The practical guidelines for lung cancer screening have been revised in 2020. In this article, we will explain the background and aims concerning the revision to the requirements for doctors engaging in the interpretation of chest roentgenograms in lung cancer screening and the implementation of case review meetings, two topics that seem very important. The requirements in the 2017 version have been assessed as difficult to understand by many local government officials, necessitating a revision of the requirements. In the 2020 version, all doctors are required to participate in a case review meeting once a year, and senior doctors are also required to have a prescribed experience in the interpretation of chest roentgenograms. The important points to bear in mind when holding a case review meeting are also described. We hope that this paper will help improve the quality assurance in lung cancer screening in the future.

"Early palliative care," which was the forerunner of evidence for advanced lung cancer, has been shown to maintain the patient quality of life and prolong the survival through a wide range of approaches, not limited to coping with pain symptoms and mental care. Appropriate recognition of the condition and confirmation of treatment goals will prevent the continuation of useless anticancer treatment and provide sufficient preparation for the end of life, as advanced-care planning is also an important part of this approach. Oncologists must be able to anticipate the clinical course of patients without being fixated on anticancer treatments with little evidence, and some prognostic indicators are also useful to this end. Communication skills that do not invade the patient are also required, and collaboration with palliative care specialists provides useful support. Oncologists need to respect the values of patients and provide them and their families with treatment that is truly beneficial.

Drug therapy for primary lung cancer, including molecular-targeted drugs and immune-check point inhibitors, has markedly progressed in the precision medicine era. The Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 have been used to determine the presence of progressive disease (PD); however, there are some drawbacks to performing such an evaluation based on the greatest diameter of the tumor alone. We herein review the limitations of the response evaluation using RECIST v1.1 and recent advances made in the early detection of the therapeutic effect and prediction of the prognosis using functional imaging modalities, such as fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), dual-energy CT, perfusion CT, and diffusion-weighted magnetic resonance imaging. In addition, we describe the atypical response patterns after immunotherapy using anti-PD-1/PD-L1 agents.

Objectives. Wedge resection (WR) is often the preferred surgical treatment for poor-risk primary lung cancer patients. However, there is still some debate regarding its indication. The aim of the present study was to investigate the surgical outcomes of WR as a compromise procedure. Methods. The study population consisted of 93 patients with primary lung cancer who underwent WR as a compromise procedure from April 2007 to March 2020. We reviewed the clinical features and outcomes of the treatment. Results. Complete resection was performed in 84 patients (90.3%). When stratified by pathological stage, the 3- and 5-year overall survival rates were 74.7% and 67.3%, respectively, in the stage IA group; 66.3% and 41.4% in the stage IB group; and 48.0% and 24.0% in the stage II group. Sex, histological type, and visceral pleural invasion were recognized as prognostic indicators. However, the prognostic impact of tumor size was not clear. Twenty-nine patients (34.5%) developed recurrence, including distant metastasis in 14 patients and locoregional recurrence in 13 patients (including 8 patients with stump recurrence); both types of recurrence were detected in 2 patients. The morbidity rate was 9.7%; however, there were no serious complications. No significant difference was found in morbidity in comparison to patients who underwent intentional WR. Conclusion. WR can be expected to achieve acceptable surgical outcomes in poor-risk stage I lung cancer patients.

Objective. The immune status of the tumor microenvironment (TME) in lung cancer patients influences the effect of immune checkpoint inhibitors (ICIs). The effective immune status of ICIs was examined using peripheral differential leukocyte counts. We also searched the relevant literature for data on the relationship between differential leukocyte counts in the peripheral blood and in tumor-infiltrating leukocytes in the TME. Method. Peripheral differential leukocyte counts at the time of ICI administration (day 1) and 42 days after ICI administration (day 43) in 83 cases of non-small cell lung cancer treated with ICIs alone at our hospital between February 2016 and October 2019 were included in a Cox regression analysis to identify factors associated with progression-free survival (PFS) and overall survival (OS). Results. Higher eosinophil counts in the peripheral blood on day 1 were associated with a significantly improved PFS, and higher monocytes were associated with significantly worse PFS and OS. Higher eosinophil and lymphocyte counts in the peripheral blood on day 43 were associated with significantly improved PFS and OS, and higher basophil and monocyte counts were associated with significantly worse PFS and OS. Conclusion. The effect of ICI treatment is related to the peripheral differential leukocyte counts.

