Lymphovascular Invasion Status Research Articles

Minimum apparent diffusion coefficient for predicting lymphovascular invasion in invasive cervical cancer.

To investigate the diagnostic performance of minimum apparent diffusion coefficient (mini-ADC) for predicting lymphovascular invasion (LVI) in invasive cervical cancer. Ninety-six patients with pathologically confirmed invasive cervical cancer (CC) underwent conventional preoperative magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) on a 3.0T MRI system. Tumor ADC, mini-ADC and mini-ADC ratio (mini-ADC value / tumor ADC value) were obtained and compared between LVI-positive and LVI-negative invasive CC, and correlation between LVI status and Ki-67, p16, p63, and clinical prognostic factors were analyzed. ADC thresholds and diagnostic performance were determined by receiver operating characteristic (ROC) analysis. Tumor ADC showed no significant difference (P = 0.300) between LVI-positive invasive CC (n = 27) and LVI-negative invasive CC (n = 69); the mini-ADC and mini-ADC ratio were significantly lower in LVI-positive invasive CC than in LVI-negative invasive CC ([0.712 ± 0.078 × 10-3 mm2 /s] vs. [0.867 ± 0.099 × 10-3 mm2 /s], P < 0.001; and [0.772 ± 0.062] vs. [0.917 ± 0.052], P < 0.001, respectively). ROC curve analysis yielded a cutoff mini-ADC value of 0.837 in the differentiation of LVI-positive and LVI-negative invasive CC, with a sensitivity of 65%, specificity of 100%, and area under the curve (AUC) of 0.885; a cutoff mini-ADC ratio of 0.875 with a sensitivity of 78%, specificity of 100%, AUC of 0.970, positive predictive value of 100%, and negative predictive value of 64%. There was a positive correlation between LVI status and Ki-67 (r = 0.241, P = 0.014) and a negative correlation between mini-ADC and LVI status (r = -0.582, P < 0.001); mini-ADC and Ki-67 (r = -0.587, P < 0.001). Mini-ADC value appears to be a simple and effective tool for the prediction of LVI status in invasive CC, and the mini-ADC ratio may be the best parameter in discriminating between LVI-positive and LVI-negative invasive CC. 1 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2017;45:1771-1779.

Predicting poor prognosis recurrence in women with endometrial cancer: a nomogram developed by the FRANCOGYN study group.

Background:The purpose of this study was to develop a nomogram to predict ‘poor prognosis recurrence' (PPR) in women treated for endometrial cancer (EC).Methods:The data of 861 women who received primary surgical treatment between January 2001 and December 2013 were abstracted from a prospective multicenter database. Data were randomly split into two sets: training and validation with a predefined 2/3 ratio. A Cox proportional hazards multivariate model of selected prognostic features was performed in the training cohort (n=574) to develop a nomogram predicting PPRs. The nomogram was validated in the validation cohort of 287 patients.Results:In the training cohort, 82 (14.3%) developed subsequent PPR. Age, histologic type and grade, lymphovascular space invasion status, FIGO stage, and nodal staging (SLN±pelvic and/or para-aortic lymphadenectomy) were independently associated with subsequent PPR. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.82 (95% confidence interval (CI), 0.73–0.89) in the training set. The validation set showed a good discrimination with an AUC of 0.75 (95% CI, 0.65–0.83).Conclusions:We have developed a robust tool that is able to predict subsequent PPRs in women with FIGO I–III EC.

Diagnostic Performance of Fused Diffusion-Weighted Imaging Using T1-Weighted Imaging for Axillary Nodal Staging in Patients With Early Breast Cancer

