Establishment and Validation of Nomogram Based on Combination of Pretreatment C-Reactive Protein/Albumin Ratio-EBV DNA Grade in Nasopharyngeal Carcinoma Patients Who Received Concurrent Chemoradiotherapy.

BACKGROUND: A higher ratio of pretreatment C-reactive protein/albumin ratio (CAR) is associated with poor prognosis in nasopharyngeal carcinoma (NPC), and Epstein-Barr virus (EBV) DNA level is known to not only participate in the occurrence of nasopharyngeal carcinoma but also affect the development and prognosis of the disease. Herein, we proposed that a combination of both these markers could improve the predictive prognostic ability. METHODS: In all, 842 NPC patients who received concurrent chemoradiotherapy (CCRT) were entered in this study. We collected all patients' blood samples and EBV DNA copy numbers within one week before any treatment. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off. We employed the Kaplan-Meier method for survival analyses and the univariate and multivariate analyses (Cox proportional hazards regression model) for statistical analysis. A nomogram was constructed based on multivariate analyses results of the validation set. The model was internally validated using 1000 bootstrap samples to avoid overfitting. Another validation of 10-fold cross-validation was also applied. Calibration curves and concordance index (C-index) were calculated to determine predictive and discriminatory capacity. RESULTS: In the whole cohort, we observed that higher CAR, EBV DNA level, and CAR-EBV DNA (C-E) grade were associated with shorter overall survival (OS) and distant metastasis-free survival (DMFS) (all P<0.05). In univariate and multivariate analyses, C-E grade was an independent prognostic factor (all P<0.05). In the training set, we gained the similar results with the whole set. According to multivariate analyses of the training set, we constructed a nomogram. The results of bootstrap samples and 10-fold cross-validation showed favorable predictive efficacy. And calibration curves of the model provided credibility to its predictive capability. CONCLUSION: C-E grade was confirmed as an independent prognostic predictor in patients with NPC who received CCRT. Higher level of pretreatment C-E grade could signify a higher risk of metastasis and shorter OS. The prognostic nomogram based on C-E grade was dependable in nasopharyngeal carcinoma patients.

Establishment of Prognostic Nomograms for Predicting the Survival of HR-Positive, HER2-Negative Metastatic Breast Cancer Patients Treated with Everolimus.

BACKGROUND: There are no clinically available prognostic models for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer treated with everolimus. We aimed to develop a tool to predict the progression-free survival (PFS) and overall survival (OS) of these patients and to identify optimal candidates who would benefit from everolimus-based treatment in this heterogeneous patient population. METHODS: The clinical data of patients with HR+, HER2- metastatic breast cancer receiving everolimus between May 2012 and January 2018 at Sun Yat-sen University Cancer Center were retrospectively retrieved. Based on potential prognostic factors derived from multivariate Cox analysis, we established predictive nomogram models for PFS and OS and evaluated their predictive values by means of the concordance index (C-index). Calibration curves were used to estimate the consistency between the actual observations and the nomogram-predicted probabilities. RESULTS: A total of 116 patients with HR+, HER2- metastatic breast cancer were enrolled in this study. Three independent prognostic factors, including the line of everolimus in the metastatic setting, everolimus clinical benefit rate and number of liver metastatic lesions, were identified from the multivariate Cox analysis. Prognostic models for individual survival prediction were established and graphically presented as nomograms. The C-index was 0.738 (95% confidence interval [CI]: 0.710-0.767) for the PFS nomogram and 0.752 (95% CI: 0.717-0.788) for the OS nomogram, which showed favourable discrimination. The calibration curves for the probabilities of 6-, 9-, and 12-month PFS and 1-, 2-, and 3-year OS suggested satisfactory consistency between the actual observations and the predicted probabilities. CONCLUSION: We constructed convenient nomogram models for patients with HR+, HER2- metastatic breast cancer to individually predict their potential benefits from everolimus in the metastatic setting. The models showed good performance in terms of accuracy, discrimination capacity and clinical application value.

High-dose tamoxifen in high-hormone-receptor-expressing advanced breast cancer patients: a phase II pilot study.

