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In this article we portray our personal journeys in a cross-cultural context resulting in professional growth. Data are presented in the form of constructed dialogues, and are reflected upon using the theories of transformative learning and intercultural competency. The role of lesson study as a vehicle for our journeys is examined. Reflection on our journeys culminates in a discussion on individuation, risk-taking, professional dialogue and the value of learning companions. We conclude by speculating on factors that may contribute to whether individuals might accept or decline engaging in similar journeys. (Contains 2 tables and 2 notes.)

The Konan groundwater basin of Kochi Prefecture, Japan, is experiencing freshwater shortages for the past few years, particularly during the winter season. The present study aimed at analyzing the problem and exploring increased groundwater withdrawals to meet burgeoning freshwater demands in various sectors. The trend analysis of water consumption indicates that the groundwater demand would increase by 43 and52% by the years 2010 and 2025, respectively, compared to 32100 m3 d-1 at present. The streamflow of the Monobe River reduces to a minimum in winter and it shows a decreasing trend in recent years. The geologic investigation results indicate that unconfined (phreatic) aquifers comprising alluvial sand and gravel and/or diluvial silty sand and gravel are dominant, and that the northwesternand western portions of the basin have greater potential for groundwater. Groundwater flows essentially from north to south into the ocean. Groundwater level fluctuations over the basin vary appreciably in space and time, indicating a wide variation of natural recharge. Field observations confirm the hypothesis that stream-aquifer interactionalso significantly contributes to groundwater recharge, besides the rainfall infiltration. Further, the pumping tests results demonstratethat though the aquifers are low-yielding, enhanced groundwater withdrawals could be possible. The aquifer hydraulic conductivity is characterized as high and ranges from 65 to 804 m d-1 (mean = 229 m d-1), thereby suggesting great aquifer heterogeneity. Finally, it is concluded that the long-term sustainability of the scarce groundwater resource of the Konan basin is doubtful, and that acomprehensive analysis of the groundwater system is essential prior to formulating plans for the future groundwater development and management. [ABSTRACT FROM AUTHOR]

Introduction: HER2 mutations are reported to occur in 2%-5% of all cases of non-small cell lung cancer (NSCLC). The clinical outcomes in patients with HER2-mutant NSCLC treated with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy as 1st line treatment still remain unclear., Methods: Using the large-scale clinico-genomic database of LC-SCRUM-Asia, the clinico-genomic characteristics and therapeutic outcomes of patients with HER2-mutant NSCLC were investigated., Results: Of the 15,251 patients with NSCLC enrolled in the LC-SCRUM-Asia database, tumor HER2 mutations were detected in 402 patients (2.6 %). The most common subtype of HER2 mutations was exon 20 in-frame insertions (79 %), followed in frequency by mutations in the tyrosine kinase domain other than Exon20ins (10 %) and mutations in extracellular domains (7 %). NSCLCs harboring HER2 mutations showed a higher tumor mutation burden (TMB) as compared with NSCLCs harboring EGFR mutations or ALK fusions (median: 4.22 vs. 2.54 and 2.52 mutation per megabase, respectively). Of the 402 patients, 268 patients had received platinum-based chemotherapy with ICIs (Chemo-ICI, n = 95) or without ICI (Chemo-alone, n = 173) as 1st line treatment. The progression-free survival (PFS) was significantly longer in the Chemo-ICI group as compared with the Chemo-alone group (median 8.5 vs. 6.3 months; HR [95 %CI]: 0.66 [0.50-0.88]; P < 0.005). Multivariate analysis identified use of ICIs in addition to platinum-based chemotherapy as an independent favorable prognostic factor for PFS. There was no significant difference in the overall survival between the patients of the Chemo-ICI and Chemo-alone groups (median 31.1 vs. 23.3 months; HR [95 %CI]: 0.80 [0.57-1.12], P = 0.20)., Conclusions: Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hibiki Udagawa reports grants from Takeda Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Amgen K.K., Taiho Pharmaceutical Co., Ltd. And MSD K.K. and honoraria for lectures from DAIICHI SANKYO COMPANY, LIMITED, CHUGAI