PurposeTo evaluate the diagnostic performance of fused diffusion-weighted imaging (DWI) using T1-weighted imaging (T1WI) for axillary nodal staging in patients with early breast cancer (stage I or II). Materials and MethodsWe enrolled 149 axillae in 147 consecutive patients who performed preoperative breast magnetic resonance imaging (MRI) and definitive surgery. All patients underwent T2-weighted imaging (T2WI), fused DWI using T1WI, and non–fat-suppressed (non-FS) T1WI. Two radiologists scored each axillary nodal status by using a 5-point scale and independently measured the apparent diffusion coefficient (ADC) values of the most suspicious lymph node and an index tumor. Diagnostic performance was calculated on a patient-by-patient basis. ResultsMacrometastasis was present in 26.2%, micrometastasis in 7.4%, and benign lymph nodes in 66.4%. Area under the receiver operating characteristic curves (AUCs) of both readers for predicting axillary lymph node metastasis were 0.676 and 0.603 for non-FS T1WI, 0.749 and 0.727 for T2WI, 0.838 and 0.790 for fused DWI, and 0.868 and 0.837 for the combined reading using ADC. AUCs of tumor ADC were 0.709 and 0.737, whereas those of lymph node ADC were 0.818 and 0.781 for both readers. With stepwise addition of tumor ADC, lymph node ADC, and lymphovascular invasion status to the fused DWI, the AUCs gradually increased from 0.838, 0.892, and 0.908 to 0.924 for reader 1 and from 0.790, 0.863, and 0.901 to 0.908 for reader 2. ConclusionFused DWI using T1WI showed better diagnostic performance than conventional T2WI and non-FS T1WI for the prediction of lymph node metastasis.

Postoperative radiation therapy is associated with a reduced risk of local recurrence among low risk Merkel cell carcinomas of the head and neck

PurposeMerkel cell carcinoma (MCC) is a rare and often aggressive skin cancer. Typically, surgery is the primary treatment. Postoperative radiation therapy (PORT) is often recommended to improve local control. It is unclear whether PORT is indicated in patients with favorable Stage IA head and neck (HN) MCC. Methods and materialsWe conducted a retrospective analysis of 46 low-risk HN MCC cases treated between 2006 and 2015. Inclusion criteria were defined as a primary tumor size of ≤ 2 cm, negative pathological margins, negative sentinel lymph node biopsy, and no immunosuppression. Local recurrence (LR) was defined as tumor recurrence within 2 cm of the primary surgical bed and estimated with the Kaplan-Meier method. ResultsOmission of PORT was offered to all 46 patients, of which 23 patients received PORT and 23 did not. No patient received adjuvant chemotherapy. There were no significant differences in surgical margins, tumor size, depth, lympho-vascular invasion status, or demographics between the two patient groups. Median follow-up for all patients was 3.7 years. Six of the 23 patients who did not receive PORT developed an LR. Compared to the group that received PORT, there was a significantly higher risk of LR in the group treated without PORT (26% vs. 0%, P = .02). Median time to LR was 11 months. All local failures were effectively salvaged. There was no difference in MCC-specific and overall survival between the 2 groups. ConclusionsFor patients with HN MCC, omission of PORT was associated with a significantly higher risk of local recurrence even among those patients with the lowest-risk tumors (i.e., Stage IA without immune suppression). Thus, it is important to weigh the benefits of PORT against the side effect profile on a case-specific basis for each patient.

Histopathologic Features of Prognostic Significance in High-Grade Osteosarcoma.

Context .- In osteosarcoma treated with neoadjuvant chemotherapy the extent of tumor necrosis on resection is considered an indicator of treatment response, and this has been shown to correlate with survival in most but not all studies. Objective .- To identify additional histologic variables of prognostic significance in high-grade osteosarcoma. Design .- Slides of pretreatment biopsy and primary postneoadjuvant chemotherapy resections from 165 patients with high-grade osteosarcoma were reviewed. Univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were performed to identify clinical and histomorphologic attributes associated with overall survival. Results .- Univariate analyses confirmed the prognostic significance of metastatic status on presentation, primary tumor size, anatomic site, and histologic subtype. Additionally, the identification of lymphovascular invasion, 10% or more residual viable tumor, and 10 or more mitoses per 10 high-powered fields assessed in posttreatment resections were associated with poor survival, retaining significance in multivariate analyses. Based on results from multivariate analysis, we developed a prognostic index incorporating primary tumor size and site, and significant histologic features assessed on resection (ie, lymphovascular invasion status, mitotic rate, and extent of viable tumor). This scoring system segregates patients into 3 risk categories with significant differences in overall survival and retained significance in an independent validation set of 42 cases. Conclusions .- The integration of clinical and microscopic features improves prognostication of patients with osteosarcoma.