BACKGROUND: Tumor progression following endocrine therapy is considered to indicate resistance to endocrine drugs due to a variety of mechanisms. An insufficient dose of endocrine drugs is one of the causes for treatment failure in some patients with high hormone-receptor (HR)-expressing advanced breast cancer. This study aimed to explore the efficacy of high-dose tamoxifen (TAM) treatment in patients with advanced breast cancer with highly expressed HR. MATERIALS & METHODS: This was a single-arm, phase II pilot study that enrolled patients with advanced breast cancer with high HR expression (estrogen receptor ⩾60% and/or progesterone receptor ⩾60%) following routine endocrine therapy. All enrolled patients received a high-dose of TAM (100 mg/day) until disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety. Exploratory endpoints included the predictive value of 16α-18F-17ß-fluoroestradiol quantitative positron emission tomography/computed tomography (18F-FES PET/CT) for treatment efficacy. RESULTS: A total of 30 patients were enrolled between September 2017 and February 2019. The median PFS was 6 months [95% confidence interval (CI) 4.9-7.1] and the median OS was 15.6 months (95% CI 8.3-22.9). Five patients experienced a partial response (PR) and none experienced a complete response (CR), with an ORR of 16.7% and CBR of 33.3%. No severe adverse events were observed. Lesions with 18F-FES maximum standardized uptake value (SUVmax) ⩾4 had a significantly longer PFS [median 9.2 months, (95% CI 6.9-11.6)] compared with lesions with a 18F-FES SUVmax <4 [median 4.8 months, (95% CI 3.9-5.6); p = 0.022]. CONCLUSION: A high-dose of TAM is effective and safe for patients with advanced breast cancer with high HR expression. 18F-FES SUVmax values may predict the local clinical benefits of high-dose TAM . TRIAL REGISTRATION: [ClinicalTrials.gov identifier: NCT0304565].

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial.

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.

Prognostic significance of the Controlling Nutritional Status (CONUT) score in surgically treated breast cancer patients.

BACKGROUND: Breast cancer is one of the most common malignancy in women with high mortality rate. Given the growing evidence shows that immune-inflammatory system influences the survival of patients with cancer, we assessed the prognostic significance of the preoperative Controlling Nutritional Status (CONUT) score in patients with breast cancer who underwent surgery. METHODS: We conducted a retrospective analysis of 1,367 breast cancer patients who underwent surgery between December 2010 and October 2012. All individual preoperative serum albumin concentration, total cholesterol concentration, and total peripheral lymphocyte count were counted to calculate CONUT. Higher CONUT score is in line with worse nutritional status. The optimal cut-off of CONUT score was set at 3 to categorize the investigated patients into two groups, namely a high- or low-CONUT score group. We adopted univariate and multivariate analyses (Cox proportional hazards regression model) statistical method. RESULTS: Patients in the high-CONUT score group had shorter overall survival (OS) and recurrence-free survival (RFS) in comparison with those in the low-CONUT score group, 66.43 vs. 69.30 months and 54.70 vs. 59.98 months respectively (all P value <0.05). Univariate and multivariate analyses revealed that the CONUT score was an independent predictor of OS (P=0.029 and 0.046, respectively) and RFS (P=0.001, P=0.013, respectively). CONCLUSIONS: The CONUT score was identified as an independent prognostic indicator in surgically treated breast cancer patients, indicating that, compared with the low CONUT score, a high CONUT score may lead to poorer prognosis.

The Prognostic Prediction Value of Systemic Inflammation Score and the Development of a Nomogram for Patients With Surgically Treated Breast Cancer.

Background: Systemic inflammation score (SIS) has been verified as a novel prognostic indicator in several cancer types. However, its prognostic value in breast cancer remains unknown. Furthermore, a nomogram based on SIS is yet to be constructed for breast cancer. We conducted this study to explore the association between SIS and prognosis of breast cancer, and to construct a good prognostic nomogram model. Methods: A total of 1,180 breast cancer patients who underwent curative surgery between December 2010 and January 2013 were recruited. They were randomly assigned to the training set (n = 944) or the validation set (n = 236). All patient blood samples were collected within 1 week prior to operation. According to previous reports, SIS was calculated for all patients, who were then classified into two groups: high-SIS and low-SIS. The Kaplan-Meier method was employed for survival analyses, and univariate and multivariate analyses (Cox proportional hazards regression model) were used for prognostic assessment. A nomogram was constructed based on the results of multivariate analysis. Calibration curves and concordance index (C-index) were compiled to determine predictive and discriminatory capacity. Results: In the training set, the median follow-up time was 6.07 years. Patients in the high-SIS group had an average OS time of 68.05 months, which is shorter than that of the low-SIS group (72.87 months; P = 0.033). Patients in the high-SIS group had average RFS and DMFS times of 56.04 and 54.46 months, respectively, which are shorter than those of the low-SIS group (60.85 and 59.47 months, respectively; P = 0.247 and P = 0.032). Univariate and multivariate analyses revealed SIS to be an independent prognostic factor for OS and DMFS time. The nomogram for the training set indicated OS and DMFS C-indexes of 0.794 (95% CI, 0.772-0.816) and 0.712 (95% CI, 0.684-0.740), respectively. In the validation set, the OS and DMFS C-indexes were 0.889 (95% CI, 0.845-0.933) and 0.696 (95%. CI, 0.611-0.781), respectively. Conclusions: SIS was confirmed as an independent prognostic predictor among patients with breast cancer who had undergone surgery with curative intent. Higher preoperative SIS may indicate higher risk of metastasis and shorter overall survival time. The prognostic nomogram based on SIS was dependable for breast cancer patients who underwent curative surgery.

