G. Zavagno

A Randomized clinical trial on sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer: results of the Sentinella/GIVOM trial.

Objective:The aim of this multicenter randomized trial was to assess the efficacy and safety of sentinel lymph node (SLN) biopsy compared with axillary lymph node dissection (ALND). Background:All studies on SLN biopsy in breast cancer report a variable false negative rate, whose prognostic consequences are still unclear. Methods:From May 1999 to December 2004, patients with breast cancer ≤3 cm were randomly assigned to receive SLN biopsy associated with ALND (ALND arm) or SLN biopsy followed by ALND only if the SLN was metastatic (SLN arm). The main aim was the comparison of disease-free survival in the 2 arms. Results:A total of 749 patients were randomized and 697 were available for analysis. SLNs were identified in 662 of 697 patients (95%) and positive SLNs were found in 189 of 662 patients (28.5%). In the ALND group, positive non-SLNs were found in 18 patients with negative SLN, giving a false negative rate of 16.7% (18 of 108). Postoperative side effects were significantly less in the SLN group and there was no negative impact of the SLN procedure on psychologic well being. At a median follow-up of 56 months, there were more locoregional recurrences in the SLN arm, and the 5-year disease-free survival was 89.9% in the ALND arm and 87.6% in the SLN arm, with a difference of 2.3% (95% confidence interval: −3.1% to 7.6%). However, the number of enrolled patients was not sufficient to draw definitive conclusions. Conclusion:SLN biopsy is an effective and well-tolerated procedure. However, its safety should be confirmed by the results of larger randomized trials and meta-analyses.

Role of axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast

BackgroundSentinel lymph node (SLN) biopsy is an effective tool for axillary staging in patients with invasive breast cancer. This procedure has been recently proposed as part of the treatment for patients with ductal carcinoma in situ (DCIS), because cases of undetected invasive foci and nodal metastases occasionally occur. However, the indications for SLN biopsy in DCIS patients are controversial.The aim of the present study was therefore to assess the incidence of SLN metastases in a series of patients with a diagnosis of pure DCIS.MethodsA retrospective evaluation was made of a series of 102 patients who underwent SLN biopsy, and had a final histologic diagnosis of pure DCIS. Patients with microinvasion were excluded from the analysis. The patients were operated on in five Institutions between 1999 and 2004.Subdermal or subareolar injection of 30–50 MBq of 99 m-Tc colloidal albumin was used for SLN identification. All sentinel nodes were evaluated with serial sectioning, haematoxylin and eosin staining, and immunohistochemical analysis for cytocheratin.ResultsOnly one patient (0.98%) was SLN positive. The primary tumour was a small micropapillary intermediate-grade DCIS and the SLN harboured a micrometastasis. At pathologic revision of the specimen, no detectable focus of microinvasion was found.ConclusionOur findings indicate that SLN metastases in pure DCIS are a very rare occurrence. SLN biopsy should not therefore be routinely performed in patients who undergo resection for DCIS. SLN mapping can be performed, as a second operation, in cases in which an invasive component is identified in the specimen. Only DCIS patients who require a mastectomy should have SLN biopsy performed at the time of breast operation, since in these cases subsequent node mapping is not feasible.

Role of resection margins in patients treated with breast conservation surgery.

After breast conservation therapy (BCT), margin status is routinely evaluated to select patients who need reexcision. The aim of this study was to investigate how margin status and other clinicopathologic factors correlate with the presence of residual tumor at reexcision.

Number of Metastatic Sentinel Nodes As Predictor of Axillary Involvement in Patients with Breast Cancer

AbstractBackground and objectives. More than half of patients with positive sentinel node (SN) have no metastases in non-sentinel nodes (NSNs) on axillary lymph node dissection (ALND).The aim of this study was to investigate factors predictive of NSNs involvement, in order to identify patients with metastatic disease confined to the SN which might avoid ALND. Methods. ALND was performed in 167 patients with metastatic SN. Axillary NSNs status was correlated with the size of SN metastases, the size of the primary tumor and the occurrence of lymphovascular invasion.In 72 cases, the radiotracer (Tc-99m albumin colloid) marked multiple (in most cases 2 or 3) nodes. In this group, NSNs status was correlated with the number of metastatic radioactive nodes (1 or >1), and with the above mentioned histopathologic factors. Results. NSNs metastases were found in 57/167 cases (34.1%), the rate increasing proportionate to the size of both SN metastases (p < 0.0001) and primary tumor (p= 0.0075), while no significant correlation was found for lymphovascular invasion (p= 0.1769). At univariate and multivariate analysis of findings from the 72 cases with multiple probe-detected hot nodes, positivity in more than one hot node was the strongest predictor of NSN involvement (p= 0.0019). Conclusions. The identification and excision of multiple hot nodes can be useful in the prediction of NSNs involvement in patients with metastatic SN.

