P. Morice

Accuracy of Magnetic Resonance Imaging in Predicting Residual Disease in Patients Treated for Stage IB2/II Cervical Carcinoma With Chemoradiation Therapy Correlation of Radiologic Findings With Surgicopathologic Results

The evaluation of residual disease (RD) after chemoradiation therapy (CRT) in stage IB2/II cervical carcinoma conventionally is based on a clinical examination and magnetic resonance imaging (MRI) performed 3 to 8 weeks after the end of treatment. Very few studies have correlated MRI and histologic findings specifically in cervix cancer. This was the objective of the current study.

What to expect from immediate salvage hysterectomy following concomitant chemoradiation and image-guided adaptive brachytherapy in locally advanced cervical cancer.

PURPOSE Concomitant chemoradiation followed by brachytherapy is the standard treatment for locally advanced cervical cancers. The place of adjuvant hysterectomy remains unclear but tends to be limited to incomplete responses to radiotherapy or local relapse. The aim was to analyse the benefit from immediate salvage surgery following radiation therapy in incomplete responders. METHODS Among the patients with locally advanced cervical cancer treated with concomitant chemoradiation followed by 3D image-guided adaptive brachytherapy and hysterectomy, cases with genuine macroscopic remnant, defined as at least 1cm in width, were identified. Their clinical data and outcomes were retrospectively reviewed and compared to the patients treated with the same modalities. RESULTS Fifty-eight patients were included, with a median follow-up of 4.2 years. After hysterectomy, 9 patients had macroscopic residual disease, 10 microscopic and the remaining 39 patients were considered in complete histological response. The 4-year overall survival and disease-free survival rates were significantly decreased in patients with macroscopic residual disease: 50 and 51% versus 92% and 93%, respectively. Intestinal grades 3-4 toxicities were reported in 10.4% and urinary grades 3-4 in 8.6% in the whole population without distinctive histological features. Planning aims were reached in only one patient with macroscopic residuum (11.1%). In univariate analysis, overall treatment time (>55 days) and histological subtype (adenocarcinomas or adenosquamous carcinomas) appeared to be significant predictive factors for macroscopic remnant after treatment completion (P=0.021 and P=0.017, respectively). In multivariate analysis, treatment time was the only independent factor (P=0.046, odds ratio=7.0). CONCLUSIONS Although immediate salvage hysterectomy in incomplete responders provided a 4-year disease-free survival of 51%, its impact on late morbidity is significant. Efforts should focus on respect of treatment time and dose escalation. Adenocarcinoma might require higher high-risk clinical target volume planning aims.

Post radiation hysterectomy in locally advanced cervical cancer: Outcomes and dosimetric impact.

PURPOSES Firstly, to evaluate the impact of completion hysterectomy after chemoradiation and image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. Secondly, to assess a potential differential dose-effect relationship for the rectum and bladder according to the realization of hysterectomy. MATERIAL AND METHODS Two cohorts of patients were identified, differing by the realization of completion hysterectomy. Inclusions were limited to FIGO stage I-II, with no para-aortic involvement. All patients received a combination of pelvic chemoradiation followed by IGABT. Their outcomes and morbidity were reviewed. Log-rank tests were used to compare survivals. Probit analyses were performed to study dose-volume effect relationships. RESULTS The two cohorts comprised 54 patients in the completion surgery group and 157 patients in the definitive radiotherapy group. They were well balanced, except for the mean follow-up, significantly longer in the post hysterectomy cohort and the use of PET-CT in the work-up, more frequent in the definitive radiotherapy cohort. Although less local relapses were reported in the hysterectomy group, the 5-year disease-free and overall survival did not differ between groups. The cumulative incidence of severe late morbidity was significantly increased in the hysterectomy cohort: 22.5% versus 6.5% at 5years (p=0.016). Dose-volume effects were observed for the bladder, with the D2cm3 corresponding with a 10% probability of late severe morbidity urinary events (ED10) of 67.8Gy and 91.9Gy in the hysterectomy and definitive radiotherapy cohorts, respectively. A D90 CTVHR of 85Gy (planning aim) corresponded with a 93.3% rate of local control in the definitive radiotherapy cohort whereas it corresponded with a 77.3% chance to have a good histologic response (complete response or microscopic residual disease) in the hysterectomy group. CONCLUSION No benefit from completion hysterectomy in terms of overall or disease-free survival rates was observed, which was moreover responsible for an increase of the severe late morbidity. The realization of post-radiation hysterectomy resulted in a shift of the ED10 of 24.1Gy.

