A 62-year-old Japanese man presented to our hospital with upper abdominal pain. He was a former smoker, and had no history of drug allergy. He had no particular previous medical history other than Helicobacter pylori infection. A chest and abdominal computed tomography (CT) scan with contrast agent showed a mass in the right lower lobe of the lung, wall thickening of the jejunum, and swelling of the lymph nodes around the jejunum. A bronchoscopy was performed and pathological examination showed a poorly differentiated adenocarcinoma. Then, a small intestinal endoscopy was performed. An ulcer was discovered in the jejunum. The mucosal surface around the lesion was normal, which suggested a metastatic tumor. Pathological examination of a biopsy from the intestinal ulcer showed a poorly differentiated adenocarcinoma. Taken together, we diagnosed the patient as having lung adenocarcinoma with multiple distant metastases (cT2bN0M1c, stage Ⅳb, epidermal growth factor receptor mutation negative, anaplastic lymphoma kinase fusion negative, and c-ros oncogene 1 fusion negative) . We initiated four courses of cisplatin (75 mg/m²) plus pemetrexed (PEM 500 mg/m²) as first-line therapy, followed by one cycle of PEM maintenance therapy. Four months after treatment initiation, a contrast-enhanced CT revealed intestinal lymphadenopathy and tumor enlargement, which we considered as progressive disease .
We then explored whether the BRAF V600E mutation was involved therein. Analysis of the lung lesion biopsy revealed the presence of this mutation, and we initiated treatment with the combination of 300 mg dabrafenib and 2 mg trametinib as second-line therapy. The Eastern Cooperative Oncology Group performance status of the patient was 1. A CT scan after 6 weeks of treatment revealed tumor regression, which we considered a partial response (PR) . The patient showed grade 1 fever, but no diarrhea or abdominal pain, and there were no other side effects .
He presented to our hospital 4 months after the commencement of dabrafenib and trametinib with abdominal pain and vomiting. A CT scan revealed bowel perforation, free air, and ascites (Fig. 1). Emergent abdominal surgery was performed, revealing a perforation in the jejunum (Fig. 2a, red arrow). A tumor was found distant from the perforation and adherent to the mesentery of the sigmoid colon (Fig. 2a, yellow arrow). The affected region of the small intestine was resected.
From the pathological analysis, there was no evidence of malignancy at the perforation site (Fig. 2b). On the anal side, we found tumor cell proliferation from the mucosa to the submucosa, which suggested metastatic lung cancer (Fig. 2c, enclosed in yellow arrows). We examined the remaining intestinal specimen; however, there were no abnormal findings, such as ulceration, scarring, intestinal fragility, and blood vessel abnormality. The patient recovered and was discharged 16 days after the surgery. He resumed dabrafenib and trametinib therapy (same doses) 32 days post-surgery, and experienced no recurrence of gastrointestinal perforation. Overall, his best response was deemed a PR, and his progression-free survival was 439 days.