Osimertinib in uncommon EGFR exon 21 L861R and EGFR exon 18 deletion-insertion mutant non-small cell lung cancer-case report.

Background: Tyrosine kinase inhibitors (TKIs) have changed the treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) found to have oncogene-driven activating epidermal growth factor receptor (EGFR) mutations. Whilst there have been a handful of case reports of sensitivity to first-generation TKIs in EGFR L861R mutations, the efficacy of the third-generation TKI osimertinib in NSCLC patients with EGFR L861R and EGFR exon 18 deletion-insertion mutations is limited. Case Description: We report two patients from our institution with uncommon EGFR mutations treated with first-line osimertinib. Our first patient, a 72-year-old male with metastatic lung adenocarcinoma was identified to harbour a rare EGFR L861R mutation and was commenced on osimertinib. After a follow-up period of 18 months, the patient is continuing to experience treatment benefit with imaging showing a good partial response. The second patient, a 60-year-old male also with metastatic lung adenocarcinoma and an EGFR exon 18 deletion-insertion mutation achieved a partial response for 6.6 months. Upon progression, he was commenced on carboplatin and pemetrexed chemotherapy however died from subsequent pneumonia. He had an overall survival (OS) from time of diagnosis of 7.6 months. Conclusions: We demonstrate clinical efficacy of first-line osimertinib in the treatment of advanced NSCLC harbouring uncommon EGFR L861R and EGFR exon 18 deletion-insertion mutations. These results may be suggestive of the wider applicability of osimertinib in the treatment of uncommon EGFR mutant NSCLC.

Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study.

BACKGROUND: Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy. METHODS: We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue. RESULTS: The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein CACNA1D mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45-17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00-26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20-6.31]). CONCLUSIONS: Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.

Laboratory Diagnosis of ANCA-Associated Vasculitis (AAV) Using a Combination of Immunofluorescence Test (IIFT) and Line Immunoassay (LIA): Single-Centre Report From India / Diagnóstico de laboratorio de vasculitis asociada a ANCA (VAA), utilizando conjuntamente test de inmunofluorescencia (IIFT) e inmunoensayo lineal (LIA): Reporte de un único centro de la India

Introduction: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a small vessel vasculitis with insufficient epidemiological estimates in India. We aimed to determine demographic, clinical features, and laboratory diagnosis of AAV patients presenting to a large tertiary care centre in India. Material and methods: 1289 patient samples were screened for ANCA by indirect immunofluorescence test (IIFT) and confirmation of ANCA target antigens was done by line immunoassay. Association between IIFT and LIA was determined in AAV. Results: By IIFT, ANCA was detected in 13.0% (168 out of 1289), of which 23.8% (40/168) were positive with P-ANCA pattern, 25.0% (42/168) were positive with C-ANCA and 47.6% (80/168) showed an atypical pattern. On evaluation with a line immunoassay, 6.7% (86/1289) were positive out of which 52.3% (45/86), 41.9% (36/86), 8.8% (6/86) were positive for anti-MPO, anti-PR3, and anti-GBM respectively. In eosinophilic granulomatosis with polyangiitis (EGPA) 87.5% (7/8), and microscopic polyangiitis (MPA/RLV) 91.3% (21/23), anti-MPO was the predominantly observed antibody. In granulomatosis with polyangiitis (GPA) anti-PR3 antibody was predominant in 87.5% (28/32) cases. Out of 168 IIF positive samples 8, 32, and 23 cases of EGPA, GPA, and MPA/RLV were observed respectively. Conclusions: The primary aim of the study was to provide single-centre data to determine the laboratory diagnosis of AAV. A combination of IIFT and LIA was found to be an optimum testing strategy for the laboratory diagnosis of AAV.(AU)

Introducción: La vasculitis asociada a anticuerpos anticitoplasma de neutrófilos –ANCA– (VAA) es una vasculitis de pequeños vasos con cálculos epidemiológicos insuficientes en India. Nuestro objetivo fue determinar las características demográficas y clínicas, y los diagnósticos de laboratorio de los pacientes con VAA que se presentaron en un gran centro de cuidados terciarios en India. Material y métodos: Se realizó un cribado de ANCA en 1.289 pacientes mediante test de inmunofluorescencia directa (IIFT), realizándose la confirmación de los antígenos diana de ANCA mediante inmunoensayo lineal. La asociación entre IIFT y LIA fue determinada en VAA. Resultados: Mediante IIFT, se detectó ANCA en el 13% de los pacientes (168 de 1.289), de los cuales, el 23,8% (40/168) fue positivo con el patrón P-ANCA, el 25% (42/168) fue positivo con C-ANCA y el 47,6% (80/168) reflejó un patrón atípico. En la evaluación con inmunoensayo lineal, el 6,7% (86/1.289) fue positivo, de los cuales, el 52,3% (45/86), 41,9% (36/86) y 8,8% (6/86) fueron positivos para anti-MPO, anti-PR3 y anti-GBM, respectivamente. En la granulomatosis eosinofílica con poliangitis (EGPA), en el 87,5% (7/8) de los casos, y en poliangitis microscópica (MPA/RLV) en el 91,3% (21/23), anti-MPO fue el anticuerpo predominantemente observado. En granulomatosis con poliangitis (GPA), el anticuerpo anti-PR3 fue predominante en el 87,5% (28/32) de los casos. De entre 168 muestras positivas de IIF, se observaron 8, 32, y 23 casos de EGPA, GPA y MPA/RLV, respectivamente. Conclusiones: El objetivo primario del estudio fue aportar los datos de un único centro para determinar el diagnóstico de laboratorio de VAA. El resultado fue que la combinación de IIFT y LIA es una estrategia óptima para el diagnóstico de laboratorio de VAA.(AU)