Detection and prognostic relevance of circulating tumour cells (CTCs) in Asian breast cancers using a label-free microfluidic platform.

OBJECTIVES: We aimed to study the prevalence of CTCs in breast cancer (BC) patients undergoing neoadjuvant or palliative therapy with a label-free microfluidic platform (ClearCell FX), and its prognostic relevance in metastatic BC (mBC). MATERIALS AND METHODS: Peripheral blood samples were collected from 108 BC patients before starting a new line of treatment ("baseline"), majority of whom had mBC (76/108; 70.4%). CTCs were retrieved by dean flow fractionation that enriched for larger cells, and enumerated using immunofluorescence-based staining. Progression-free survival (PFS) in mBC patients was analysed using Kaplan-Meier method; cox proportional hazard models were used for univariable and multivariable analyses. RESULTS: The detection rate of CTCs before starting a new line of treatment was 75.9% (n = 108; median: 8 CTCs/7.5 ml blood) at a cut off of ≥2 CTCs. PFS was inferior for mBC patients with baseline CTC count ≥5 CTCs/7.5 ml blood vs. those with < 5 CTCs/7.5 ml blood (median PFS: 4.3 vs. 7.0 months; p-value: 0.037). The prognostic relevance of CTCs was most significant in patients with HER2- mBC (median PFS: 4.1 vs. 8.3 months; p-value: 0.032), luminal (HR+HER2-) subtype (median PFS: 4.2 vs. 8.3 months; p-value: 0.048), and patients who had one or more prior treatments (median PFS: 4.2 vs. 7.0 months; p-value: 0.02). On multivariable analysis, baseline CTC level (hazard ratio (HR): 1.84, p-value: 0.02) and pre-treatment status (HR: 1.87, p-value: 0.05) were independent predictors of PFS. CONCLUSIONS: This work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform.

Validation of a Risk Score Incorporating Tumor Characteristics into the American Joint Committee on Cancer Anatomic Stage for Breast Cancer.

PURPOSE: The American Joint Committee on Cancer 8th edition (AJCC8) prognostic stage (PS) was implemented January 1, 2018, but it is complex due to multiple permutations. A North American group proposed a simpler system using the anatomic stage with a risk score system (RSS) of 1 point each for grade 3 tumor and human epithelial growth factor receptor 2 (HER2) and estrogen receptor (ER) negativity. Here we aimed to evaluate this risk score system with our database of Asian breast cancer patients and compare it against the AJCC8 PS. METHODS: Patients diagnosed with breast cancer stage I-IV in 2006-2012 were identified in the SingHealth Joint Breast Cancer Registry. Five-year breast cancer-specific survival (CSS) and overall survival (OS) were calculated for each anatomic stage according to the risk score and compared with the AJCC8 PS. RESULTS: A total of 6,656 patients were analyzed. The median follow-up was 61 (interquartile range, 37-90) months. There was a high receipt of endocrine therapy (84.6% of ER+ patients), chemotherapy (84.3% of node-positive patients), and trastuzumab (86.0% of HER2+ patients). Within each anatomic stage, there were significant differences in survival in all sub-stages except IIIB. On multivariate analysis, the hazard ratio for negative ER was 1.74 (1.48-2.06), for negative HER2 was 1.49 (1.26-1.74), and for grade 3 was 1.84 (1.55-2.19). On multivariate analysis controlled for age, ethnicity, and receipt of chemotherapy, the RSS (Akaike information criterion [AIC] = 10,649.45; Harrell's Concordance Index [C] = 0.85) was not inferior to the AJCC8 PS (AIC = 10,726.65; C = 0.84) for CSS, nor was the RSS (AIC = 14,714.4; C = 0.82) inferior to the AJCC8 PS (AIC = 14,784.69; C = 0.81) for OS. CONCLUSION: The RSS is comparable to the AJCC8 PS for a patient population receiving chemotherapy as well as endocrine- and HER2-targeted therapy and further stratifies stage IV patients.

Medication Safety: A Need to Relook at Double-Checking Medicines?

OBJECTIVE: To present a structured evaluation process that provides evidence that the single-checking (SC) system is not only a viable option in reducing medication errors, but also has the added advantage of increasing staff satisfaction. METHODS: The structured evaluation involved one work improvement process and conducting a survey establishing registered nurses' (RNs') attitude toward SC of medicines. The survey questionnaire included 12 questions with a 5-point Likert scale. RESULTS: In spite of the increased number of patients, the number of medication errors actually reduced (P < 0.001; two-sample test of proportions) with the implementation of SC of medication for competent and experienced staff. A survey was conducted to establish RNs' attitudes toward SC of medicines 3 years post SC implementation. RNs viewed the single-nurse checking protocol positively. In particular, the nurses considered single-nurse checking as an encouragement to update their drug knowledge and as a time-saving measure, enhancing the quality of patient care. Nonetheless, they also expressed concerns on single-nurse checking. CONCLUSIONS: The findings provide evidence that SC system is a viable way to reducing medication errors and also confer the added advantage of staff satisfaction. Assuring quality and safety involves the need to challenge the status quo based on revealed evidence.

Impact of comorbidity on tolerability and survival following curative intent intensity modulated radiotherapy in older patients with nasopharyngeal cancer.

OBJECTIVE: This study aimed to evaluate the predictive factors for survival and acute toxicities in older patients with NPC treated with curative intent IMRT. MATERIALS AND METHODS: Older patients aged 65 years and above with non-metastatic NPC treated with curative intent IMRT between 2003 and 2013 were retrospectively analysed. Variables examined were gender, age, overall stage, chemotherapy use, Eastern Cooperative Oncology Group (ECOG) performance status and comorbidity. The comorbidity severity was determined by adult comorbidity evaluation (ACE-27). We considered hospitalization or placement of feeding tube during and up to one month post radiotherapy as surrogate endpoint for significant acute toxicities. Other endpoints examined were: OS (overall survival), DFS (disease free survival), DSS (disease specific survival). RESULTS: A total of 185 patients were eligible for analysis. Median age was 70 (65-86 years). Most of the patients presented with Stage III and IVA/B (n = 127, 68.7%), of good performance status of ECOG 0-1 (n = 176, 95.1%) and had low comorbidities with ACE-27 score of 0-1 (n = 141, 76.2%). Chemotherapy was delivered to 84 patients (45.4%). OS, DFS, and DSS were 64.5%, 51.4%, and 72.8% respectively. High comorbidity burden but not chemotherapy had significant impact on OS and DFS in patients with advanced stage. Fifty patients (27%) required tube feeding or hospitalization during the course of RT. Males, chemotherapy use and ECOG score ≥2 were significant predictors of tube feeding or hospitalization during RT. CONCLUSION: Curative IMRT was associated with excellent survival outcomes in older patients with NPC. Comorbidity but not chemotherapy was associated with prognosis in advanced stage. Careful monitoring and intensive support should be instituted in older males with ECOG score ≥2 receiving chemo-radiotherapy.