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Background and purpose: The incidence of ductal carcinoma in situ (DCIS) has increased annually with the popularity of mammography screening. However, current treatment strategies are mostly based on the results of prospective randomized clinical trials in western countries. This study aimed to explore the clinical characteristics, recurrence patterns and prognostic factors of Chinese DCIS patients, hoping to optimize clinical decision-making. Methods: Medical records of 1 185 DCIS patients treated in Fudan University Shanghai Cancer Center from January 2008 to January 2017 were retrospectively analyzed. The local recurrence-free survival (LRFS) rate, disease-free survival (DFS) rate and overall survival (OS) rate were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the COX proportional hazards regression model. Results: With a median follow-up of 61 months, 50 treatment failure events were observed, including 16 locoregional recurrences, 30 contralateral breast cancer events and 4 distant metastases. The 5-year OS rate, LRFS rate and DFS rate were 99.9%, 98.7% and 96.6%, respectively. In the multivariate analysis, the positive status of human epidermal growth factor receptor 2 (HER2) was related to higher risk of local recurrence and the LRFS rate was poor (P=0.029). Conclusion: The patient with DCIS was associated with favorable prognosis. HER2 positivity was the risk factor for poor LRFS.

Background: Breast cancer brain metastases (BCBM) are highly heterogenous with widely differing survival. The prognosis of the oligometastatic breast cancer (BC) patients with brain metastases (BM) has not been well studied. We aimed to investigate the prognosis of BCBM patients with limited intracranial and extracranial metastatic lesions. Methods: Four hundred and forty-five BCBM patients treated between 1st January 2008 and 31st December 2018 at our institute were included. Clinical characteristics and treatment information were obtained from patient's medical records. The updated breast Graded Prognostic Assessment (Breast GPA) was calculated. Results: The median OS after diagnosis of BM were 15.9 months. Median OS for patients with GPA 0–1.0, 1.5–2, 2.5–3 and 3.5–4 were 6.9, 14.2, 21.8, 42.6 months respectively. The total number of intracranial and extracranial metastatic lesions, in addition to the Breast GPA, salvage local therapy and systemic therapy (anti-HER2 therapy, chemotherapy and endocrine therapy) were demonstrated to be associated with prognosis. One hundred and thirteen patients (25.4%) had 1–5 total metastatic lesions at BM diagnosis. Patients with 1–5 total metastatic lesions had a significantly longer median OS of 24.3 months compared to those with greater than 5 total metastatic lesions with a median OS of 12.2 months (P < 0.001; multivariate HR 0.55, 95% CI, 0.43–0.72). Among the patients with 1–5 metastatic lesions, median OS for GPA 0–1.0 was 9.8 months, compared to 22.8, 28.8 and 71.0 for GPA 1.5–2.0, 2.5–3.0 and 3.5–4.0 respectively, which is much longer than the corresponding patients with greater than 5 total metastatic lesions, with medium OS of 6.8, 11.6, 18.6 and 42.6 months respectively for GPA 0–1.0, 1.5–2.0, 2.5–3.0 and 3.5–4.0. Conclusions: The patients with 1–5 total metastatic lesions demonstrated better OS. The prognostic value of the Breast GPA and the survival benefit of salvage local therapy and continuation of systemic therapy after BM were confirmed. [ABSTRACT FROM AUTHOR]

Background: Primary squamous cell carcinoma of the breast (PSCCB) is a rare clinical classification of breast tumors. Little is known about its clinicopathological features, prognosis and potential therapeutic strategies. The purpose of this study is to evaluate the effect of postoperative radiotherapy (PORT) on patients with squamous cell carcinoma (SCC) of the breast. Methods: We retrospectively analyzed patients diagnosed with PSCCB in our center. All pathological slides were reviewed by an experienced pathologist to confirm the diagnosis. Furthermore, we searched the public database for patients with SCC of the breast. Then, we analyzed the clinicopathological features, treatment methods and patient outcomes. Results: We identified 14 patients with primary SCC of the breast in our center. Additionally, 739 patients with SCC of the breast from the Surveillance, Epidemiology and End Results (SEER) database were diagnosed between 1975 and 2016. Only 453 patients who underwent surgery were included in this study. Patients from the SEER database had a more advanced tumor node metastasis (TNM) stage than patients from our center. The median overall survival (OS) of all patients was 104 months (95% confidence interval [CI], 87.2–120.8 months), and the 5‐year OS was 60.8% (95% CI, 56.1%–65.5%). Most of the patients (58%) tested negative for hormonal receptor expression. Multivariate analysis showed that PORT was an independent prognostic factor for OS. Conclusion: The results of our study demonstrate that SCC of the breast presents aggressive behavior with unique clinical characteristics. PORT improved OS significantly in patients with SCC of the breast. Longer‐term studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Ductal carcinoma in situ with microinvasion (DCISM) represents ~1% of all breast cancer cases and is arguably a more aggressive subtype of ductal carcinoma in situ (DCIS). Lacking studies with a large population, the survival outcomes of DCISM are still poorly understood and the treatment recommendations remain controversial. This study aims to investigate the long‐term outcome of patients with DCISM, potential risk factors for their prognosis, and the difference of survival between patients treated with breast‐conserving surgery plus radiotherapy (BCT + RT) and mastectomy only. Methods: In total, 1299 patients from 2008 to 2019 with DCISM were retrospectively retrieved. Clinicopathological features were analyzed. Subgroup analysis was conducted between patients who underwent BCT + RT and mastectomy only. Univariate and multivariate analyses were performed to identify prognostic factors for survival. Differences of survival between two groups were compared using the log‐rank test. Results: Totally, 1286 patients had follow‐up information, the median follow‐up is 54.57 months, the 5‐year local–regional‐free survival (LRFS), distant metastasis‐free survival (DMFS), and overall survival (OS) were 98.6%, 97.1%, and 99.4%, respectively, two deaths were due to breast cancer. Multivariate analysis identified age <40 (p = 0.028) and close margin (≤2 mm) as independent negative prognostic factors for LRFS. No prognostic factors were identified for DMFS and OS. The 5‐year LRFS, DMFS, and OS of patients who had DCIS component ≥5 cm and underwent mastectomy without adjuvant radiotherapy were 100%, 98.4%, and 98.4%, respectively. After propensity score matching (PSM), no survival difference was observed between patients treated with BCT + RT or mastectomy only. Conclusions: DCISM patients had a good survival, even those with DCIS component ≥5 cm. Patients aged <40 or with close margin (≤2 mm) had a poorer LRFS, but not DMFS or OS. BCT + RT is a feasible choice for DCISM patients. [ABSTRACT FROM AUTHOR]

