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A giant-fruited mutant of European pear (Pyrus communis L.), Giant La France (GLaF), that arose from a bud sport of normal 'La France', exhibited receptacle-specific DNA reduplication resulting in an approx. 1.6-fold increase in fruit size compared with normal 'La France' fruit. To identify the genes responsible for this receptacle-specific DNA reduplication, we focussed on the regulatory genes WEE1 and CCS52A, which have been reported to increase the ploidy level of tomato fruit flesh. Full-length cDNAs of WEE1 and CCS'52/1, referred to as PcWEEl and PcCCS52A, were cloned from P. communis L., 'La France'. We determined the genomic sequences of these two genes, clarified their exon-intron structures, and compared cDNA sequences between 'La France' and GLaF. The predicted amino acid sequences were similar to other species and retained their conserved domains. No differences were found between the PcWEEl and PcCCS52A cDNA sequences of'La France' and GLaF. However, analysis revealed that the levels of expression of PcWEEl and PcCCS52A were higher in the receptacles of GLaF than in those of 'La France' 1 week before the full-bloom stage. Our results suggest that PcWEEl and PcCCS52A may play important roles in the occurrence and persistence of DNA reduplication in the receptacles, and hence fruit, of GLaF. [ABSTRACT FROM AUTHOR]

We studied Giant La France (GLaF), a sport that sets large fruit and that appeared spontaneously on a European pear (Pyrus communis L.) 'La France' tree. It is known that GLaF exhibits DNA reduplication, specifically in the receptacle, before full bloom. To identify the genes related to DNA reduplication in GLaF, we performed 454 pyrosequencing to obtain mRNA sequences from GLaF and 'La France' and to examine their levels of expression. In total, 1,166,675 sequences were obtained from the poly(A)-enriched complimentary DNA libraries of GLaF and 'La France' and assembled into 49,181 contigs. A further 78,431 sequences were obtained as singletons. Comparisons of the total RNA sequence abundance between GLaF and 'La France' revealed that the levels of expression of 26 genes changed significantly in GLaF. However, none of these genes had an obvious functional role that could explain the difference in fruit size between the GLaF sport and 'La France'. We also identified 61 core cell cycle genes by transcriptome analysis, but their involvement in the larger fruit size of GLaF remains to be elucidated. This study presents the first large-scale RNA sequence database for European pear using next-generation sequencing technology. The resuhs obtained can assist in various studies concerning pear physiology, including clarification of the molecular basis for the GLaF sport mutation. [ABSTRACT FROM AUTHOR]

Objective:  This study aimed to investigate whether the calculated predicted value of the estimated glomerular filtration rate from serum creatinine levels (eGFRcreat-PV) from multiple regression equations using the anteroposterior diameter of the renal sinus (APDRS) measured on multidetector row computed tomography (MDCT) axial images and easily obtainable chronic kidney disease (CKD) risk factors (age and body mass index, BMI) is useful for separating CKD stages., Material and Methods:  The Review Board approved this study, and the additional approval requirement was waived for this retrospective study. We investigated the association between eGFRcreat and age, BMI, and APDRS using stepwise multivariate regression analysis in 98 patients who underwent MDCT and calculated eGFRcreat-PV from the obtained multiple regression equation. We investigated significant differences in eGFRcreat-PV according to the variation in the CKD stage 3 categories and cutoff value. Additionally, we analyzed the area under the curve (AUC), sensitivity, and specificity of eGFRcreat-PV to differentiate between the patients with greater and less than CKD stage 3., Results:  Age, BMI, and APDRS scores were independent factors influencing eGFRcreat. The difference in eGFRcreat-PV between the groups with greater and less than CKD stage 3 was significant. Additionally, the cutoff value, AUC, sensitivity, and specificity of eGFRcreat-PV used to distinguish between the two groups of greater and less than CKD stage 3 were 61.5, 0.801, 63.9%, and 80.6%, respectively., Conclusion:  The eGFRcreat-PV from the APDRS, measured on MDCT axial images, along with age and BMI, helps differentiate the less and more than CKD stage 3., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Edogawa Hospital Ethics Committee issued approval 2024092734. The Review Board approved this study, and the requirement for informed consent was waived for this retrospective study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Inokuchi et al.)