PHARMACEUTICAL CO., LTD., Novartis Pharma K.K., Taiho Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., and MSD K.K. outside the current study. Shingo Matsumoto reports grants from Merck, Chugai Pharmaceutical, MSD and Janssen Pharmaceutical and honoraria for lectures from Eli Lilly outside the current study. Hiroki Izumi reports grants from Amgen, Eisai, Takeda Pharmaceutical Co, Bristol-Myers Squibb Japan, Chugai, AstraZeneca, Ono Pharmaceutical Co, MSD and Merck outside the current study. Yuichiro Ohe reports grants from AstraZeneca, Chugai, Eli Lilly, Kirin, Sumitomo, Pfizer, Taiho, Novartis, Takeda, Daiichi-Sankyo and Janssen and honoraria for lectures from AstraZeneca, Chugai, Chugai, ONO, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin, Eisai and Daiichi-Sankyo and payment for expert testimony from AstraZeneca, Chugai, ONO, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku, Boehringer Ingelheim, AnHeart Therapeutics Inc., PharmaMar outside the current study. Terufumi Kato reports grants from Abbvie, Amgen, Arrivent, AstraZeneca, Bayer, BeiGene, BluePrint, Bristol-Meyers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Haihe, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Regeneron and Takeda and honoraria for lectures from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Meyers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda and other from AstraZeneca, BeiGene, Chugai, Daiichi-Sankyo, Janssen, Merck KGaA, MSD, Novartis, Pfizer outside the current study. His spouse is an employer of Eli Lilly. Kazumi Nishino reports grants from ONO PHARMACEUTICAL CO., LTD., TAIHO PHARMACEUTICAL CO., LTD., MSD, AbbVie, DAIICHI SANKYO COMPANY, LIMITED, Amgen, Eisai Co., Ltd., Sanofi K.K., Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Pfizer, Eli Lilly Japan, Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co.,Ltd., AstraZeneca, Merus NV, Gilead Sciences, CHUGAI PHARMACEUTICAL CO., LTD, Bayer Yakuhin, Ltd and AMGEN and honoraria for lectures from AstraZeneca, Nippon Boehringer Ingelheim, Eli Lilly Japan, MSD, Novartis Pharmaceuticals, Pfizer, Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., Bristol Myers Squibb, Nippon Kayaku, ONO PHARMACEUTICAL CO., LTD., Takeda Pharmaceutical Co.,Ltd., CHUGAI PHARMACEUTICAL CO., LTD, AMGEN, DAIICHI SANKYO COMPANY, LIMITED, Nippon Boehringer Ingelheim Co., Ltd. outside the current study. Yuki Sato reports honoraria for lectures from AstraZeneca, MSD, Novartis, Chugai Pharmaceutical, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Nippon Kayaku, Bristol Myers Squibb, Eli Lilly, Takeda, Kyowa Kirin, Daiichi Sankyo and Boehringer Ingelheim outside the current study. Ryo Toyozawa reports grants from Abbvie, Amgen, AnHeart Therapeutics, Daiichi Sankyo, Eli Lilly Japan, MSD, Novartis Pharma, Pfizer Japan and Takeda Pharmaceutical and honoraria for lectures from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical and Thermo Fisher Scientific outside the current study. Koichi Azuma reports honoraria for lectures from AstraZeneca K.K., Ono Pharmaceutical, Chugai Pharmaceutical, MSD, Bristol-Myers Squibb and Takeda Pharmaceutical outside the current study. Tetsuya Sakai reports grants from Amgen, GlaxoSmithKline K.K, Daiichi Sankyo and NEC and honoraria for lectures from AstraZeneca, Novartis, Thermo Fisher Scientific, Takeda, OLYMPUS, Taiho, Chugai, MSD, Merck, Daiichi Sankyo, RIKEN GENESIS and Amco outside the current study. Yuji Shibata reports grants from MSD, Blueprint Medicines Corporation and Novartis and honoraria for lectures from Pfizer, Bristol-Myers Squibb, AstraZeneca, Ono Pharmaceutical Co., Ltd., Chugai, Takeda, Merck and Eli Lilly Japan outside the current study. Kaname Nosaki reports grants from Takeda, AstraZeneca, MSD K.K, Abbvie, Chugai Pharma, Daiichi Sankyo/UCB Japan and AnHeart Therapeutics and honoraria for lectures from AstraZeneca, Chugai Pharma, Lilly, MSD, Pfizer, Taiho Pharmaceutical, Janssen, Ono Pharmaceutical, Takeda, Novartis and Merck outside the current study. Yoshitaka Zenke reports grants from AstraZeneca, Daiichi-Sankyo, Amgen, GSK, Roche, MSD and Merck and honoraria for lectures from AstraZenca, Lilly, Chugai, Ono, Bristol-Meyers Squibb, Takeda, Boheringer-Ingelheim, Taiho, MSD, Novartis, Pfizer, Nihon Kayaku, Kyowa Kirin and Amgen outside the current study. Shigeki Umemura reports grants from Taiho pharmaceutical, Lilly and MSD and honoraria for lectures from MSD, Chugai Pharmaceutical, Takeda, AstraZeneca and Daiichi sankyo outside the current study. Kiyotaka Yoh reports grants