Sentinel node biopsy and ultrasound scanning in cutaneous melanoma: clinical and technical considerations

1.5 mm and in all cases with two metastatic SNs, further positive additional nodes were found. The mean counts per 10 s (CP10S) ratio for SN and non-SN values was 5.62 (1.29-23.51) and 3.09 (1.03-10.99) in the intra-operative and extra-operative phases, respectively. US scanning and preoperative lymphoscintigraphy associated with PBD allows preoperative patient selection and accurate SN(s) identification. Breslow thickness and the number of metastatic SN(s), but not their type, are correlated with disease spread; CP10S contributed to the differentiation amongst the nodes and the determining of procedures completion.

Support vector machine learning model for the prediction of sentinel node status in patients with cutaneous melanoma.

Background:Currently, approximately 80% of melanoma patients undergoing sentinel node biopsy (SNB) have negative sentinel lymph nodes (SLNs), and no prediction system is reliable enough to be implemented in the clinical setting to reduce the number of SNB procedures. In this study, the predictive power of support vector machine (SVM)-based statistical analysis was tested.Methods:The clinical records of 246 patients who underwent SNB at our institution were used for this analysis. The following clinicopathologic variables were considered: the patient’s age and sex and the tumor’s histological subtype, Breslow thickness, Clark level, ulceration, mitotic index, lymphocyte infiltration, regression, angiolymphatic invasion, microsatellitosis, and growth phase. The results of SVM-based prediction of SLN status were compared with those achieved with logistic regression.Results:The SLN positivity rate was 22% (52 of 234). When the accuracy was ≥80%, the negative predictive value, positive predictive value, specificity, and sensitivity were 98%, 54%, 94%, and 77% and 82%, 41%, 69%, and 93% by using SVM and logistic regression, respectively. Moreover, SVM and logistic regression were associated with a diagnostic error and an SNB percentage reduction of (1) 1% and 60% and (2) 15% and 73%, respectively.Conclusions:The results from this pilot study suggest that SVM-based prediction of SLN status might be evaluated as a prognostic method to avoid the SNB procedure in 60% of patients currently eligible, with a very low error rate. If validated in larger series, this strategy would lead to obvious advantages in terms of both patient quality of life and costs for the health care system.

Analysis of technical and clinical variables affecting sentinel node localization in patients with breast cancer after a single intradermal injection of 99mTc nanocolloidal albumin

AimTo investigate the technical, clinical and pathological findings that can, potentially, affect pre-operative lymphoscintigraphy in visualizing sentinel lymph node (SLN) and intra-operative probe detection of SLN in patients with breast cancer. MethodsOne hundred and forty-two consecutive female patients with, clinically, a solitary, small breast cancer and clinically N0 axilla were enrolled. Preoperative lymphoscintigraphy was performed by a single intradermal injection of 99mTc nacolloidal albumin (Nanocoll) the day before surgery. For radioguided surgery two gamma probes with diameters of 11 mm and 15 mm, and set up with a count rate ranging from 1 to 4 s were used. The following variables were evaluated: patients age, radiotracer dose, volume of injectate, primary tumour location, primary tumour size, and presence and extension of axillary nodal metastases. ResultsLymphoscintigraphy showed high sensitivity in visualizing the SLN (98% success rate) and it resulted in a rapid technique since SLN was visualized within 30 min from injection in 85.21% of cases for the whole series. The probe detection rate was also very high (97.8% success rate): the mean per cent uptake in the SLN was 0.98. Statistical analysis showed that no parameter was found to have significantly influenced either SLN visualization at lymphoscintigraphy or SLN probe detection at surgery. ConclusionIn our experience, lymphoscintigraphy performed by a single intradermal injection of Nanocoll was an effective and rapid technique for visualizing axilla SLNs in breast cancer patients. Moreover, this technique appeared to be independent of any technical, clinical and pathological findings.