Background: Non-small-cell lung cancer (NSCLC) is associated with a high incidence of brain metastasis (BM), and the prognosis of patients with NSCLC and BM is poor. This study aimed to identify the prognostic factors and elucidate the survival rates of Japanese patients with NSCLC and BM at initial diagnosis., Methods: HOT 1701 is a retrospective multicenter study of patients with NSCLC and BM at initial diagnosis. The medical records of all consecutive patients diagnosed with advanced or recurrent NSCLC and BM at 14 institutions of the Hokkaido Lung Cancer Clinical Study Group Trial (HOT) in Japan were reviewed. The participants were categorized based on the presence or absence of driver mutations. The Kaplan-Meier method was used to estimate median overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors in these patients., Results: Among 566 patients with NSCLC and BM, the median OS was 11.8 months. Patients with driver mutations survived longer than those without driver mutations. The univariate and multivariate analyses revealed 6 independent prognostic factors: age ≥65 years, poor performance status, T factor, absence of driver gene mutations, presence of extracranial metastases, and number of BM. According to the prognostic score based on these 6 factors, the patients were stratified into 3 risk groups: low-, intermediate-, and high-risk, with median OS of 27.8, 12.2, and 2.8 months, respectively., Conclusions: We developed a new prognostic model for patients with NSCLC and BM, which may help determine prognosis at diagnosis., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

In the long history of human relations with flowering cherry trees in Japan, 'Somei-Yoshino' occupies an exceptional position among a variety of flowering trees: it is a self-incompatible interspecific hybrid but has been enthusiastically planted by grafting throughout Japan, due most likely to its flamboyant appearance upon full bloom. Thus, 'Somei-Yoshino' gives us a rare opportunity to trace and investigate the occurrence and distribution of somatic mutations within a single plant species through analysis of the genomes of the clonally propagated trees grown under a variety of geographical and artificial environments. In the studies presented here, a total of 46 samples of 'Somei-Yoshino' trees were collected and their genomes were analysed. We identified 684 single nucleotide mutations, of which 71 were present in more than two samples. Clustering analysis of the mutations indicated that the 46 samples were classified into eight groups, four of which included 36 of the 46 samples analysed. Interestingly, all the four tree samples collected in Ueno Park of Tokyo were members of the four groups mentioned above. Based on comparative analysis of their mutations, one of the four trees growing in Ueno Park was concluded to be the closest to the original ancestor. We propose that somatic mutations may be used as tracers to establish the ancestral relationship amongst clonally propagated individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

Introduction: Oligometastasis and oligoprogression (OP) has not been adequately defined in extensive-stage SCLC (ES-SCLC) and may be a good indication for adding local treatment. Therefore, this multicenter study aimed to investigate the prognostic impact of oligometastasis and OP in ES-SCLC., Methods: We enrolled patients who received chemoimmunotherapy between September 2019 and June 2022. Patients were classified into oligometastasis and non-oligometastasis groups by determining the number of original tumor lesions and distant metastases (worsening or newly appearing lesions) at the time of initial diagnosis and disease progression after first-line treatment., Results: We retrospectively analyzed 265 consecutive patients with ES-SCLC. Synchronous oligometastasis (SOM) and OP was defined as less than or equal to five lesions in less than or equal to two organs, including lungs; 21.0% and 53.2% of patients had SOM and OP, respectively. Median progression-free survival was 5.8 months and 4.9 months in patients with and without SOM, respectively (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.51-1.02, p  = 0.065). Median overall survival