CT Radiomics for Predicting Pathological Complete Response of Axillary Lymph Nodes in Breast Cancer After Neoadjuvant Chemotherapy: A Prospective Study.

BACKGROUND: The diagnostic effectiveness of traditional imaging techniques is insufficient to assess the response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC), especially for pathological complete response (pCR). A radiomics model based on computed tomography (CT) could be helpful. PATIENTS AND METHODS: Prospective consecutive breast cancer patients with positive axillary LNs initially were enrolled, who received NAC prior to surgery. Chest contrast-enhanced thin-slice CT scan was performed both before and after the NAC (recorded as the first and the second CT respectively), and on both of them, the target metastatic axillary LN was identified and demarcated layer by layer. Using pyradiomics-based software that was independently created, radiomics features were retrieved. A pairwise machine learning workflow based on Sklearn (https://scikit-learn.org/) and FeAture Explorer was created to increase diagnostic effectiveness. An effective pairwise auto encoder model was developed by the improvement of data normalization, dimensionality reduction, and features screening scheme as well as the comparison of the prediction effectiveness of the various classifiers. RESULTS: A total of 138 patients were enrolled, and 77 (58.7%) in the overall group achieved pCR of LN after NAC. Nine radiomics features were finally chosen for modeling. The AUCs of the training group, validation group, and test group were 0.944 (0.919-0.965), 0.962 (0.937-0.985), and 1.000 (1.000-1.000), respectively, and the corresponding accuracies were 0.891, 0.912, and 1.000. CONCLUSION: The pCR of axillary LNs in breast cancer following NAC can be precisely predicted using thin-sliced enhanced chest CT-based radiomics.

Preoperative MRI features predict failed breast-conserving surgery: construction of a predictive model.

Background: Breast-conserving surgery (BCS) is the preferred method for early breast cancer, and the accurate preoperative prediction of the feasibility of BCS can formulate the surgical plan and reduce the violation of the patient's will. The present study proposed to explore the preoperative magnetic resonance imaging (MRI) features associated with failed BCS and constructed an MRI-based model to predict BCS. Methods: This retrospective study included patients between March 2015 and July 2016, who planned to undergo BCS, had preoperative MRI examination, and had at least 2 years of follow-up. A total of 30 patients with failed BCS were identified and matched with 90 patients with successful BCS (ratio 1:3) according to age, neoadjuvant therapy, and hormone receptor expression. The patients were divided into the training group for model construction and the testing group for model validation. The MRI features, including the site of the tumor, the lesion type, and the lesion and breast volume, were compared between failure and successful BCS groups. A multivariate logistic model for predicting failed BCS was constructed using independent factors associated with failed BCS from the training group and was evaluated in the testing group. The performance of the model was evaluated using the receiver operating characteristic (ROC) curve. Results: The mean age of the cohort was 45.7±10.3 years. A significantly more non-mass lesion and multifocality, the larger volume of lesion, and the ratio of lesion and breast volume were observed in failed BCS group compared to the successful BCS group. The ratio of lesion and breast volume and multifocality were independent factors associated with failed BCS, odds ratios were 1.044 (95% CI: 1.016-1.074) and 11.161 (95% CI: 1.739-71.652), respectively. An MRI-based model for predicting failed BCS was established, the area under the ROC curves in the training and testing group were 0.902 and 0.821, respectively. Conclusions: This model might help clinicians predict failed BCS preoperatively and make an accurate surgical strategy.

Predictive value of DCE-MRI for early evaluation of pathological complete response to neoadjuvant chemotherapy in resectable primary breast cancer: A single-center prospective study.

