D. Lefkopoulos

Clinical outcomes of definitive chemoradiation followed by intracavitary pulsed-dose rate image-guided adaptive brachytherapy in locally advanced cervical cancer

OBJECTIVE To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided adaptive brachytherapy (IGABT). METHODS Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/- para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations. RESULTS Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage≥IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4+/-10.3Gy and 67.7+/-6.1Gy. After a median follow-up of 38.8months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p=0.06). Local control rates at 3years were 95.6% in the group of patients with D90 of HR-CTV≥85Gy, 88.8% in those with D90 between 80 and 85Gy, and 80% when D90<80Gy (p=0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%. CONCLUSIONS CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases.

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.

Comparison between the ICRU rectal point and modern volumetric parameters in brachytherapy for locally advanced cervical cancer

PURPOSE The implementation of image-guided brachytherapy in cervical cancer raises the problem of adapting the experience acquired with 2D brachytherapy to this technique. The GEC-ESTRO (Groupe européen de curiethérapie - European Society for Radiotherapy and Oncology) has recommended reporting the dose delivered to the rectum in the maximally exposed 2 cm(3) volume, but so far, the recommended dose constraints still rely on 2D data. The aim of this study was to evaluate the relationship between the doses evaluated at the ICRU rectal point and modern dosimetric parameters. MATERIAL AND METHODS For each patient, dosimetric parameters were generated prospectively at the time of dosimetry and were reported. For analysis, they were converted in 2 Gy equivalent doses using an α/β ratio of 3 with a half-time of repair of 1.5 hours. RESULTS The dosimetric data from 229 consecutive patients treated for locally advanced cervical cancer was analyzed. The mean dose calculated at ICRU point (DICRU) was 55.75 Gy ± 4.15, while it was 59.27 Gy ± 6.16 in the maximally exposed 2 cm(3) of the rectum (P=0.0003). The D2 cm(3) was higher than the DICRU in 78% of the cases. The mean difference between D2 cm(3) and DICRU was 3.53 Gy ± 4.91. This difference represented 5.41% ± 7.40 of the total dose delivered to the rectum (EBRT and BT), and 15.49% ± 24.30 of the dose delivered when considering brachytherapy alone. The two parameters were significantly correlated (P=0.000001), and related by the equation: D2 cm(3)=0.902 × DICRU + 0.984. The r(2) coefficient was 0.369. CONCLUSION In this large cohort of patients, the DICRU significantly underestimates the D2 cm(3). This difference probably results from the optimization process itself, which consists in increasing dwell times above the ICRU point in the cervix. Considering these findings, caution must be taken while implementing image-guided brachytherapy and dose escalation.

Thyroid Radiation Dose and Other Risk Factors of Thyroid Carcinoma Following Childhood Cancer

CONTEXT Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other factors requires additional investigation. OBJECTIVE This study aimed to investigate the role of potential modifiers of the dose response. DESIGN We followed a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986 over an average of 27 years. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered. RESULTS Fifty-five patients developed thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (relative risk [RR] = 2.3; 95% confidence interval [CI], 1.3-4.0), high radiation doses (>5 Gy) to pituitary gland lowered this risk (RR = 0.2; 95% CI, 0.1-0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95% CI, 2.5-15.7) higher risk than those who did not. The excess RR per Gy of radiation to the thyroid was 4.7 (95% CI, 1.7-22.6). It was 7.6 (95% CI, 1.6-33.3) if body mass index at time of interview was equal or higher than 25 kg/m(2), and 4.1 (95% CI, 0.9-17.7) if not (P for interaction = .1). CONCLUSION Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.

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.

Implementation of the global risk analysis in pulsed-dose rate brachytherapy: methods and results.

PURPOSE To report the application of the global risk analysis (GRA) in the pulsed-dose rate (PDR) brachytherapy workflow. MATERIAL AND METHODS Analyses were led by a multidisciplinary working group established within the unit with the guidance of a quality engineer. First, a mapping of hazardous situations was developed as a result of interactions between the patient workflow for a treatment using PDR brachytherapy split into 51 sub-phases with a comprehensive list of the hazards that he/she faces (44). Interactions, when relevant, were sorted by level of priority: to be treated immediately, secondarily (the group is not entitled to treat the situation), or later (safe situation). Secondly, for each high priority dangerous situation, scenarios were developed to anticipate their potential consequences. Criticality was assessed, using likelihood and severity scales and a matrix, which allocated risks into categories: acceptable (C1), tolerable under control (C2) and unacceptable (C3). Then, corrective actions were proposed and planned when relevant, after assessment of their feasibility with a scale of effort. Finally, the criticality of the scenarios was reevaluated, taking into account the implementation of these actions, leading to a residual risk mapping, which could trigger additional proposals of actions. RESULTS Two thousand one hundred and eighty-four potential interactions between the list of hazards and the workflow were analyzed. Mapping of dangerous situations identified 213 relevant interactions, from which 61 were considered with high priority. One hundred and twenty-six scenarios were generated: 68 with a low criticality (74.3%), 58 with an intermediate score (25.7%). No scenario with the highest criticality was individualized. Twenty-one corrective actions were planned. Mapping of residual risk resulted in the disappearance of most C2 risks, leaving 5 C2 scenarios (4%), for which four monitoring indicators were implemented in addition to the corrected actions decided on. CONCLUSION The implementation of the GRA appeared feasible, and led to implement 21 corrective actions, based on scenarios and not on incidents.

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,