from Abbvie, Amgen, ArriVent Biopharma, AstraZeneca, Boehringer Ingelheim, Chugai Pharma, Daiichi sankyo, Lilly, MSD, Taiho and Takeda and consulting fees from Boehringer Ingelheim and Abbvie and honoraria for lectures from Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai Pharma, Daiichi sankyo, Kyowa kirin, Lilly, MSD, Ono Pharmaceutical and Takeda outside the current study. Masahiro Seike reports grants from Chugai Pharmaceutical, Eli Lilly, Kyowa Hakko Kirin, Taiho Pharmaceutical and Nippon Kayaku and honoraria for lectures from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Bristol-Myers Squibb, Pfizer, Nippon Kayaku, Daiichi-Sankyo, Merck Biopharma, MSD K.K, Taiho Pharmaceutical, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Takeda Pharmaceutical, Kyowa Hakko Kirin, Novartis and Amgen inc outside the current study. Koichi Goto reports grants from Amgen K.K., Astellas Pharma Inc., AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Bristol-Myers Squibb K.K., CHUGAI PHARMACEUTICAL CO., LTD., DAIICHI SANKYO COMPANY, LIMITED, Eisai Co., Ltd., Janssen Pharmaceutical K.K., Kyowa Kirin Co., Ltd., Merck Biopharma Co., Ltd., MEDICAL& BIOLOGICAL LABORATORIES CO., LTD., MSD K.K., Novartis Pharma K.K., ONO PHARMACEUTICAL CO., LTD., Pfizer R&D Japan G.K., Sumitomo Pharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Bayer Yakuhin, Ltd., Merus N.V. and Takeda Pharmaceutical Co., Ltd. for the present manuscript. Koichi Goto also reports grants from Amgen Inc., AbbVie GK, AnHeart Therapeutics Inc., Blueprint Medicines Corporation., Craif Inc., Guardant Health Asia, Middle East & Africa, Inc, Haihe Biopharma Co., Ltd., Ignyta,Inc., Life Technologies Japan Ltd., Loxo Oncology, Inc., Lunit Inc., Precision Medicine Asia Co., Ltd., RIKEN GENESIS CO., LTD., Spectrum Pharmaceuticals, Inc., Sysmex Corporation., Turning Point Therapeutics,Inc. and honoraria for lectures from Amgen K.K., Amoy Diagnosties Co.,Ltd., AstraZeneca K.K., Bayer U.S., Bristol-Myers Squibb K.K., CHUGAI PHARMACEUTICAL CO., LTD., DAIICHI SANKYO COMPANY, LIMITED, Eisai Co., Ltd., Eli Lilly Japan K.K., Guardant Health Japan Corp., iTeos Therapeutics Inc., Janssen Pharmaceutical K.K., Thermo Fisher Scientific K.K., Merck Biopharma Co., Ltd., Nippon Kayaku Co.,Ltd., Novartis Pharma K.K., ONO PHARMACEUTICAL CO., LTD., Pharma Mar, S.A., RIKEN GENESIS CO., LTD., Taiho Pharmaceutical Co., Ltd. And Takeda Pharmaceutical Co., Ltd. And other from Amgen Inc., Amgen K.K., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Bristol-Myers Squibb K.K., DAIICHI SANKYO COMPANY, LIMITED, Eli Lilly Japan K.K., GlaxoSmithKline K.K., Haihe Biopharma Co., Ltd., Janssen Pharmaceutical K.K. and SYNEOS HEALTH CLINICAL K.K. Other authors report no potential conflict of interest to disclose.., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Mobocertinib is a novel, synthetic, orally administered tyrosine kinase inhibitor that inhibits many activated forms of epidermal growth factor receptor (EGFR), including those containing exon 20 insertion (ex20ins) mutations. This study aimed to assess the efficacy of mobocertinib in Japanese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR ex20ins mutations., Methods: This was a phase 2, open-label study. Patients with NSCLC harboring EGFR ex20ins mutations who had not had previous systemic treatment received mobocertinib 160 mg once daily. The primary endpoint was the confirmed objective response rate. A planned interim analysis was completed for the first 14 patients with a centrally confirmed EGFR ex20ins mutation, with enrollment stopped if the number of patients with an objective response was five or fewer., Results: In total, 33 patients were enrolled into the study (63.6% women; median age: 66 years). At the interim analysis, the objective response rate evaluated by a central independent review committee was 28.6% (4/14, 90% confidence interval: 10.4-54.0); therefore, enrollment was stopped for futility. In the full analysis set, the objective response rate was 18.2% (6/33, 95% confidence interval: 7.0-35.5); of the six responders, one patient (3.0%) had a complete response and five patients (15.2%) had partial responses. The most common treatment-related adverse events were diarrhea, paronychia, stomatitis, and nausea., Conclusion: Although study enrollment was terminated early owing to futility, our results showed modest activity of mobocertinib in Japanese patients with NSCLC with EGFR ex20ins mutations with no additional safety concerns., (© 2024. Takeda Pharmaceutical Company Limited.)