Sentinel node biopsy for breast cancer: is it already a standard of care? A survey of current practice in an Italian region

BackgroundAlthough sentinel node biopsy (SNB) is becoming the standard approach for axillary staging in patients with small breast cancer, criteria for patient selection and some technical aspects of the procedure have yet to be clearly defined. The aim of the present survey was therefore to investigate the way in which SNB is used by general surgeons working in the Veneto region, Italy.MethodsA 29-item questionnaire regarding various aspects of SNB practice was mailed to surgeons in charge of breast surgery in all the 56 surgical centres of the region.ResultsThe rate of response to the questionnaire was 82.1% (n = 46); 69.6% (n = 32) of the respondents routinely perform SNB in their clinical practice. Most of the interviewed surgeons (93.5%) expressed the belief that the acceptable false negative rate should be ≤5%. However, among the surgeons who perform SNB, only 34.4% performed more than 20 SNB during the learning phase. Indications are limited to tumours of ≤1 cm by 31.2% (n = 10) of respondents, ≤2 cm by 46.9% (n = 15) and ≤3 cm by 21.9% (n = 7). Almost all respondents (93.7%) agreed that a clinically positive axilla is a contraindication to SNB, while opinions differed widely concerning other potential contraindications. In most of the centres considered, SN identification is undertaken on the day before surgery using a subdermal injection of 30–50 MBq of 99mTc-albumin-nanocolloid followed by lymphoscintigraphy.ConclusionsSNB is currently performed in the majority of hospitals in the Veneto region. However, the training phase and criteria used for patient selection differ from centre to centre. Certified training courses and shared guidelines are therefore highly desirable.

Separate cavity margins excision as a complement to conservative breast cancer surgery

BACKGROUND Positive lumpectomy margins (LM) usually mandate re-excision. However, approximately half of these patients have no residual tumour in the re-excision specimen. The aim of this study was to investigate if separate cavity margin (CM) excision can safely reduce the need of re-operation. METHODS Rate of re-operation for margin involvement and incidence of residual tumour in the re-excision specimen were retrospectively evaluated in 237 patients (group A) who underwent lumpectomy alone, and in 271 patients (group B) treated by lumpectomy and CM excision. Patients with positive LM (group A) or CM (group B) underwent re-excision. RESULTS In the group A, 50/237 patients (21.1%) had LM+ and underwent re-excision. In the group B, 74/271 patients (27.3%) had LM+, but tumour was found within the CM specimen in 46 patients (17.0%), 24 LM+ and 22 LM-, and reached the CM cut edge in only 15 (5.5%), who finally underwent re-excision. Residual tumour was found in the re-excision specimen in 28/50 patients (56.0%) of the group A and in 7/15 patients (46.7%) of the group B. CONCLUSIONS Separate CM excision strongly decreases the rate of re-operation for involved margin. However, the finding of various combinations of LM and CM status and the evidence that CM excision does not improve the positive predictive value of margin involvement suggest prudent conclusions. Only long term follow up of patients treated according to the CM status can exclude that the reduced rate of re-operations allowed by this procedure would expose to an increased risk of local recurrence.

Maximizing the clinical usefulness of a nomogram to select patients candidate to sentinel node biopsy for cutaneous melanoma

AIMS Investigators from the Memorial Sloan Kettering Cancer Centre (MSKCC) have proposed a nomogram for predicting the sentinel node (SN) status in patients with cutaneous melanoma. The negative predictive value (NPV) of this test, which might help identify low-risk patients who might be safely spared SN biopsy (SNB), has not been yet investigated. METHODS We tested the discrimination (area under the curve [AUC]), the calibration (linear regression) and the NPV of MSKCC nomogram in 543 patients treated at our institution. Different cut-off values were tested to assess the NPV, the reduction of SNB performed and the overall error rate obtained with the MSKCC nomogram. RESULTS SN was positive in 147 patients (27%). Mean predicted probability was 17.8% (95%CI: 16.8-18.8%). Nomogram discrimination was significant (area under the curve = 0.68; P < 0.0001) and mean predicted probabilities of SN positivity well correlated with the observed risk (R(2) = 0.99). Cut-off values between 4% and 9% led to a NPV, SNB reduction and overall error rates ranging between 100 and 91.2%, 2.2 and 27.2%, and 0 and 2.3%, respectively. CONCLUSION In our series, the nomogram showed a significant predictive accuracy, although the incidence of SN metastasis was higher than that observed in the MSKCC series (27% vs 16%). Using the nomogram, a NPV greater than 90% could be obtained, which would be associated with a clinically meaningful reduction of the SNB rate and an acceptable error rate. If validated in large prospective series, this tool might be implemented in the clinical setting for SNB patient selection.