Objective. In clinical practice, durvalumab has been used as a standard maintenance treatment after chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). However, it is unknown as to how often practitioners avoid using durvalumab. The present study aimed to analyze the factors that influence decision-making in relation to the administration of durvalumab. Methods. We retrospectively analyzed the treatment of locally advanced NSCLC in 12 hospitals with lung cancer specialists. We evaluated patients with NSCLC who were treated with CRT from May 2018 to December 2019 and compared the characteristics between patients who received durvalumab and those who did not. We also conducted a questionnaire-based survey to determine the reasons for avoidingdurvalumab.Results. Among199patientswhoreceivedCRT,durvalumabwas administered to 169 patients (84.9%). The median age of the patients in the non-administration group was significantly higher than that in the administration group (70 vs. 67 years, p=0.0465), and the performance status (PS) ≥1 in the non-administration group was significantly higher than that in the administration group (65.5 vs. 40.4%, p=0.0148). According to the questionnaire responses, durvalumab administration was avoided for the following reasons: adverse events due to CRT (n=7); patient needs (n=5); disease progression (n=4); poor PS (n=3); driver mutation of NSCLC (n=3); and complications of autoimmune disease (n=2). Conclusion. Durvalumab was administered to 84.9% of patients in this study. Each practitioner considered age, PS, adverse events due to CRT, and driver mutations of NSCLC, before prescribing durvalumab.

Objective. The pleural effusion-cell block procedure has recently been recognized as an effective tool for diagnosing malignant pleural mesothelioma (MPM). We retrospectively analyzed the usefulness of pleural effusion-cell block for diagnosing MPM in our institution. Patients and Methods. Forty-four patients who underwent a video-assisted thoracoscopic pleural biopsy due to suspicion of MPM between January 2018 and December 2018 were enrolled in this retrospective study. We compared the results of a preoperative cytological examination, including cell block, with those of a pathological examination by a pleural biopsy. Results. Of the 44 patients, 25 preoperatively underwent a cytological examination, including the cell block procedure. The cytological examination revealed malignant cells suspected of being MPM in 18 patients, atypical cells in 3 patients and no malignant cells in 4 patients. A pathological examination by a pleural biopsy revealed MPM in 22 patients, including 3 patients in whom a cytological examination revealed atypical cells and 1 in whom a cytological examination revealed no malignant cells. The sensitivity, specificity and positive and negative predictive values of the cytological examination in this study were 81.8% (18/22), 100% (3/3) and 100% (18/18) and 42.9% (3/7), respectively. Conclusions. Our findings suggest that a cytological examination with the cell block procedure is useful for diagnosing MPM.

Background. Pulmonary epithelial hemangioendothelioma is a relatively rare low-grade tumor, and there is no established treatment for this disease. In slowly progressing cases, most patients are followed up without any treatment. Case. The patient in the present case was a 70-year-old man. Chest computed tomography (CT) taken during a chest injury revealed multiple pulmonary nodules. The patient did not complain of any respiratory symptoms. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed no abnormal accumulation throughout the entire body, and did not demonstrate the presence of any lung lesions; however, CT images taken approximately six months later revealed a slight increase in multiple lung nodules. We identified granulomatous disease, an infectious nodule, and the possibility of multiple lung metastases from an unknown primary cancer and performed thoracoscopic partial lung resection to obtain a diagnosis. The lesion was elastic and hard, and the cut surface was a solid yellowish-white. No invasion of the surrounding area was observed. A pulmonary epithelial hemangioendothelioma was diagnosed because immunohistochemical staining of factor VIII-related antigen was positive in the pathological examination. There is no established treatment for this disease; thus, we decided to follow the patient without any treatment. Conclusion. Although it is a rare disease, pulmonary epithelioid hemangioendothelioma should be considered in the differential diagnosis of cases with multiple diffuse pulmonary nodules on CT. In this case, careful follow-up will be required in the future.