Tepotinib is a highly selective MET tyrosine kinase inhibitor (TKI) that has demonstrated robust and durable clinical activity in patients with MET exon 14 (METex14) skipping non-small-cell lung cancer (NSCLC). In the Phase II VISION study, patients received oral tepotinib 500 mg once daily. The primary endpoint was an objective response by an independent review committee (IRC) according to RECIST v1.1 criteria. The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Here we report the analysis of the efficacy and safety of tepotinib in all Japanese patients with advanced METex14 skipping NSCLC from VISION (n = 38) with >18 months' follow-up. The median age of the Japanese patients was 73 years (range 63-88), 39.5% of patients were ≥75 years old, 68.4% were male, 55.3% had a history of smoking, 76.3% had adenocarcinoma, and 10.5% of patients had known brain metastases at baseline. Overall, the objective response rate (ORR) was 60.5% (95% confidence interval (CI): 43.4, 76.0) with a median DOR of 18.5 months (95% CI: 8.3, not estimable). ORR in treatment-naïve patients (n = 18) was 77.8% (95% CI: 52.4, 93.6), and in patients aged ≥75 years (n = 15), ORR was 73.3% (95% CI: 44.9, 92.2). The most common treatment-related adverse event (AE) with any grade was blood creatinine increase (65.8%), which resolved following tepotinib discontinuation. Other common treatment-related AEs were peripheral edema (60.5%), hypoalbuminemia (34.2%), diarrhea (28.9%), and nausea (15.8%). In summary, tepotinib demonstrated robust and durable clinical activity irrespective of age or therapy line, with a manageable safety profile in Japanese patients with METex14 skipping NSCLC enrolled in VISION., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The factors that predict the clinical response to ramucirumab plus docetaxel (RD) after first-line chemoimmunotherapy are unresolved. We explored whether the therapeutic efficacy of prior chemoimmunotherapy could predict the outcome of RD as sequential therapy in patients with advanced non-small cell lung cancer (NSCLC)., Methods: Our study comprised 288 patients with advanced NSCLC who received RD as the second-line treatment after first-line chemoimmunotherapy at 62 Japanese institutions. Chemoimmunotherapy consisted of a platinum-based regimen and immune checkpoint inhibitors (ICIs). The association between several variables and the therapeutic outcome of RD was determined via logistic regression analysis., Results: Of the 288 patients, 225 (78.1%) received maintenance therapy and 108 (37.5%) received both ICI treatment for >180 days and maintenance therapy. All of 108 patients having ICIs for >180 days received maintenance therapy. Univariate analysis identified performance status, histology (adenocarcinoma), maintenance therapy, and ICI treatment >180 days as significant predictors of better progression-free survival (PFS) and overall survival (OS) after RD administration. Multivariate analysis confirmed that these factors independently predicted favorable PFS and OS. The therapeutic response and PD-L1 expression were not closely associated with outcome after RD treatment. In particular, maintenance therapy >4 cycles was more predictive of the better prognosis for RD treatment., Conclusion: Extended ICI treatment after chemoimmunotherapy and maintenance therapy enhanced the efficacy of second-line RD treatment in patients with advanced NSCLC., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: COVID-19 incidence is high in patients with cancer. The fatality rate was high for the Delta variant, necessitating infection prevention by vaccination. This study evaluated the safety of a SARS-CoV-2 vaccine in patients with advanced lung cancer receiving anticancer therapy., Methods: We prospectively enrolled patients receiving anticancer drugs for advanced lung cancer and planning SARS-CoV-2 vaccination. Early side effects within 7 days of vaccination were evaluated using patient-reported outcome (PRO) surveys. Chi-square test and multivariate logistic regression analyses were used., Results: Post-vaccination PROs were collected from 406 patients (252 were males). The mean age was 72 years. Treatment at the time of initial vaccination included chemotherapy, immune checkpoint inhibitors (ICI), a combination of chemotherapy and ICI, targeted therapy including tyrosine kinase inhibitors, and others in 115, 93, 45, 147, and six cases, respectively. The