IOERT versus external beam electrons for boost radiotherapy in stage I/II breast cancer: 10-year results of a phase III randomized study.

BACKGROUND: Intraoperative radiotherapy with electrons (IOERT) boost could be not inferior to external beam radiotherapy (EBRT) boost in terms of local control and tissue tolerance. The aim of the study is to present the long-term follow-up results on local control, esthetic evaluation, and toxicity of a prospective study on early-stage breast cancer patients treated with breast-conserving surgery with an IOERT boost of 10 Gy (experimental group) versus 5 × 2 Gy EBRT boost (standard arm). Both arms received whole-breast irradiation (WBI) with 50 Gy (2 Gy single dose). METHODS: A single-institution phase III randomized study to compare IOERT versus EBRT boost in early-stage breast cancer was conducted as a non-inferiority trial. Primary endpoints were the evaluation of in-breast true recurrences (IBTR) and out-field local recurrences (LR) as well as toxicity and cosmetic results. Secondary endpoints were overall survival (OS), disease-free survival (DFS), and patient's grade of satisfaction with cosmetic outcomes. RESULTS: Between 1999 and 2004, 245 patients were randomized: 133 for IOERT and 112 for EBRT. The median follow-up was 12 years (range 10-16 years). The cumulative risk of IBTR at 5-10 years was 0.8% and 4.3% after IOERT, compared to 4.2% and 5.3% after EBRT boost (p = 0.709). The cumulative risk of out-field LR at 5-10 years was 4.7% and 7.9% for IOERT versus 5.2% and 10.3% for EBRT (p = 0.762). All of the IOERT arm recurrences were observed at > 100 months' follow-up, whereas the mean time to recurrence in the EBRT group was earlier (55.2 months) (p < 0.05). No late complications associated with IOERT were observed. The overall cosmetic results were scored as good or excellent in physician and patient evaluations for both IOERT and EBRT. There were significantly better scores for IOERT at all time points in physician and patient evaluations with the greatest difference at the end of EBRT (p = 0.006 objective and p = 0.0004 subjective) and most narrow difference at 12 months after the end of EBRT (p = 0.08 objective and p = 0.04 subjective analysis). CONCLUSION: A 10-Gy IOERT boost during breast-conserving surgery provides high local control rates without significant morbidity. Although not significantly superior to external beam boosts, the median time to local recurrences after IOERT is prolonged by more than 4 years.

Risk stratification of the patients with Brugada type electrocardiogram: a community-based prospective study.

AIMS: Risk stratification of patients with Brugada electrocardiogram (ECG) is being strongly debated. Conflicting results have been suggested from international registries, which enrolled non-consecutive cases, studied with different programmed electrical stimulation (PES) protocols. The aim of this study was to prospectively evaluate the incidence of arrhythmic events and the prognostic role of clinical presentation, ECG, and of a standardized PES protocol in consecutive cases from a community-based population. METHODS AND RESULTS: A total of 166 consecutive patients (45 +/- 14 years) with Brugada ECG were enrolled. Type 1 ECG was observed spontaneously in 72 (43%) and after pharmacological testing in 94 (57%). One hundred and three (62%) were asymptomatic, 58 (35%) had syncope, and five (3%) had a prior cardiac arrest. One hundred and thirty-five (81%) underwent PES with two extra stimuli up to ventricular refractoriness and 34% had ventricular fibrillation (VF) induced. Arrhythmic events occurred in nine patients at a mean follow-up of 30 +/- 21 months (2.2 events per 100 person-year): in three (60%) patients with aborted sudden death (aSD), five (8.6%) of those with syncope, and one (1%) of the asymptomatic. The only predictors of events were a history of syncope or aSD (P = 0.02) and induction at PES (P = 0.004). CONCLUSION: Clinical presentation is the most important parameter in the risk stratification of patients with Brugada ECG. Programmed electrical stimulation seems valuable, particularly in patients with previous syncope.

Sentinel lymph node biopsy in women with pT1a or "microinvasive" breast cancer.

The role of sentinel lymph node biopsy (SLNB) in pT1a and "microinvasive" breast cancer has not been extensively studied. We report our experience with SLNB in patients with "minimal" breast cancer to determine the incidence and type of SLN metastases, and to study the potential impact on their surgical or oncological management. Among some 3387 women operated upon for primary breast cancer who underwent sentinel lymph node biopsy at nine institutions participating in the Rome Breast Cancer Study Group, 251 were staged pT1a or pT1mic (7.4%). There were 13 cases of sentinel lymph node metastases identified in this group of patients (5.2%), seven macrometastases and six micrometastases. Additionally, ITC were diagnosed by immunohistochemistry in four cases (1.6%). The incidence of SLN metastases was 7/174 (4%) and 6/77 (7.8%) in patients with pT1a and pT1mic tumors, respectively (p=0.2). Age and histological grade were predictive factors for SLN metastases. Chemotherapy was seldom directed by axillary node status (8/38 patients). As the incidence of SLN metastases in these patients is very small, particularly in the pT1a group, the indications for even a minimally invasive procedure, such as sentinel lymph node biopsy, should be probably individualized.

