Sentinel lymph node identification in early stage ovarian cancer: is it still possible after prior tumor resection?

Objective Sentinel lymph node (SLN) detection in ovarian cancer is feasible when tracers are injected before the pathological ovary is resected. This study aims to investigate whether the SLN identification is also feasible in patients whose ovarian tumor has already been resected with injection of the tracer into the ovarian ligaments stumps, i.e. in the event that a frozen section confirms malignancy. Methods Patients who underwent laparotomy with frozen section confirming an ovarian malignancy, and those who underwent a second staging laparotomy after prior resection of a malignant ovarian mass, were included. Blue dye and a radioactive isotope were injected in the stumps of the ligamentum ovarium proprium and the ligamentum infundibulo-pelvicum. After an interval of at least 15-min, the sentinel node(s) were identified using either the gamma-probe and / or blue dye. Results A total of 11 patients were included in the study, the sentinel node (SLN) procedure was completed in all 11 patients. At least one SLN was identified in 3 patients, resulting in a rather low detection rate of 27,3%. Conclusion In this study we showed that SLN procedure after (previous) resection of the tumor seems inferior to detect sentinel nodes when compared to injection of the tracer in the ovarian ligaments before tumor resection. Trial registration NCT02540551

Sentinel node involvement with or without completion axillary lymph node dissection: treatment and pathologic results of randomized SERC trial

Based on results of clinical trials, completion ALND (cALND) is frequently not performed for patients with breast conservation therapy and one or two involved sentinel nodes (SN) by micro- or macro-metastases. However, there were limitations despite a conclusion of non-inferiority for cALND omission. No trial had included patients with SN macro-metastases and total mastectomy or with >2 SN macro-metastases. The aim of the study was too analyze treatment delivered and pathologic results of patients included in SERC trial. SERC trial is a multicenter randomized non-inferiority phase-3 trial comparing no cALND with cALND in cT0-1-2, cN0 patients with SN ITC (isolated tumor cells) or micro-metastases or macro-metastases, mastectomy or breast conservative surgery. We randomized 1855 patients, 929 to receive cALND and 926 SLNB alone. No significant differences in patient’s and tumor characteristics, type of surgery, and adjuvant chemotherapy (AC) were observed between the two arms. Rates of involved SN nodes by ITC, micro-metastases, and macro-metastases were 5.91%, 28.12%, and 65.97%, respectively, without significant difference between two arms for all criteria. In multivariate analysis, two factors were associated with higher positive non-SN rate: no AC versus AC administered after ALND (OR = 3.32, p < 0.0001) and >2 involved SN versus ≤2 (OR = 3.45, p = 0.0258). Crude rates of positive NSN were 17.62% (74/420) and 26.45% (73/276) for patient’s eligible and non-eligible to ACOSOG-Z0011 trial. No significant differences in patient’s and tumor characteristics and treatment delivered were observed between the two arms. Higher positive-NSN rate was observed for patients with AC performed after ALND (17.65% for SN micro-metastases, 35.22% for SN macro-metastases) in comparison with AC administered before ALND.

Targeted Axillary Dissection after Chemotherapy: Feasibility Study with Clip and Carbon Dye Tattoo – Neotarget Trial

<b><i>Background:</i></b> Axillary staging in patients with complete response after neoadjuvant chemotherapy (NAC) is still controversial. Our objective was to test tattoo alone and subsequentially tattoo plus clip as markers in the targeted axillary dissection of ycN0 patients. <b><i>Methods:</i></b> Prospective cohort of cT1-T3, cN1 (proven histologically), M0 patients scheduled to receive NAC. Exclusion criteria were lobular histology, prior axillary surgery, and clinical N2/3. In cohort 1 this positive node (Neotarget node) was tattooed at diagnosis. If ycN0, a targeted axillary dissection was performed. After an interim analysis with negative results we changed the protocol in order to do a double marking procedure (Cohort 2): the positive node was clipped at diagnosis and after NAC a tattoo was done before surgery. <b><i>Results:</i></b> Thirteen patients in Cohort 1 and 18 patients in Cohort 2. Failure to identify the Neotarget node with multiple nodes retrieved in 9/13 (69%) of Cohort 1 patients. Also in 5/13 (38%) of Cohort 1 patients and 3/18 (17%) of Cohort 2 there was a failure to clearly identify tattooed nodes. In Cohort 2, clip identification by surgical specimen radiography allowed the identification of the tagged node in 17/18 (94,4%) of cases. The concordance between the clipped node and sentinel nodes was 16/18 (89%). <b><i>Conclusions:</i></b> The introduction of double marking by clipping the metastatic node and verifying their removal by surgical specimen radiography, using carbon ink as a tracer, allowed the identification of the metastatic node in 94% of cases, with a simple, reproducible, and easy-to-implement targeted axillary dissection procedure.

