Explore the vast range of titles available.

Chemotherapy‐induced nausea and vomiting (CINV) is one of the most problematic adverse events that affects the well‐being of cancer patients. Risk factors for CINV and its elimination are necessary to increase the indications for and effectiveness of chemotherapy. We enrolled 1549 chemotherapy‐naïve patients in two phase II trials and one phase III trial of palonosetron between 2005 and 2007. Treatment failure (any emetic episodes or any administration of rescue medication) and/or nausea, and their associations with patient factors were evaluated in acute and in delayed phases using univariate and multivariate analyses. Female gender (odds ratio, 95% confidence interval: 2.96, 2.09–4.20), age <55 years (2.56, 1.94–3.37), non‐habitual alcohol intake (1.90, 1.43–2.51) and non‐smoker (1.40, 1.04–1.90) were associated with treatment failure in the acute phase. In contrast, only female gender (1.88, 1.34–2.64) was associated with treatment failure in the delayed phase. The number of risk factors was significantly associated with CINV in both acute and delayed phases. Patient risk factors were significantly associated with CINV. Depending on the relationship between CINV‐related risk factors and a tailored antiemetic treatment, high‐risk patients defined by the listed risk factors may be candidates for future clinical trials.

In patients with locally advanced non–small-cell lung cancer who have undergone concurrent chemotherapy and radiation therapy, the use of durvalumab in the year after completing treatment significantly prolonged disease-free and overall survival as compared with placebo.

Relapse is common in patients with locally advanced unresectable lung cancer after concurrent chemotherapy and radiation therapy. In a randomized study, addition of the anti–PD-L1 antibody durvalumab every 2 weeks for 12 months increased relapse-free survival by 47%.

In the open‐label, phase III CheckMate 816 study (NCT02998528), neoadjuvant nivolumab plus chemotherapy demonstrated statistically significant improvements in event‐free survival (EFS) and pathological complete response (pCR) versus chemotherapy alone in patients with resectable non‐small‐cell lung cancer (NSCLC). Here we report efficacy and safety outcomes in the Japanese subpopulation. Patients with stage IB–IIIA, resectable NSCLC were randomized 1:1 to nivolumab plus chemotherapy or chemotherapy alone for three cycles before undergoing definitive surgery within 6 weeks of completing neoadjuvant treatment. The primary end‐points (EFS and pCR) and safety were assessed in patients enrolled at 16 centers in Japan. Of the Japanese patients randomized, 93.9% (31/33) in the nivolumab plus chemotherapy arm and 82.9% (29/35) in the chemotherapy arm underwent surgery. At 21.5 months' minimum follow‐up, median EFS was 30.6 months (95% confidence interval [CI], 16.8–not reached [NR]) with nivolumab plus chemotherapy versus 19.6 months (95% CI, 8.5–NR) with chemotherapy; hazard ratio, 0.60 (95% CI, 0.30–1.24). The pCR rate was 30.3% (95% CI, 15.6–48.7) versus 5.7% (95% CI, 0.7–19.2), respectively; odds ratio, 7.17 (95% CI, 1.44–35.85). Grade 3/4 treatment‐related adverse events were reported in 59.4% versus 42.9% of patients, respectively, with no new safety signals identified. Neoadjuvant nivolumab plus chemotherapy resulted in longer EFS and a higher pCR rate versus chemotherapy alone in Japanese patients, consistent with findings in the global population. These data support nivolumab plus chemotherapy as a neoadjuvant treatment option in Japanese patients with resectable NSCLC. We report efficacy and safety outcomes in the Japanese subpopulation of patients with resectable non‐small‐cell lung cancer (NSCLC) in the global, randomized, open‐label, phase III CheckMate 816 study (NCT02998528). At a minimum follow‐up of 21.5 months, neoadjuvant nivolumab plus chemotherapy versus chemotherapy alone resulted in longer event‐free survival (median, 30.6 [95% CI, 16.8–not reached] vs. 19.6 [95% CI, 8.5–not reached] months) and a higher pathological complete response rate (30.3% [95% CI, 15.6–48.7] vs. 5.7% [95% CI, 0.7–19.2]) in Japanese patients, consistent with findings in the global population; no new safety signals were identified. Results support the use of neoadjuvant nivolumab plus chemotherapy in Japanese patients with resectable NSCLC.

