Long-term treatment with ALK inhibitors for postoperative recurrence of ALK-rearranged lung cancer.

We encountered a 40-year-old female patient who developed, in chronological order, carcinomatous pleuritis and lymphangitis, multiple lymph node metastases, brain metastases, and intramedullary spinal cord metastases after resection of lung adenocarcinoma followed by adjuvant chemotherapy. Echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) fusion gene, variant 2 was identified in her cancer cells. By changing the ALK inhibitors from the 1st to 3rd generation each time when metastases were identified and incorporating local treatments in a timely fashion, such as metastasectomy or radiation therapy, she has survived for more than 11 years since the start of treatment, while maintaining a good Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0. To our knowledge, this is the first reported case in which ALK fusion variant 2 was identified and prolonged disease control was achieved with the continuous prescription of ALK tyrosine kinase inhibitors (TKIs) and timely consolidative treatments.

The histological diagnosis and molecular testing of lung cancer by surgical biopsy for intrathoracic lesions.

OBJECTIVES: Accurate histological diagnosis and molecular testing using a sufficient tumor sample of advanced lung cancer, especially non-small cell lung cancer (NSCLC), are crucial for precision medicine. The aim of this study was to assess the feasibility and safety of surgical biopsy for intrathoracic lesions, and, in addition, overall survival after surgical biopsy. METHODS: One hundred-one patients who underwent surgical biopsy for intrathoracic lesions of lung cancer at our hospital between 2011 and 2019 were retrospectively reviewed. Their clinical and pathologic records were reviewed. In addition to evaluating the oncologic safety of the surgical biopsy, the overall survival based on the biopsy results was estimated. RESULTS: The total number of surgical sites of the 101 patients was 131, and common biopsy sites were the lungs (82, 62.6%) followed by hilar/mediastinal lymph nodes (27, 20.6%). There were 13 postoperative complications (12.9%) without surgery-related deaths. The median time from surgical biopsy to the initiation of treatment was 27 days. Appropriate amounts of specimens for diagnosis and molecular testing were obtained from all patients (100%). When limited to treatment-naïve patients with stage IV adenocarcinoma, patients treated with tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) based on molecular testing had a better prognosis. CONCLUSIONS: Surgical biopsy for intrathoracic lesions of lung cancer may be a safe and effective method to make a definitive diagnosis, including companion diagnostics for advancing precision therapy in selected patients with inoperable advanced NSCLC.

Surgery to avoid fatal complications and secure radicality after definitive chemoradiotherapy for clinical T4N2M0 stage IIIB non-small cell lung cancer: a case report.

BACKGROUND: Chemoradiotherapy (CRT) is the standard treatment for c-stage IIIB non-small cell lung cancer (NSCLC); however, patients who respond to CRT are at risk of developing fatal complications such as massive hemoptysis or infection. In such cases, surgery is an alternative option. Currently, there are limited reports on surgery for complications arising during definitive CRT for locally advanced NSCLC. We report a case of hemoptysis after definitive CRT for c-T4N2M0 stage IIIB NSCLC that was successfully treated with lower bilobectomy combined with left atrial resection. CASE PRESENTATION: A 72-year-old man with c-T4N2M0 stage IIIB NSCLC with left atrial invasion developed hemoptysis during CRT, which was discontinued to control hemoptysis. Chest computed tomography revealed a regressed and cavitated tumor. Three weeks after discontinuation of CRT, surgery was performed to avoid fatal complications and secure radicality. We performed lower bilobectomy combined with partial left atrial resection, which was performed using an automatic tri-stapler. The bronchial stump was covered with an omental flap. The resected specimen pathologically showed complete response with fistula between the intermediate bronchus and necrotic cavity in the tumor. His postoperative course was uneventful, and the patient was disease free at 10 months after surgery. CONCLUSIONS: We successfully performed surgery after definitive CRT in a patient with c-T4N2M0 stage IIIB NSCLC. Partial left atrial resection was safely performed with an automatic tri-stapler. A complete pathological response to CRT was achieved. In a case with a chance of complete (R0) resection, when the risk of developing fatal complications might outweigh the risk of post-CRT surgery perioperative complications, surgery should be considered as a treatment option.

Concurrent combination of irradiation and immune checkpoint inhibitor for recurrent pleomorphic carcinoma of the lung.

We report the case of a 49-year-old patient who developed brain, sternal, and spine metastases almost simultaneously after the radical resection of a yp-T4N0M0 pulmonary pleomorphic carcinoma of the right upper lobe following induction chemotherapy. The left occipital brain metastasis was surgically removed and followed by radiation therapy. The sternal and vertebral metastases were treated with radiation therapy. Concurrently, the immune checkpoint inhibitor nivolumab was administered. After 12 cycles of nivolumab, the two bone metastases were well-controlled. However, the brain metastasis recurred and was surgically removed again. We were able to investigate the tumor-infiltrating lymphocytes in brain metastases resected before and after radio-immunotherapy. The results revealed the increased number of CD8- and CD68-positive cells after the combined therapy compared with before the therapy. In addition, the high-level expression of program death-ligand 1 was maintained in the brain metastasis.

Successful treatment of advanced thymic carcinoma with lymph node and pleural metastases: A case report.

Thymic carcinoma is a rare type of cancer that is more aggressive and is associated with a poorer prognosis compared with thymoma. No definitive clinical management of this disease has been established to date. This report describes the 20-year clinical course of a 50-year-old male patient who was successfully treated for initially diagnosed stage IVb thymic carcinoma. Thymo-thymectomy combined with resection of the surrounding organs was performed on December 1995 with curative intent (R0) after neoadjuvant chemoradiotherapy. From June 2008 until present, four pleural and subclavicular lymph node metastases have been treated with chemotherapy, radiotherapy and surgery, followed by low-dose oral steroid therapy. The patient has remained disease-free for the last 20 months since the initiation of prednisolone treatment. Thus, multidisciplinary treatment may achieve long-term survival in patients with stage IVb thymic carcinoma.

Anaplastic lymphoma kinase-positive squamous cell carcinoma of the lung: A case report.

It is widely known that echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement mostly occurs in the adenocarcinoma subtype of non-small-cell lung cancer (NSCLC). Patients with squamous cell carcinoma harboring the ALK rearrangement are extremely rare. This is a case report of a squamous cell carcinoma patient with EML4-ALK rearrangement. An elderly man with a heavy smoking history presented with a mass lesion in the right main bronchus. Bronchoscopic biopsy of the tumor confirmed a diagnosis of squamous cell carcinoma, and it was proven to harbor ALK rearrangement, based on fluorescence in situ hybridization, but not epidermal growth factor receptor mutations. The patient underwent radiation therapy, with a markedly favorable response. ALK-targeted treatment may be a viable option if disease progression occurs in such a case in the future.