PMC8100222_01
Patient's imaging before and during anti-tumor treatment. (A) The baseline chest computed tomography (CT) scan before treatment. (B) Bone isotope scanning suggested extensive bone metastases after 12 months of Osimertinib treatment.
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Her chest computed tomography (CT) showed a lesion in the upper lobe of the left lung ( Figure 1A ) and the patient was diagnosed with lung adenocarcinoma. T790M mutation and a negative PD-L1 expression. Then, the patient received Osimertinib (80 mg/d) for 12 months, after which an extensive bone metastasis was found using bone isotope scanning ( Figure 1B ).
Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing on tumor tissues of case 1. Wild type KRAS (top) and acquired KRAS mutations. (A) Wild type KRAS before treatment (top) and a KRAS Q61H mutation (bottom) after receiving Osimertinib. (B) Wild type KRAS before treatment (top) and a KRAS G12D mutation (bottom) after receiving Osimertinib.
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Re-biopsy of bone metastasis (not decalcification) and another genetic test indicated that the patient was negative for the EGFR-T790 mutation, but positive for the KRAS exon 2 (G12D, MAF:13.34%) and exon 3 (Q61H, MAF:0.43%) mutations, as well as for an EGFR exon 19 deletion (MAF:22.58%) mutation ( Figure 2 ).
PMC8100222_02
Five lines of treatment for case 2. (A) CT scan before (top) and after (bottom) receiving gefitinib, which produced a partial response (PR) in the right lung with 5 months of progression-free survival (PFS). (B) CT scan before (top) and after (bottom) receiving afatinib, which showed no objective response with less than one month of PFS. (C) CT scan before (top) and after (bottom) receiving pemetrexed, cisplatin and bevacizumab which brought a PR effect with 6 months of PFS. (D) CT scan before (top) and after (bottom) receiving Osimertinib, which induced no objective response with four months of PFS. (E) CT scan before (top) and after (bottom) receiving paclitaxel (albumin-bound) plus nivolumab which induced a PR effect with more than 18 months of PFS.
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TG (-), ALK (-), ROS-1 (-) invasive adenocarcinoma. Next generation sequencing (NGS) on tumor biopsy tissues revealed an EGFR exon 19 deletion without a KRAS mutation. The patient then accepted gefitinib (250 mg/d) which, as shown in contrasted CT, produced a partial response in the right lung ( Figure 3A ). Based on these findings, the treatment was changed to afatinib (40 mg/d); however, disease progression in the right lung was soon identified ( Figure 3B ). In December 2017, the patient began receiving a six-cycle chemotherapy regimen with pemetrexed, cisplatin, and bevacizumab, which was partially effective, but new lesions quickly appeared in both lungs ( Figure 3C ). Re-biopsy of the right lower lung of the patient revealed no EGFR mutation but tested positive for the KRAS exon 3 (R68S, MAF:5.4%) mutation by MSK-IMPACT sequencing ( Figure 3D ). Therefore, the patient received four cycles of paclitaxel (albumin-bound) plus nivolumab treatment and acquired a partial response ( Figure 3E ).