C. Kirkove

Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer

BACKGROUND The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown. METHODS We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer. RESULTS Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P=0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P=0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P=0.02). Acute side effects of regional nodal irradiation were modest. CONCLUSIONS In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; ClinicalTrials.gov number, NCT00002851.).

ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer

BACKGROUND AND PURPOSE Delineation of clinical target volumes (CTVs) is a weak link in radiation therapy (RT), and large inter-observer variation is seen in breast cancer patients. Several guidelines have been proposed, but most result in larger CTVs than based on conventional simulator-based RT. The aim was to develop a delineation guideline obtained by consensus between a broad European group of radiation oncologists. MATERIAL AND METHODS During ESTRO teaching courses on breast cancer, teachers sought consensus on delineation of CTV through dialogue based on cases. One teacher delineated CTV on CT scans of 2 patients, followed by discussion and adaptation of the delineation. The consensus established between teachers was sent to other teams working in the same field, both locally and on a national level, for their input. This was followed by developing a broad consensus based on discussions. RESULTS Borders of the CTV encompassing a 5mm margin around the large veins, running through the regional lymph node levels were agreed, and for the breast/thoracic wall other vessels were pointed out to guide delineation, with comments on margins for patients with advanced breast cancer. CONCLUSION The ESTRO consensus on CTV for elective RT of breast cancer, endorsed by a broad base of the radiation oncology community, is presented to improve consistency.

Vessel based delineation guidelines for the elective lymph node regions in breast cancer radiation therapy - PROCAB guidelines

OBJECTIVE A national project to improve the quality of breast radiation therapy was started, named PROCAB (PROject on CAncer of the Breast). One of the objectives was to reach a national consensus guideline for the delineation of the regional lymph node areas in breast radiation therapy. METHODS The realization of the new guidelines was a step by step process that started with multiple expert meetings where the existing guidelines were analyzed and the delineations of the lymph node regions were performed together with a surgeon, specialized in the anatomy of the drainage of the breast. RESULTS The delineation guidelines are vessel-based. Since the occurrence of pathological lymph nodes is typically around the veins, the cranial and caudal borders of all different nodal regions are based on a 5mm margin around the veins, except for the parasternal lymph node area. Compared to the existing guidelines there are some major changes. CONCLUSION With this project a national as well as a European (ESTRO) consensus guideline for the delineation of the regional lymph node areas in breast RT is reached. The new delineation atlas is vessel-based and no longer field-based.

Internal and external validation of an ESTRO delineation guideline – dependent automated segmentation tool for loco-regional radiation therapy of early breast cancer

BACKGROUND AND PURPOSE To internally and externally validate an atlas based automated segmentation (ABAS) in loco-regional radiation therapy of breast cancer. MATERIALS AND METHODS Structures of 60 patients delineated according to the ESTRO consensus guideline were included in four categorized multi-atlas libraries using MIM Maestro™ software. These libraries were used for auto-segmentation in two different patient groups (50 patients from the local institution and 40 patients from other institutions). Dice Similarity Coefficient, Average Hausdorff Distance, difference in volume and time were computed to compare ABAS before and after correction against a gold standard manual segmentation (MS). RESULTS ABAS reduced the time of MS before and after correction by 93% and 32%, respectively. ABAS showed high agreement for lung, heart, breast and humeral head, moderate agreement for chest wall and axillary nodal levels and poor agreement for interpectoral, internal mammary nodal regions and LADCA. Correcting ABAS significantly improved all the results. External validation of ABAS showed comparable results. CONCLUSIONS ABAS is a clinically useful tool for segmenting structures in breast cancer loco-regional radiation therapy in a multi-institutional setting. However, manual correction of some structures is important before clinical use. The ABAS is now available for routine clinical use in Danish patients.

Quality assessment of delineation and dose planning of early breast cancer patients included in the randomized Skagen Trial 1

BACKGROUND AND PURPOSE To report on a Quality assessment (QA) of Skagen Trial 1, exploring hypofractionation for breast cancer patients with indication for regional nodal radiotherapy. MATERIAL AND METHODS Deviations from protocol regarding target volume delineations and dose parameters (Dmin, Dmax, D98%, D95% and D2%) from randomly selected dose plans were assessed. Target volume delineation according to ESTRO guidelines was obtained through atlas based automated segmentation and centrally approved as gold standard (GS). Dice similarity scores (DSC) with original delineations were measured. Dose parameters measured in the two delineations were reported to assess their dosimetric outcome. RESULTS Assessment included 88 plans from 12 centres in 4 countries. DSC showed high agreement in contouring, 99% and 96% of the patients had a complete delineation of target volumes and organs at risk. No deviations in the dosimetric outcome were found in 76% of the patients, 82% and 95% of the patients had successful coverage of breast/chestwall and CTVn_L2-4-interpectoral. Dosimetric outcomes of original delineation and GS were comparable. CONCLUSIONS QA showed high protocol compliance and adequate dose coverage in most patients. Inter-observer variability in contouring was low. Dose parameters were in harmony with protocol regardless original or GS segmentation.

Dosimetric assessment of an Atlas based automated segmentation for loco-regional radiation therapy of early breast cancer in the Skagen Trial 1: A multi-institutional study

Highlights • 40 dose plans from the Skagen Trial 1 collected from Denmark, Belgium and Norway.• Atlas-based automated segmentation of each CT scan was obtained using MIM Maestro™.• DSC and difference in volume with manual segmentation were collected.• HI, V95 and V90% measured on the two different segmentations were compared.• Inter-observer variability was low and dose parameters were comparable.

