I. Dumas

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

PURPOSEnThe 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.nnnMATERIAL AND METHODSnFor 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.nnnRESULTSnThe 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.nnnCONCLUSIONnIn 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.

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

PURPOSEnConcomitant 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.nnnMETHODSnAmong 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.nnnRESULTSnFifty-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).nnnCONCLUSIONSnAlthough 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.

PURPOSESnFirstly, 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.nnnMATERIAL AND METHODSnTwo 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.nnnRESULTSnThe 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.nnnCONCLUSIONnNo 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.

Interstitial pulsed-dose-rate brachytherapy for the treatment of squamous cell anal carcinoma: A retrospective single institution analysis

OBJECTIVEnTo examine the outcome of patients receiving interstitial pulsed-dose-rate brachytherapy (PDR-BT) after pelvic radiation therapy for treatment of an anal squamous cell carcinoma.nnnMETHODS AND MATERIALSnTwenty-one patients were identified: 13, six, and two with stages I, II, and III tumors, respectively. After receiving received pelvic irradiation +/- concurrent chemotherapy, patients were delivered a PDR-BT boost to the residual tumor, with intention to deliver a minimal total dose of 60 Gy. The greatest dimension of residual tumor at the time of brachytherapy procedure was 12.5 mm (range: 0-20 mm). Brachytherapy implantation was performed according to the Paris system, only one plane implant being used.nnnRESULTSnMedian dose delivered through BT was 20 Gy (range: 10-30 Gy). Median number of pulses was 48 (range: 20-80 pulses). Median treated volume was 9 cm(3) (range: 5-16 cm(3)). Median dose per pulse was 40 cGy (range: 37.5-50 cGy). No Grade 3 or more acute toxicity was reported. No Grade 3 or more delayed toxicity was seen among 18 patients with more than 6 months follow-up. Median followup was 47 months (range: 6-73 months). Twenty patients (95%) were alive at last follow-up. Tumor relapses were experienced in four patients (19%), including local relapse in three patients (14%).nnnCONCLUSIONnWith almost 4 years median followup, this study confirms previous data suggesting that PDR-BT is effective and safe in this indication. Local control rate and toxicity were in the range of what was seen with continuous low-dose-rate BT.

Mise au pointCuriethérapie de débit de dose pulsé dans les cancers du col utérin : pourquoi, comment ?Pulsed-dose rate brachytherapy in cervical cancers: Why, how?

The end of the production of 192 iridium wires terminates low dose rate brachytherapy and requires to move towards pulsed-dose rate or high-dose rate brachytherapy. In the case of gynecological cancers, technical alternatives exist, and many teams have already taken the step of pulsed-dose rate for scientific reasons. Using a projector source is indeed a prerequisite for 3D brachytherapy, which gradually installs as a standard treatment in the treatment of cervical cancers. For other centers, this change implies beyond investments in equipment and training, organizational consequences to ensure quality.

Curiethérapie de débit de dose pulsé dans les cancers du col utérin : pourquoi, comment ?

The end of the production of 192 iridium wires terminates low dose rate brachytherapy and requires to move towards pulsed-dose rate or high-dose rate brachytherapy. In the case of gynecological cancers, technical alternatives exist, and many teams have already taken the step of pulsed-dose rate for scientific reasons. Using a projector source is indeed a prerequisite for 3D brachytherapy, which gradually installs as a standard treatment in the treatment of cervical cancers. For other centers, this change implies beyond investments in equipment and training, organizational consequences to ensure quality.

Contribution of image-guided adaptive brachytherapy to pelvic nodes treatment in locally advanced cervical cancer

PURPOSEnWith the increasing use of simultaneous integrated boost in the treatment of cervical cancer, there is a need to anticipate the brachytherapy (BT) contribution at the level of the pathologic pelvic lymph nodes. This study aimed to report the dose delivered at their level during BT.nnnMETHODS AND MATERIALSnPatients with pelvic nodal involvement and treated with a combination of chemoradiation followed by image-guided adaptive pulsed-dose-rate BT were selected. On per BT three-dimensional images, pelvic lymphadenopathies were delineated, without planning aim. For the purposes of the study, D100, D98, D90, and D50 were reviewed and converted in 2-Gy equivalent doses, using the linear quadratic model with an α/β of 10xa0Gy.nnnRESULTSnNinety-one patients were identified, allowing evaluation at the level of 226 lymphadenopathies. The majority of them were external iliac (48%), followed by common iliac (25%), and internal iliac (16%) regions. The 2-Gy equivalent doses D98 were 4.4xa0±xa01.9xa0Gy, 5.4xa0±xa03.1xa0Gy, and 4.3xa0±xa02.1xa0Gy for the obturator, internal iliac, and external iliac, respectively, and 2.8xa0±xa02.5xa0Gy for the common iliac. The contribution to the common iliac nodes was significantly lower than the one of external and internal iliac (p < 0.001).nnnCONCLUSIONSnBT significantly contributes to the treatment of pelvic nodes at the level of approximately 5xa0Gy in the internal, external, and obturator areas and 2.5xa0Gy in the common iliac, allowing the anticipation of nodal boost with the simultaneous integrated boost technique. However, important individual variations have been observed, and evaluation of the genuine BT contribution should be recommended.

