Christine Haie-Meder

Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (IV): Basic principles and parameters for MR imaging within the frame of image based adaptive cervix cancer brachytherapy.

The GYN GEC-ESTRO working group issued three parts of recommendations and highlighted the pivotal role of MRI for the successful implementation of 3D image-based cervical cancer brachytherapy (BT). The main advantage of MRI as an imaging modality is its superior soft tissue depiction quality. To exploit the full potential of MRI for the better ability of the radiation oncologist to make the appropriate choice for the BT application technique and to accurately define the target volumes and the organs at risk, certain MR imaging criteria have to be fulfilled. Technical requirements, patient preparation, as well as image acquisition protocols have to be tailored to the needs of 3D image-based BT. The present recommendation is focused on the general principles of MR imaging for 3D image-based BT. Methods and parameters have been developed and progressively validated from clinical experience from different institutions (IGR, Universities of Vienna, Leuven, Aarhus and Ljubljana) and successfully applied during expert meetings, contouring workshops, as well as within clinical and interobserver studies. It is useful to perform pelvic MRI scanning prior to radiotherapy (“Pre-RT-MRI examination”) and at the time of BT (“BT MRI examination”) with one MR imager. Both low and high-field imagers, as well as both open and close magnet configurations conform to the requirements of 3D image-based cervical cancer BT. Multiplanar (transversal, sagittal, coronal and oblique image orientation) T2-weighted images obtained with pelvic surface coils are considered as the golden standard for visualisation of the tumour and the critical organs. The use of complementary MRI sequences (e.g. contrast-enhanced T1-weighted or 3D isotropic MRI sequences) is optional. Patient preparation has to be adapted to the needs of BT intervention and MR imaging. It is recommended to visualise and interpret the MR images on dedicated DICOM-viewer workstations, which should also assist the contouring procedure. Choice of imaging parameters and BT equipment is made after taking into account aspects of interaction between imaging and applicator reconstruction, as well as those between imaging, geometry and dose calculation. In a prospective clinical context, to implement 3D image-based cervical cancer brachytherapy and to take advantage of its full potential, it is essential to successfully meet the MR imaging criteria described in the present recommendations of the GYN GEC-ESTRO working group.

Ovarian transposition for patients with cervical carcinoma treated by radiosurgical combination

OBJECTIVE To assess the indications, effectiveness, and complications of ovarian transposition before pelvic irradiation for cervical cancer. DESIGN Prospective study. SETTING Gynecologic oncology department at a French cancer center. PATIENT(S) One hundred seven patients treated for cervical cancer. INTERVENTION(S) Ovarian transposition to the paracolic gutters with radical hysterectomy and lymphadenectomy. MAIN OUTCOME MEASURE(S) Clinical and laboratory follow-up tests for ovarian function. RESULT(S) Bilateral ovarian transposition was achieved in 104 patients (98%). Twelve patients were lost to follow-up or excluded because of evolution of the disease. Preservation of ovarian function was achieved in 83% of the patients having follow-up. The rates of ovarian preservation were 100% for patients treated exclusively by surgery, 90% for patients treated by postoperative vaginal brachytherapy, and 60% for patients treated by postoperative external radiation therapy and vaginal brachytherapy. The main risk for ovarian failure was found in patients treated by external radiation therapy. CONCLUSION(S) Ovarian transposition is a safe and effective procedure for preserving ovarian function in patients treated by a radiosurgical combination. This procedure should be performed in patients <40 years of age with a small invasive cervical carcinoma (<3 cm) treated by initial surgery. In such selected cases, the risk of ovarian metastasis is low.

Impact of 3D image-based PDR brachytherapy on outcome of patients treated for cervix carcinoma in France: results of the French STIC prospective study.