OBJECTIVE: This study proposed to establish a predictive model using dynamic enhanced MRI multi-parameters for early predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: In this prospective cohort study, 170 breast cancer patients treated with NAC were enrolled and were randomly grouped into training sample (136 patients) and validation sample (34 patients). DCE-MRI parameters achieved at the end of the first cycle of NAC were screened to establish the predictive model by using multivariate logistic regression model according to pCR status. Receiver operating characteristic curves were conducted to assess the predictive capability. The association between MRI-predicted pCR and actual pCR in survival outcomes was estimated by using the Kaplan-Meier method with log-rank test. RESULTS: Multivariate analysis showed ΔAreamax and ΔSlopemax were independent predictors for pCR, odds ratio were 0.939 (95%CI, 0.915 to 0.964), and 0.966 (95%CI, 0.947 to 0.986), respectively. A predictive model was established using training sample as "Y = -0.063*ΔAreamax - 0.034*ΔSlopemax", a cut-off point of 3.0 was determined. The AUC for training and validation sample were 0.931 (95%CI, 0.890-0.971) and 0.971 (95%CI, 0.923-1.000), respectively. MRI-predicted pCR patients showed similar RFS (p = 0.347), DDFS (p = 0.25) and OS (p = 0.423) with pCR patients. CONCLUSION: The multi-parameter MRI model can be potentially used for early prediction of pCR status at the end of the first NAC cycle, which might allow timely regimen refinement before definitive surgical treatment.

[Reliability of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression in breast cancer evaluated by immunohistochemistry].

OBJECTIVE: To evaluate the reliability of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression in breast cancer by immunohistochemistry and discuss their influencing factors. METHODS: The pretreatment biopsy specimens were collected from 148 patients (from Beijing Cancer Hospital between 2004 to 2010) with invasive breast cancer. After reslicing and staining (ER:SP1, PR: 1E2, HER-2: 4B5), the status of ER, PR and HER-2 was analyzed by a pathological expert with automated imaging system Ariol MB-8. And their results were compared with the original reports. RESULTS: The concordance rates between original reports and automated image system were ER:76.35%, PR:49.32%, HER-2:63.51% while Kappa values 0.12 (P = 0.020) , 0.18 (P = 0.002) and 0.08 (P = 0.200) respectively. And the concordance rates between expert reports and automated image system were ER:93.92%, PR:81.08% and HER-2:76.35% while Kappa values 0.77 (P < 0.001) , 0.67 (P < 0.001) and 0.32 (P < 0.001) respectively. CONCLUSION: For the expressions of ER, PR and HER-2, the disaccording results of original reports and automated image system may be mainly due to the differences of antibodies, staining methods and interpretations.

[Analysis of associations between molecular subtypes and responses to neoadjuvant chemotherapy in primary breast cancer patients].

OBJECTIVE: To explore the correlations between molecular subtypes and responses to neoadjuvant chemotherapy in primary breast cancer patients. METHODS: The core-needle biopsy specimens were collected from 563 patients undergoing 4-8 cycles of neoadjuvant chemotherapy between January 2001 to January 2009. And immunohistochemical assays were employed to detect the levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 proliferation index simultaneously. Molecular subtypes were divided on the basis of immunohistochemical results. And the associations between molecular subtypes and responses to neoadjuvant chemotherapy were analyzed in 563 patients. RESULTS: The pathological complete response (pCR) rates of patients with hormone receptor-negative/HER2-negative subtype (HR-/HER2-) , HER2-positive subtype (HER2+) and hormone receptor-positive/HER2-negative subtype (HR+/HER2-) were 38.9%, 17.9% and 8.3% respectively. In univariate analysis, there were significant differences in pCR rates among the groups (P < 0.001) . In multivariate analysis, the patients with HER2+ subtype had a significantly higher pCR rate than those with HR+/HER2- subtype (OR = 0.344, P = 0.002) . Whereas the patients with HER2+ subtype had a significantly lower pCR rate than those with HR-/HER2- subtype (OR = 2.453, P = 0.007) . Among HR+/HER2-subtypes, a higher pCR rate was observed in the group of high expression level of Ki-67 proliferation index (Ki-67 ≥ 20%) (P = 0.004) . But no significant differences existed in pCR rates between the group of high expression level of hormone receptor and the group of non-high expression level (P = 0.256) . CONCLUSION: There were correlations between molecular subtypes and responses to neoadjuvant chemotherapy in primary breast cancer patients. Patients of HER2+and HR-/HER2- subtype are more likely to respond to neoadjuvant chemotherapy. Among HR+/HER2-subtypes, those with a high level of Ki-67 proliferation index tend to benefit from neoadjuvant chemotherapy.

