Luigi Cataliotti

Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial

BACKGROUND If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. METHODS Patients with T1-2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. FINDINGS Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6·1 years (IQR 4·1-8·0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0·43% (95% CI 0·00-0·92) after axillary lymph node dissection versus 1·19% (0·31-2·08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0·00-5·27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. INTERPRETATION Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. FUNDING EORTC Charitable Trust.

Quality indicators in breast cancer care

To define a set of quality indicators that should be routinely measured and evaluated to confirm that the clinical outcome reaches the requested standards, Eusoma has organised a workshop during which twenty four experts from different disciplines have reviewed the international literature and selected the main process and outcome indicators available for quality assurance of breast cancer care. A review of the literature for evidence-based recommendations have been performed by the steering committee. The experts have identified the quality indicators also taking into account the usability and feasibility. For each of them it has been reported: definition, minimum and target standard, motivation for selection and level of evidence (graded according to AHRO). In overall 17 main quality indicators have been identified, respectively, 7 on diagnosis, 4 on surgery and loco-regional treatment, 2 on systemic treatment and 4 on staging, counselling, follow-up and rehabilitation. Breast Units in Europe are invited to comply with these indicators and monitor them during their periodic audit meetings.

Accelerated Partial Breast Irradiation With IMRT: New Technical Approach and Interim Analysis of Acute Toxicity in a Phase III Randomized Clinical Trial

PURPOSE To evaluate with a randomized clinical trial the possibility of treating the index quadrant with external intensity-modulated radiotherapy (IMRT) in a selected group of patients with early-stage breast cancer and to analyze the acute toxicity. METHODS AND MATERIALS From September 2005, a randomized Phase III clinical trial has been conducted to compare conventional (tangential field) fractionated whole breast treatment (Arm A) with accelerated partial breast irradiation plus intensity-modulated radiotherapy (Arm B). For intensity-modulated radiotherapy, the clinical target volume was drawn with a uniform 1-cm margin around the surgical clips in three dimensions. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk. All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations. RESULTS In September 2008, 259 patients were randomized and treated. The mean clinical target volume in Arm B was 44 cm(3) and the mean planning target volume was 123 cm(3). The mean value of the ratio between the planning target volume and the ipsilateral breast volume was 21%. The rate of Grade 1 and Grade 2 acute skin toxicity was 22% and 19% in Arm A (Radiation Therapy Oncology Group scale), respectively. The tolerance in Arm B was excellent with only 5% Grade 1 and 0.8% Grade 2 acute skin toxicity. The planning constraints were fully satisfied in most patients. In a very few cases, this was not possible because of very unfavorable anatomy. Quality assurance procedures were performed according to our internal quality assurance protocol, with excellent results. CONCLUSION In the present preliminary analysis, we have demonstrated that accelerated partial breast irradiation is feasible, with very low acute toxicity.

Breast‐conserving therapy for paget disease of the nipple

The purpose of the current study was to assess the outcome of breast‐conserving therapy by means of a cone excision and radiotherapy in patients with Paget disease of the nipple without associated invasive breast carcinoma.

European guidelines for quality assurance in the surgical management of mammographically detected lesions

European guidelines for quality assurance in the surgical management of mammographically detected lesions.

The requirements of a specialist Breast Centre.

INTRODUCTION In recognition of the advances and evidence based changes in clinical practice that have occurred in recent years and taking into account the knowledge and experience accumulated through the voluntary breast unit certification programme, Eusoma has produced this up-dated and revised guidelines on the requirements of a Specialist Breast Centre (BC). METHODS The content of these guidelines is based on evidence from the recent relevant peer reviewed literature and the consensus of a multidisciplinary team of European experts. The guidelines define the requirements for each breast service and for the specialists who work in specialist Breast Centres. RESULTS The guidelines identify the minimum requirements needed to set up a BC, these being an integrated Breast Centre, dealing with a sufficient number of cases to allow effective working and continuing expertise, dedicated specialists working with a multidisciplinary approach, providing all services throughout the patients pathway and data collection and audit. It is essential that the BC also guarantees the continuity of care for patients with advanced (metastatic) disease offering treatments according to multidisciplinary competencies and a high quality palliative care service. The BC must ensure that comprehensive support and expertise may be needed, not only through the core BC team, but also ensure that all other medical and paramedical expertise that may be necessary depending on the individual case are freely available, referring the patient to the specific care provider depending on the problem. CONCLUSIONS Applying minimum requirements and quality indicators is essential to improve organisation, performance and outcome in breast care. Efficacy and compliance have to be constantly monitored to evaluate the quality of patient care and to allow appropriate corrective actions leading to improvements in patient care.

Non-palpable lesions of the breast detected by mammography — Review of 1182 consecutive histologically confirmed cases

We report on 1182 consecutive histologically confirmed non-palpable breast lesions detected by mammography (infiltrating carcinoma 427, in situ carcinoma 121, benign 634). The proportion of cancer cases varied according to age (< 50 years = 33%; 50-59 years = 46%; > 59 years = 63%), mammographic pattern (regular opacities = 8%, parenchymal distortions = 20%, isolated calcifications = 42%, irregular opacities = 62%, stellate opacities = 73%), and calendar period (1970-1985 = 29%, 1986-1989 = 56%; 1990-1992 = 69%). A sharp decrease of the benign/malignant biopsy ratio was evident after routine fine-needle aspiration cytology (sonography-guided or stereotaxic) was introduced in 1986. The independent significant association of cancer frequency to age, calendar period and mammographic pattern was confirmed by multivariate analysis. A significant trend over time in favour of conservative surgery was also observed for cancer cases (1970-1979 = 6%, 1980-1985 = 41%, 1986-1992 = 83%). Among invasive cancers, node involvement was observed in 11.5% of cases, being associated with tumour size (pT1a = 0%, pT1b = 7%, pT1c = 13%, pT2a = 33%). Five-, ten- and fifteen-year overall survivals of invasive cancers were 98.1, 95.7 and 87.3%, respectively.