was 20.5 months and 15.0 months in patients with and without SOM (HR = 0.58, 95% CI: 0.37-0.95, p  = 0.027) from the initiation of first-line treatment. The OP group revealed a better progression-free survival of 5.2 months (versus 3.2 mo, HR = 0.69, 95% CI: 0.50-0.96, p  = 0.026) and overall survival of 15.1 months (versus 7.5 mo, HR = 0.44, 95% CI: 0.29-0.66, p  = 0.027) from the initiation of second-line treatment compared with the non-OP group. The Lung Immune Prognostic Index score was significantly lower in the SOM and OP group., Conclusions: ES-SCLC in patients with SOM and OP may be more indolent than that of the nonoligometastasis group, therefore, new treatment strategies, including the addition of local treatment, should be explored., Clinical Trial Registration: This study was registered at UMIN-CTR (UMIN000053402)., Competing Interests: Dr. Asahina reported receiving grants from 10.13039/100004325AstraZeneca, receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Chugai Pharmaceutical, Merck Sharp & Dohme, Bristol-Myers Squib, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, Ono Pharmaceutical, Merck, KyowaHakko-Kirin and reported participation on a data safety monitoring board or advisory board of AstraZeneca. Dr. Yokouchi reported receiving grants from Chugai Pharmaceuticals Co., Ltd., AstraZeneca, AbbVie, Daiichi Sankyo, Bristol-Myers Squibb Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Sanofi, and personal fees from Chugai Pharmaceutical Co., Ltd. and AstraZeneca during the conduct of the study. Dr. Megumi Furuta reported receiving honoraria from AstraZeneca K.K., Daiichi Sankyo Co, Ltd., Nippon Kayaku Co, Ltd., and Chugai Pharmaceutical Co. during the conduct of the study. Dr. Konno reported receiving grants from 10.13039/100010795Chugai Pharmaceutical. Dr. Hosomi reported receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, and educational events from AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Kyowa Kirin, Nippon Kayaku, Takeda, Eisai, Novartis, Pfizer, Merck Sharp & Dohme during the conduct of the study. Dr. Oizumi reports receiving grants from 10.13039/100006483AbbVie, 10.13039/100002429Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Merck Sharp & Dohme, Pfizer, Sanofi, Taiho Pharmaceutical, and Takeda Pharmaceutical; honoraria from AstraZeneca, Chugai Pharmaceutical, Merck Sharp & Dohme. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Backgrounds and objectives Renal sinus fat (RSF) is an indicator of obesity-related complications. However, the measurement and imaging process are complicated. For a simple measurement of RSF, we focused on the kidney's shape change caused by RSF accumulation. Thus, this study aimed to investigate whether the anteroposterior diameter of the renal sinus (APDRS) on a computed tomography (CT) axial image is useful for evaluating RSF accumulation. Materials and methods The correlation between APDRS and RSF was investigated in 98 outpatients who underwent abdominal CT. In addition, the correlation between APDRS or RSF and obesity indicators (estimated glomerular filtration rate from serum creatinine levels (eGFRcreat), body mass index (BMI), and visceral adipose tissue (VAT)) was also investigated. We classified patients based on the presence or absence of at least one underlying disease (chronic kidney disease (CKD), cardiovascular diseases (CVD), hypertension, and type 2 diabetes (T2D)) and investigated significant differences between the two groups at APDRS and RSF. The intraclass correlation coefficient (ICC) was also calculated for APDRS. Results There was a strong positive correlation between RSF and APDRS (r = 0.802, P < 0.01). The obesity indicators (eGFRcreat, BMI, and VAT) were correlated with RSF and APDRS (P < 0.01). Out of 98 outpatients, 48 had at least one underlying disease. There were statistically significant differences in APDRS and RSF between the patients with and without at least one of the underlying diseases caused by obesity (P < 0.01). The inter-reader ICC for the measurement of the APDRS was 0.98. Conclusions APDRS on a CT axial image may be useful for the evaluation of RSF accumulation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Inokuchi et al.)