Place de la radiothérapie dans la prise en charge postopératoire des patientes atteintes de cancer de l’endomètre

The treatment of patients with endometrial cancer has been extensively modified in recent years. Several randomized studies have redefined the indications for adjuvant therapy in tumours staged 1. In the absence of poor prognostic factors, the management tends to be less aggressive than before, often limited to vaginal brachytherapy. Conversely, for more advanced lesions, for which prognosis is poor, combinations of chemoradiation are currently being evaluated. This literature review aims to provide an update on recent developments in the management of adjuvant radiotherapy for endometrial carcinoma.

OC-0129: Image-guided adaptive brachytherapy in cervical cancer: towards a personalization of planning aims

not received. SP-0128 Patient reported quality of life with IGABT in cervical cancer R.A. Nout, K. Kirchheiner, K. Tanderup, J.C. Lindegaard, R. Pötter Leiden University Medical Center (LUMC), Department of Radiotherapy, Leiden, The Netherlands Comprehensive Cancer Center Medical University of Vienna/General Hospital of Vienna, Department of Radiation Oncology, Vienna, Austria Aarhus University Hospital, Department of Oncology,

OC-40 IMAGE GUIDED BRACHYTHERAPY ENDS THE DEBATE OF SYSTEMATIC RADICAL HYSTERECTOMY IN LOCALLY ADVANCED CERVICAL CANCER

Purpose/Objective: To evaluate the outcomes of 3D image guided brachytherapy (IGABT) after concomitant chemoradiation (CCT) in locally advanced cervical cancer. Materials and Methods: As part of the retro-EMBRACE revisory group, clinical data from patients treated at Institut Gustave-Roussy from 2004 to 2009 with curative intent IGABT after CCT were reviewed. Patients received pelvic +/para-aortic CCT (45-50.4 Gy) followed by MRI or CT guided pulsed dose rate BT. BT was performed according to GEC-ESTRO guidelines. Additional nodal or parametrial EBRT boosts were performed when indicated. In a first period, stage I or II patients systematically underwent radical hysterectomy or were offered a randomized study comparing hysterectomy versus observation in case of complete remission. Following the results of this trial, hysterectomy was limited to salvage treatment. Results: Of 163 patients identified, 27% had stage 1B, 6% IIA, 51% IIB, 3% IIIA, 9% IIIB and 3% IVA. At diagnosis, median tumour volume was 55 cm 3 (3-269). Squamous cell carcinoma was the commonest histological subtype (87%). Nodal involvement was noticed in 37% of the patients; among them, 15% had para aortic involvement. Ninety percents received concomitant chemotherapy and 18% received pelvic plus para-aortic EBRT. BT was based on MRI in 88% of the cases and on CT for the remaining 12%. Vaginal personalized mould was used in the majority of applications (95%), with an intracavitary technique in all cases except two. The doses delivered (EBRT + BT, in EqD2) were 67.1+/-6.4 Gy (α/β=10) to 90% of the IR-CTV, 78.1+/-9.6 Gy (α/β=10) to 90% of the HR-CTV. The D2cc for the bladder, rectum and sigmoid were 67.8+/-6.7 Gy, 58.8+/-5.9 Gy and 58.3 Gy+/-5.7 (α/β=3) respectively. Sixty-one patients (37%) underwent a radical hysterectomy. Macroscopic residual disease was found in 13 cases. With a median follow-up of 36 months (5-79), 45 patients had relapsed. Twelve local relapses were reported (5 central and 7 lateral +/central), of which 4 were isolated. There were 22 nodal failures (10 pelvic and 12 para-aortic) and 28 metastatic relapses. At the time of failure, 70.4% of the patients had distant metastasis, and this was isolated in more than a half. The 3 year OS and DFS were 84% and 73% respectively. Local control was 92% and pelvic control was 86%. Local control decreased in relation to the initial tumour width: 97% for <5cm (n=74), 91 for 5-6cm (n=50) and 81% for ≥6cm(n=39), p=0.036. According to the Common Toxicity Criteria 3.0, 7.4% of patients experienced late grade 3/4 toxicity. Seventy-five percent (9/12) of those with a grade 3/4 toxicity had undergone post-radiation radical surgery. Conclusions: IGABT combined with CCT provides excellent locoregional control rates with low treatment related morbidity, justifying the elimination of radical hysterectomy in the absence of obvious local failure. Distant metastasis remains an important site of first relapse and may warrant more aggressive systemic treatment.