Marine calcifying organisms, such as stony corals, are under threat by rapid ocean acidification (OA) arising from the oceanic uptake of anthropogenic CO 2 . To better understand how organisms and ecosystems will adapt to or be damaged by the resulting environmental changes, field observations are crucial. Here, we show clear evidence, based on boron isotopic ratio (δ 11 B) measurements, that OA is affecting the pH of the calcification fluid (pH CF ) in Porites corals within the western North Pacific Subtropical Gyre at two separate locations, Chichijima Island (Ogasawara Archipelago) and Kikaijima Island. Corals from each location have displayed a rapid decline in δ 11 B since 1960. A comparison with the pH of the ambient seawater (pH SW ) near these islands, estimated from a large number of shipboard measurements of seawater CO 2 chemistry and atmospheric CO 2 , indicates that pH CF is sensitive to changes in pH SW. This suggests that the calcification fluid of corals will become less supersaturated with respect to aragonite by the middle of this century (pH CF  = ~8.3 when pH SW  = ~8.0 in 2050), earlier than previously expected, despite the pH CF -upregulating mechanism of corals.

The ocean may have played a central role in the atmospheric p CO 2 rise during the last deglaciation. However, evidence on where carbon was exchanged between the ocean and the atmosphere in this period is still lacking, hampering our understanding of global carbon cycle on glacial–interglacial timescales. Here we report a new surface seawater p CO 2 reconstruction for the western equatorial Pacific Ocean based on boron isotope analysis—a seawater p CO 2 proxy—using two species of near-surface dwelling foraminifera from the same marine sediment core. The results indicate that the region remained a modest CO 2 sink throughout the last deglaciation.

BackgroundAmrubicin (AMR) is one of the most active agents for small-cell lung cancer (SCLC). However, hematologic toxicity and infection at a commonly used dose (40 mg/m2) is problematic; the optimal dose remains undetermined.Patients and methodsTo evaluate the optimal dose of AMR in terms of efficacy and safety, we reviewed consecutive data on patients with relapsed SCLC who received AMR at doses of 40, 35, and 30 mg/m2 (on days 1–3) at Nippon Medical School Hospital between October 2010 and November 2021.ResultsWe reviewed the data of 86 patients (20, 45, 27 who received AMR doses of 40, 35, 30 mg/m2, respectively) according to our study criteria. For patients  ≥ 75 years, the proportion who received second-line treatment tended to be higher in the 30–35 mg/m2 group. Objective response rates were 37/46/35%, median progression-free survival (PFS) were 3.0/4.7/3.2 months, and median overall survival (OS) were 7.8/16.3/8.0 months, respectively. Grade 4 neutropenia occurred in 58/39/31% of patients, which was higher for the 40 mg/m2 group. The incidence of febrile neutropenia did not differ between groups. Multivariate analysis identified the AMR dose was not associated with longer PFS and OS.ConclusionTreatment with AMR between 30 and 35 mg/m2 showed relatively mild hematologic toxicity compared with AMR at 40 mg/m2, without any significant difference in efficacy. Lower dose of AMR for relapsed SCLC could be a promising treatment option.

Overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is critical in combating EGFR-mutant non-small cell lung cancer (NSCLC). We tried to construct a novel therapeutic strategy to conquer the resistance to second-and third-generation EGFR-TKIs in EGFR-positive NSCLC patients. We established afatinib- and osimertinib-resistant lung adenocarcinoma cell lines. Exome sequencing, cDNA array and miRNA microarray were performed using the established cell lines to discover novel therapeutic targets associated with the resistance to second-and third-generation EGFR-TKIs. We found that ANKRD1 which is associated with the epithelial-mesenchymal transition (EMT) phenomenon and anti-apoptosis, was overexpressed in the second-and third-generation EGFR-TKIs-resistant cells at the mRNA and protein expression levels. When ANKRD1 was silenced in the EGFR-TKIs-resistant cell lines, afatinib and osimertinib could induce apoptosis of the cell lines. Imatinib could inhibit ANKRD1 expression, resulting in restoration of the sensitivity to afatinib and osimertinib of EGFR-TKI-resistant cells. In EGFR-mutant NSCLC patients, ANKRD1 was overexpressed in the tumor after the failure of EGFR-TKI therapy, especially after long-duration EGFR-TKI treatments. ANKRD1 overexpression which was associated with EMT features and anti-apoptosis, was commonly involved in resistance to second-and third-generation EGFR-TKIs. ANKRD1 inhibition could be a promising therapeutic strategy in EGFR-mutant NSCLC patients.

