Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer.

BACKGROUND: Marking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node-positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment-positive marked lymph nodes (MLNs) together with SLNs. METHODS: This was a multicentre retrospective analysis of patients with clinically node-positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately. RESULTS: At least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent). CONCLUSION: Excision of the pretreatment-positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node-positive disease resulted in a higher identification rate and improved detection of residual axillary disease.

ANTECEDENTES: En el cáncer de mama con ganglios positivos clínicamente tras el tratamiento neoadyuvante sistémico, se ha propuesto la utilización de iodo radioactivo (Marking Axilla with Radioactive Iodine, MARI) y de la biopsia de ganglio linfático centinela para la estadificación axilar. En este estudio se evaluó la tasa de identificación y detección de enfermedad residual cuando se combinó la exéresis de los ganglios linfáticos marcados antes del tratamiento (marked lymph nodes, MLN) junto con los ganglios centinela (sentinel lymph nodes, SLN). MÉTODOS: Se realizó un análisis retrospectivo multicéntrico de pacientes con cáncer de mama con ganglios positivos clínicamente que se sometieron a tratamiento neoadyuvante sistémico y en las que se combinaron ambas técnicas (con o sin disección axilar). Se calcularon las tasas de identificación y detección de enfermedad residual axilar para MLN y SLN por separado y en conjunto. RESULTADOS: En 138/139 pacientes se identificaron ≥ 1 MLN y/o SLN combinando ambas técnicas (tasa de identificación del 99,3%). La tasa de identificación fue de 92,8% para MLN y del 87,8% para SLN. Combinando ambas técnicas se detectó enfermedad axilar residual en 88/139 (63,3%) pacientes. Se detectó enfermedad residual en 20/88 (22,7%) pacientes utilizando únicamente MLN, en 10/88 (11,4%) pacientes utilizando únicamente SLN y en 58/88 (65,9%) combinando ambas técnicas. CONCLUSIÓN: La exéresis conjunta de los ganglios marcados con iodo radioactivo antes del tratamiento neoadyuvante sistémico y de los ganglios centinela después del tratamiento en pacientes con cN+ logró una tasa de identificación más alta y una mejor detección de la enfermedad axilar residual.

89Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study.

BACKGROUND: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. METHODS: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. RESULTS: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of -48% and -90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was -79% and -94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. CONCLUSIONS: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.

Does 99mTc-tilmanocept, as next generation radiotracer, meet with the requirements for improved sentinel node imaging?

INTRODUCTION AND OBJECTIVES: To evaluate the migration of 99mTc-tilmanocept from the injection site (IS) as well as the uptake in sentinel nodes (SNs) and non-SNs for lymphatic mapping in patients with breast cancer and melanoma, scheduled for SN biopsy after interstitial tracer administration. MATERIALS AND METHODS: For 29 primary tumours in 28 patients (mean age: 62y, range: 45-81y) scheduled for SN biopsy planar images were acquired 10 and 120min after administration of 74MBq 99mTc-tilmanocept, in order to evaluate lymphatic drainage as well as uptake ratios between injection site (IS), SN and non-SN. SPECT-CT was performed immediately after delayed planar images to enable anatomical lymph node localization. RESULTS: SNs were visualized in all patients (100%) with drainage to 34 basins. Uptake in non-SNs was perceived in 16 basins (47%). Number of SNs was concordant between early and delayed images in all basins excepting five (86%). In 24 patients tracer migrated to one lymph node basin (LNB), in three to 2 and in one to 4. When IS was included (N=29) on image, IS/SN ratio could be measured per LNB. The IS/SN ratio at 2h compared to 15min decreased with an average of 66% (range: 15-96%). SN/non-SN 2h ratio in LNBs with visible non-SNs averaged 6.6 (range: 2.3-15.6). In 9 patients with two SNs SN1/SN2 ratio averaged 1.9 on delayed images. At histopathology, SNs were found to be tumour positive in 7 basins (20%). CONCLUSION: 99mTc-tilmanocept appears to meet the requirements for improved SN imaging in breast cancer and melanoma on the basis of early and persistent SN visualization frequently accompanied by no or markedly less non-SN uptake. This is associated to rapid migration from the injection site together with increasing SN uptake and retention as expressed by decreasing IS/SN and persistently high SN/non-SN ratios. Further head-to-head comparison of 99mTc-tilmanocept with standard SN radiotracers in larger series of patients is necessary.

