In February 2020, a 68 years-old woman with an ECOG performance status of zero presented with dry cough and hemoptysis. She never smoked and had a medical history of arterial hypertension, an adrenal non-progressing hyperplasia, a gastric bypass and a cholecystectomy. In the familial oncological history, we note an adrenal carcinoma in two brothers and a metastatic neoplasia of unknown origin in her father. A genetic testing for germinal mutations was not performed.
Chest computed tomography (CT) revealed pulmonary infiltration of the left lower lobe, with small mediastinal lymph nodes.
Bronchial left lower lobe biopsy revealed a lung adenocarcinoma, TTF1 (+), P40(-). The NGS (QiaSeq targeted DNA Panel CDHS-15662Z-617) testing for oncogenic driver mutations showed a p.773-774HVdelinsLM variant located in exon 20 of the EGFR gene and a TP53 co-mutation ( Table 1 ). ALK and ROS immunochemistry staining were negative, whereas PD-L1 expression was estimated to be 90% with the 22C3 antibody (Dako PharmDx assay).
The work-up was completed by a PET-CT and a brain MRI. Three asymptomatic brain metastases were observed on MRI, leading to the diagnosis of a cT3N2M1 lung adenocarcinoma. Afterwards, the disease was evaluated every three months by chest and abdominal CT, brain MRI and PET-CT on progression of single lesions.
In the multidisciplinary tumour board first-line immuno-chemotherapy was initially considered as an appropriate treatment option, because specific exon-20 targeted therapies were not yet available at the time of diagnosis and single agent immunotherapy is considered as less effective in EGFR-mutated lung carcinomas even with high PDL1 expression.
The treatment options were discussed at our multidisciplinary molecular tumor board (MTB). As a case report reported a favorable response in a patient presenting this specific mutation, our patient was put on osimertinib treatment at a daily dose of 80mg.
She noted significant regression of coughing after one month of treatment.
At the first tumor assessment after 3 months of treatment, there was a partial response according to the RECIST 1.1 criteria with a moderate decrease in the pulmonary tumor infiltration, a significant regression of the brain metastases and disappearance of the cerebral perilesional oedema, the main lesion decreasing from 12,5 x 13 mm to 7.5 x 8 mm.
Stereotaxic radiotherapy of an occipital 8 mm brain lesion was performed after 8 months, as some asymptomatic perilesional edema had reappeared without change in size of the lesion.
After 20 months of treatment, stereotaxic radiotherapy was performed on a second frontal brain lesion that increased discretely from 3 to 5 mm. Osimertinib treatment was continued as there was no progression of the other tumor locations ( Figure 1  - April 2022).
In August 2022, 30 months after the initiation of osimertinib, the patient presented a focal asymptomatic progression in the main left thoracic lesion, without signs of other extracerebral or cerebral progression, as confirmed by PET-scan ( Figure 2 ) and brain MRI. The thoracic progression was treated by stereotaxic radiotherapy, and osimertinib was continued.
At the last tumor evaluation on April the 26th 2023, 38 months after diagnosis, the patient is still on Osimertinib and free of symptoms, without signs of progression on brain MRI and thoraco-abdominal CT.
Timeline of the combined targeted treatment and stereotaxic radiotherapy on focal progressing lesions