PMC9768476_01
Chest CT scan of baseline (A, B), pathological examination (H&E stain) showing lung adenocarcinoma (C) and chest CT scan of best response PR after the treatment of Erlotinib (D). CT, computed tomography; PR, partial response.
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Chest computed tomography (CT) scan showed a mass in the upper lobe of the right lung accompanied by multiple small nodules in both lungs, enlarged mediastinal and hilum lymph nodes ( Figure 1A, B ). The pathology results indicated lung adenocarcinoma ( Figure 1C ), and the genetic testing found EGFR 19del mutation. EGFR 19del. Erlotinib as the first-line therapy was given, and the best response was partial response (PR) ( Figure 1D ).
Chest CT scan of PD resistant to erlotinib (A), photomicrograph of re-biopsy (H&E stain) showing lung adenocarcinoma (B) and chest CT scan of best response PR after the treatment of chemotherapy combined with PD-1 inhibitor (C). CT, computed tomography; PD, progressive disease; PR, partial response; PD-1, programmed cell death 1.
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Then the patient underwent progressive disease (PD) ( Figure 2A ). PD-1 inhibitor (toripalimab) plus pemetrexed and carboplatin, followed by 2 cycles of toripalimab plus pemetrexed as maintenance treatment. PR was achieved again ( Figure 2C ).
Chest CT scan of PD after 8 cycles of chemotherapy combined with PD-1 inhibitor (A-C), photomicrograph of the third biopsy (H&E stain) showing SCLC transformation (D), Chest CT scan after 2 cycles of EC chemotherapy showing the main lesion of RUL significantly shrank (E), while intrapulmonary metastatic nodules increased and enlarged (F, G), the pathology (H&E stain) of the enlarged metastatic lesion of RLL (red arrow) showing NSCLC (H), and chest CT scan of PR after 2 cycles of combination therapy of osimertinib and EC chemotherapy (I-K). CT, computed tomography; PD, progressive disease; PD-1, programmed cell death 1; SCLC, small cell lung cancer; EC, etoposide plus carboplatin; RUL, right upper lobe; RLL, right lower lobe; NSCLC, non-small cell lung cancer; PR, partial response.
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Then the patient experienced the second PD ( Figures 3A-C ), and the third biopsy of RUL lesion was performed. Unexpectedly, histologic analysis showed a transformation to SCLC ( Figure 3D ) with immunohistochemical staining confirmed as Syn (+) and Ki-67 (70%+). After 2 cycles of EC chemotherapy (PFS 1.9 months), the main lesion located in RUL significantly shrank ( Figure 3E ), however, the intrapulmonary metastatic nodules increased and enlarged ( Figures 3E-G ). The pathological results revealed NSCLC ( Figure 3H ) with the genetic testing showing EGFR 19del and T790M (+). EC chemotherapy combined with the 3rd-generation of EGFR-TKI, osimertinib. Encouragingly, after 2 cycles of combination therapy, the main lesion in RUL continued to shrink ( Figure 3I ), and the metastatic nodules in both lungs decreased significantly ( Figure 3J,K ).
Timeline of the patient. RUL, right upper lobe; EGFR, epidermal growth factor receptor; PR, partial response; PD, progressive disease; PD-L1, programmed death ligand 1; TPS, tumor proportion score; SCLC, small cell lung cancer; RLL, right lower lobe; NSCLC, non-small cell lung cancer.
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The timeline of the treatment process is shown in  Figure 4 .