Durvalumab has been administered to patients with unresectable stage III non-small cell lung cancer (NSCLC). However, it remains unclear whether durvalumab benefits these patients with epidermal growth factor receptor (EGFR) mutation. We conducted a retrospective, multicenter study of patients with EGFR mutation who received chemoradiotherapy (CRT) between June 2018 and March 2021. We assessed patient characteristics, efficacy of durvalumab, and durvalumab safety before and after targeted therapy. We collected data on a total of 673 patients, of whom 401 (59.6%) underwent EGFR mutation testing. Fifty-one patients were EGFR positive and 311 were EGFR negative. In the EGFR-positive group, there were higher proportions of females, never-smokers, and patients with adenocarcinoma histology. Of the 51 patients in the positive group and 311 in the negative group who received CRT, 45 (88.2%) and 247 (79.4%) received durvalumab, with median progression-free survival of 23.0 and 24.2 months in the positive and negative groups, respectively (hazard ratio 1.03; 95% confidence interval: 0.64-1.67). The main adverse event was pneumonitis (positive group: 62.2%; 4.4% grade 3; negative group: 62.3%; 6.9% grade 3). No treatment-related deaths were observed. Of the 45 patients in the positive group who received durvalumab, 14 (31.1%) received targeted therapy after durvalumab at the data cutoff. One patient discontinued targeted therapy after developing pneumonitis. In patients with unresectable stage III NSCLC with EGFR mutation, durvalumab after CRT is potentially safe and effective. This may be a suitable treatment sequence for these patients., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The performance of electric double-layer capacitors and lithium-ion batteries deteriorates with increasing humidity. The desirable effect of bound water on the energy-storage properties of physically dry cellulose nanofiber (Na-ACF) supercapacitors with sodium (Na) carboxylate radicals was investigated using infrared and near-infrared spectroscopy, and nuclear magnetic resonance spectroscopy, alternating current impedance analyses, and first-principles calculations. The storage capacity decreased gradually upon heating to 423 K and reached zero upon exceeding 483 K, accompanied by increasing electrical resistance, forming a distorted semicircle in Nyquist diagram and drawing the phase angle to zero in Bode diagram. This is attributed to the water in the hydration gel bound to the Na + -ions that cross-link the cellulose chains, evaporating as the temperature increases, and finally becoming Na 2 O. The increased band-gap energy from the increase in bound water prevents leakage from the supercapacitor. In contrast to ordinary batteries, bound water is necessary for developing Na-ACF supercapacitors., (© 2023. Springer Nature Limited.)

Purpose: Immune-checkpoint inhibitors (ICIs) are effective against advanced non-small cell lung cancer (NSCLC). However, whether the efficacy and safety of ICI treatment in elderly patients are similar to those in younger patients is unclear. This study was designed to address this question., Methods: We enrolled patients who received ICI monotherapy in Japan between December 2015 and December 2017; those ≥75 years of age comprised the elderly group. We compared the efficacy and safety of ICI monotherapy in elderly patients with those in younger patients and explored prognostic factors in elderly patients., Results: We enrolled 676 patients; 137 (20.3%) were assigned to the elderly group. The median age of the elderly and younger groups was 78 (range, 75-85) and 66 (range, 34-74) years. The median progression-free survival (4.8 months vs. 3.3 months, p = 0.1589) and median overall survival (12.3 months vs. 13.0 months, p = 0.5587) were similar between the elderly and younger groups. Multivariate analysis revealed that a significantly better OS in the elderly group was associated with better responses to first- or second-line ICI treatment (p = 0.011) and more immune-related adverse events (irAEs) (p = 0.02). IrAEs that led to ICI discontinuation occurred in 34 of 137 patients (24.8%) in the elderly group, and their survival was significantly higher than that in those who did not have irAEs., Conclusion: ICI is also effective in elderly NSCLC patients, and treatment discontinuation due to irAEs may be a good prognostic marker., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Cells of interest can be prepared from somatic cells by forced expression of lineage-specific transcription factors, but it is required to establish a vector-free system for their clinical use. Here, we report a protein-based artificial transcription system for engineering hepatocyte-like cells from human umbilical cord-derived mesenchymal stem cells (MSCs)., Methods: MSCs were treated for 5 days with 4 artificial transcription factors (4F), which targeted hepatocyte nuclear factor (HNF)1α, HNF3γ, HNF4α, and GATA-binding protein 4 (GATA4). Then, engineered MSCs (4F-Heps) were subjected to epigenetic analysis, biochemical analysis and flow cytometry analysis with antibodies to marker proteins of mature hepatocytes and hepatic progenitors such as delta-like homolog 1 (DLK1) and trophoblast cell surface antigen 2 (TROP2). Functional properties of the cells were also examined by injecting them to mice with lethal