Fluorescent guided lymph node harvest in laparoscopic Wilms nephroureterectomy - a new technique

Lymph node harvest is an integral part of Wilms tumor surgery with both SIOP and COG protocols asking for more than 6 lymph nodes to best evaluate for nodal spread and a subsequent need for intensification of treatment. The majority of studies show that in both open and minimally invasive resections the median number of nodes removed is 4. Indocyanine green and near infrared fluorescence may be the key to solving this problem. In adult gynaecology, colorectal and breast cancers, ICG is used to identify sentinel nodes and facilitate nodal harvest. This report describes its use in Wilms tumor

False-negative frozen section of sentinel nodes in early breast cancer (cT1-2N0) patients

Background Sentinel lymph node biopsy (SLNB) is the standard approach for the axillary region in early breast cancer patients with clinically negative nodes. The present study investigated patients with false-negative sentinel nodes in intraoperative frozen sections (FNSN) using real-world data. Methods A case–control study with a 1:3 ratio was conducted. FNSN was determined when sentinel nodes (SNs) were negative in frozen sections but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) sections. The control was defined as having no metastasis of SNs in both frozen and FFPE sections. Results A total of 20 FNSN cases and 60 matched controls from 333 SLNB patients were enrolled between April 1, 2005, and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between the FNSN and control groups. The FNSN patients had larger tumor sizes on preoperative mammography (P = 0.033) and more lymphatic tumor emboli on core biopsy (P < 0.001). Four FNSN patients had metastasis in nonrelevant SNs. Another 16 FNSN patients had benign lymphoid hyperplasia of SNs in frozen sections and metastasis in the same SNs from FFPE sections. Micrometastasis was detected in seven of 16 patients, and metastases in nonrelevant SNs were recognized in two patients. All FNSN patients underwent a second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed breast cancer recurrence. The disease-free survival, breast cancer-specific survival, and overall survival in FNSN were not inferior to those in controls. Conclusions Patients with a larger tumor size and more lymphatic tumor emboli have a higher incidence of FNSN. However, the outcomes of FNSN patients after completing ALND were noninferior to those without SN metastasis. ALND provides a correct staging for patients with metastasis in nonsentinel axillary lymph nodes.

Axillary management in T1-3N1M0 breast cancer patients with needle biopsy proven nodal metastases at presentation after neoadjuvant chemotherapy (ATNEC).

TPS600 Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillary nodes in 40% to 70% of patients. This raises questions about the benefit of further axillary treatment in those patients with no evidence of residual nodal disease (ypN0) after NACT. Methods: Design: ATNEC is a phase 3, randomised (1:1), multi-centre trial, with embedded economic evaluation, comparing standard axillary treatment (axillary lymph node dissection [ALND] or axillary radiotherapy [ART]) with no further axillary treatment in T1-3N1M0 breast cancer patients with needle biopsy proven axillary nodal metastases, who after NACT have no residual nodal disease (ypN0) on dual tracer sentinel node biopsy (SNB) and removal of at least 3 nodes (sentinel nodes and marked involved node). Stratification: Institution, type of surgery (breast conserving surgery vs mastectomy), receptor status (triple negative vs HER2 positive vs ER positive and/or PR positive and HER2 negative). Inclusion criteria are: Age ≥ 18, Male or female, T1-3N1M0 breast cancer at diagnosis (pre-NACT), FNA or core biopsy confirmed axillary nodal metastases at presentation, ER and HER2 status evaluated on primary tumour, received standard NACT as per local guidelines, ultrasound of the axilla at completion of NACT, dual tracer SNB after NACT and at least 3 nodes removed (sentinel nodes and marked node), no evidence of nodal metastases post NACT (ypN0). Exclusion criteria are: bilateral invasive breast cancer, SNB prior to NACT, marked node not removed except where at least one node removed shows evidence of down-staging with complete pathological response e.g. fibrosis/scarring and at least 3 nodes removed, previous ipsilateral axillary surgery, previous cancer within last 5 years or concomitant malignancy except basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, in situ or stage 1 melanoma, contra- or ipsilateral in situ breast cancer. Aims: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy - who after NACT have no residual nodal disease on SNB (ypN0) - is non-inferior to axillary treatment in terms of disease free survival, and reduces the risk of lymphoedema at 5 years. Statistical methods: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Radiotherapy quality assurance: Study has in-built radiotherapy QA programme that will be co-ordinated by National Radiotherapy Trials QA (RTTQA) group. Target accrual: 1900. Trial status: Recruiting. Number of sites: 100. Clinical trial information: NCT04109079.