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Compared to chemotherapy alone, monoclonal antibodies like ipilimumab and nivolumab, with or without chemotherapy, improve the prognosis of patients with non-small cell lung cancer (NSCLC), albeit with a higher incidence of immune-related adverse events (irAEs) than those with immune checkpoint inhibitor (ICI) monotherapy. Therefore, we aimed to investigate if baseline overall tumor burden was associated with the development of Grade ≥ 3 irAEs (severe irAEs) when treated with first-line ipilimumab plus nivolumab with or without chemotherapy.We retrospectively examined consecutive patients with advanced NSCLC who received nivolumab plus ipilimumab with or without chemotherapy at Hakodate Goryoukaku Hospital between December 2020 and December 2021. Baseline overall tumor burden was measured as the sum of unidimensional diameters of up to five target lesions according to the Response Evaluation Criteria in Solid Tumors, version 1.1. We defined irAEs as ICI therapy-related toxicities according to the Common Terminology Criteria for Adverse Events, version 5.0.A significant difference in tumor burden was observed between patients with and without severe irAEs (100 mm vs. 67.5 mm, p = 0.001). We evaluated various clinical parameters, including baseline overall tumor burden, before treatment initiation. Of the various parameters, only high tumor burden correlated with severe irAEs, independent of complementary chemotherapy. The multivariate odds ratio of severe irAEs and high tumor burden was 6.62.Conclusively, baseline overall tumor burden may be a risk factor for severe irAEs in patients treated with first-line combination ICI therapy. Therefore, patients with large tumor burden should be carefully monitored to prevent irAEs.

Pembrolizumab treatment is associated with a favorable prognosis in patients with non-small-cell lung cancer (NSCLC). Here, we investigated the associations among pre-treatment clinical factors, baseline overall tumor burden, and development of severe immune-related adverse events (irAEs; grade ≥ 3) after pembrolizumab treatment with or without chemotherapy. We retrospectively examined consecutive patients with advanced NSCLC who received pembrolizumab with or without chemotherapy at Hakodate Goryoukaku Hospital from March 2017 to February 2021. The baseline overall tumor burden was measured as the sum of the unidimensional diameters of up to five target lesions. We defined irAEs as toxicities related to immune checkpoint inhibitors based on the Common Terminology Criteria for Adverse Events, version 5.0. Tumor burden differed significantly between patients with and without severe irAEs (85 vs. 65 mm, p = 0.0367). The cutoff value for overall tumor burden was set to 80 mm. Good performance status (PS = 0) and PD-L1 expression 80%, but not overall tumor burden, were correlated with severe irAEs, regardless of complementary chemotherapy. The multivariate odds ratios of good PS and high PD-L1 expression for severe irAEs were 3.27 (95% confidence interval [CI]: 1.22-8.77, p = 0.019) and 4.44 (95% CI: 1.59-12.42, p = 0.0044), respectively. Baseline overall tumor burden, good PS, and high PD-L1 expression were associated with severe irAEs in patients with NSCLC treated with first-line pembrolizumab with or without chemotherapy. Patients with these factors should be carefully monitored to prevent irAEs.

A 66‐year‐old man with squamous cell carcinoma had been receiving chemoradiation therapy after stereotactic radiotherapy for brain metastases. Atezolizumab was initiated as second‐line therapy, after which the patient became progression‐ and recurrence‐free. Four days after his second dose of tozinameran (BNT162b2, Pfizer‐BioNTech), the patient developed persistent hemoptysis. The patient had no thrombocytopenia or coagulation abnormalities. Bronchoscopy revealed active bleeding from the left lingual tracheal branch. The patient was intubated and admitted to the intensive care unit because of increased bleeding. Subsequently, left bronchial artery embolization was performed using a Serescue. Hemostasis was achieved after the procedure, and the patient was discharged 7 days after the onset of hemoptysis. Vaccination against coronavirus disease has been reported to be associated with thrombosis and cerebral hemorrhage, and the hemoptysis in this case was suspected to be induced by vaccination. In summary, the benefits of vaccination exceeded the risks of adverse events in a patient with cancer. However, in conditions such as after chemoradiation, especially in patients with radiation pneumonitis wherein the vasculature is vulnerable, patients should be carefully monitored for hemorrhagic events after vaccination., Patients in conditions such as after chemoradiation, especially in patients with radiation pneumonitis wherein the vasculature is vulnerable, should be carefully monitored for hemorrhagic events after vaccination.

Pseudocirrhosis is a radiological diagnosis of cirrhosis without histological evidence and occurs as a complication of liver metastases from solid tumors. A 50‐year‐old man without any previous history of liver disease was diagnosed with adenocarcinoma of the left upper lung lobe and liver metastasis. After chemotherapy, the liver metastases shrank; however, over time, the liver shrank and showed cirrhosis‐like morphological changes. His performance status deteriorated due to ascites and leg edema, and chemotherapy was terminated. Physicians treating lung adenocarcinoma with liver metastases should be aware that pseudocirrhosis is a rare but important complication that can worsen performance status (PS) and hinder treatment continuation., Liver metastasis from adenocarcinoma of the lung with abundant stromal growths showed cirrhosis‐like morphological changes in the course of treatment, ascites and marked leg edema. Pseudocirrhosis due to liver metastasis from lung adenocarcinoma is a rare but important complication that can worsen performance status and hinder treatment continuation.

