Publications

The only currently commercialized point-of-care assay for tuberculosis (TB) that measures lipoarabinomannan (LAM) in urine (Alere LF-LAM) has insufficient sensitivity. We evaluated the potential of 100 novel monoclonal antibody pairs targeting a variety of LAM epitopes on a sensitive electrochemiluminescence platform to improve the diagnostic accuracy. In the screening, many antibody pairs showed high reactivity to purified LAM but performed poorly at detecting urinary LAM in clinical samples, suggesting differences in antigen structure and immunoreactivity of the different LAM sources. The 12 best antibody pairs from the screening were tested in a retrospective case-control study with urine samples from 75 adults with presumptive TB. The best antibody pair reached femtomolar analytical sensitivity for LAM detection and an overall clinical sensitivity of 93% (confidence interval [CI], 80% to 97%) and specificity of 97% (CI, 85% to 100%). Importantly, in HIV-negative subjects positive for TB by sputum smear microscopy, the test achieved a sensitivity of 80% (CI, 55% to 93%). This compares to an overall sensitivity of 33% (CI, 20% to 48%) of the Alere LF-LAM and a sensitivity of 13% (CI, 4% to 38%) in HIV-negative subjects in the same sample set. The capture antibody targets a unique 5-methylthio-d-xylofuranose (MTX)-dependent epitope in LAM that is specific to the complex and shows no cross-reactivity with fast-growing mycobacteria or other bacteria. The present study provides evidence that improved assay methods and reagents lead to increased diagnostic accuracy. The results of this work have informed the development of a sensitive and specific novel LAM point-of-care assay with the aim to meet the WHO's performance target for TB diagnosis.

BACKGROUND

The aim of this study was to determine if, in inflammatory breast cancer (IBC), baseline metabolic activity (maximum standardized uptake value [SUVmax]) of primary tumor and involved regional lymph nodes (IRLN) are prognostic markers of response after neoadjuvant systemic therapy (NAS).

PATIENTS AND METHODS

Baseline 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography scans were retrospectively reviewed among 61 women with IBC who received NAS, had mastectomy, and had available pathology reports. Primary tumor and IRLN SUVmax were compared between patients with a pathologic complete response (pCR) versus those with residual disease after NAS. A multivariate Cox model was fit to evaluate the effects of SUVmax on overall survival, adjusting for pCR and stratified by receptor status and disease stage.

RESULTS

SUVmax in primary IBC tumors tended to increase with tumor grade (trend test P = .06) and was lower for stage III, non-triple-negative (TN) versus stage III, TN and stage IV, non-TN disease (P = .04). Neither primary tumor nor IRLN SUVmax was significantly different comparing pCR versus residual disease after NAS. Adjusting for pathology response in the overall survival model stratified by stage and receptor status, baseline SUVmax in primary IBC tumor was associated with an estimated hazard ratio of 1.10 (95% confidence interval, 0.97-1.25; P = .15) for patients with stage III, TN and stage IV, non-TN disease. This hazard ratio corresponded to a 1.74-fold risk of death with 1 standard deviation (SD = 5.9) increase in baseline SUVmax in primary IBC tumor.

CONCLUSION

2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography provides prognostic information for newly diagnosed IBC. Larger studies are needed to confirm these findings and assess how such early information could affect treatment choices for IBC in the neoadjuvant setting.