The recurrence with isolated intra-abdominal lymph node in patients with colorectal cancer: A study of the Turkish Descriptive Oncological Researches Group (intra-abdominal lymph node and colon cancer)

Abstract Background This study aimed to identify the risk factors related in recurrence with isolated intra-abdominal lymph node metastasis in patients with colorectal cancer. Methods This is a retrospective, cross-sectional study of 21 colorectal cancer patients with isolated intra-abdominal lymph node metastases. Preoperative demographic and laboratory/postoperative histological features of these patients were been analyzed. Results Lymphovascular and perineural invasion and mutant-type K-ras status were more common in the study patients. In addition, a significant correlation was been detected between lymphovascular and perineural invasion, preoperative serum CEA level, preoperative thrombocyte count, mutant-type K-ras status, and pathological N3 disease. Mutant-type K-ras status and the presence of lymphovascular invasion were independent prognostic risk factors for isolated intra-abdominal lymph node metastasis. Conclusions The presence of lymphovascular invasion and mutant-type K-ras status may be poor prognostic risk factors for isolated intra-abdominal lymph node metastasis in patients with colorectal cancer. However, studies involving larger patient series, molecular indicators, and cohorts with metastasis in other areas are been needed to verify this study.

The prognostic role of lymphovascular invasion in urothelial carcinoma of the bladder.

Outcome prediction in patients with bladder cancer has improved through the development of nomograms and predictive models. However, integration of further characteristics such as lymphovascular invasion (LVI) might increase the accuracy and clinical utility of these instruments. Assessment and reporting of LVI in specimens from transurethral resection of the bladder tumour (TURBT) or biopsy in patients with non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) might enable improved staging, prognostication and clinical decision-making. In NMIBC, presence of LVI in TURBT and biopsy samples seems to be associated with understaging and increased risks of disease recurrence and progression. In MIBC, presence of LVI is associated with features of aggressive disease and predicts recurrence and survival. Integration of LVI status into predictive models might aid clinical decision-making regarding intravesical instillation schedules and regimens, early radical cystectomy in patients with high-grade T1 disease and perioperative chemotherapy. However, LVI assessment is hampered by insufficient reproducibility and reliability, lack of routine evaluation and limited concordance between findings in TURBT and radical cystectomy specimens. Standardization of the pathological criteria defining LVI is warranted to improve its reporting in routine clinical practice and its utility as a care-changing prognostic marker.

Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair-Proficient Stage II Colon Cancer.

Prognostic markers that identify patients with stage II colon cancers who are at the risk of recurrence are essential to personalize therapy. We evaluated the potential of GIV/Girdin as a predictor of recurrence risk in such patients. Expression of full-length GIV was evaluated by IHC using a newly developed mAb together with a mismatch repair (MMR)-specific antibody panel in three stage II colon cancer patient cohorts, that is, a training (n = 192), test (n = 317), and validation (n = 181) cohort, with clinical follow-up data. Recurrence risk stratification models were established in the training cohort of T3, proficient MMR (pMMR) patients without chemotherapy and subsequently validated. For T3 pMMR tumors, GIV expression and the presence of lymphovascular invasion (LVI) were the only factors predicting recurrence in both training (GIV: HR, 2.78, P = 0.013; LVI: HR, 2.54, P = 0.025) and combined test and validation (pooled) cohorts (GIV: HR, 1.85, P = 0.019; LVI: HR, 2.52, P = 0.0004). A risk model based on GIV expression and LVI status classified patients into high- or low-risk groups; 3-year recurrence-free survival was significantly lower in the high-risk versus low-risk group across all cohorts [Training: 52.3% vs. 84.8%; HR, 3.74, 95% confidence interval (CI), 1.50-9.32; Test: 85.9% vs. 97.9%, HR, 7.83, 95% CI, 1.03-59.54; validation: 59.4% vs. 84.4%, HR, 3.71, 95% CI, 1.24-11.12]. GIV expression status predicts recurrence risk in patients with T3 pMMR stage II colon cancer. A risk model combining GIV expression and LVI status information further enhances prediction of recurrence. Further validation studies are warranted before GIV status can be routinely included in patient management algorithms. Clin Cancer Res; 22(14); 3488-98. ©2016 AACR.

