Patients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)–negative breast cancer have poor prognoses. The benefit of adjuvant chemotherapy in these patients remains unclear. We randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival. The result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% confidence interval [CI], 0.53 to 0.92; P=0.01). Overall survival was longer in the capecitabine group than in the control group (89.2% vs. 83.6% of the patients were alive at 5 years; hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). Among patients with triple-negative disease, the rate of disease-free survival was 69.8% in the capecitabine group versus 56.1% in the control group (hazard ratio for recurrence, second cancer, or death, 0.58; 95% CI, 0.39 to 0.87), and the overall survival rate was 78.8% versus 70.3% (hazard ratio for death, 0.52; 95% CI, 0.30 to 0.90). The hand–foot syndrome, the most common adverse reaction to capecitabine, occurred in 73.4% of the patients in the capecitabine group. After standard neoadjuvant chemotherapy containing anthracycline, taxane, or both, the addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative breast cancer who had residual invasive disease on pathological testing. (Funded by the Advanced Clinical Research Organization and the Japan Breast Cancer Research Group; CREATE-X UMIN Clinical Trials Registry number, UMIN000000843.)

Corneal endothelial cell (CEC) disorders, such as Fuchs’s endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density.

Although the overall incidence of bone metastasis (BM) is unknown, BMs are a frequent complication in patients with advanced cancer. The most common human cancers such as breast, prostate, and lung have a great avidity for bone, leading to painful skeletal symptoms. How long patients live with a tumor is likely to influence whether BMs will occur. For example, in patients who quickly die of cancer because of an aggressively growing primary tumor, BMs will be relatively uncommon, simply because they have not adequate time to develop. This in no way implies that the tumor cells lacked the potential to grow in bone.¹ x 1 Mundy, GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002; 2: 584–593 Crossref | PubMed | Scopus (1735) | Google Scholar See all References ,² x 2 Coleman, RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001; 27: 165–176 Abstract | Full Text PDF | PubMed | Scopus (1046) | Google Scholar See all References In the case of advanced non–small-cell lung cancer (NSCLC), the median survival time (MST) has increased from 8 to 12 months to 15 to 17 months, during the past 10 years.³ x 3 Schiller, JH, Harrington, D, Belani, CP..., and Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002; 346: 92–98 Crossref | PubMed | Scopus (4075) | Google Scholar See all References ^{, 4} x 4 Ohe, Y, Ohashi, Y, Kubota, K et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-Arm Cooperative Study in Japan. Ann Oncol. 2007; 18: 317–323 Crossref | PubMed | Scopus (456) | Google Scholar See all References ^{, 5} x 5 Paz-Ares, L, Marinis, FD, Dediu, M et al. PARAMOUNT: final overall survival (OS) results of the phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo (plb) plus BSC immediately following induction treatment with pem plus cisplatin (cis) for advanced nonsquamous (NS) non-small cell lung cancer (NSCLC). ASCO Meeting Abstracts. 2012; 30: 7507 Google Scholar See all References ^{, 6} x 6 Katakami, N, Gemma, A, Sakai, H et al. Randomized phase III trial of S-1 plus cisplatin versus docetaxel plus cisplatin for advanced non-small-cell Lung cancer (TCOG0701)—CATS TRIAL (cisplatin and TS-1 TRIAL). ASCO Meeting Abstracts. 2012; 30: 7515 Google Scholar See all References Furthermore, when stage IIIB or stage IV NSCLC patients harboring a sensitive epidermal growth factor receptor (EGFR) gene mutation were treated with gefitinib, MST lengthened to 21.6 to 38.8 months.⁷ x 7 Yang, CH, Fukuoka, M, Mok, TS et al. Final overall survival (OS) results from a phase III, randomised, open-label, first-line study of gefitinib (G) v carboplatin/paclitaxel (C/P) in clinically selected patients with advanced nonsmall cell lung cancer (NSCL) in Asia (IPASS). Ann Oncol. 2010; 21: LBA 2 Google Scholar See all References ^{, 8} x 8 Inoue, A, Kobayashi, K, Maemondo, M et al. Final overall survival results of NEJ002, a phase III trial comparing gefitinib to carboplatin (CBDCA) plus paclitaxel (TXL) as the first-line treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. ASCO Meeting Abstracts. 2011; 29: 7519 Google Scholar See all References ^{, 9} x 9 Mitsudomi, T, Morita, S, Yatabe, Y et al. Updated overall survival results of WJTOG 3405, a randomized phase III trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer harboring mutations of the epidermal growth factor receptor (EGFR). ASCO Meeting Abstracts. 2012; 30: 7521 Google Scholar See all References On the other hand, for patients in limited stage (LD) small-cell lung cancer (SCLC), the MST is approximately 2 years.¹⁰ x 10 Noda, K, Nishiwaki, Y, Kawahara, M..., and Japan Clinical Oncology Group. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002; 346: 85–91 Crossref | PubMed | Scopus (1042) | Google Scholar See all References ,¹¹ x 11 Hanna, N, Bunn, PA Jr, Langer, C et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006; 24: 2038–2043 Crossref | PubMed | Scopus (436) | Google Scholar See all References For patients with extensive stage (ED) SCLC, survival is much more limited, ranging from 9.3 to 12.8 months.¹² x 12 Turrisi, AT 3rd, Kim, K, Blum, R et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999; 340: 265–271 Crossref | PubMed | Scopus (991) | Google Scholar See all References ,¹³ x 13 Takada, M, Fukuoka, M, Kawahara, M et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002; 20: 3054–3060 Crossref | PubMed | Scopus (439) | Google Scholar See all References Accordingly, the chance of developing BM has increased, both in advanced NSCLC and LD-SCLC.

The unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates ongoing control measures. Given its rapid spread, the new Omicron subvariant BA.5 requires urgent characterization. Here, we comprehensively analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1. Although in vitro growth kinetics of BA.5 was comparable among the Omicron subvariants, BA.5 was much more fusogenic than BA.1 and BA.2. Airway-on-a-chip analysis showed that, among Omicron subvariants, BA.5 had enhanced ability to disrupt the respiratory epithelial and endothelial barriers. Furthermore, in our hamster model, in vivo pathogenicity of BA.5 was slightly higher than that of the other Omicron variants and less than that of ancestral B.1.1. Notably, BA.5 gains efficient virus spread compared with BA.1 and BA.2, leading to prompt immune responses. Our findings suggest that BA.5 has low pathogenicity compared with the ancestral strain but enhanced virus spread /inflammation compared with earlier Omicron subvariants.

Purpose: Predictive value and accuracy of the acute pain trajectory were compared with those of pain intensity at 1 day after the surgery for pain prevalence at 6 months after the surgery. Materials and methods: Female patients scheduled for breast cancer surgery were eligible for this study. Patients were questioned about pain intensity daily during the 7 days after surgery. Presence of pain, its location, and intensity as well as the Japanese version of the quality of the recovery-40 (QOR-40) were determined in an interview prior to and at 6 months after the surgery. Acute pain trajectory was determined by a group-based trajectory modeling analysis that was based on the pain intensity at 1–7 days after surgery. Predictive value of the acute pain trajectory for the presence of pain at 6 months after the surgery was assessed by a logistic regression model. The predictive value was compared with pain intensity at 1 day after the surgery. Results: A total of 123 participants completed the 6-month follow-up. The three-cluster model (mild, moderate, and severe pain) was considered to be the most statistically appropriate model for the acute pain trajectory. After 6 months, 51.2% and 8.9% of participants reported pain and severe pain, respectively. Presence of pain at 6 months after the surgery was associated with poor recovery. The severe pain cluster was significantly associated with the presence of pain at 6 months after the surgery (adjusted odds ratio, 9.40; P<0.001 vs mild pain cluster). Conclusion: Classification of patients according to the acute pain trajectory, when compared with the classification according to pain intensity at 1 day after the surgery, made it possible to predict with better precision those patients who will develop persistent postsurgical pain.