Since the clinical introduction of immune checkpoint inhibitors (ICI) for non-small-cell lung cancer (NSCLC), pharmacotherapy for lung cancer has progressed significantly. In recent years, first-line treatment of advanced NSCLC with no driver gene mutations or alteration has become an important treatment option for ICI monotherapy, or a combination immunotherapy including an anti-CTLA-4 antibody with platinum-based chemotherapy. Combination immunotherapy, ICIs with cytotoxic anticancer agents, has been approved in Japan due to extensive clinical trial results. When choosing appropriate combination immunotherapies, it is important to consider the efficacy and adverse events of each combination immunotherapy, as well as the patient background, PD-L1 expression, and histological type.

Although the progression-free survival and overall survival in patients with non-small-cell lung cancer (NSCLC) have improved in recent years with the clinical introduction of immune checkpoint inhibitors, the long-term survival rates are still low. One possible reason for this is that the inflammatory cytokine interleukin-1β (IL-1β) may suppress anti-tumor immune responses by enhancing tumor-associated inflammation in the tumor microenvironment (TME). Canakinumab, a human monoclonal antibody that targets IL-1β, was shown to significantly lower the incidence and mortality rate of lung cancer in the CANTOS trial. It has been suggested that canakinumab may enhance the anti-tumor immune response and suppress tumor growth by inhibiting IL-1β activity. We herein report the association between tumor and inflammation and the role of IL-1β in the TME. We also provide an overview of ongoing clinical research of canakinumab as a promising future treatment option for NSCLC.

Background. Owing to advances in chemotherapy, long-term survivors have been reported even in cases of advanced non-small-cell lung cancer (NSCLC). Because EGFR mutation-positive NSCLC responds well to EGFR-tyrosine kinase inhibitors (TKIs), active treatments including invasive surgery can be considered despite medical complications. To our knowledge, we experienced the world's first case of a long-term survivor of advanced NSCLC treated by valve replacement during EGFR-TKI treatment. Case. In a 76-year-old male (heavy smoker) with EGFR mutation-positive NSCLC, cTxN0M1a (stage IVA), aortic valvular replacement under extracorporeal circulation was performed for aortic stenosis at 38 months after the initiation of effective treatment with an EGFR-TKI for lung cancer. In addition, aggressive treatments for cardiovascular complications, such as PCI (percutaneous coronary intervention) for triple-vessel coronary artery disease and bypass surgery for common femoral artery aneurysm, were also performed during EGFR-TKI treatment, resulting in a long-term survival of 70 months in total. Conclusion. A long-term survival can be achieved even in cases of advanced NSCLC with serious medical complications by performing appropriate multidisciplinary treatments, including invasive surgery, when primary lung cancer is controlled medically. It should be stressed that a capable medical team contributes to better medical care in regional core hospitals.

Background. We examined two cases of non-small cell lung carcinoma with co-expression of TTF-1 and p40 in the same tumor cells. However, the cases were diagnosed as squamous cell carcinoma at a later date because of negative immunohistochemical (IHC) staining with a different TTF-1 antibody clone. Case Reports. Case 1: An 82-year-old man was referred to our hospital with left back pain. Chest computed tomography (CT) revealed a 41-mm nodule in the S⁶ segment of the left lung, which was diagnosed as non-small cell carcinoma (cT2bN0M0 stage IIA), so we performed thoracoscopic left lower lobectomy. We pathologically diagnosed the tumor as non-small cell carcinoma with co-expression of TTF-1 and p40. Case 2: A 65-year-old man was referred to our hospital with the complaints of dyspnea and dysphagia. Chest CT revealed a 44-mm mass at the tracheal bifurcation. A biopsy led to a diagnosis of non-small cell carcinoma with co-expression of TTF-1 and p40. However, repeat IHC staining with a different TTF-1 antibody clone at a later date led to a change in the diagnosis to squamous cell carcinoma for both cases 1 and 2 because of negative staining for TTF-1. Conclusion. TTF-1 expression differs between clones. We should not use clone SPT24 but rather clone 8G7G3/1 for distinguishing adenocarcinoma from squamous cell carcinoma.