Principles and guidelines for surgeons—management of symptomatic breast cancer

The European Society of Surgical Oncology is actively involved in the promotion of a high standard of surgical oncology throughout Europe. Such an ambition involves recognition of Centres of Excellence in the management of cancer patients throughout Europe. These centres have a multi-disciplinary system involved in the total care of patients with cancer and are concerned with the delivery of care to the highest available standards. It is accepted that not all patients with cancer can, nor should, necessarily be treated in such highly specialized centres. Yet all cancer patients should be guaranteed a high standard of care. High surgical standards can be ensured if surgeons treating cancer are trained in specialist centres and, when in independent practice, follow established guidelines or protocols of treatment. In common with many national surgical oncology societies, the European Society of Surgical Oncology is in the process of establishing good practice guidelines in the treatment of solid tumours. This document on the management of symptomatic breast cancer is the first of a series of guidelines to be proposed by ESSO. It draws heavily on excellent documents already in existence from the British Association of Surgical Oncology and from the Danish Breast Cancer Co-Operative Group. It is hoped that this document will be sufficiently clear and purposeful to be of help to the individual surgeon and yet sufficiently flexible to allow it to be adopted in the different medical systems throughout Europe.

Intraductal breast carcinoma :review of a multicenter series of 350 cases

A multicentrer series of 350 intraductal breast cancers (DCIS) is reported. Mammography was the most sensitive test but suspicion arose only at palpation in 13% of cases whereas in 10% of cases bio...A multicentrer series of 350 intraductal breast cancers (DCIS) is reported. Mammography was the most sensitive test but suspicion arose only at palpation in 13% of cases whereas in 10% of cases biopsy was recommended for a benign lesion and DCIS was an unexpected finding. Mammography, physical examination and cytology must be combined to achieve optimal sensitivity. Systematic biopsy of apparently benign masses would increase DCIS detection rates but the cost-effectiveness of such a policy is questionable. A trend of conservative surgery was evident over time (from 1968-79, 28%; 1985-1989, 50%) but breast irradiation followed only in one fourth of the cases. The local recurrence rate was significantly higher in cases of limited surgery (with or without irradiation) with respect to mastectomy (1.2 vs 0.2 × 100 patient-years at risk). Most recurrences (7 of 8) in the conserved breast were infiltrating, but no recurrence was seen in subclinical DCIS cases. Three patients died of breast cancer after local recurrence in the conserved breast (2 cases) or mastectomy scar (1 case). Eligibility for conservative surgery of DCIS needs to be carefully discussed to avoid under-treatment. Contralateral breast cancer was recorded in 44 cases and the incidence of further metachronous cancer to the other breast was ten times higher than expected in normal breasts. Four patients died of contralateral breast cancer, free of ipsilateral recurrence. A careful follow-up of the contralateral breast in DCIS cases looks as important as surveillance of the conserved breast.

Indications for breast magnetic resonance imaging. Consensus document “Attualità in senologia”, Florence 2007

The clinical use of breast magnetic resonance (MR) imaging is increasing, especially for applications requiring paramagnetic contrast-agent injection. This document presents a synthetic list of acceptable indications with potential advantages for women according to evidence from the literature and the expert opinion of the panel that developed this statement. We generally recommend that breast MR imaging be performed in centres with experience in conventional breast imaging [mammography and ultrasonography (US)] and needle-biopsy procedures (under stereotactic or US guidance) as well as in breast MR imaging and second-look US for findings not revealed by conventional imaging performed before MR imaging. In our opinion, there is no evidence in favour of breast MR imaging as a diagnostic tool to characterise equivocal findings at conventional imaging when needle-biopsy procedures can be performed, nor for the study of asymptomatic, non-high-risk women with negative conventional imaging. After a description of technical and methodological requirements, we define the indications and limitations of breast MR imaging for surveillance of high-risk women, local staging before surgery, evaluation of the effect of neoadjuvant chemotherapy, breast previously treated for carcinoma, carcinoma of unknown primary syndrome, nipple discharge and breast implants.RiassuntoLa RM mammaria è in fase di crescente utilizzo clinico, soprattutto per le applicazioni che richiedono la somministrazione di mezzo di contrasto (MdC) paramagnetico. Il presente documento propone una codificazione sintetica delle indicazioni accettabili con potenziale vantaggio per le donne, secondo la valutazione delle evidenze presenti in letteratura e l’opinione del gruppo di esperti estensori del documento. In generale si raccomanda che l’indagine sia eseguita presso centri che siano in grado di combinare l’esperienza senologica relativa all’imaging convenzionale e ai prelievi agobioptici con quella specifica in RM mammaria e che garantiscano l’esecuzione del second look ecografico per i reperti non rilevati all’imaging convenzionale pre-RM. Non si ritiene che vi siano evidenze in favore dell’utilizzo della RM quale approccio diagnostico nella caratterizzazione di reperti equivoci all’imaging convenzionale in tutte le situazioni nelle quali sia praticabile il prelievo agobioptico sotto guida ecografica o stereotassica né in favore dello studio di donne non ad alto rischio asintomatiche e con imaging convenzionale negativo. Sono qui definiti i requisiti tecnici e metodologici di esecuzione dell’indagine e indicazioni e limiti relativi a: sorveglianza delle donne ad alto rischio di tumore mammario; stadiazione locale pretrattamento chirurgico; valutazione dell’effetto della chemioterapia neoadiuvante; mammella trattata per carcinoma; carcinoma unknown primary syndrome; mammella secernente; protesi mammarie.