hepatic failure., Results: Epigenetic analysis revealed that a 5-day treatment of 4F upregulated the expression of genes involved in hepatic differentiation, and repressed genes related to pluripotency of MSCs. Flow cytometry analysis detected that 4F-Heps were composed of small numbers of mature hepatocytes (at most 1%), bile duct cells (~19%) and hepatic progenitors (~50%). Interestingly, ~20% of 4F-Heps were positive for cytochrome P450 3A4, 80% of which were DLK1-positive. Injection of 4F-Heps significantly increased survival of mice with lethal hepatic failure, and transplanted 4F-Heps expanded to more than 50-fold of human albumin-positive cells in the mouse livers, well consistent with the observation that 4F-Heps contained DLK1-positive and/or TROP2-positive cells., Conclusion: Taken together with observations that 4F-Heps were not tumorigenic in immunocompromised mice for at least 2 years, we propose that this artificial transcription system is a versatile tool for cell therapy for hepatic failures., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Genotyping technologies for single nucleotide polymorphisms (SNPs) and other mutation types have evolved to become essential tools in various fields. Although high-throughput genotyping technologies occupy a key position in handling large amounts of SNP data, simple, low-cost, and conventional genotyping technologies remain in demand. Allele-specific (AS) polymerase chain reaction (PCR) and its related improved methods can effectively identify target SNPs and allele types using AS primers that introduce instability through mismatched bases at and around the SNP site. In this chapter, we present what is known from the literature on primer design with mismatches for AS-PCR and describe three cases of mutation detection (SNPs and insertions/deletions) associated with functional genes of crop species, which could be useful to guide future AS-PCR experiments., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The aim of the study is to investigate the feasibility for hepatic function and fibrosis visual assessment using transitional phase imaging based on the uptake process of Gd-EOB-DTPA., Materials and Methods: We retrospectively selected 105 consecutive patients who underwent Gd-EOB-DTPA enhanced MRI examination at 1.5 Tesla for intrahepatic lesion evaluation from June 2020 to June 2022. Data were classified into two groups defined by the signal intensity (SI) difference in the hepatic vein against that of the hepatic parenchyma at transitional phase as follows: High and Iso-SI group: hepatic vein SI equal to or greater than the hepatic parenchymal SI; and Low-SI group: hepatic vein SI lower than hepatic parenchymal SI. We evaluated whether significant differences in ALBI score, FIB-4, APRI and LSR of hepatobiliary phase between two groups. We measured cut-off values between two groups in all items according to receiver operating characteristic analysis. Furthermore, the inter-reader reproducibility of the visual assessment on transitional phase images between two readers was evaluated using the ICC., Results: The visual assessment results were as follows: High and Iso- and Low-SI groups included 48, 57, patients, respectively. Significant differences were observed in ALBI score, FIB-4, APRI and LSR between two groups. The cut-off values of ALBI score, FIB-4, APRI and LSR were -2.69, 2.28, 0.49 and 2.15. ICC of transitional phase image visual assessment between two readers was 0.86., Conclusions: Hepatic function and fibrosis might be assessed by visual assessment of transitional phase images in Gd-EOB-DTPA enhanced MRI., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors have read and approved the submitted manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare that they have no conflict of interest. The manuscript has not been submitted elsewhere nor published elsewhere in whole or in part. All relevant ethical safeguards had been met., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A co-culture of a novel thermoacidophilic, obligate symbiotic archaeon, designated as strain MJ1 T , with its specific host archaeon Metallosphaera sedula strain MJ1HA was obtained from a terrestrial hot spring in Japan. Strain MJ1 T grew in the co-culture under aerobic conditions. Coccoid cells of strain MJ1 T were 200-500 nm in diameter, and attached to the MJ1HA cells in the co-culture. The ranges and optima of the growth temperature and pH of strain MJ1 T in the co-culture were 60-75 °C (optimum, 65-70 °C) and pH 1.0-4.0 (optimum, pH 2.5), respectively. Core lipids of dialkyl glycerol tetraethers (GDGT)-3 and GDGT-4 were highly abundant in MJ1 T cells concentrated from the co-culture. Strain MJ1 T has a small genome (0.67 Mbp) lacking genes for biosynthesis of essential biomolecules, such as nucleotides, lipids and ATP. The genomic DNA G+C content was 24.9 mol%. The 16S rRNA gene sequence of strain MJ1 T was most closely related to that of the cultivated species, ' Nanopusillus acidilobi' strain N7A (85.8 % similarity). Based on phylogenetic and physiological characteristics, we propose the name Nanobdella aerobiophila gen. nov., sp. nov. to accommodate the strain MJ1 T (=JCM 33616 T =DSM 111728 T ). In addition, we propose the names Nanobdellaceae fam. nov., Nanobdellales ord. nov., and Nanobdellia class. nov. to accommodate the novel genus.