Efficacy of Moxifloxacin plus Treatment of Physician's Choice in Patients with Metastatic Breast Cancer.

LESSONS LEARNED: Moxifloxacin plus continuation of the previous treatment of physician's choice shows promising efficacy in patients with metastatic breast cancer. The addition of moxifloxacin shows well-tolerated toxicities. BACKGROUND: Recent studies have confirmed bacterial infection as an important contributor in cancer. Elimination of tumor-associated microbes may lead to a reduction in tumors and improved survival. Moxifloxacin is an orally administrated fourth-generation quinolone with broad-spectrum coverage against tumor-associated bacteria. METHODS: In this study, we assessed the efficacy and safety of moxifloxacin in combination with treatment of physician's choice (TPC) in patients with metastatic breast cancer (MBC). In this single-arm, phase II study, we recruited 30 patients with MBC who had a trend toward disease progression (stable disease [SD] with increased tumor size) during TPC before enrollment at Sun Yat-sen University Cancer Center between January 1 and July 30, 2018. Eligible patients were given moxifloxacin once daily at a dose of 400 mg from days 1 to 7 of a 28-day cycle, in addition to continuing to receive the therapy previously selected by their physicians. Tumor response was determined according to RECIST (version 1.1). Progression-free survival (PFS) was calculated using the Kaplan-Meier method. RESULTS: The concomitant use of moxifloxacin and previous TPC yielded a median PFS of 6.6 months (95% confidence interval [CI]: 4.0-9.1) and a 1-year PFS of 25.9% (95% CI: 10.0%-41.9%). Objective responses were achieved in seven (23.3%, 95% CI: 7.3%-39.4%) patients. The clinical benefit rate was 46.7% (95% CI: 27.7%-65.6%). No grade 4 adverse events (AEs) and four grade 3 AEs were observed, none of which were considered to have definite relation to moxifloxacin. CONCLUSION: The combination of moxifloxacin with previous TPC shows promising efficacy and well-tolerated toxicities in patients with MBC.

The prognostic value of androgen receptor (AR) in HER2-enriched metastatic breast cancer.

The significance of androgen receptor (AR) in metastatic breast cancer (MBC) remains unclear, and it is still largely unknown how AR expression level influences HER2-positive tumors. This study aimed to investigate the prognostic and predictive value of AR in HER2-enriched MBC. Primary and/or paired metastatic tumors of 304 patients with pathologically confirmed HER2-enriched MBC were collected and immunohistochemically assessed for AR expression. The associations of AR and other clinicopathological characteristics were compared using the Chi-square test. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and log-rank test. Cox regression analysis was used to determine independent prognostic factors. AR-positivity with a cut-off value of 10% was observed in 237 (78.0%) cases and was associated with longer PFS, 13.2 months, as compared to that of 8.2 months (P = 0.004) in patients with AR-negativity. Moreover, a significant increase in the 5-year OS rate (65.3% vs 36.2%, P < 0.001) was also observed for patients with AR-positive tumors. Cox regression analysis identified AR-positivity as an independent prognostic factor of both PFS (hazard ratio = 0.71, P = 0.039) and OS (HR = 0.53, P = 0.013). Additionally, for those who received first-line Trastuzumab therapies, prolonged PFS (15.8 months vs 8.2 months, P = 0.005) and 5-year OS rate (66.2% vs 26.2%, P = 0.009) were observed in AR-positive tumors compared to AR-negative ones. In conclusion, AR was identified as an independent prognostic factor for favorable PFS and OS and could also predict the efficacy of first-line Trastuzumab treatment in patients with HER2-enriched MBC.