Background: Knowledge-based planning (KBP) is a promising technique that can improve plan quality and increase planning efficiency. However, no attempts have been made to extend the domain of KBP for planners with different planning experiences so far. The purpose of this study was to quantify the potential gains for planners with different planning experiences after implementing KBP in intensity modulated radiation therapy (IMRT) plans for left-sided breast cancer patients.Methods: The model libraries were populated with 80 expert clinical plans from treated patients who previously received left-sided breast-conserving surgery and IMRT with simultaneously integrated boost. The libraries were created on the RapidPlanTM. 6 planners with different planning experiences (2 beginner planners, 2 junior planners and 2 senior planners) generated manual and KBP optimized plans for additional 10 patients, similar to those included in the model libraries. The plan qualities were compared between manual and KBP plans.Results: All plans were capable of achieving the prescription requirement. There were almost no statistically significant differences in terms of the planning target volume (PTV) coverage and dose conformality. It was demonstrated that the doses for most of organs-at-risk (OARs) were on average lower or equal in KBP plans compared to manual plans except for the senior planners, where the very small differences were not statistically significant. KBP data showed a systematic trend to have superior dose sparing at most parameters for the heart and ipsilateral lung. The observed decrease in the doses to these OARs could be achieved, particularly for the beginner and junior planners. Many differences were statistically significant.Conclusions: It is feasible to generate acceptable IMRT plans after implementing KBP for left-sided breast cancer. KBP helps to effectively improve the quality of IMRT plans against the benchmark of manual plans for less experienced planners without any manual intervention. KBP showed promise for homogenizing the plan quality by transferring planning expertise from more experienced to less experienced planners. [ABSTRACT FROM AUTHOR]

Aims To examine, in nasopharyngeal carcinoma ( NPC), the correlation of Krüppel-like factor 4 ( KLF4) expression with clinicopathological features including patient prognosis. Methods and results Using real-time PCR and immunohistochemistry, expression of KLF4 m RNA and protein was examined in NPC and nasopharyngeal tissues. The relationship of KLF4 expression levels with clinical features and prognosis of NPC patients was analysed. m RNA expression was markedly lower in NPC than in the nasopharyngeal tissues. Using immunohistochemistry, staining for KLF4 protein was found in the nuclei and cytoplasm of nasopharyngeal and malignant epithelial cells, but decreased cytoplasmic expression was observed in atypical hyperplasia and NPC samples compared to normal and squamous epithelium samples ( P < 0.001). In addition, levels of cytoplasmic KLF4 protein were correlated inversely with the nodal (N) status (T NM classification; P = 0.002) and overall clinical stage ( P < 0.001) of NPC patients. Patients with NPC showing lower cytoplasmic KLF4 expression had a significantly shorter overall survival time than those with high NPC KLF4 expression. Multivariate analysis suggested that the level of KLF4 expression was an independent prognostic indicator ( P = 0.008) for NPC survival. Conclusion Low levels of cytoplasmic KLF4 expression are a potentially unfavourable prognostic factor for patients with NPC. [ABSTRACT FROM AUTHOR]

Background: A major contributor to disability after hemorrhagic stroke is secondary brain damage induced by the inflammatory response. Following stroke, global increases in numerous cytokines—many associated with worse outcomes—occur within the brain, cerebrospinal fluid, and peripheral blood. Extracellular vesicles (EVs) may traffic inflammatory cytokines from damaged tissue within the brain, as well as peripheral sources, across the blood–brain barrier, and they may be a critical component of post-stroke neuroinflammatory signaling. Methods: We performed a comprehensive analysis of cytokine concentrations bound to plasma EV surfaces and/or sequestered within the vesicles themselves. These concentrations were correlated to patient acute neurological condition by the Glasgow Coma Scale (GCS) and to chronic, long-term outcome via the Glasgow Outcome Scale-Extended (GOS-E). Results: Pro-inflammatory cytokines detected from plasma EVs were correlated to worse outcomes in hemorrhagic stroke patients. Anti-inflammatory cytokines detected within EVs were still correlated to poor outcomes despite their putative neuroprotective properties. Inflammatory cytokines macrophage-derived chemokine (MDC/CCL2), colony stimulating factor 1 (CSF1), interleukin 7 (IL7), and monokine induced by gamma interferon (MIG/CXCL9) were significantly correlated to both negative GCS and GOS-E when bound to plasma EV membranes. Conclusions: These findings correlate plasma-derived EV cytokine content with detrimental outcomes after stroke, highlighting the potential for EVs to provide cytokines with a means of long-range delivery of inflammatory signals that perpetuate neuroinflammation after stroke, thus hindering recovery. [ABSTRACT FROM AUTHOR]