Background. Durvalumab is effective as a consolidation therapy after radical chemoradiotherapy and is being used as the standard treatment for unresectable stage III non-small cell lung cancer. However, managing pulmonary toxicity, a major adverse event, is important during durvalumab treatment. Case. A 65-year-old man with squamous cell carcinoma of the right upper lobe (cT3N1M0) received concurrent chemoradiotherapy as an initial treatment. The tumor reduced in size; therefore, durvalumab treatment was started seven days after the completion of radiation therapy. The patient developed a fever and right chest pain after eight courses of durvalumab administration; chest computed tomography (CT) showed a broadly infiltrating shadow and ground-glass opacities predominantly in the right upper lobe. Although steroid therapy was started along with antibiotic administration, the infiltrating shadow changed to a broad cavity on a repeated CT examination performed eight days later. The cavity was consistent with the irradiation field and extended beyond the interlobar region, and the interlobar pleura inside the cavity remained. No significant pathogens were detected on bronchoscopy. His condition deteriorated because of infection and disseminated intravascular coagulation, and he died about one month after the appearance of lung injury. Based on the clinical course and autopsy findings, lung injury and pulmonary necrosis were considered to have resulted from the use of durvalumab and irradiation. Conclusion. We experienced a case of non-small cell lung cancer that developed extensive lung necrosis during durvalumab treatment after chemoradiotherapy.

Background. Immune checkpoint inhibitors (ICIs) have been used for patients with several cancers, including non-small cell lung cancer, and sometimes result in various immune-related adverse events (irAEs), such as peripheral neuropathy. The time to the onset of peripheral neuropathy post-ICI administration ranges between five days and five months. We herein report a patient with advanced lung adenocarcinoma who developed acute demyelinating polyneuropathy four days after the administration of nivolumab. Case. A 77-year-old man with advanced lung adenocarcinoma presented with symmetric and lower limb-predominant motor and sensory disturbance 4 days after nivolumab administration and became unable to walk. Nerve conduction studies resulted in a diagnosis of demyelinating polyneuropathy. The motor and sensory disturbance ameliorated with intravenous immunoglobulin plus methylprednisolone pulse therapy. Conclusions. On comparison with previous reports of peripheral neuropathy post-ICI administration, the time to the onset of peripheral neuropathy in our patient was the shortest. Clinicians should be aware of acute demyelinating polyneuropathy as an irAE that can occur within one week after nivolumab administration.

Background. Fetal adenocarcinoma is a rare tumor classified as a special type of lung adenocarcinoma by the World Health Organization classification (4th edition). It occurs in relatively young patients and has a good prognosis. Case. A 33-year-old woman was referred to our hospital because of an abnormal shadow on a chest roentgenogram. Chest computed tomography showed a 7.5-cm tumor in the right upper lobe, which was in contact with the superior vena cava and chest wall. Bronchoscopy revealed an exposed tumor in the upper lobe of the bronchus, and a biopsy was performed. The tumor was diagnosed as a lung adenocarcinoma (cT4N0M0 Stage IIIA). We considered performing neoadjuvant chemoradiation; however, we decided to perform upfront surgery because no mediastinal lymph node metastasis was found and invasion of the surrounding organs was not confirmed. We performed a right upper lobectomy with bronchial wedge resection and bronchoplasty. The tumor was completely resected grossly without any invasion of the neighboring organs. Histopathologically, the tumor was a low-grade fetal adenocarcinoma (pT4N0M0 Stage IIIA). Adjuvant chemotherapy was administered, and the patient lived recurrence-free for three and a half years after surgery. Conclusion. In relatively young patients with large lung tumors, we should consider low-grade fetal adenocarcinoma as a differential diagnosis and discuss the treatment plan.

