PMC7328355_01
Clinical summary of the patient. (A) Pathology results including
hematoxylin-eosin staining, positivity with immunohistochemical markers of
MPM including calretinin and D2-40 and negative TTF-1 expression. (B-E)
Thoracic CT scans of primary lung lesions at (B) baseline (15.03 x 9.8 cm);
(C) PR at 2 months of alectinib therapy (10.7 x 5.7 cm); (D) PD after a
total of 4.5 months of alectinib therapy (17.59 x 12.09 cm); (E) PR within
1 month of lorlatinib therapy (14.14 x 9.94 cm). (F) An illustrated summary
of the treatment received by the patient, including the best OR and PFS in
each line of treatment. Mutations and their corresponding allelic fractions
detected during the course of treatment using targeted NGS are also
tabulated at the bottom of the figure. (G) Plot summarizing the serum levels
of the tumor biomarkers including NSE, SCC, CA-125, and CEA during the
treatment course.. ALK, anaplastic lymphoma kinase; CA, carbohydrate antigen; CEA,
carcinoembryonic antigen; CT, computed tomography; MPM, malignant pleural
mesothelioma; ND, not detected; NGS, next-generation sequencing; NSE,
neuron-specific enolase; OR, objective response; PD, progressive disease;
PFS, progression-free survival; PR, partial response; SCC, squamous cell
carcinoma antigen; TTF-1, thyroid transcription factor
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Based on his comprehensive clinical workup including histopathology (Figure 1A), and imaging results (Figure 1B), he was diagnosed with stage IIIB (cT4N2M0) MPM based on recent National Comprehensive Cancer Network (NCCN) guidelines on MPM staging (v.1.2018). After 1 month of alectinib therapy, his cough and asthma were alleviated; with a significant reduction in the blood tumor markers, particularly neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC) (Figure 1G). Consistent with the continuous improvement in clinical symptoms (ECOG-PS 1), CT images after 2 months of therapy showed marked shrinkage of the primary lesion, evaluated as partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 (Figure 1C). Blood tumor markers including NSE, SCC, and CA-125 were also observed to be increased (Figure 1G). PD was thus confirmed after a total of 4.5 months of alectinib therapy (Figure 1D). His therapy was then switched to lorlatinib, resulting in remarkable shrinkage of the primary lesion (~34%), and achieving PR within a month (Figure 1E).