A 63-year-old male (an ex-smoker that quit 20 years ago, with smoking history of 15 pack-years) was referred to our outpatient clinic with NSCLC diagnosis to assess treatment options. The tumour was located in the right lung and spread to the mediastinal and supraclavicular lymph nodes. The lesion was detected in the chest CT (April, 2015) performed due to recurring mild exertional dyspnoea, decrease in exercise tolerance and dry paroxysmal cough. On histopathological examination of mediastinal lymph nodes biopsy obtained at mediastinoscopy and the right supraclavicular lymph nodes from fine-needle biopsy metastatic lung adenocarcinoma (TTF1+, Napsin A+) was diagnosed (June, 2015). The patient denied any weight loss. His medical history included mild prostatic hyperplasia, past lithotripsy due to urolithiasis, and in his youth hepatitis A. He is a farm worker.\nThe results of laboratory testing were within normal limits. The chest CT revealed suspicious additional changes in the lung parenchyma as well as bone lesions suggestive of metastases. In PET scan distant metastases were ruled out, however, due to significant regional spread of tumour (stage IIIB) the patient was not eligible for radical radiotherapy. In parallel to the staging procedures, the status of EGFR activating mutations was assessed and the exon 19 deletion was detected. The patient was therefore started on afatinib 40 mg QD.\nAfter 4 weeks of treatment the patient presentedwith a facial rash (grade 1). After 12 weeks of treatment diarrhoea ensued, however, the patient remained professionally active. Diet modification and loperamide as needed were advised. In the chest CT performed after 12 weeks of treatment there was a partial tumour response. With no laboratory abnormalities, the patient continued therapy for 12 months. The rash with no need of treatment persisted.\nIn August 2016 the patient experienced a pathological vertebral fracture with no evidence of lung cancer progression on chest imaging and no evidence of disease progression in the brain MRI. However, a few days later there appeared progressive paraparesis. The spine MRI revealed metastases in vertebral bodies of Th1, Th7 and Th8 with protrusion into the epidural space and spinal cord compression. The patient underwent neurosurgery (posterior decompression and C4-Th11 stabilisation), rehabilitation (physiotherapy and kinesitherapy) and palliative radiotherapy (30 Gy in 10 fractions) for affected area. The treatment with afatinib was continued.\nIn December 2016 (15th month of afatinib treatment) the chest CT revealed progression of the disease in the lungs. Genetic examination of circulating free DNA (cfDNA) was performed and EGFR T790M mutation was found. In December 2016 the treatment with osimertinib 80 mg QD was initiated. The severity of the neurological deficits was slowly improving and the patient recovered the ability to move his legs. Follow-up chest CT, performed after 2 months of treatment, revealed partial regression. In the following examination further regression was observed, with the sum of measurable dimensions of the lesions reduced in size by 38%. Currently, the patient is still experiencing a clinical benefit after 8 months of osimertinib treatment.
The patient was a 68-year-old woman with a medical history of postoperative treatment of NSCLC with bone metastasis 1 year 8 mo before presentation.\nA review of the patient’s medical history revealed nothing significant other than lung cancer and hypertension.\nA review of the patient’s medical history revealed nothing significant other than lung cancer and hypertension.\nThe patient had no significant personal or family history.\nThe patient presented with multiple erythematous papules mainly on the face and thigh on day 74. Seventy-eight days later, the patient developed several oral blisters and scattered erythema papules that rapidly developed into mucosal erosion and systemic epidermal abscission including the skin on the face and back (Figure ). The large area of exfoliation involved 30% of the body surface area. Nikolsky’s sign was positive. Despite the severity of the disease, the patient’s general condition is acceptable.\nRoutine laboratory examination revealed normal alanine aminotransferase (ALT 22 U/L, normal limits 13-69 U/L). Laboratory markers of systemic involvement indicated anemia, leucopenia, hypoalbuminemia, and hyponatremia. More importantly, there was no short-term drug or diet exposure before the outbreak. In addition, the interval between the first administration of AZD-9291 and the onset of disease was consistent with hypersensitivity latency. Bacterial cultures of blood, urine, and blisters revealed no evidence of bacterial infection. A drug lymphocyte-stimulation test was positive for AZD-9291, with a stimulation index of 2.6. As the above information was indicative enough, and the patient refused to have a pathological examination, biopsy was not performed.\nChest computed tomography (CT) showed pulmonary lesions in posterior segment of right upper lobe, and peripheral lung cancer with multiple pulmonary metastases. Multiple metastases of the thoracic vertebrae, sternum, and ribs were considered (Figure and ), which were similar to previous CT images (Figure and ). Follow-up was recommended.