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

PURPOSEnTo report the application of the global risk analysis (GRA) in the pulsed-dose rate (PDR) brachytherapy workflow.nnnMATERIAL AND METHODSnAnalyses 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.nnnRESULTSnTwo 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.nnnCONCLUSIONnThe implementation of the GRA appeared feasible, and led to implement 21 corrective actions, based on scenarios and not on incidents.

Image-guided adaptive brachytherapy in primary vaginal cancers: A monocentric experience

PURPOSEnPrimary vaginal cancer is a rare disease for which treatment has been modeled based on cervical cancer. We report our experience in the use of image-guided adaptive brachytherapy (IGABT) in this indication.nnnMETHODS AND MATERIALSnPatients treated for vaginal cancer with a combination of external beam radiation therapy and IGABT were identified through electronic search. The Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology recommendations for cervical cancer have been extrapolated with the definition of two clinical target volumes (CTVs) corresponding to the residual disease after external beam radiation therapy (CTVBT), assessed from clinical and imaging findings, and the so-called CTVi, comprising the CTVBT with directional margins and at least the initial disease at diagnosis.nnnRESULTSnTwenty-seven patients were identified. MRI was used for brachytherapy guidance in 82% of the cases. An interstitial component was used in 59% of the cases. The D90 CTVBT and D90 CTVi were 73.1xa0±xa012.8xa0Gy and 66.6xa0±xa06.7xa0Gy, respectively. After a median followup of 40.1xa0months, nine recurrences in 8 patients were observed of which four were local. Local relapses occurred within the CTVBT. Three-year local control and disease-free rates were 82% and 65%, respectively. At 2xa0years, the Grade 2-4 gastrointestinal or urinary morbidity accrual rate was 9%. Twelve patients experienced late sexual morbidity, including three patients with Grade 3xa0stenosis.nnnCONCLUSIONnIGABT is feasible in vaginal cancer with promising outcomes. Harmonizing the definition of CTVs is required to allow comparisons between experiences and to perform multicenter studies.

SP-0005: Role of brachytherapy in the management of paediatric tumours

ESTRO 35 2016 _____________________________________________________________________________________________________ the expense of radiation-induced late toxicity. Progressive cell depletion and inflammation are the leading mechanisms of acute toxicity which is observed during or shortly after treatment. The pathogenetic pathways of late toxicity, developing 90 days or later after the onset of radiotherapy, are more complex and involve processes such as vascular sclerosis and fibrosis. Since many patients have become longterm survivors, awareness and recognition of radiationrelated toxicity has gained in importance and increased efforts are made for its prevention and management. Technical innovations contribute to a reduction in radiotherapy-associated toxicity. The steep dose gradients of highly-conformal radiotherapy techniques allow for an accurate dose delivery with optimal sparing of the normal tissues. Several studies have demonstrated the dosimetrical benefit of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT) compared to conventional radiotherapy techniques. It has been shown that the dosimetrical benefit of IMRT translated into a clinically significant reduction in lower gastrointestinal toxicity compared with three-field conventional radiotherapy. In the near future MRI-linacs and proton therapy are likely to broaden the therapeutic window further. Prone positioning on a bellyboard reduces small bowel toxicity by pushing away the small bowel loops from the high dose region. Imageguided radiotherapy allows for an accurate definition, localization and monitoring of tumor position, size and shape before and during treatment and may help to reduce set-up margins. Small randomized controlled trials have shown that the administration of several agents might have a beneficial effect for the prevention of acute (e.g. intrarectal amifostine, oral sulfasalazine and balsalazide) and/or lateonset radiation-induced toxicity (intrarectal beclomethasone and oral probiotics). Once severe toxicity develops, total replacement of the diet with elemental formula may be appropriate. Probiotics influence the bacterial microflora and seem promising in reducing the incidence and severity of radiation-induced diarrhea. Currently there is insufficient evidence for cytoprotective and anti-inflammatory drugs in the management of radiation-induced toxicity. Future challenges lie in the prediction of treatment-related toxicity, which might be a promising step towards an individualized risk-adapted treatment.