Can lymphovascular invasion replace the prognostic value of lymph node involvement in patients with upper tract urothelial carcinoma after radical nephroureterectomy?

This study aimed to evaluate whether lymphovascular invasion (LVI) can replace lymph node (LN) involvement as a prognostic marker in patients who do not undergo lymph node dissection (LND) during surgery in patients with upper tract urothelial carcinoma (UTUC). A total of 505 patients who underwent radical nephroureterectomy (RNU) were recruited from four academic centres and divided into four groups: node negative (N0, Group 1); node positive (N+, Group 2); no LND without LVI (NxLVI-, Group 3); and no LND with LVI (NxLVI+, Group 4). Patients in Group 2 had larger tumours, a higher incidence of left-sided involvement, more aggressive T stage and grade, and a higher positive surgical margin rate than patients in other groups. Pathological features (T stage and grade) were poorer in Group 4 than in Groups 1 and 3. Compared to other groups, Group 2 had the worst prognostic outcomes regarding locoregional/distant metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). LVI and LN status in Group 4 was not associated with MFS in multivariate analysis. Among Nx diseases, LVI was not an independent predictor of MFS or CCS. The small number of cases in Groups 2 and 4 is a major limitation of this study. Clinical outcomes according to LVI did not correlate with those outcomes predicted by LN involvement in patients with UTUC. Therefore, LVI may not be used as a substitute for nodal status in patients who do not undergo LND at the time of surgery.

Patterns of Recurrence in Upper Tract Transitional Cell Carcinoma: Imaging Surveillance.

The objective of our study was to evaluate recurrence patterns of upper tract transitional cell carcinomas (UT-TCCs) after radical nephroureterectomy (RNU). Sixty-eight patients (mean age, 78 years; 34 men and 34 women) with UT-TCC after having undergone RNU from 2001 to 2008 were included in this study. Radiologic examinations and clinical notes were reviewed to record tumor location, tumor morphology, histologic T stages and grades, lymphovascular invasion (LVI) status, and surgical procedures. Five-year imaging and clinical follow-up (2001-2013) findings were noted at 3, 6, 12, 18, 24, 36, 48, 60, and more than 60 months after RNU for recurrence pattern and tumor-free survival. Kaplan-Meier survival curves and Cox regression models were used to assess tumor-free survival and to perform a multivariate analysis. Forty-one postoperative recurrences were noted in 20 patients. The mean time to relapse was 16 months, and time to relapse ranged from 1 to 66 months. Tumor site (multifocal lesions involving both renal collecting system and ureter), tumor morphology (mass), T stage (muscle invasion [T2-T4]), histologic grade (grade 3), and the presence of LVI were identified as risk factors for postoperative recurrence in UT-TCC. T stage was the only independent risk factor. Urinary tract, lymph node, liver, bone, and lung recurrences were common in patients with UT-TCC and were detected most frequently at 3-24 months. Tumor site, tumor morphology, T stage, grade, and LVI status were associated with recurrence after RNU. T stage was the only independent predictor of tumor-free survival. Close surveillance for extra-urinary tract recurrences in high-risk groups and a shorter-interval follow-up of the urinary tract in low-risk patients with adjuvant chemotherapy are recommended. Identifying recurrence patterns in UT-TCC can aid in planning an effective tailored imaging surveillance strategy.

