M.H. Nielsen

Delineation of target volumes and organs at risk in adjuvant radiotherapy of early breast cancer: National guidelines and contouring atlas by the Danish Breast Cancer Cooperative Group

Abstract During the past decade planning of adjuvant radiotherapy (RT) of early breast cancer has changed from two-dimensional (2D) to 3D conformal techniques. In the planning computerised tomography (CT) scan both the targets for RT and the organs at risk (OARs) are visualised, enabling an increased focus on target dose coverage and homogeneity with only minimal dose to the OARs. To ensure uniform RT in the national prospective trials of the Danish Breast Cancer Cooperative Group (DBCG), a national consensus for the delineation of clinical target volumes (CTVs) and OARs was required. Material and methods. A CT scan of a breast cancer patient after surgical breast conservation and axillary lymph node (LN) dissection was used for delineation. During multiple dummy-runs seven experienced radiation oncologists contoured all CTVs and OARs of interest in adjuvant breast RT. Two meetings were held in the DBCG Radiotherapy Committee to discuss the contouring and to approve a final consensus. The Dice similarity coefficient (DSC) was used to evaluate the delineation agreement before and after the consensus. Results. The consensus delineations of CTVs and OARs are available online and a table is presented with a contouring description of the individual volumes. The consensus provides recommendations for target delineation in a standard patient both in case of breast conservation or mastectomy. Before the consensus, the average value of the DSC was modest for most volumes, but high for the breast CTV and the heart. After the consensus, the DSC increased for all volumes. Conclusion. The DBCG has provided the first national guidelines and a contouring atlas of CTVs and OARs definition for RT of early breast cancer. The DSC is a useful tool in quantifying the effect of the introduction of guidelines indicating improved inter-delineator agreement. This consensus will be used by the DBCG in our prospective trials.

Inter-observer variation in delineation of the heart and left anterior descending coronary artery in radiotherapy for breast cancer: A multi-centre study from Denmark and the UK

BACKGROUND AND PURPOSEnTo determine the extent of inter-observer variation in delineation of the heart and left anterior descending coronary artery (LADCA) and its impact on estimated doses.nnnMETHODS AND MATERIALSnNine observers from five centres delineated the heart and LADCA on fifteen patients receiving left breast radiotherapy. The delineations were carried out twice, first without guidelines and then with a set of common guidelines.nnnRESULTSnFor the heart, most spatial variation in delineation was near the base of the heart whereas for the LADCA most variation was in its length at the apex of the heart. Common guidelines reduced the spatial variation for the heart and the length of the LAD, but increased the variation in the anterior-posterior/right-left plane. The coefficients of variation (CV) in the estimated doses to the heart were: mean dose 7.5% without and 3.6% with guidelines, maximum dose 8.7% without and 4.0% with guidelines. The CVs in the estimated doses to the LADCA were: mean dose 27% without and 29% with guidelines, maximum dose 39% without and 31% with guidelines.nnnCONCLUSIONSnFor the heart, there was little inter-observer variation in the estimated dose, especially when guidelines were used. In contrast, for the LADCA there was substantial variation in the estimated dose, which was not reduced with guidelines.

TAXTOX – a retrospective study regarding the side effects of docetaxel given as part of the adjuvant treatment to patients with primary breast cancer in Denmark from 2007 to 2009

Abstract Background. In 2007 docetaxel was introduced as part of the adjuvant setting offered to high risk breast cancer patients in Denmark. Meta-analyses had shown that taxane-containing chemotherapy reduced the relative risk of relapse and death by 20–30%, apparently with moderate side effects. The treatment was given as three cycles of cyclophosphamide (600 mg/m2) and epirubicin (90 mg/m2) followed by three cycles of docetaxel (100 mg/m2). Because of an apparent high incidence of side effects, especially febrile neutropenia (FN) and non-hematologic side effects, the DBCG (The Danish Breast Cancer Cooperative Group) initiated a retrospective study of adverse reactions to the newly introduced regime and all patients were offered primary prophylaxis with growth factors (G-CSF) pr 1/1-2008. Material and methods. Two medical doctors examined available journals and nurse charts from the 13 oncology departments in Denmark, and graded all side effects according to NCI CTC version 2.0. To be enrolled, the patients should have received three cycles of EC and at least one cycle of docetaxel. The side effects were investigated before and after routine use of G-CSF. Results. One thousand one hundred and forty-three patients entered the study. In 2007 (before G-CSF) the incidence of FN was 25% and 90.6% of the patients completed the planned treatment. In 2008 (after the introduction of G-CSF) the incidence of FN was 10% and 94.5% completed the treatment. The incidence of non-hematological adverse events, in 2007 and 2008 combined, was for neuropathy 35%, mucositis 75%, muscle and joint pain 53%, skin rash 25% and fatigue 43% (all grades). Conclusion. The introduction of G-CSF was justified because of the high incidence of FN. However, it could not have been predicted after reviewing the published literature. The incidence of non-hematological adverse events had been reported in some, but not all adjuvant taxanes studies. In the future, focus should be more on the side effects, especially when introducing new toxic systemic regimes.

The Growth Pattern of in Situ Carcinoma in the Female Breast

The histopathological growth pattern of in situ carcinoma in the female breast is divided into three forms: 1) microfocal, 2) diffuse, and 3) tumour forming. This classification is clearly correlated to our diagnostic findings and forms furthermore the basis for our planning of treatment, as the growth pattern is probably of prognostic relevance.

