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Simple Summary: In this two-part study, we assessed the risk factors associated with FN. On top of commonly associated risk factors such as age and body mass index, we found that there are ethnic differences in terms of FN incidence. Notably, patients of non-Chinese ethnicity had a higher FN incidence. This trend remained significant even after multiple adjustments with other patients, tumors, and treatment characteristics. Further analysis exploring differences across ethnicities revealed that Indian patients were more likely to experience greater dips in absolute neutrophil count during chemotherapy and Malay patients were more likely to be administered with anthracyclines, both of which contribute to higher FN risk. Importantly, we also found that non-Chinese patients were more likely to experience multiple FN episodes during chemotherapy. Additional research is needed to investigate the possibility of pharmacogenetic differences across these ethnicities. The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first FN from the start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in various characteristics across ethnicities. FN was observed in 170 of 1014 patients in SGBCC. The Cox model showed that non-Chinese were at higher risk of developing FN (HRMalay [95% CI]:2.04 [1.44–2.88], p < 0.001; HRIndian:1.88 [1.11–3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients. Univariable Cox models identified ethnicity, a lower baseline absolute neutrophil count, non-luminal A proxy subtypes, and anthracycline-containing regimens as risk factors. Disparities across ethnicities' risk (HRMalay:1.29 [1.07–1.54], p = 0.006; HRIndian:1.50 [1.19–1.88], p < 0.001) remained significant even after further adjustments. Finally, an age-adjusted multinomial model showed that Malays (p = 0.006) and Indians (p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Ethnic differences in chemotherapy-induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the cost-effectiveness of pertuzumab with trastuzumab biosimilar and docetaxel as initial treatment for HER2-positive metastatic breast cancer (MBC) in Singapore.Methods: A partitioned survival model with three health states was developed to evaluate the cost-effectiveness of trastuzumab biosimilar and docetaxel with or without pertuzumab from a healthcare system perspective over a 15-year time horizon for patients with HER2-positive MBC. Key clinical inputs were derived from the CLEOPATRA trial. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions.Results: The base-case resulted in an incremental cost-effectiveness ratio (ICER) of SGD366,658 (USD272,244) per quality-adjusted life-year (QALY) gained. One-way sensitivity analyses showed that the ICER was sensitive to utilities in the progression-free state, price of pertuzumab and time horizon. When the price for trastuzumab reference biologic (branded) was applied, the ICER was even higher (SGD426,996 [USD317,045]/QALY).Conclusion: Although trastuzumab biosimilar reduced the cost of the pertuzumab combination regimen, the ICER remained high and was not cost effective in Singapore's context. As pertuzumab contributed 80% of the overall combination treatment cost, price reductions for pertuzumab will be required to improve the cost-effectiveness of combination treatment to an acceptable level. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the improvements in the survival rates observed in various types of cancer in recent years, the mortality rates remain high in ovarian cancer. This is primarily caused by the advanced disease stage at presentation and the lack of effective screening methods. An important clinical objective is represented by the ability to perform a post-surgical risk stratification to identify better and more effective intervention strategies to minimize recurrence and maximize survival. Here, we sought to leverage the availability of publicly available ovarian cancer RNA sequencing data and the use of bioinformatics methods to identify a prognostic gene panel in non-metastatic high-grade serous ovarian carcinoma. Moreover, we found an association between mortality rates and tumor-infiltrating immune cells. Ovarian cancer is the eighth global leading cause of cancer-related death among women. The most common form is the high-grade serous ovarian carcinoma (HGSOC). No further improvements in the 5-year overall survival have been seen over the last 40 years since the adoption of platinum- and taxane-based chemotherapy. Hence, a better understanding of the mechanisms governing this aggressive phenotype would help identify better therapeutic strategies. Recent research linked onset, progression, and response to treatment with dysregulated components of the tumor microenvironment (TME) in many types of cancer. In this study, using bioinformatic approaches, we identified a 19-gene TME-related HGSOC prognostic genetic panel (19 prognostic genes (PLXNB2, HMCN2, NDNF, NTN1, TGFBI, CHAD, CLEC5A, PLXNA1, CST9, LOXL4, MMP17, PI3, PRSS1, SERPINA10, TLL1, CBLN2, IL26, NRG4, and WNT9A) by assessing the RNA sequencing data of 342 tumors available in the TCGA database. Using machine learning, we found that specific patterns of infiltrating immune cells characterized each risk group. Furthermore, we demonstrated the predictive potential of our risk score across different platforms and its improved prognostic performance compared with other gene panels. [ABSTRACT FROM AUTHOR]

Previous efforts to derive lung progenitor cells from human embryonic stem (hES) cells using embryoid body formation or stromal feeder cocultures had been limited by low efficiencies. Here, we report a step-wise differentiation method to drive both hES and induced pluripotent stem (iPS) cells toward the lung lineage. Our data demonstrated a 30% efficiency in generating lung epithelial cells (LECs) that expresses various distal lung markers. Further enrichment of lung progenitor cells using a stem cell marker, CD166 before transplantation into bleomycin-injured NOD/SCID mice resulted in enhanced survivability of mice and improved lung pulmonary functions. Immunohistochemistry of lung sections from surviving mice further confirmed the specific engraftment of transplanted cells in the damaged lung. These cells were shown to express surfactant protein C, a specific marker for distal lung progenitor in the alveoli. Our study has therefore demonstrated the proof-of-concept of using iPS cells for the repair of acute lung injury, demonstrating the potential usefulness of using patient's own iPS cells to prevent immune rejection which arise from allogenic transplantation. [ABSTRACT FROM AUTHOR]

Ovarian clear cell carcinoma (CCC) has an East Asian preponderance. It is associated with endometriosis, a benign condition where endometrial (inner lining of the uterus) tissue is found outside the uterus and on the peritoneal surface, in the abdominal or pelvic space. CCC is relatively more resistant to conventional chemotherapy compared to other ovarian cancer subtypes and is associated with a poorer prognosis. In this study, we recruited and obtained tumour tissues from seven patients across the four stages of CCC. The tumour and the tumour microenvironment (TME) from 7 CCC patients spanning clinical stages 1-4 were transcriptionally profiled using high-resolution scRNA-seq to gain insight into CCC's biological mechanisms. Firstly, we built a scRNA-seq resource for the CCC tumour microenvironment (TME). Secondly, we identified the different cell type proportions and found high levels of immune infiltration in CCC. Thirdly, since CCC is associated with endometriosis, we compared CCC with two publicly available endometriosis scRNA-seq datasets. The CCC malignant cells showed similarities with glandular secretory and ciliated epithelial cells found in endometriosis. Finally, we determined the differences in cell-cell communication between various cell types present in CCC TME and endometriosis conditions to gain insights into the transformations in CCC., Competing Interests: Conflict of interest statement None declared.