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Background: In Japan, over 25% of the population is elderly. As the risk of lung cancer increases with age, the number of elderly patients with lung cancer also increases. Given the challenges of an aging society, it is critical that elderly patients receive safe therapies., Aim: We assessed the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) aged ≥80 years., Methods: We retrospectively reviewed NSCLC patients aged ≥80 years old who received ICIs in the National Hospital Organization Kyoto Medical Center. We collected data on patient characteristics, prior treatments, number of cycles, response, and immune-related adverse events (irAEs) during ICI monotherapy., Results: A total of 45 patients were reviewed. The patients' median age was 85 years. Twenty-one, 17, and 7 patients received nivolumab, pembrolizumab, and atezolizumab, respectively. The disease control rate (partial response [PR] + stable disease [SD]) was 60.0%, and the progression-free survival was 3.4 months. In patients with nivolumab, seven patients (33.3%) achieved SD, and three patients (14.2%) achieved PR. In patients treated with pembrolizumab, seven patients (41.2%) achieved SD, and six patients (35.3%) achieved PR. In patients with atezolizumab, three patients (42.9%) achieved SD, and one patient (14.2%) achieved PR. Sixteen (36%) patients presented with a poor performance status. Three patients treated with pembrolizumab experienced grade 3 pneumonia, while one patient treated with nivolumab experienced grade 5 pneumonia., Conclusion: This study suggested that ICIs are an acceptable treatment option for NSCLC patients aged ≥80 years. Oncologists should pay attention to severe irAEs., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Introduction: Granulocyte colony-stimulating factor (G-CSF), including pegfilgrastim, increases the peripheral blood leukocyte count and is widely used in clinical practice in combination with cytotoxic chemotherapy. The most frequent side effects of G-CSF are pain and fever; aortitis, in contrast, is a rare and serious side effect. Case Presentation: A 73-year-old man with small-cell lung cancer was treated with a full dose of a combination of carboplatin/etoposide/durvalumab and pegfilgrastim. The patient developed fever and right ear pain 12 days after pegfilgrastim administration and was diagnosed with aortitis by contrast-enhanced computed tomography 5 days later. Because the patient had already been administered the immune checkpoint inhibitor and had a history of hepatitis B, the patient was followed up without corticosteroid administration, and the patient's symptoms resolved spontaneously. Conclusion: In situations where immunosuppression should be avoided, we believe that follow-up without corticosteroids for G-CSF-induced aortitis is a promising option. [ABSTRACT FROM AUTHOR]

While immunotherapy with immune checkpoint inhibitors has achieved promising effects in advanced lung cancer treatment, it can induce some unique adverse events, known as immunotherapy-related adverse events (irAEs). Immunotherapy-related interstitial pneumonitis is one of the irAEs, and its incidence is reported as 3.5–8.3% in phase III trials of nivolumab with or without ipilimumab for advanced non-small cell lung cancer patients. However, in the real-world setting, pathology is not routinely used in the diagnostic process of interstitial pneumonitis because diagnosis is usually made using chest computed tomography (CT). Here, we report an educational case of pathologically diagnosed pulmonary lymphangitis carcinomatosa mimicking immunotherapy-related interstitial pneumonitis. The patient was diagnosed with advanced adenocarcinoma of the right lung (stage IVA) and received immunochemotherapy for 6 months. He manifested acute respiratory failure, and a chest CT scan revealed the emergence of diffuse grand-grass opacity predominantly in the left lung. Immunotherapy-induced interstitial pneumonitis was clinically suspected because the primary lesion was stable, and the level of the serum carcinoembryonic antigen decreased. However, the detection of adenocarcinoma cells in the bronchoalveolar lavage sample from the left lung confirmed the diagnosis of pulmonary lymphangitis carcinomatosa. Clinicians' assumptions can sometimes mislead treatment methods; hence, this case draws attention to the perils of misdiagnoses. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Malignant melanoma is a rare and high-grade cancer. It most commonly affects the skin, but it has the potential to involve all areas of the body. Primary pulmonary malignant melanoma is rare, accounting for only 0.01% of all pulmonary tumors. We present a case of primary pulmonary malignant melanoma in a 90-year-old patient. The pretreatment computed tomography (CT) showed a pulmonary mass in the right upper lobe, multiple pleural nodules, enlarged mediastinal lymph nodes, and bone metastases. Positron emission tomography-CT showed a region of fluorodeoxyglucose hyperaccumulation that was consistent with the abnormal shadows. Advanced stage lung cancer was initially suspected, but bronchoscopy revealed a malignant melanoma. The patient was diagnosed with a primary pulmonary malignant melanoma. Although the patient was older, he wanted to receive immediate treatment. Thus, he was treated with immune checkpoint inhibitors. He responded well to the medication, and neither major adverse events nor tumor size reduction was observed. We report a rare case of primary pulmonary malignant melanoma in an older adult. Immune checkpoint inhibitor therapy, as in this case, was a viable treatment option for older adults. [ABSTRACT FROM AUTHOR]