Methodological aspects of 99mTc-sestamibi guided biopsy in breast cancer.

PURPOSE: This review aims to discuss the methodological aspects of dedicated molecular breast imaging (MBI) using 99mTc-sestamibi as radiotracer to guide biopsy of occult or unclear breast lesions on mammography (MG) and ultrasound (US) that are suspicious on MBI (BI-RADS criteria 4 and 5), including its advantages, limitations and future clinical applications. METHODS: Literature search was performed using the PubMed/MEDLINE database and "99mTc-sestamibi", "biopsy" and "breast cancer" as keywords. The search was restricted to English language. RESULTS: There are few studies on 99mTc-sestamibi guided biopsy methods; to our knowledge, no full studies have yet been reported on clinical validation of this new biopsy procedure. This review describes technical aspects of 99mTc-sestamibi guided biopsy and discusses the advantages and limitations of this procedure in comparison with MG, US and MRI-guided biopsy. CONCLUSIONS: MBI-guided biopsy appears to be a complementary modality and is principally indicated in the case of occult or unclear breast lesions on MG/US, that are suspicious on MBI. The future indication is in targeted biopsies in patients with large heterogeneous tumours. Further studies are needed to define the accuracy of this biopsy procedure.

Large-vessel vasculitis: interobserver agreement and diagnostic accuracy of 18F-FDG-PET/CT.

INTRODUCTION: (18)F-FDG-PET visualises inflammation. Both atherosclerosis and giant cell arteritis cause vascular inflammation, but distinguishing the two may be difficult. The goal of this study was to assess interobserver agreement and diagnostic accuracy of (18)F-FDG-PET for the detection of large artery involvement in giant cell arteritis (GCA). METHODS: 31 (18)F-FDG-PET/CT scans were selected from 2 databases. Four observers assessed vascular wall (18)F-FDG uptake, initially without and subsequently with predefined observer criteria (i.e., vascular wall (18)F-FDG uptake compared to liver or femoral artery (18)F-FDG uptake). External validation was performed by two additional observers. Sensitivity and specificity of (18)F-FDG-PET were determined by comparing scan results to a consensus diagnosis. RESULTS: The highest interobserver agreement (kappa: 0.96 in initial study and 0.79 in external validation) was observed when vascular wall (18)F-FDG uptake higher than liver uptake was used as a diagnostic criterion, although agreement was also good without predefined criteria (kappa: 0.68 and 0.85). Sensitivity and specificity were comparable for these methods. The criterion of vascular wall (18)F-FDG uptake equal to liver (18)F-FDG uptake had low specificity. CONCLUSION: Standardization of image assessment for vascular wall (18)F-FDG uptake promotes observer agreement, enables comparative studies, and does not appear to result in loss of diagnostic accuracy compared to nonstandardized assessment.

Development of antigen detection assay for diagnosis of tuberculosis using sputum samples.

The rising incidence of tuberculosis worldwide means an increasing burden on diagnostic facilities, so tests simpler than Ziehl-Neelsen staining are needed. Such tests should be objective, reproducible, and have at least as good a detection limit as 10(4) bacteria/ml. A capture enzyme-linked immunosorbent assay (ELISA) was developed for detection of lipoarabinomannan (LAM) in human sputum samples. As a capture antibody, we used a murine monoclonal antibody against LAM, with rabbit antiserum against Mycobacterium tuberculosis as a source of detector antibodies. The sensitivity of the capture ELISA was evaluated by using purified LAM and M. tuberculosis whole cells. We were able to detect 1 ng of purified LAM/ml and 10(4) M. tuberculosis whole cells/ml. LAM could also be detected in culture filtrate of a 3-week-old culture of M. tuberculosis. The culture filtrate contained approximately 100 microgram of LAM/ml. The detection limit in sputum pretreated with N-acetyl-L-cysteine and proteinase K was 10(4) M. tuberculosis whole cells per ml. Thirty-one (91%) of 34 sputum samples from 18 Vietnamese patients with tuberculosis (32 smear positive and 2 smear negative) were positive in the LAM detection assay. In contrast, none of the 25 sputum samples from 21 nontuberculous patients was positive. This specific and sensitive assay for the detection of LAM in sputum is potentially useful for the diagnosis of tuberculosis.