materials and Methods: A total of 88 patients affected by LACC (FIGO IB2-IVA) and treated with CRT were enrolled. An MRI protocol consisting in two acquisitions (T2-w and DWI) in two times (before treatment and at mid-therapy) was applied. Gross Tumor Volume (GTV) was delineated and ERITCP was calculated for both imaging modalities. Surgery was performed for each patient after nCRT: pCR was considered in case of absence of any residual tumor cells. The predictive performance of ERITCP, GTV volumes (calculated on T2-w and DW MR images) and ADC parameters were evaluated in terms of area (AUC) under the Receiver Operating Characteristic (ROC) curve considering pCR and two-years survival parameters as clinical outcomes.Results: ERITCP and GTV volumes calculated on DW MR images (ERIDWI and Vmid_DWI) significantly predict pCR (AUC = 0.77 and 0.75 respectively) with results superior to those observed considering T2-w MR images or ADC parameters. Significance was also reported in the prediction of 2-years local control and disease free-survival. Conclusion: This study identified ERITCP and Vmid as good predictor of pCR in case of LACC, especially if calculated considering DWI. Using these indicators, it is possible to early identify not responders and modifying the treatment, accordingly.(c) 2022 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 174 (2022) 30-3

Stereotactic body radiotherapy in oligometastatic cervical cancer (MITO-RT2/RAD study): a collaboration of MITO, AIRO GYN, and MaNGO groups

Objective This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of patients with oligometastatic/persistent/recurrent cervical cancer. Methods A standardized data collection from several radiotherapy centers that treated patients by stereotactic body radiotherapy between March 2006 and February 2021 was set up. Clinical and stereotactic body radiotherapy parameters were collected. Objective response rate was defined as a composite of complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. The primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2 year actuarial local control rate on a 'per lesion' basis. The secondary end points were progression-free survival and overall survival, as well as toxicity. Results A total of 83 patients with oligometastatic/persistent/recurrent cervical cancer bearing 125 lesions treated by stereotactic body radiotherapy at 15 different centers were selected for analysis. Of the sites of metastatic disease, lymph node metastases were most common (55.2%), followed by parenchyma lesions (44.8%). Median total dose was 35 Gy (range 10-60), in five fractions (range 1-10), with a median dose/fraction of 7 Gy (range 4-26). Complete, partial, and stable response were found in 73 (58.4%), 29 (23.2%), and 16 (12.8%) lesions, respectively, reaching 94.4% of the clinical benefit rate. Forty-six (55.4%) patients had a complete response. Patients achieving complete response on a 'per lesion' basis experienced a 2 year actuarial local control rate of 89.0% versus 22.1% in lesions not achieving complete response (p<0.001). The 2 year actuarial progression-free survival rate was 42.5% in patients with complete response versus 7.8% in patients with partial response or stable or progressive disease (p=0.001). The 2 year actuarial overall survival rate was 68.9% in patients with complete response versus 44.3% in patients with partial response or stable or progressive disease (p=0.015). Fifteen patients (18.1%) had mild acute toxicity, totaling 29 side events. Late toxicity was documented in four patients (4.8%) totaling seven adverse events. Conclusion Our analysis confirmed the efficacy of stereotactic body radiotherapy in oligometastatic/persistent/recurrent cervical cancer patients. The low toxicity profile encourages the wider use of stereotactic body radiotherapy in this setting