Guidelines for time-to-event end point definitions in breast cancer trials: Results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials). [Ann Oncol, 26, (2015), 873-879] doi: 10.1093/annonc/mdv106

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)† S. Gourgou-Bourgade1,2*, D. Cameron3, P. Poortmans4, B. Asselain5, D. Azria6, F. Cardoso7, R. A’Hern8, J. Bliss8, J. Bogaerts9, H. Bonnefoi10, E. Brain11, M. J. Cardoso7, B. Chibaudel12, R. Coleman13, T. Cufer14, L. Dal Lago15, F. Dalenc16, E. De Azambuja15, M. Debled10, S. Delaloge17, T. Filleron16, J. Gligorov18, M. Gutowski19, W. Jacot20, C. Kirkove21, G. MacGrogan10, S. Michiels22,23, I. Negreiros24, B. V. Offersen25, F. Penault Llorca26,27, G. Pruneri28,29, H. Roche16, N. S. Russell30, F. Schmitt31,32, V. Servent33, B. Thürlimann34, M. Untch35, J. A. van der Hage36, G. van Tienhoven37, H. Wildiers38,39, J. Yarnold40, F. Bonnetain41, S. Mathoulin-Pélissier42,43, C. Bellera42,43 & T. S. Dabakuyo-Yonli44 Biostatistic Unit, Montpellier Cancer Institute, Montpellier; Data Center for Cancer Clinical Trials, CTD-INCa, Montpellier, France; Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital, Edinburgh, UK; Department of Radiation Oncology, Institute Verbeeten, Tilburg, The Netherlands; Department of Biostatistics, Institut Curie, Paris; Department of Radiation Oncology, Montpellier Cancer Institute, Montpellier, France; Breast Cancer Unit, Champalimaud Cancer Center, Lisbon, Portugal; Institute of Cancer Research, London, UK; EORTC Data Center (European Organization of Research and Treatment of Cancer Statistics Department), Brussels, Belgium; Institut Bergonié, Comprehensive Cancer Centre, Bordeaux; Departments of Clinical Research and Medical Oncology, Institut Curie Hôpital René Huguenin, Saint-Cloud; Department of Medical Oncology, Hôpital Saint-Antoine, Paris, France; FRCP, FRCPE YCR National Institute for Health Research Cancer Research Network (NCRN), Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield Cancer Research Centre, Sheffield, UK; University Clinic Golnik, Golnik, Slovenia; Institut Jules Bordet, University ‘Libre’ of Brussels, Brussels, Belgium; Institut Claudius Régaud, Toulouse; Breast Cancer Group, Gustave Roussy Institute, Villejuif; APHP Tenon – University Cancer Institute – Pierre & Marie Curie, Sorbonne University, Paris; Departments of Surgery; Medical Oncology, Montpellier Cancer Institute, Montpellier, France; Université catholique Louvain, Louvain-la-Neuve, Belgium; Biostatistic and Epidemiology Unit, Gustave Roussy, Villejuif; University of Paris-Sud, Villejuif, France; Breast Unit, Hospital CUF Descobertas, Lisbon, Portugal; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; Centre Jean Perrin, Clermont-Ferrand; ERTICA EA4677, UFR Medicine, University of Clermont-Ferrand 1, Clermont-Ferrand, France; European Institute of Oncology, Milan; University of Milan, School of Medicine, Milan, Italy; Department of Radiotherapy, The Netherlands Cancer Institute Antoni van Leeuwnhoek Hospital, Amsterdam, The Netherlands; IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto), Porto; Medical Faculty of Porto University, Porto, Portugal; Oscar Lambret Comprehensive Cancer Center, Lille, France; Kantonsspital St Gallen, Breast Center, St Gallen, Switzerland; Clinic for Gynecology, Gynecologic Oncology and Obstetrics—Interdisciplinary Breast Cancer Center, HELIOS Klinikum Berlin-Buch, Berlin, Germany; Department of Surgical Oncology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam; Academic Medical Center Amsterdam, Amsterdam, The Netherlands; Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven; Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium; The Institute of Cancer Research, Royal Cancer Hospital, London, UK; Methodological and Quality of Life Unit in Oncology (EA3181), CHU Besançon, Besançon; Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux; Clinical Epidemiology Unit, INSERM CIC 14.01 (Clinical Epidemiology), Bordeaux; Biostatistics and Quality of Life Unit (EA4184), Centre Georges François Leclerc Comprehensive Cancer Centre, Dijon, France

PO-0778: Delineation of the regional nodal areas in breast radiotherapy: What are the most problematic regions?

volume delineation. Reasons for non-compliance are mostly problems with target coverage. Thirty-eight percent of the centers reported issues with target coverage; in 1 center they interpret the Dose Volume Histogram differently and are now looking at the 85% coverage of the planning target volume instead of the 95%. Conclusions: The introduction of new delineation guidelines for the RNA in breast radiotherapy has a major impact on the treatment planning and dosimetry with especially introducing newer treatment techniques to achieve better target coverage. Surprisingly, not all centers use the centrally reviewed and corrected target delineation to guide their radiotherapy to the RNA.