Background: A synergistic effect of cyclooxygenase inhibitors (COX‐I) and immune checkpoint inhibitors (ICIs) has been suggested. However, the impact of COX‐I on the efficacy of ICIs is unclear. Here, we aimed to evaluate the relationship between COX‐I use and the efficacy of ICI in patients with non‐small cell lung cancer (NSCLC). Methods: We retrospectively reviewed NSCLC patients who received ICI monotherapy. We defined COX‐I use as regular use of COX‐I other than low‐dose aspirin during the initiation of ICIs to the first evaluation of efficacy. The efficacy of ICIs was evaluated with response rate (RR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Differences in baseline characteristics by COX‐I use were controlled by using an inverse probability of treatment weighting (IPW) adjusted analysis. Results: A total of 198 patients with NSCLC received ICIs; 128, 50, and 20 patients received nivolumab, pembrolizumab, and atezolizumab, respectively; there were 65 (32.8%) COX‐I users. While there was no significant difference in RR (15.4% vs. 13.5%; p = 0.828), DCR (41.5% vs. 49.6%; p = 0.294), PFS (median, 2.69 vs. 3.68 months; 95% confidence intervals [CI], 1.77–5.19 vs. 2.20–4.60 months; p = 0.630), COX‐I users had significantly shorter OS than non‐COX‐I users (median, 6.08 vs. 16.10 months; 95% CI: 3.78–11.66 vs. 9.49–19.68 months; p = 0.003). On IPW adjusted analysis, there was no significant difference in OS (median, 7.85 vs. 15.11 months; 95% CI: 5.03–14.92 vs. 9.49–19.32 months; p = 0.081). Conclusions: There was no additional or negative impact of COX‐I use on the efficacy of ICIs in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Over the past two decades, antiresorptive agent‐related osteonecrosis of the jaw (ARONJ) has become a growing concern. We examined the incidence of ARONJ and identified its risk factors in lung cancer patients in the real‐world clinical setting. To our knowledge, we are the first to do so. Patients and methods: We retrospectively analyzed lung cancer patients with bone metastases who had received anti‐resorptive agents (zoledronate or denosumab) at the National Hospital Organization Kyoto Medical Center from October 2012 to September 2018. All ARONJ cases were diagnosed by the dentists according to the established diagnostic criteria. Results: A total of 171 patients were reviewed, 13 (7.6%) of whom experienced ARONJ. Among the 13 patients, six (46.2%), four (30.8%) and three (23.1%) had adenocarcinoma, squamous carcinoma and not otherwise specified, respectively. ARONJ was stage 2 in three (23.1%) patients and stage 3 in 10 (76.9%). More cycles of antiresorptive agents (odds ratio [OR] = 11.54; 95% confidence interval [CI], 2.47–53.99; P < 0.01), use of immune checkpoint inhibitors (ICIs; OR = 5.05; 95% CI, 1.56–16.37; P < 0.01) and longer survival duration (≥2 years; OR = 12.16; 95% CI, 3.17–46.65; P < 0.01) were independently associated with ARONJ in a multivariate analysis. Conclusions: The incidence of ARONJ was relatively high in lung cancer patients with bone metastases. When using antiresorptive agents, oncologists should closely monitor patients for ARONJ during the course of treatment and regularly consult with dentists, especially in patients receiving ICIs. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the efficacy and safety of retreatment with anti‐programmed death 1 (anti‐PD‐1) antibodies in patients with advanced non‐small cell lung cancer (NSCLC) after prior treatment with anti‐programmed death‐ligand 1 (anti‐PD‐L1) antibodies. Methods: Data (N = 15) on patients' characteristics, number of cycles, regimens, their best response and immune‐related adverse events (irAEs) were recorded retrospectively. Results: NSCLC was initially treated with anti‐PD‐L1 antibody atezolizumab (N = 14) or durvalumab (N = 1). No patients had a high (≥50%) tumor expression of PD‐L1. The median cycles for atezolizumab were five (range 1–15), and median progression‐free survival was 2.8 and 6.0 months for atezolizumab and durvalumab, respectively. Five (33.3%) and nine (60.0%) patients showed stable and progressive disease as their best response, respectively. No differences in irAEs between anti‐PD‐L1 and anti‐PD‐1 antibodies occurred. Conclusion: Patients treated with anti‐PD‐L1 antibodies for NSCLC received limited benefits from retreatment with anti‐PD‐1 antibodies. [ABSTRACT FROM AUTHOR]