Background. A number of different diseases are characterized by airspace consolidation in the lungs. The early diagnosis and treatment in cases of lung cancer with airspace consolidation can thus be challenging. Case. A 74-year-old man with prostate cancer underwent thoracoabdominal computed tomography (CT) as part of an examination prior to treatment, which revealed ground-glass opacity in the basal segment of the right lower lobe. Follow-up CT performed one year later further showed extended ground-glass opacity and irregular airspace consolidation, and bronchoscopy did not lead to a definitive diagnosis. Another follow-up CT performed one year later showed that the ground-glass opacity had extended to the entire right lower lobe and that airspace consolidation had extended primarily from the basal segment of the right lower lobe. In addition, the volume of the right lower lobe had decreased. These findings were specific to the right lobe, and none of the other lung lobes were affected. Thoracoscopic right lower lobectomy was performed for the diagnosis and treatment of airspace consolidation that had slowly expanded in the right lower lobe. On pathology, the region characterized by airspace consolidation was diagnosed as lepidic-predominant alveolar cell adenocarcinoma (pT4N0M0, p-stage IIIA). Conclusion. Findings of airspace consolidation with slow expansion indicate the presence of neoplastic disease, which requires a careful diagnosis and treatment.

Background. A long-term clinical response is sometimes seen in patients with lung cancer treated with immune checkpoint inhibitors. However, immune-related adverse events, such as drug-induced lung injury, may also occur in the long run. Case. A 71-year-old man had been administered pembrolizumab for lung adenocarcinoma for the past 2 years, and his lung cancer had almost disappeared. However, chest computed tomography revealed new infiltrative shadows in the upper and lower lobes of the left lung. Furthermore, adenocarcinoma cells were detected in specimens collected by bronchoscopy from the upper lobe lesions. Because of the rapid expansion of the infiltrates after pembrolizumab withdrawal, corticosteroid therapy was initiated, which led to the disappearance of nearly all of the infiltrates except for a nodule in the left upper lobe. The patient was therefore diagnosed with recurrent lung cancer coexisting with delayed pembrolizumab-induced lung injury. Conclusion. In some cases, it is difficult to distinguish between recurrent lung cancer and drug-induced lung injury based solely on imaging findings; a pathological examination of specimens obtained by bronchoscopy and the response to steroids should therefore also be considered when making a diagnosis.

Background. Carcinoid tumors are neuroendocrine tumors; however, carcinoid tumors originating in the middle mediastinum are rare. Case. The patient was a 60-year-old man with an abnormal shadow on a chest X-ray that was identified in a medical check-up. CT showed a tumor on the ventral side of the trachea. Contrast-enhanced CT and MRI showed a solid part with a heterogeneous contrast effect; however, PET-CT showed low accumulation of FDG. Six months later, CT showed that the tumor increased in size from 20 mm to 24 mm. The operative findings showed that the tumor was located from the lower part of the thyroid to the middle mediastinum, without invasion of the surrounding tissue. No lymphadenopathy was found. Histopathologically, the tumor cells were uniform and polygonal, which were relatively small in size, with round nuclei. Neither necrosis nor mitosis was found. Based on these findings, the tumor was diagnosed as a typical carcinoid tumor. The patient did not receive postoperative adjuvant chemotherapy, and a disease-free status was achieved. Conclusion. The prognosis of carcinoid tumor varies depending on the histological grade. Surgical resection is required for tumors originating in the middle mediastinum because of the difficulty in making a histological diagnosis.

Background. The efficacy of immune checkpoint inhibitors for the treatment of large-cell neuroendocrine carcinoma of the lung has not been sufficiently investigated. We experienced five cases of large-cell neuroendocrine carcinoma of the lung that were treated with nivolumab. Case. The cases involved five men who were 64-74 years old. Of these, two patients were diagnosed using biopsy specimens obtained via endobronchial ultrasound-guided trans-bronchial needle aspiration, and three were diagnosed using surgical specimens. The programmed death-ligand 1 (PD-L1) tumor expression was high in one patient, and nivolumab was effective only in that patient. Conclusion. We experienced a case of large-cell neuroendocrine carcinoma of the lung that was effectively treated using nivolumab. The PD-L1 expression may be a predictive biomarker for the efficacy of nivolumab treatment in large-cell neuroendocrine carcinoma of the lung. Further studies are needed.