[Safety of omitting axillary lymph node dissection in primary breast cancer patients with negative sentinel lymph nodes].

OBJECTIVE: To explore the safety of omitting axillary lymph node dissection (ALND) in primary invasive breast cancer patients with negative sentinel lymph nodes (SLN). METHODS: Between June 2005 and June 2011, all SLN negative patients omitting ALND were analyzed retrospectively. They were all primary invasive breast cancer patients without clinic cytological evidence of axillary node involvement. SLN biopsy was performed prior to systemic treatment. And the tracer was (99)Tc(m) labeled Rituximab. RESULTS: A total of 1807 eligible patients were enrolled. Their median age was 50 years (21-87). And the median number of SLN was 2. The patients of T1, T2 and T3 were 1069 (59.2%), 712 (39.4%) and 26 (1.4%) respectively. After a median follow-up of 36 months, 14 (0.77%) cases of ipsilateral axillary recurrence were observed. Among them, 10 (0.55%) had single axillary recurrence. Second primary cancer occurred in 22 patients (1.2%). And distant metastases were found in 26 patients (1.4%). The 3-year axillary recurrence rate was 0.7%, disease-free survival 96.4% (95%CI 95.4%-97.4%) and recurrence-free survival 97.1% (95%CI 96.1%-98.1%). CONCLUSION: The omitting of ALND is safe in breast cancer patients with negative SLN.

[Survival analysis for different molecular subtypes of breast cancers after treatment].

OBJECTIVE: To explore the survival status after treatment for patients with different molecular subtypes of breast cancers. METHODS: A total of 4491 patients with invasive breast cancer from January 2000 to July 2011 were retrospectively recruited to receive pathological verification and treatment at our clinic. According to the immunohistochemical results of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2), they were assigned into 3 groups of HR+/HER2-, HER2+ and HR-/ HER2-. Survival analyses were conducted to examine the effects of molecular subtypes and lymph node status on survival. RESULTS: The 3-year recurrence free survival for HR+/HER2-, HER2+ and HR-/HER2- were 94.9%, 89.5% ane 92.3% respectively. Different molecular subtypes presented different survival patterns (P = 0.0001). The 3-year recurrence-free survival (RFS) for LN+ and LN- was 87.1% and 97.8% respectively. And statistical difference existed (P < 0.01). No difference was detected among three molecular subtypes of LN- (P = 0.102); However, for LN+ patients, HR+/HER2- showed a higher RFS than HER2+ and HR-/HER2 (P = 0.001). CONCLUSION: Different molecular subtypes of breast cancers have varying survival. And lymph node status is probably an important prognostic factor.

[Diagnostic value and health economic evaluation of ultrasound-combined fine-needle aspiration cytology in primary breast cancer].

OBJECTIVE: To explore the diagnostic value and health economic evaluation of ultrasound-combined fine-needle aspiration cytology for axillary lymph node status in breast cancer. METHODS: We reviewed retrospectively collected the data from 2503 cases of biopsy-proved breast cancer (T0-2) at our breast center between May 2005 and June 2010. The diagnostic fees of ultrasound-combined fine-needle aspiration cytology and clinical examination were calculated and assessed with cost-minimization analysis. RESULTS: Ultrasound-combined fine-needle aspiration cytology prevented 10.9 percent of the patients with positive clinical findings from unnecessary sentinel lymph node biopsy and achieved a saving of 155.55 RMB per patient. However, only 29.4 percent of the cases were diagnosed with ultrasonographic abnormal axillary nodes. CONCLUSIONS: Ultrasound-combined fine-needle aspiration cytology has great application values. The ultrasonic diagnostic criteria of abnormal axillary nodes should be loosened.

[Impact of response of positive axillary nodes to neoadjuvant chemotherapy on breast cancer survival].

