Anne Tailleur

Impact of treatment time and dose escalation on local control in locally advanced cervical cancer treated by chemoradiation and image-guided pulsed-dose rate adaptive brachytherapy.

PURPOSE To report the prognostic factors for local control in patients treated for locally advanced cervical cancer with image guided pulsed-dose rate brachytherapy. MATERIALS/METHODS Patients treated with curative intent by a combination of external beam radiotherapy and pulsed-dose rate brachytherapy were selected. Local failure was defined as any relapse in the cervix, vagina, parametria, or uterus during follow-up. Prognostic factors were selected based on log rank tests and then analyzed with a Cox model. Dose/effect correlations were performed using the probit model. RESULTS Two hundred and twenty-five patients treated from 2006 to 2011 were included. According to the FIGO classification, 29% were stage IB, 58% stage II, 10% stage III, and 3% stage IVA; 95% received concomitant chemotherapy. Thirty patients were considered having incomplete response or local failure. Among the selected parameters, D90 for HR-CTV, D90 for IR-CTV, the overall treatment time, the TRAK, and the HR-CTV volume appeared significantly correlated with local control in univariate analysis. In multivariate analysis, overall treatment time >55days and HR-CTV volume >30cm(3) appeared as independent. The probit analysis showed significant correlations between the D90 for both CTVs, and the probability of achieving local control (p=0.008 and 0.024). The thresholds to reach to warrant a probability of 90% of local control were 85Gy to the D90 of the HR-CTV and 75Gy to 90% of the IR-CTV (in 2Gy equivalent, α/β=10). To warrant the same local control rate, the D90 HR-CTV should be significantly increased in stage III-IV tumors, in case of HR-CTV >30cm(3), excessive treatment time, or tumor width at diagnosis >5cm (97, 92, 105, and 92Gy respectively). CONCLUSIONS Overall treatment time and HR-CTV volume were independent prognostic factors for local control. The D90 for HR and IR CTV were significantly correlated with local control, and D90 HR-CTV should be adapted to clinical criteria.

Adaptive 3D Image-Guided Brachytherapy: A Strong Argument in the Debate on Systematic Radical Hysterectomy for Locally Advanced Cervical Cancer

PURPOSE To evaluate the outcomes of patients with locally advanced cervical cancer treated with three-dimensional image-guided brachytherapy (IGABT) after concomitant chemoradiation (CCRT). MATERIALS AND METHODS Data from patients treated with CCRT followed by magnetic resonance imaging-guided or computed tomography-guided pulsed-dose-rate brachytherapy, performed according to the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology guidelines, were reviewed. At first, stage I or II patients systematically underwent radical hysterectomy or were offered a randomized study evaluating hysterectomy. Then, hysterectomy was limited to salvage treatment. RESULTS Of 163 patients identified, 27% had stage IB, 57% had stage II, 12% had stage III, and 3% had stage IVA disease. The mean dose delivered (in 2-Gy dose equivalents) to 90% of the high-risk clinical target volume was 78.1 ± 9.6 Gy, whereas the doses delivered to organs at risk were maintained under the usual thresholds. Sixty-one patients underwent a hysterectomy. Macroscopic residual disease was found in 13 cases. With a median follow-up of 36 months (range, 5-79 months), 45 patients had relapsed. The 3-year overall survival rate was 76%. Local and pelvic control rates were 92% and 86%, respectively. According to the Common Toxicity Criteria 3.0, 7.4% of patients experienced late grade 3 or 4 toxicity. Most of those had undergone postradiation radical surgery (2.9% vs. 14.8; p = .005). CONCLUSION IGABT combined with CCRT provides excellent locoregional control rates with low treatment-related morbidity, justifying the elimination of hysterectomy in the absence of obvious residual disease. Distant metastasis remains an important first relapse and may warrant more aggressive systemic treatment.

Pulsed-dose rate image-guided adaptive brachytherapy in cervical cancer: Dose-volume effect relationships for the rectum and bladder

PURPOSE To establish dose-volume effect correlations for late bladder and rectum side effects in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate image-guided adaptive brachytherapy. MATERIAL AND METHODS The dosimetric data, converted in 2 Gy equivalent, from 217 patients were confronted to late morbidity defined as any event lasting or occurring 90 days after treatment initiation. Toxicity was assessed using the CTC-AE 3.0. Probit analyses and Log rank tests were performed to assess relationships. RESULTS One hundred and sixty-one urinary and 58 rectal events were reported, affecting 98 (45.1%) and 51 (23.5%) patients, respectively. Cumulative incidences for grade 2-4 bladder and rectal morbidity were 24.3% and 9.6% at 3 years, respectively. Significant relationships were observed between grade 2-4 and 3-4 events and D0.1cm(3) and D2 cm(3) for the bladder and between grade 1-4 and 2-4 event probability and rectal D2 cm(3). The effective doses for 10% grade 2-4 morbidity were 65.3 Gy (59.8-81.3), and 55.4 Gy (15.7-63.6), respectively, for the rectum and bladder. Without considering urinary and rectal incontinence, for which the pertinence of correlating them with D2 cm(3) is questionable, ED10 were 68.5 Gy (62.9-110.6) and 65.5 Gy (51.4-71.6 Gy). When sorting patients according to D2 cm(3) levels, patients with high D2 cm(3) had significantly lower morbidity free survival rates for grade 1-4 and 2-4 urinary and rectal morbidity. CONCLUSION Significant dose-volume effect relationships were demonstrated between the modern dosimetric parameters and the occurrence of late rectal and urinary morbidity in patients treated with pulsed-dose-rate brachytherapy. Further studies are required to refine these relationships according to clinical cofactors, such as comorbidities.