vaccines administered were BNT162b2 and mRNA273 in 361 and three cases, respectively and unknown in 42 cases. A total of 16.1% of patients developed fever (38°C) after the second mRNA vaccination (95% confidence interval: 12.6%-20.1%). This rate is comparable to data previously reported in 120 patients and slightly higher than that of healthy participants of the BNT162b2 study. Patients receiving treatment with cytotoxic anticancer agents were more likely to have high fever. Multivariate analysis showed no correlation between fever frequency and patient background. No serious initial adverse events due to vaccination were observed., Conclusions: Anti-SARS-CoV-2 mRNA vaccination is safe; however, post-vaccination fever is more common in patients undergoing lung cancer treatment than in healthy individuals., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Since 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become prevalent worldwide. In severe cases, the case fatality rate is high, and vaccine prevention is important. This study evaluated the safety of receiving SARS-CoV-2 vaccine in patients with advanced lung cancer receiving anticancer therapy., Methods: We prospectively enrolled patients receiving anticancer drugs for advanced lung cancer who planned to receive SARS-CoV-2 vaccination. Early adverse events within 7 days of vaccine injection were evaluated using patient-reported surveys. The chi-square test and multivariate logistic regression analyses were used., Results: Among 120 patients receiving lung cancer treatment, 73 were men; the mean age of the patients was 73.5 years. The treatments received for lung cancer at the time of the first vaccine injection were chemotherapy, ICIs, combined chemotherapy and ICIs, and targeted therapies, including tyrosine kinase inhibitors, in 30, 28, 17, and 45 patients, respectively. All patients received SARS-CoV-2 messenger RNA (mRNA) vaccine. After the second mRNA vaccine dose, 15.4% of patients had fever of 38°C (95% confidence interval: 9.34%-23.2%); this rate was slightly higher than that for healthy participants at the time of the BNT162b2 trial. Patients treated with cytotoxic anticancer drugs tended to have high fever. In the multivariate analyses, male sex was associated with higher fever frequencies. However, there were no serious early adverse events due to vaccination., Conclusions: Anti-SARS-CoV-2 mRNA vaccination tends to be safe, but fever following vaccination tends to be more common among patients undergoing lung cancer treatment than among healthy individuals., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: MET exon 14 skipping is an oncogenic driver occurring in 3-4% of non-small cell lung cancer (NSCLC). The MET inhibitor tepotinib has demonstrated clinical efficacy in patients with MET exon 14 skipping NSCLC. Here, we present data from Japanese patients in the Phase II VISION study, evaluating the efficacy and safety of tepotinib., Methods: In the open-label, single-arm, Phase II VISION study, patients with advanced/metastatic NSCLC with MET exon 14 skipping received oral tepotinib 500 mg once daily. The primary endpoint was objective response by independent review. Subgroup analyses of Japanese patients were preplanned., Results: As of 1 January 2020, 19 Japanese patients received tepotinib and were evaluated for safety, 15 of whom had ≥9 months' follow-up and were also analysed for efficacy. By independent review, objective response rate (ORR) was 60.0% (95% confidence interval [CI]: 32.3, 83.7), median duration of response was not reached (95% CI: 6.9, not estimable [ne]), and progression-free survival was 11.0 months (95% CI: 1.4, ne). ORR in patients with MET exon 14 skipping identified by liquid biopsy (n = 8) was 87.5% (95% CI: 47.3, 99.7), and by tissue biopsy (n = 12) was 50.0% (95% CI: 21.1, 78.9). Patients' quality of life was maintained with tepotinib treatment. Among patients evaluated for safety, the most common treatment-related adverse events (any grade) were blood creatinine increase and peripheral oedema (12 and nine patients, respectively)., Conclusions: Tepotinib demonstrated robust and durable clinical efficacy in Japanese patients with advanced NSCLC harbouring MET exon 14 skipping, identified by either liquid or tissue biopsy. The main adverse events, blood creatinine increase and peripheral oedema, were manageable., (© The Author(s) 2021. Published by Oxford University Press.)