Trends in breast cancer in the elderly in Denmark, 1980–2012

Abstract Background Breast cancer is the most frequent malignancy among women worldwide and the second most common cause of cancer-related death in developed countries. The aim of the present analysis is to describe trends in incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on age, comparing persons aged 70 years or more with those aged less than 70 years. Material and methods Cancer of the breast was defined as ICD-10 code C50. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. Results The proportion of patients diagnosed with breast cancer over the age of 70 years increased with time to 29% of women and 44% of men in 2012. Incidence rates increased with time and peaked around 2010 in all age groups except for those aged 90 years or more. Mortality rates were clearly separated by age with increasing mortality rates by increasing age group for both women and men. Relative survival increased over time in all age groups, but patients aged 70 years or more had a poorer relative survival than those aged less than 70 years. In 2012, 58 521 persons (all ages) were alive in Denmark after a diagnosis of breast cancer. Conclusion Poorer survival of Danish breast cancer patients over the age of 70 years is likely to be due to inferior treatment and non-adherence to treatment guidelines. There is a need for clinical trials focusing on patients over the age of 70 years.

OC-0142: Hypo- vs normofractionated radiation of early breast cancer in the randomised DBCG HYPO trial

ESTRO 35 2016 _____________________________________________________________________________________________________ improvement in 2-year overall survival, suggesting TRT should be considered for all patients with ES-SCLC who respond to chemotherapy. An additional analysis showed that in patients with a response but residual disease after chemotherapy, the difference in 1-year survival was significantly better after TRT (Lancet 2015,385,1292-3). We carried out a European survey to determine the impact of the publication on clinical practice.

Is DBCG abreast of new developments

Birgitte V. Offersen, Bent Ejlertsen, Eva Balslev, Henrik Flyger , Anne-Marie Gerdes, Mads K. Hansen, Lisbet R. Hølmich, Maj-Britt Jensen, Bent Kristensen, Anne-Vibeke Laenkholm, Henning T. Mouridsen, Mette H. Nielsen, Jens Overgaard, Malgorzata Tuxen, Ilse Vejborg and Peer Christiansen Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Danish Breast Cancer Group (DBCG) Secretariat and Statistical Office, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Oncology, Copenhagen University Rigshospitalet, Copenhagen, Denmark; Department of Pathology, Herlev University Hospital, Herlev, Denmark; Department of Breast Surgery, Herlev University Hospital, Herlev, Denmark; Department of Clinical Genetics, Copenhagen University Rigshospitalet, Copenhagen, Denmark; Lillebaelt Hospital, Vejle, Denmark; Department of Plastic Surgery, Herlev University Hospital, Herlev, Denmark; Department of Clinical Physiology & Nuclear Medicine, Herlev University Hospital, Herlev, Denmark; Department of Surgical Pathology, Zeeland University Hospital, Slagelse, Denmark; Department of Oncology, Odense University Hospital, Odense, Denmark; Department of Oncology, Herlev University Hospital, Herlev, Denmark; Department of Radiology, Copenhagen University Rigshospitalet, Copenhagen, Denmark; Breast Unit, Aarhus University Hospital/Randers Regional Hospital, Aarhus, Denmark

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

BACKGROUND AND PURPOSEnTo report on a Quality assessment (QA) of Skagen Trial 1, exploring hypofractionation for breast cancer patients with indication for regional nodal radiotherapy.nnnMATERIAL AND METHODSnDeviations 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.nnnRESULTSnAssessment 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.nnnCONCLUSIONSnQA 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.

Nurse-led counselling and replacement therapy is effective for smoking cessation in oral cancer patients

The incidence of lip and oral cancer cases was 300,000 worldwide in 2012, with a 2:1 male/female ratio (1). The most common etiological factors of developing oral cancer are tobacco use and alcohol abuse, and the two combined increases the risk 30-fold (2). Studies have shown that continued smoking after diagnosis increases the risk of recurrence and second primary neoplasms, treatment failure and patient mortality (3). The aim of this study was to examine if combined nurse-led counselling and nicotine replacement therapy (NRT) could lead to successful smoking cessation in oral cancer patients. This study was conducted with data from November 2011 to August 2016 at the Department of Plastic and Reconstructive Surgery at Odense University Hospital, Denmark. The follow-up was 6 months with the primary outcome being smoking cessation. The study followed the Declaration of Helsinki on medical protocol ethics and was approved by the Danish Data Protection Authority. The inclusion criteria were 18 years of age, current smokers, newly diagnosed oral cancer treated surgically. Nonand ex-smokers patients who were inoperable/received primary radiotherapy or those who suffered from severe cognitive impairment were excluded. According to current literature, counselling may reduce the number of smokers by 40% (4–6). We calculated the sample size to 70 patients in order to dectect an increase to 60%with a power of 90% and a significant level of 5%. Three hundred six patients were referred to our department with oral cancer. One hundred sixty-seven (55%) patients were tobacco users, 76 (25%) patients were never-smokers and 63 (21%) were ex-smokers. A few patients suffered from severe cognitive impairment and about 40 patients were either inoperable or received primary radiotherapy. One hundred twenty-three patients where eligible for the study and 114 of these agreed to participate. Tobacco and alcohol use was registered at baseline, after 3 and 6 months. At the time of diagnosis, age range was between 34 and 85 years (median 63 years). Most patients were male 78 (68%) and 36 (32%) were female. Many of the patients (n = 49/114, 43%) had previously tried to quit smoking. The majority of patients 69/114 (61%) used NRT as a part of the study. The number of patients with an alcohol abuse was 41/114 (36%), consuming up to 280 units per week. See Table 1. At the initial consultation, patients were advised to stop smoking by a consultant plastic surgeon. This * Mia C. W. Steffenssen Mia.Charlotte.W.Steffenssen@rsyd.dk