[Sentinel lymph node biopsy in breast cancer. Experience of the Rome Breast Cancer Study Group]. / I1 linfonodo sentinella nel cancro della mammella. Esperienza del Rome Breast Cancer Study Group.

We report our multicentric experience with sentinel lymph node biopsy for breast cancer patients. Patients with breast cancer operated on from January 1999 to March 2005 in 6 different institutions in the Rome area were retrospectively reviewed. All patients gave written informed consent. 1440 consecutive patients were analysed, with a median age of 59 years (range: 33-81) and a median tumour diameter of 1.3 cm (range: 0.1-5). Patients underwent lymphatic mapping with Tc99 nanocolloid (N = 701; 49%), with Evans Blue (N = 70; 5%), or with a combined injection (N = 669, 46%). The majority of patients were mapped with an intradermal or subdermal injection (N = 1193; 84%), while an intraparenchymal or peritumoral injection was used in 41 (3%) and 206 patients (13%), respectively. Sentinel lymph nodes were identified in 1374/1440 cases (95.4%), and 2075 sentinel lymph nodes were analysed (average 1.5/patient). A total of 9305 additional non-sentinel lymph-nodes were removed (median 6/patient). Correlations between sentinel lymph nodes and final lymph node status were found in 1355/1374 cases (98.6%). There were 19 false-negative cases (5%). Lymph node metastases were diagnosed in 325 patients (24%). In this group, micrometastases (< 2 mm in diameter) were diagnosed in 103 cases (7.6%). Additionally, isolated tumour cells were reported in 61 patients (4,5%). In positive cases, additional metastases in non-sentinel lymph-nodes were identified in 117/325 cases after axillary dissection (36%). Axillary dissection was avoided in 745/1440 patients (52%). At a median follow-up of 36 months, only 1 axillary recurrence has been reported. Sentinel lymph node biopsy improves staging in women with breast cancer because it is accurate and reproducible, and allows detection of micrometastases and isolated tumour cells that would otherwise be missed. Our multicentric study confirms that this is the preferred axillary staging procedure in women with breast cancer.

Elaboration of a nomogram to predict nonsentinel node status in breast cancer patients with positive sentinel node, intraoperatively assessed with one step nucleic amplification: Retrospective and validation phase.

BACKGROUND: Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro- and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND). METHODS: The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper. RESULTS: The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary (<31%) or recommended (>31%). CONCLUSIONS: The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure.

Depression in patients with acute myocardial infarction: influence on autonomic nervous system and prognostic role. Results of a five-year follow-up study.

BACKGROUND: Although previous studies demonstrated an association between depressive symptoms and cardiac mortality after acute myocardial infarction (AMI) little is known about the possible mechanisms of this association. The aim of this study was to determine whether depressed patients present a cardiac autonomic dysfunction and whether this could represent the mediator of the influence of depression on their prognosis. METHODS: One hundred consecutive patients with AMI were recruited between January and December 1999. Major Depressive Disorder (MDD) was diagnosed by structured clinical interview and the presence of symptoms of depression was evaluated with self-administered Beck Depression Inventory (BDI). The influence of depression on autonomic nervous system was investigated measuring heart rate variability (HRV) and heart rate (HR) during 24-hour electrocardiographic monitoring. The end-points of the study were all-cause mortality, recurrent-AMI, revascularization and a composite end-point of all the previous. Potential confounders for depression status and events were entered into a multivariate regression model. RESULTS: Fifteen patients met the criteria for MDD and 35 patients showed mild-to-moderate symptoms of depression; women had a higher prevalence of depression than men (35% vs 9%; p<0.01). Depression was not related to the severity of ischaemic disease or to other clinical and demographic variables. Patients with MDD showed lower HRV (76+/-25 SD vs 99+/-33 SD ms; p<0.01) and higher HR (77+/-12 SD vs 68+/-9 SD bpm; p<0.01) than patients without MDD; moreover mild to moderate symptoms of depression (BDI score > or = 10) were associated with lower HRV (84+/-25 SD vs 102+/-35 SD ms; p=0.01) but not with significantly higher HR. After a mean follow-up of 60 months MDD was associated with an increase of all-cause mortality (OR 12; 95% CI 2.6-56; p<0.01) and of composite end-point (OR 2; 95% CI 1.2-3.6; p=0.01) but not with re-AMI and revascularization. In a simple regression model HRV values were predictors of mortality (p<0.01). However when added in the multiple regression model HRV did not have an independent correlation with the end-points considered and did not modify the correlation between depression and mortality. CONCLUSIONS: Patients with post-AMI depression have a cardiac autonomic dysfunction as reflected by decreased HRV and increased HR. This autonomic dysfunction seems not to be an independent mediator of the increased mortality observed in depressed patients during a 5-year follow-up.