PURPOSE In 2005 a French multicentric non randomized prospective study was initiated to compare two groups of patients treated for cervix carcinoma according to brachytherapy (BT) method: 2D vs 3D dosimetry. The BT dosimetric planning method was chosen for each patient in each center according to the availability of the technique. This study describes the results for 705 out of 801 patients available for analysis. PATIENTS AND METHODS For the 2D arm, dosimetry was planned on orthogonal X-Rays using low dose rate (LDR) or pulsed dose rate (PDR) BT. For the 3D arm, dosimetry was planned on 3D imaging (mainly CT) and performed with PDR BT. Each center could follow the dosimetric method they were used to, according to the chosen radioelement and applicator. Manual or graphical optimization was allowed. PATIENTS AND METHODS Three treatment regimens were defined: Group 1: BT followed by surgery; 165 patients (2D arm: 76; 3D arm: 89); Group 2: EBRT (+chemotherapy), BT, then surgery; 305 patients (2D arm: 142; 3D arm: 163); Group 3: EBRT (+chemotherapy), then BT; 235 patients, (2D arm: 118; 3D arm: 117). PATIENTS AND METHODS The DVH parameters for CTVs (High Risk CTV and Intermediate Risk CTV) and organs at risk (OARs) were computed as recommended by GYN GEC ESTRO guidelines. Total doses were converted to equivalent doses in 2Gy fractions (EQD2). Side effects were prospectively assessed using the CTCAEv3.0. RESULTS The 2D and 3D arms were well balanced with regard to age, FIGO stage, histology, EBRT dose and chemotherapy. For each treatment regimen, BT doses and volumes were comparable between the 2D and 3D arms in terms of dose to point A, isodose 60 Gy volume, dose to ICRU rectal points, and TRAK. RESULTS Dosimetric data in the 3D arm showed that the dose delivered to 90% of the High Risk CTV (HR CTV D90) was respectively, 81.2Gy(α/β10), 63.2Gy(α/β10) and 73.1Gy(α/β10) for groups 1, 2 and 3. The Intermediate Risk (IR) CTV D90 was respectively, 58.5Gy(α/β10), 57.3Gy(α/β10) and 61.7Gy(α/β10) for groups 1, 2 and 3. For the OARs, doses delivered to D2cc ranged 60-70Gy(α/β3) for the bladder, 33-61Gy(α/β3) for the rectum, and 44-58Gy(α/β3) for the sigmoid according to the regimen. RESULTS At 24 months, local relapse-free survival was 91.9% and 100% in group 1, 84.7% and 93% in group 2, 73.9% and 78.5% in group 3; grade 3-4 toxicity rate was 14.6% and 8.9% in group 1, 12.5% and 8.8% in group 2, and 22.7% and 2.6% in group 3 for 2D and 3D arm. CONCLUSION This multicentric study has shown that 3D BT is feasible and safe in routine practice. It has improved local control with half the toxicity observed with 2D dosimetry. The combined treatment with radiotherapy and surgery was more toxic than definitive radiotherapy. For patients with advanced tumors, it is necessary to improve coverage of target volumes without raising toxicity.

GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas.

Both primary and recurrent squamous cell carcinoma of the head and neck are classic indications for brachytherapy. A high rate of local tumor control at the cost of limited morbidity can be achieved with brachytherapy through good patient selection, meticulous source implantation and careful treatment planning. However, no randomized trials have been performed, and there is scant evidence in the literature especially regarding practical clinical recommendations for brachytherapy for head and neck subsites. The Head and Neck Working Group of the European Brachytherapy Group (Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) therefore decided to formulate the present consensus recommendations for low-dose rate, pulsed-dose rate and high-dose rate brachytherapy. The use of brachytherapy in combination with external beam radiotherapy and/or surgery is also covered as well as the use of brachytherapy in previously irradiated patients. Given the paucity of evidence in the literature, these recommendations are mainly based on clinical experience accumulated by the members of the working group over several decades and the respective publications. The recommendations cover in a general part (1) patient selection, the pre-treatment work up and patient care, (2) treatment strategy, (3) target definition, (4) implant techniques, (5) dose and dose rate prescription, (6) treatment planning and reporting, (7) treatment monitoring (8) catheter removal, and (9) post-treatment patient care and follow-up. The recommendations are then specified for the classical brachytherapy tumor sites following an analogue more focussed structure (patient selection, implant technique, target definition, dose and dose rate prescription, results): lip, oral mucosa, mobile tongue, floor of mouth, oropharynx, nasopharynx, paranasal sinuses.