Ipilimumab and nivolumab improve the prognosis of patients with non-small cell lung cancer (NSCLC), albeit with a higher incidence of immune-related adverse events (irAEs) than immune checkpoint inhibitor (ICI) monotherapy. In this study, we investigated whether baseline tumor burden is associated with the development of severe irAEs during treatment with ipilimumab plus nivolumab with or without chemotherapy. Consecutive patients with NSCLC receiving nivolumab plus ipilimumab with or without chemotherapy were retrospectively examined at the Hakodate Goryoukaku Hospital between December 2020 and December 2021. Total tumor burden was measured according to the Response Evaluation Criteria in Solid Tumors, version 1.1. We defined irAEs as ICI therapy-related toxicities according to the Common Terminology Criteria for Adverse Events, version 5.0. Tumor burden differed significantly between patients with and without severe irAEs (100 mm vs. 67.5 mm, p = 0.001). A high tumor burden correlated with severe irAEs, independent of the complementary chemotherapy. The multivariate odds ratio of severe irAEs and high tumor burden was 6.72 (95% confidence interval = 2.05–22.0, p = 0.0017). Baseline tumor burden is a potential risk factor for severe irAEs in patients treated with combination ICI therapy; thus, careful monitoring of adverse events is needed.

Immune checkpoint inhibitors (ICIs) have been used for various carcinomas. However, immune‐related adverse events have been observed. There have been few reports of treatment with biologics for severe bronchial asthma induced by ICI; therefore, their efficacy is unknown. We report two cases of severe bronchial asthma requiring systemic steroid administration while using anti‐programmed death‐ligand 1 (PD‐L1) antibody for advanced non‐small‐cell lung cancer. The anti‐interleukin‐5 antibody, mepolizumab, was introduced, resulting in the discontinuation of systemic prednisolone and good asthma control. These reports suggest that treatment with biologics may be effective in severe cases of poorly controlled bronchial asthma during ICI therapy., We report two cases of severe bronchial asthma requiring systemic steroid administration while using anti‐programmed death‐ligand 1 (PD‐L1) antibody for advanced non‐small cell lung cancer. In each case, mepolizumab was introduced, resulting in discontinuation of systemic prednisolone and good control of asthma.

The total synthesis of stevastelin B3, stevastelin C3 and 5-deoxy derivative of stevastelin C3, novel 13-membered cyclic depsipeptides, is described. This study unambiguously confirmed the proposed absolute structure of stevastelin B3, and revealed that the structure of stevastelin C3 is incorrect. The correct structure of stevastelin C3 was established by the total synthesis to be 5-deoxy derivative of the proposed structure.

Waveguide modes in semipolar InGaN quantum-well (QW) laser diodes (LDs) with cleaved-facet cavity mirrors have been theoretically investigated using a 4 × 4 transfer matrix technique. It is shown that the waveguide mode can be controlled by changing the refractive-index contrast in the waveguide structures, although previous studies suggest that the waveguide modes are either ordinary or extraordinary due to the birefringence of the material itself, and that optical gain cannot be fully utilized for lasing because the polarization direction which determines optical gain in the devices does not coincide with the polarization direction in the waveguide mode. This behavior can be explained based on the competition between the layer-structural effect and the material birefringence. From the results of our calculations, it is concluded that the utilization of a high refractive-index-contrast waveguide structure is effective in enhancing the optical gain in semipolar LDs with cleaved-facet cavity mirrors.

The total syntheses of stevastelins B, B3, C3, and the 5-deoxy derivative of stevastelin C3, novel cyclic depsipeptides starting from L-quebrachitol, and amino acids are described. Stereoselective introduction of two methyl groups into L-quebrachitol, followed by regioselective cleavage of the cyclohexane ring by way of the Baeyer-Villiger reaction effectively afforded the fatty acid moiety of stevastelins. Introduction of the peptide and subsequent macrolactamization gave stevastelin B. Stevastelins C3 and B3 were also synthesized by a similar way. The direct comparison of synthetic stevastelins with natural compounds revealed that the synthetic stevastelins B and B3 are identical to the natural products, confirming the proposed structures. However, the synthetic stevastelin C3 was found to not be identical with the natural product. To elucidate the structure of stevastelin C3, degradation of the natural product was carried out to show the possibility that the natural product could be a 5-deoxy derivative of the proposed structure. Thus, the 5-deoxy derivative of the fatty acid moiety was prepared and transformed into a macrocycle. The synthetic 5-deoxy compound was fully identical to natural stevastelin C3. Based on these studies, it was shown that the structure of stevastelin C3 should be revised.