OBJECTIVE: To compare the distant disease-free survival between breast cancer patients with nodal pathological complete response (pCR) and those with nodal residual disease (RD) after neoadjuvant chemotherapy. METHODS: The clinical and pathological data of 376 needle biopsy proved node positive breast cancer patients undergoing neoadjuvant chemotherapy were retrospectively analyzed. RESULTS: The median follow-up time was 24 months (range: 5 - 100). The pCR rate of axillary lymph node was 30.9%. And the three-year distant disease-free survival (DDFS) rates were 91.7% and 78.8% in the patients with axillary lymph node pCR and RD respectively. According to the Log-rank test, there were significant differences in survival curves (P = 0.016). Multivariate analysis showed that the relative risk of DDFS for patients with RD was 2.14 folds of than that of the pCR group (P = 0.047). No significant difference existed between the disease-free survival (DFS) curve in two groups. DDFS had significant differences between the patients with the number of lymph node metastasis ≤ 3 and ≥ 4 in the RD group (P = 0.001). CONCLUSION: The distant disease-free survival of node positive breast cancer is associated with the status of axillary lymph node after neoadjuvant chemotherapy.

[Fatality and secular trend of bloodstream infections during hospitalization in China: a systematic review and meta-analysis].

OBJECTIVE: To get an overview of the fatality and secular trend of bloodstream infection (BSI) during hospitalization in China. METHODS: Papers published between 1990 and Aug. 2008 on the core journals included by Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and VIP Chinese Periodical Database were systematically searched. Studies providing data of BSI fatality during hospitalization with a non-comparative, observational design were included. Meta-analysis was done using the generic inverse variance model. RESULTS: Overall, 72 studies were included for this analysis. The weighted BSI fatality in-hospital based on them was 28.7% (95%CI: 27.2%-30.3%), with substantial differences between study and heterogeneity. For BSI cases from across all departments of hospitals, the weighed fatality was 20.7% (95%CI: 17.8%-24.0%). In the departments of burn, hematology and/or malignant tumors, and ICU, BSI fatalities were even higher, but were relatively low among BSI cases from neonatal wards, and patients with liver diseases, or diabetes mellitus. Fatality of hospital acquired BSI (HA-BSIs, 26.8%, 95%CI: 22.4%-32.0%) was significantly higher than that of community acquired BSI (CA-BSIs). For the past decades, BSI fatality has declined in various kinds of inpatients. CONCLUSION: BSI fatality during hospitalization was at a high level in China, but with a downward trend over the past decades.

Design of the anti-tuberculosis drugs induced adverse reactions in China National Tuberculosis Prevention and Control Scheme Study (ADACS).

BACKGROUND: More than 1 million tuberculosis (TB) patients are receiving the standard anti-TB treatment provided by China National Tuberculosis Prevention and Control Scheme (CNTS) in China every year. Adverse reactions (ADRs) induced by anti-TB drugs could both do harm to patients and lead to anti-TB treatment failure. The ADACS aimed to explore ADRs' incidences, prognoses, economical and public health impacts for TB patients and TB control, and build a DNA bank of TB patients. METHODS/DESIGN: Multiple study designs were adopted. Firstly, a prospective cohort with 4488 sputum smears positive pulmonary tuberculosis patients was established. Patients were followed up for 6-9 months in 52 counties of four regions. Those suspected ADRs should be checked and confirmed by Chinese State Food and Drug Administration (SFDA). Secondly, if the suspected ADR was anti-TB drug induced liver injury (ATLI), a nested case-control study would be performed which comprised choosing a matched control and doing a plus questionnaire inquiry. Thirdly, health economical data of ADRs would be collected to analyze financial burdens brought by ADRs and cost-effectiveness of ADRs' treatments. Fourthly, a drop of intravenous blood for each patient was taken and saved in FTA card for DNA banking and genotyping. Finally, the demographic, clinical, environmental, administrative and genetic data would be merged for the comprehensive analysis. DISCUSSION: ADACS will give an overview of anti-TB drugs induced ADRs' incidences, risk factors, treatments, prognoses, and clinical, economical and public health impacts for TB patients applying CNTS regimen in China, and provide suggestions for individualized health care and TB control policy.