D2cm3/DICRU ratio as a surrogate of bladder hotspots localizations during image-guided adaptive brachytherapy for cervical cancer: Assessment and implications in late urinary morbidity analysis

PURPOSE To evaluate the efficiency and potential implications of the lowest dose evaluated in the maximally exposed 2cm(3) of the bladder/dose evaluated at the International Commission for Radiation Units and Measurements (ICRU) bladder point (D2cm(3)/DICRU) ratio as surrogate to locate the D2cm(3) in patients treated with MRI-guided adaptive brachytherapy for cervical cancer. METHODS AND MATERIALS The D2cm(3) area of the bladder was located in 69 patients, using the Digital Imaging and Communications in Medicine coordinates of its barycenter, with respect to the ICRU bladder point. The D2cm(3)/DICRU ratio was correlated with the longitudinal coordinate of the D2cm(3). Afterward, the ratio was used in a retrospective cohort of 216 patients to evaluate its impact in dose-effect analyses for late urinary incontinence. RESULTS The mean position of the D2cm(3) was 1.73±0.98 cm cranially, 0.59±0.65 cm backwardly, and 0.02±0.89 cm to the right of the ICRU point. It was located above the ICRU point in 95.7% of the patients. Its position was lower in patients with vaginal involvement at diagnosis (p=0.03). The D2cm(3)/DICRU ratio was correlated with the position of the D2cm(3) (R²=0.716, p<10(-6)). In speculating that a ratio greater than one would predict a D2cm(3) located above the ICRU point, the sensibility, specificity, positive, and negative predictive values were 95.2%, 100%, 100%, and 66.8%, respectively. Among the retrospective cohort, 85 patients had a ratio lower than 1.1, reflecting a D2cm(3) located in the lower bladder. In these patients, analyses showed significant dose relationship with Grade 2-4 incontinence (p=0.017), whereas no correlation was demonstrated in the remaining patients. CONCLUSIONS The D2cm(3)/DICRU ratio is a relevant surrogate to estimate the localization of the D2cm(3). Significant dose-effect correlations for incontinence were established in patients with low values for this ratio.

Adjuvant brachytherapy for endometrial cancer: Advantages of the vaginal mold technique

PURPOSE Treatment of endometrial carcinoma in the adjuvant setting includes in most cases vaginal brachytherapy. In our institution, we use the customized vaginal mold technique. Herein, we report the advantages of this personalized applicator in terms of target coverage, normal tissue preservation, the incidence of air pockets, and its potential impact on dosimetry. METHODS AND MATERIALS A total of 15 patients receiving postoperative vaginal cuff high-dose-rate brachytherapy with the mold applicator technique were enrolled in this prospective data collection study. Patients were treated with either two or four fractions of 5 Gy prescribed to the clinical target volume, which consisted of an irradiation of the vaginal cuff and the upper third of the vagina. Target coverage; dose to organs at risk, in addition to the volume; and the dosimetric impact of air pockets surrounding the mold were evaluated. RESULTS In 15 patients, a total of 27 air pockets were identified. The average number of air pockets per patient was 1.8 (range, 0-4), with the average total air pocket volume being 0.1 cc (range, 0.01-0.54). The average dose reduction at 5mm from the air pocket was 26% (range, 6-45%). The minimal clinical target volume coverage reported was 95% and the maximal dose received by 2 cc of the bladder, rectum, and sigmoid never exceeded 110% of the prescribed dose. CONCLUSIONS Vaginal cuff high-dose-rate brachytherapy using the molded applicator provides personalized tailored treatment in terms of anatomical conformity. This translates into a dosimetrical advantage with smaller and fewer air pockets than reported in the literature with the use of cylinders.

Vaginal dose assessment in image-guided brachytherapy for cervical cancer: Can we really rely on dose-point evaluation?

PURPOSE Although dose-volume parameters in image-guided brachytherapy have become a standard, the use of posterior-inferior border of the pubic symphysis (PIBS) points has been recently proposed in the reporting of vaginal doses. The aim was to evaluate their pertinence. METHODS AND MATERIALS Nineteen patients who received image-guided brachytherapy after concurrent radiochemotherapy were included. Per treatment, CT scans were performed at Days 2 and 3, with reporting of the initial dwell positions and times. Doses delivered to the PIBS points were evaluated on each plan, considering that they were representative of one-third of the treatment. The movements of the applicator according to the PIBS point were analysed. RESULTS Mean prescribed doses at PIBS -2, PIBS, PIBS +2 were, respectively, 2.23 ± 1.4, 6.39 ± 6.6, and 31.85 ± 36.06 Gy. Significant differences were observed between the 5 patients with vaginal involvement and the remaining 14 at the level of PIBS +2 and PIBS: +47.60 Gy and +7.46 Gy, respectively (p = 0.023 and 0.03). The variations between delivered and prescribed doses at PIBS points were not significant. However, at International commission on radiation units and measurements rectovaginal point, the delivered dose was decreased by 1.43 ± 2.49 Gy from the planned dose (p = 0.019). The delivered doses at the four points were strongly correlated with the prescribed doses with R(2) ranging from 0.93 to 0.95. The movements of the applicator in regard of the PIBS point assessed with the Digital Imaging and Communications in Medicine coordinates were insignificant. CONCLUSION The doses evaluated at PIBS points are not impacted by intrafractional movements. PIBS and PIBS +2 dose points allow distinguishing the plans of patients with vaginal infiltration. Further studies are needed to correlate these parameters with vaginal morbidity.

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.