Purpose: An increasing number of advanced non-small cell lung cancer (NSCLC) cases are being reported in the ageing population. However, studies on the use of afatinib in elderly patients are scarce. We conducted a prospective multicentre, single-arm, and open-label phase II trial for low-dose afatinib (30 mg/day) use in elderly patients with NSCLC with EGFR mutation to assess quality-of-life (QOL) and pharmacokinetic (PK)/pharmacogenomic (PGx) parameters., Patients and Methods: The primary end-point was the objective response rate (ORR), and the planned number of registered cases was 35, with a threshold ORR of 50%, an expected ORR of 75%, α of 0.05, and β of 0.1. Secondary end-points were progression-free survival (PFS), overall survival (OS), the incidence rate of adverse events (AEs), QOL survey (FACT-L), and trough plasma concentration of afatinib at steady state (Css) and at the occurrence of clinically significant AEs., Results: The median age of the patients was 79 years. The ORR was 80.0% and the disease control rate was 91.4%. The median PFS and OS were 15.6 and 29.5 months, respectively. Four patients discontinued because of AEs. Treatment-related death was not observed. No significant change in QOL was observed at baseline and after 4, 8, and 12 weeks. Css was comparable with those in previous reports and was significantly higher in patients with grade 3 AEs. Direct correlations between afatinib treatment and PGx profiles were not observed., Conclusions: An afatinib starting dose of 30 mg/day could be an effective and safe treatment option for elderly patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Osimertinib is a standard of care therapy for previously untreated epidermal growth factor receptor mutation-positive non-small cell lung cancer. However, limited data exist regarding the efficacy and safety of osimertinib as a first-line therapy for elderly patients aged 75 years or older. To assess the potential clinical benefits of osimertinib in this population, this retrospective multi-institutional observational study included 132 patients with non-small cell lung cancer (age ≥ 75 years), who received osimertinib as first-line treatment. The proportion of patients with 1-year progression-free survival was 65.8% (95% confidence interval 57.1-73.5). The median progression-free survival was 19.4 (95% confidence interval 15.9-23.9) months. The median overall survival was not reached (95% confidence interval 24.6-not reached). The frequency of pneumonitis was 17.4%, with a grade 3 or higher rate of 9.1%. More than two-thirds of treatment discontinuations due to pneumonitis occurred within 3 months of starting osimertinib, and the prognosis of patients with pneumonitis was unsatisfactory. Osimertinib is one of the effective first-line therapeutic options for patients aged 75 years or older; however, special caution should be exercised due to the potential development of pneumonitis., (© 2021. The Author(s).)

Objectives: Limited information is available on the appropriate treatment duration of immune checkpoint inhibitors (ICIs). We aimed to identify candidates who would benefit from ICI discontinuation after one year of treatment for metastatic non-small cell lung cancer (NSCLC)., Materials and Methods: This retrospective multi-institutional observational study examined medical records of all consecutive patients with advanced or recurrent NSCLC, who started ICI monotherapy at 15 institutions in Japan between December 2015 and December 2017. Patients who received initial ICI therapy for >1 year without progressive disease were defined as the long-term treatment (LT) group; others were defined as the non-long-term treatment (NLT) group. Primary outcomes included the prognostic factors in the LT group, whereas secondary outcomes included efficacy of ICI rechallenge, safety, and survival outcomes in the overall population., Results: In total, 676 patients were enrolled, and 114 (16.9 %) were assigned to the LT group. The median time interval from the start of initial ICI administration to data cutoff was 34.3 months (range, 24.1-47.8); thus, all surviving patients were followed-up for at least 2 years from the start of initial ICI. Median progression-free survival (PFS) was longer in the LT than in the NLT group (33.6 months vs. 2.7 months; p < 0.001). On multivariate analysis, significantly better PFS was associated with smoking (hazard ratio [HR]=0.36, p = 0.04), and complete response (CR; HR=uncomputable, p < 0.001) in the LT group. Thirty-seven patients (5.5 %) received ICI rechallenge, including 10 in the LT group. Among patients receiving rechallenge treatment, the median PFS was 2.2 months, with no difference between the LT and NLT groups., Conclusions: In the LT group, smoking and achieving CR were significantly associated with better PFS. Since rechallenge treatment was not effective, careful consideration is required for discontinuing ICI. However, these prognostic factors are helpful in considering candidates for ICI discontinuation., Trial Registration: UMIN ID, UMIN000041403., (Copyright © 2021 Elsevier B.V. All rights reserved.)