PHYSICS CONTRIBUTIONS AND CLINICAL OUTCOME WITH 3D-MRI-BASED PULSED-DOSE-RATE INTRACAVITARY BRACHYTHERAPY IN CERVICAL CANCER PATIENTS

PURPOSE To assess the physics contributions and clinical outcome with three-dimensional magnetic resonance imaging-guided pulsed-dose-rate (PDR) intracavitary brachytherapy in cervical cancer patients. METHODS AND MATERIALS The data from 45 patients with primary locally advanced cervical carcinoma were analyzed. The median tumor cervical volume was 64.0 cm(3) (range, 3-178). Of the 45 patients, 24 (53%) had histologic and/or radiologic pelvic involvement. After pelvic with or without para-aortic concomitant chemoradiotherapy, a PDR brachytherapy boost was delivered to a three-dimensional magnetic resonance imaging-based clinical target volume, taking into account the dose-volume constraints for critical organs and optimization of the target volume coverage. RESULTS At a median follow-up of 26 months (range, 9-47), the 2-year overall survival and disease-free survival rate was 78% and 73%, respectively. At the last follow-up visit, the disease of all patients remained locally controlled. Adding external beam radiotherapy and PDR using the equivalent dose in 2-Gy fractions model, the median dose received by 100% and 90% of the target was 54.4 Gy(alpha/beta10) and 63.5 Gy(alpha/beta10) for the intermediate-risk clinical target volume and 61.6 Gy(alpha/beta10) and 74.9 Gy(alpha/beta10) for the high-risk clinical target volume, respectively. Of the 45 patients, 23 and 2 developed acute Grade 1-2 and Grade 3 complications, respectively; 21 patients presented with delayed Grade 1-2 complications. One other patient presented with Grade 3 vesicovaginal fistula. No Grade 4 or greater complications, whether acute or delayed, were observed. CONCLUSION Magnetic resonance imaging-guided PDR brachytherapy with optimization integrating the limits of tolerance to critical organs allows for excellent local control rates. Moreover, the present results have confirmed that the ability to optimize dwell times can contribute to an improvement in local control rates with a low level of late side effects.

Analysis of complications in a prospective randomized trial comparing two brachytherapy low dose rates in cervical carcinoma

PURPOSE The analysis of complications in a prospective randomized trial comparing two preoperative brachytherapy low-dose rates in early stage cervical cancer is presented. METHODS AND MATERIALS Between 1985 and 1988, 204 patients with Stage I and limited Stage II cervical cancer were randomized to receive one of two preoperative brachytherapy low-dose rates (0.4 and 0.8 Gy/hr). The objective of this trial was to determine the benefits, if any, of the higher-dose rate within the therapeutic arsenal for this patient population, in terms of survival, local control, and complications. The type and severity of all complications were evaluated according to a common glossary and a strict follow-up schedule was established given that the treatment of cervical cancer is multidisciplinary, involving gynecologists, surgeons, and radiotherapists. RESULTS Overall survival: 85% at 2 years and local control: 93% at 2 years, were similarly distributed between the two groups. Regardless of their nature and severity, 139 and 175 complications were observed among 63% and 75% of patients, in the 0.4 and 0.8 Gy/h dose rate groups respectively. Gynecologic and urinary complications were the most frequent (38% and 28% of all complications), followed by vascular (15%), digestive (10%), nervous (5%) and cutaneous (5%). A total of 14 and 17 severe complications (Grade 3) were observed in 7% and 13% of patients, respectively in the 0.4 and 0.8 Gy/h dose rate groups (p = 0.12). Nonparametric survival methods used to compare the time to the first complication did not show a significant difference between the two groups: 62% and 72% at 2 years (p = 0.27). When the first complication and its evolution were considered (early complications), the prevalence of complications was not significantly different between the two groups: 28% vs. 34% at 2 years (p = 0.31). In this prospective trial, patients were regularly followed-up and complications of varying nature and severity were observed in succession during follow-up. When successive complications and their evolution were taken into account, the prevalence of complications was significantly greater in the higher-dose rate group: 30% vs. 45% at 2 years (p = 0.03). CONCLUSION The results of this trial showed that long-term effects of treatment, when represented by prevalence of complications over time, were more frequent in the higher dose rate group. This underlines the importance of the regular follow-up of patients and of coding, not only the occurrence of all complications, but also their evolution over time.

Results of a randomized clinical trial comparing two radiation schedules in the palliative treatment of brain metastases

In 216 patients with brain metastases two schedules of brain irradiation were compared in a randomized trial: one course of 18 Gy/3 fractions/3 days versus the same fractionation followed by a second course of radiotherapy with a one-month time interval. The second course was identical to the first one or delivered 25 Gy/10 fractions/14 days. No difference in overall survival, nor in the neurologic response or in the incidence of complications was demonstrated. Two clinical factors appeared to be prognostic of the overall survival: the presence of multiple brain metastases and the presence of extracerebral metastases.

