Chest X-ray Dose Equivalent Low-dose CT with Tin Filtration: Potential Role for the Assessment of Pectus Excavatum.

RATIONALE AND OBJECTIVES: To determine the value of chest CT with tin filtration applying a dose equivalent to chest x-ray for the assessment of the Haller index for evaluation of pectus excavatum. MATERIALS AND METHODS: Two hundred seventy-two patients from a prospective single center study were included and underwent a clinical standard dose chest CT (effective dose 1.8 ± 0.7 mSv) followed by a low-dose CT (0.13 ± 0.01 mSv) in the same session. Two blinded readers independently evaluated all data sets. Image quality for bony chest wall assessment was noted. Radiologists further assessed (a) transverse thoracic diameter, (b) anteroposterior thoracic diameter, and calculated (c) Haller index by dividing transverse diameter by anteroposterior diameter. The agreement of both readers in standard dose and low-dose CT was assessed using Lin's concordance correlation coefficient (pc). RESULTS: Subjective image quality was lower for low dose compared to standard dose CT images by both readers (p < 0.001). In total, 99% (n = 540) of low-dose CT scans were rated as diagnostic for bony chest wall assessment by both readers. There was a high agreement for assessment of transverse diameter, anteroposterior diameter and Haller index comparing both readers in standard dose and low-dose CT with pc values indicating substantial agreement (i.e., 0.95> and ≤0.99) in 12/18 (67%) and almost perfect agreement (i.e., >0.99) in 6/18 (33%). CONCLUSION: Our study suggests that low-dose CT with tin filtration applying a radiation dose equivalent to a plain chest X-ray is excellent for assessing the Haller index.

Sequential somatic mutations upon secondary anti-HER2 treatment resistance in metastatic ERBB2S310F mutated extramammary Paget's disease.

Metastatic extramammary Paget's disease is a rare adenocarcinoma with poor prognosis. Several reports of human epidermal growth factor receptor 2 alterations point to its pathogenic role in the disease. However, the occurrence of treatment resistance to anti-HER2 therapy demand the need for further knowledge. We report of a patient with metastatic penoscrotal extramammary Paget's disease, with an ERBB2S310F mutation, in which near complete response was achieved upon treatment with trastuzumab and carboplatin. However, after 10 cycles of trastuzumab and carboplatin, widespread metastasis re-occurred. Analysis of a newly developing metastasis revealed additional genomic alterations including ERBB3A232V and PIK3CAG106V point mutations as well as MET and CDK6 amplification, providing a potential mechanism of acquired treatment resistance. Therefore, ERBB family inhibitor afatinib was initiated. Unfortunately, the patient succumbed to disease-related complications shortly after treatment initiation. This is the first report of ERBB2S310F mutated, metastatic extramammary Paget's disease with secondary resistance to trastuzumab / carboplatin, potentially due to additional acquired genomic alterations. This case contributes to the growing evidence of HER2 in the pathogenesis of metastatic extramammary Paget's disease and emphasizes the importance of repetitive, genomic analysis in rare diseases.