Although it ameliorates lung cancer, immunotherapy with immune checkpoint inhibitors (ICIs) presents complications of infectious diseases, including tuberculosis. Incidence of tuberculosis during immunotherapy remains unclear. We found that 1.7% of patients developed active tuberculosis during immunotherapy at our institution. In patients with a positive interferon-gamma release assay status before ICI therapy, physicians should pay close attention to developing tuberculosis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In the treatment of immunotherapy with immune checkpoint inhibitors, we often experience immune‐related adverse event which manifest most frequently as a skin disorder, and very rarely as a renal disorder. In our manuscript, we report the case of a 71‐year‐old man with nivolumab‐induced severe acute kidney injury (AKI) in which the time from treatment initiation to the onset of AKI was the longest among the previously reported cases (377 days). Prolonged follow‐up is therefore warranted to detect late‐onset AKI. In the treatment of immunotherapy with immune checkpoint inhibitors, we often experience immune‐related adverse event which manifest most frequently as a skin disorder, and very rarely as a renal disorder. In our manuscript, we report the case of a 71‐year‐old man with nivolumab‐induced severe acute kidney injury (AKI) in which the time from treatment initiation to the onset of AKI was the longest among the previously reported cases (377 days). Prolonged follow‐up is therefore warranted to detect late‐onset AKI. [ABSTRACT FROM AUTHOR]

Key message: It is well known that a phenomenon called hyperprogressive disease (HPD) often occurs during immunotherapy with immune checkpoint inhibitors. In the present case, we experienced a case of HPD in a potential metastatic thyroid tumour during immunotherapy. HPD can be life‐threatening depending on where it appears, so clinicians need to be careful. [ABSTRACT FROM AUTHOR]

Immunotherapy with immune checkpoint inhibitors (ICIs), while ameliorating lung cancer, can cause infectious diseases, including tuberculosis, in addition to immune-related noninfectious complications. In the clinical setting, the efficacy of ICIs to treat mycobacterial infection remains controversial. We report 3 cases of acute Mycobacterium avium complex lung disease during immunotherapy with ICIs. [ABSTRACT FROM AUTHOR]