Background. Spontaneous regression of cancer has been reported as a very rare phenomenon. We herein report a case of pathologically diagnosed lung cancer that regrew after spontaneous regression and was surgically resected. Case. A 75-year-old man was diagnosed with squamous cell carcinoma of the lung after a 1.7 cm nodule in the upper lobe of the right lung was detected by computed tomography (CT) at his previous doctor's office in March 20XX. The patient was referred to our department in May, and surgery was scheduled in June. CT performed 2 days before the surgery showed that the tumor had shrunk to 0.6 cm in length and diameter. The planned surgery was thus cancelled, and the patient was followed up. However, CT performed in October showed regrowth of the tumor. We decided to operate and performed the surgery in December. The postoperative pathological diagnosis was squamous cell carcinoma of the lung, pT1bN0M0, p-stage IA2. Conclusion. There have been various reports on factors responsible for spontaneous tumor regression. The present patient showed an increase in the percentage of regulatory T cells in surgical specimens, a phenomenon suggested to be related to tumor regrowth. Even after spontaneous regression of lung cancer, the tumor can reincrease in size, as in the present patient, so careful follow-up is necessary.

Background. Non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation responds to EGFR tyrosine kinase inhibitor (TKI) treatment well; however, it subsequently develops resistance to these drugs. Several mechanisms underlying the development of resistance to EGFR-TKI have been reported. Although transformation to small cell lung cancer (SCLC) accounts for 2-15% of such cases, little is known about treatments or clinical outcomes. Case 1. A 66-year-old woman with EGFR-mutated NSCLC was observed to have pleural effusion and dissemination during the administration of osimertinib. Transformation to SCLC was found in the pathological cell block examination of pleural effusion. Case 2. A 47-year-old man with EGFR-mutated NSCLC was found to have elevated tumor marker levels (NSE and ProGRP) and progressive pleural dissemination during S-1 treatment. Transformation to SCLC was detected in the pathological examination of pleural dissemination. Case 3. A 67-year-old man with EGFR-mutated NSCLC was found to have enlargement of his primary tumor. Transformation to SCLC was observed in the rebiopsy specimen of the primary tumor. All three patients received cisplatin and irinotecan, and their disease was controlled after transformation to SCLC. Conclusion. Cisplatin and irinotecan may be potential treatments for patients with EGFR-mutated NSCLC after transformation to SCLC. However, the accumulation of cases is required as there are few detailed reports on this treatment.

Background. Since there is no insurance-approved drug for thymic carcinoma in Japan, drugs for other cancers are being used provisionally. In 2021, lenvatinib was approved for unresectable thymic carcinoma. Case. A 54-year-old woman visited a nearby doctor with a complaint of left chest pain. Chest CT showed an anterior mediastinal tumor, multiple masses of the left pleura, and left pleural effusion. She was diagnosed with thymic carcinoma (pT2N0M1a, stage IVA) by surgical biopsy. Due to the difficulty of hospitalization due to the COVID-19 pandemic and the wish of the patient, lenvatinib was introduced as the first-line treatment in an outpatient setting. However, her condition worsened and her chest pain increased. When carboplatin and nab-paclitaxel were given as second-line treatment, the tumor in the anterior mediastinum, multiple pleural tumors, and mediastinal lymph nodes were remarkably reduced, the left pleural effusion decreased in volume, and the symptoms were alleviated. Conclusion. We experienced a case in which carboplatin and nab-paclitaxel treatment were effective for advanced thymic carcinoma that was resistant to lenvatinib. Although lenvatinib was newly approved, platinum-based chemotherapy is considered an important option in chemotherapy for thymic carcinoma.

Background. Inflammatory myofibroblastic tumors (IMTs) of the lung are mesenchymal tumors composed of myofibroblastic spindle cells admixed with inflammatory cells, and are occasionally difficult to distinguish from malignant tumors. Case. A 19-year-old man was found to have an abnormal shadow in the left lower lung field on chest radiography, and was referred to our hospital. Chest computed tomography (CT) revealed a well-circumscribed nodular lesion of the left lower lung lobe, that progressively increased in size over 6 months. The nodule showed increased accumulation on 18F-fluorodeoxyglucose positron emission tomography. We performed left lower lobectomy and lymph node dissection. A histological analysis of the lesion revealed IMT. Conclusion. We reported a case of IMT that progressively increased in size, and which was resected on suspicion of lung malignancy. Cases of post-surgical relapse have been reported, highlighting the necessity of follow-up.