Prognostic Significance of Transverse Relaxation Rate (R2*) in Blood Oxygenation Level-Dependent Magnetic Resonance Imaging in Patients with Invasive Breast Cancer

ObjectiveTo examine the relationship between magnetic resonance transverse relaxation rate (R2*) and prognostic factors.Materials and MethodsA total of 159 women with invasive ductal carcinomas (IDCs) underwent breast magnetic resonance imaging (MRI) including blood oxygenation level-dependent (BOLD) sequence at 3 T. The distribution of the measured R2* values were analyzed, and the correlation between R2* and various prognostic factors (age, tumor size, histologic grade, lymphovascular invasion, and axillary lymph node status, as well as expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, p53, and Ki-67) were retrospectively assessed using patient medical records.ResultsThe baseline R2* values of the IDCs were very heterogeneous with wide range among the patients. The mean R2* value was (32.8 ± 14.0) Hz with a median of 29.3 Hz (range 13.5–109.4 Hz). In multivariate analysis, older age was associated with decreased R2* value (P = 0.011) and IDCs with p53-overexpression showed higher R2* values than those without p53-overexpression group (P = 0.031). Other prognostic factors were not significantly correlated with R2* value.ConclusionIn this study, R2* values were significantly correlated with age and expression of p53. Further studies are necessary to determine the prognostic value of BOLD-MRI.

Predictors of 5-year local, regional, and distant recurrent events in a population-based cohort of breast cancer patients

BackgroundThe study purpose was to identify tumor and surgeon predictors of local recurrence (LR), regional recurrence (RR), and distant metastasis (DM) after breast cancer (BC) surgery in a population-based cohort. MethodsConsecutive BC surgical cases from 12 hospitals in South Central Ontario between May 2006 and October 2006 were included. Data collected on chart review included patient and tumor factors, surgery type, adjuvant treatment, surgeon specialty, surgeon case volume, and practice type. Univariate and multivariable survival analyses were performed. ResultsMedian follow-up was 5.5 years for 402 patients (97% of sample). LR, RR, and DM occurred in 18 (4.5%), 10 (2.5%), and 47 (12%) patients, respectively. Significant predictors of BC recurrence (LR or RR or DM) were tumor size and grade, nodal status, and lymphovascular invasion on multivariable analysis. ConclusionTumor factors such as size, grade, lymphovascular invasion, and nodal status predicted BC recurrence, while practice type, surgeon specialty, and case volume did not.

Clinical and Pathological Factors Affecting the Sentinel Lymph Node Metastasis in Patients with Breast Cancer.

Sentinel lymph node biopsy has become the routine procedure in axilla-negative breast cancer patients at most medical centers for axillary staging and local control in the recent years. Sentinel lymph node is the only focus in axillary lymph metastasis in a large portion of patients. In our trial, we investigated the clinical and pathological factors that affect the positive status of sentinel lymph node. We included 89 patients, who underwent sentinel lymph node biopsy (SLNB) with methylene blue and/or technetium-99m Sulphur Colloid due to early-stage breast cancer. Five patients, in whom SLN was not detected and who underwent axillary dissection, were excluded from the trial. The patient age, location of the tumor, the type of the tumor, the T stage by the TNM staging system, the histological grade and type of the tumor, the status of multifocality, the lymphovascular invasion status of the tumor, and the ER, PR, and HER-neu2 status were recorded. The median age of the 89 patients was 52, 9 (±10) years. Fifty-seven (64%) and 32 (36%) of the 89 patients were detected to have positive and negative SLN, respectively. Assessing the SLNB positivity and the patient age, tumor size, tumor grade, multifocality, tumor localization, the T stage by the TNM staging, the ER/PR positivity/negativity, and the HER/neu2 and p53 status, the data revealed no statistically significant results with respect to SLN metastasis. The lymphovascular invasion status (LVI) was observed to statistically affect the SLN positivity (p < 0.016). We showed that LVI could be an important marker in predicting the SLN positivity in patients with axilla-negative early-stage breast cancer. In the future, upon introduction of new biomarkers and with relevant studies, it may be possible to predict the SLNB status of patients at an adequately high accuracy and a low risk.

Prognostic factors and predictive tools for upper tract urothelial carcinoma: a systematic review.