Gynaecological cancers in pregnancy

Cervical and ovarian cancers are the most common gynaecological cancers diagnosed during pregnancy. In early-stage cervical cancer during the first and at the beginning of the second trimester, the two main considerations for management of the patient are the tumour size (and stage) and nodal staging. MRI and laparoscopic lymphadenectomy are useful for clinicians planning a potentially conservative approach. The management of patients with locally advanced cervical disease is controversial and should be discussed on a case-by-case basis according to the tumour size, radiological findings, the term of pregnancy, and the patients wishes. Different histological types of malignant ovarian diseases arise during pregnancy and their management depends on the diagnosis (histological subtypes, tumour differentiation, and nodal status), the tumour stage, and the trimester of the pregnancy. In patients with peritoneal spread or high-risk early-stage disease, neoadjuvant chemotherapy with pregnancy preservation could be appropriate.

Nodal-staging surgery for locally advanced cervical cancer in the era of PET

Chemoradiation therapy is deemed the standard treatment by many North American and European teams for treatment of locally advanced cervical cancer. The prevalence of para-aortic nodal metastasis in these tumours is 10-25%. PET (with or without CT) is the most accurate imaging modality to assess extrapelvic disease in such tumours. The true-positive rate of PET is high, suggesting that surgical staging is not necessary if uptake takes place in the para-aortic region. Nevertheless, false-negative results (in the para-aortic region) have been recorded in 12% of patients, rising to 22% in those with uptake during PET of the pelvic nodes. In such situations, laparoscopic surgical para-aortic staging still has an important role for detection of patients with occult para-aortic spread misdiagnosed on PET or PET-CT, allowing optimisation of treatment (extension of radiation therapy fields to include the para-aortic area). Complications of the laparoscopic procedure were noted in 0-7% of patients. Survival of individuals (missed by PET) with para-aortic nodal metastasis of 5 mm or less (and managed by extended field chemoradiation therapy) seems to be similar to survival of those without para-aortic spread, suggesting a positive therapeutic effect of the addition of staging surgery. Nevertheless, the effect on survival of potential delay of chemoradiation owing to use of PET and staging surgery, and acute and late complications of surgery followed by chemoradiation therapy (particularly in case of extended field chemoradiation to para-aortic area), need to be studied.

Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study

PURPOSE Image guided brachytherapy (IGBT) for locally advanced cervical cancer allows dose escalation to the high-risk clinical target volume (HRCTV) while sparing organs at risk (OAR). This is the first comprehensive report on clinical outcome in a large multi-institutional cohort. PATIENTS AND METHODS From twelve centres 731 patients, treated with definitive EBRT±concurrent chemotherapy followed by IGBT, were analysed. Kaplan-Meier estimates at 3/5years were calculated for local control (LC, primary endpoint), pelvic control (PC), overall survival (OS), cancer specific survival (CSS). In 610 patients, G3-4 late toxicity (CTCAEv3.0) was reported. RESULTS Median follow up was 43months, percent of patients per FIGO stage IA/IB/IIA 22.8%, IIB 50.4%, IIIA-IVB 26.8%. 84.8% had squamous cell carcinomas; 40.5% lymph node involvement. Mean EBRT dose was 46±2.5Gy; 77.4% received concurrent chemotherapy. Mean D90 HRCTV was 87±15Gy (EQD210), mean D2cc was: bladder 81±22Gy, rectum 64±9Gy, sigmoid 66±10Gy and bowel 64±9Gy (all EQD23). The 3/5-year actuarial LC, PC, CSS, OS were 91%/89%, 87%/84%, 79%/73%, 74%/65%. Actuarial LC at 3/5years for IB, IIB, IIIB was 98%/98%, 93%/91%, 79%/75%. Actuarial PC at 3/5years for IB, IIB, IIIB was 96%/96%, 89%/87%, 73%/67%. Actuarial 5-year G3-G5 morbidity was 5%, 7%, 5% for bladder, gastrointestinal tract, vagina. CONCLUSION IGBT combined with radio-chemotherapy leads to excellent LC (91%), PC (87%), OS (74%), CSS (79%) with limited severe morbidity.