Four cycles of etoposide plus cisplatin and accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard of care for limited-stage small-cell lung cancer (SCLC). Irinotecan plus cisplatin significantly improved overall survival compared with etoposide plus cisplatin for extensive-stage SCLC. We compared these regimens for overall survival of patients with limited-stage SCLC. We did this phase 3 study in 36 institutions in Japan. Eligibility criteria included age 20–70 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and adequate organ functions. Eligible patients with previously untreated limited-stage SCLC received one cycle of etoposide plus cisplatin (intravenous etoposide 100 mg/m2 on days 1–3; intravenous cisplatin 80 mg/m2 on day 1) plus AHTRT (1·5 Gy twice daily, 5 days a week, total 45 Gy over 3 weeks). Patients without progressive disease following induction therapy were randomised (1:1 ratio, using a minimisation method with biased-coin assignment balancing on ECOG performance status [0 vs 1], response to induction chemoradiotherapy [complete response plus near complete response vs partial response and stable disease], and institution) to receive either three further cycles of consolidation etoposide plus cisplatin or irinotecan plus cisplatin (intravenous irinotecan 60 mg/m2 on days 1, 8, 15; intravenous cisplatin 60 mg/m2 on day 1). Patients, physicians, and investigators were aware of allocation. The primary endpoint was overall survival after randomisation; primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00144989, and the UMIN Clinical Trials Registry, number C000000095. 281 patients were enrolled between Sept 1, 2002, and Oct 2, 2006. After induction etoposide plus cisplatin and AHTRT, 258 patients were randomised to consolidation etoposide plus cisplatin (n=129) or irinotecan plus cisplatin (n=129). In the etoposide plus cisplatin group, median overall survival was 3·2 years (95% CI 2·4–4·1). In the irinotecan and cisplatin group, median overall survival was 2·8 years (95% CI 2·4–3·6); overall survival did not differ between the two groups (hazard ratio 1·09 [95% CI 0·80–1·46], one-sided stratified log-rank p=0·70). The most common adverse events of grade 3 or 4 were neutropenia (120 [95%] in the etoposide plus cisplatin group vs 101 [78%] in the irinotecan plus cisplatin group), anaemia (44 [35%] vs 50 [39%]), thrombocytopenia (26 [21%] vs six [5%]), febrile neutropenia (21 [17%] vs 18 [14%]), and diarrhoea (two [2%] vs 13 [10%]). There was one treatment-related adverse event leading to death in each group (radiation pneumonitis in the etoposide plus cisplatin group; brain infarction in the irinotecan plus cisplatin group). Four cycles of etoposide plus cisplatin and AHTRT should continue to be the standard of care for limited-stage SCLC. National Cancer Center and the Ministry of Health, Labour, and Welfare of Japan.

While biogeochemical and physical processes in the Southern Ocean are thought to be central to atmospheric CO 2 rise during the last deglaciation, the role of the equatorial Pacific, where the largest CO 2 source exists at present, remains largely unconstrained. Here we present seawater pH and pCO 2 variations from fossil Porites corals in the mid equatorial Pacific offshore Tahiti based on a newly calibrated boron isotope paleo-pH proxy. Our new data, together with recalibrated existing data, indicate that a significant pCO 2 increase (pH decrease), accompanied by anomalously large marine 14 C reservoir ages, occurred following not only the Younger Dryas, but also Heinrich Stadial 1. These findings indicate an expanded zone of equatorial upwelling and resultant CO 2 emission, which may be derived from higher subsurface dissolved inorganic carbon concentration.