Upper tract urothelial carcinoma (UTUC) is a rare and heterogeneous disease. Several clinical and biological prognostic factors have been identified in multi-institutional collaborative works with the aim of helping decision-making in pursuit of tailored individual patient care. This review provides an overview of these existing prognostic factors and predictive tools for the management of patients with UTUC. A systematic literature search was performed using PubMed/MEDLINE, Web of Science and Scopus databases regarding articles published in English between January 2000 and November 2015 according to PRISMA guidelines. Thresholds of 100 and 300 patients were applied for studies on biomarkers and clinical studies, respectively. All the studies on predictive tools were included for analysis. Outcomes of interest were features associated with advanced-stage UTUC, disease recurrence and survival. A total of 116 studies were included in this review. These large and/or multi-institutional studies have confirmed the prognostic value of standard pathological factors (i.e., tumor stage, grade and lymph node metastasis) and identified novel features such as lymphovascular invasion, tumor architecture, multifocality, concomitant CIS, variant histology and biomarker status among others. Based on these variables, several predictive tools have been developed; however, they often lack of validation. The value of these features and tools needs prospective testing. Efforts provided by international collaboration groups have permitted to validate established features and identify new features of biologically and clinically aggressive UTUC. Further investigation on prognostic factors and biomarkers is still needed to assess the benefit of these features and tools on clinical decision-making.

Higher expression of EpCAM is associated with poor clinical and pathological responses in breast cancer patients undergoing neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) is a standard regimen in treatment of breast cancer patients, but some are resistant to NAC. We hypothesized that breast cancer cells overexpressing epithelial cell adhesion molecule (EpCAM) could be resistant to NAC, contributing to a poor prognosis. Seventy patients with breast cancer were treated with NAC. Core needle biopsy (CNB) specimens and resected tumors before and after NAC, respectively, were examined for expression of EpCAM. In resected tumors, high EpCAM expression correlated with lymphovascular invasion status and nuclear grade (P = 0.01 and 0.008, respectively), and was associated with poor pathological and clinical responses (P < 0.001). High tumoral EpCAM expression in resected tumor was independently related to a poor pathological response. Patients with high EpCAM expression before and after NAC (high-to-high group) showed worse pathological and clinical responses (P = 0.008 and <0.001, respectively) than the patients with high and low EpCAM expression before and after NAC, respectively (high-to-low group). The overall survival rate of the high-to-high group appeared shorter compared with the high-to low-group (P = 0.049). Our findings imply that higher levels of EpCAM in breast cancer may be associated with poor response to NAC via a potential chemoresistant effect.

Association between preoperative serum total cholesterol level and biochemical recurrence in prostate cancer patients who underwent radical prostatectomy.

The aim of this study was to investigate the association between serum total cholesterol (TC) level and biochemical recurrence (BCR) following radical prostatectomy (RP). The study included 562 patients with T1-3N0M0 prostate cancer, who underwent RP at our institution between 2002 and 2010. No patients received neoadjuvant and/or adjuvant therapy. The associations between preoperative TC level, clinicopathological factors and BCR were assessed using univariate and multivariate analyses. During follow-up (mean, 54.0 months), 168 patients (168/562, 29.9%) experienced BCR, with a 5-year BCR-free rate of 67.2%. Of the clinicopathological characteristics investigated, statin use and lymphovascular invasion (LVI) status were associated with lower TC level (P=0.003 and P=0.014, respectively). In the univariate analysis, a higher serum prostate-specific antigen (PSA) level at diagnosis, extracapsular extension, positive surgical margin, seminal vesicle invasion, LVI, perineural invasion, higher Gleason score (GS ≥8) based on the RP specimen, increased body mass index, and low preoperative TC level, were significantly associated with BCR. In the multivariate analysis, the TC level was an independent predictor of BCR (hazard ratio = 0.925 per 10 mg/dl; 95% confidence interval: 0.879-0.973; P=0.003), as was the serum PSA level, extracapsular extension, positive surgical margin and the GS. Low preoperative serum TC levels were associated with an increased risk of BCR among prostate cancer patients who underwent RP. Our findings suggest that the preoperative serum TC level may provide important clinical information that may prove to be useful in patient counseling.

Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition.

Cervical cancer is the third most common cancer in females worldwide. The treatment options for advanced cervical cancer are limited, leading to high mortality. Ezrin is a membrane-cytoskeleton-binding protein recently reported to act as a tumor promoter, and we previously indicated that the aberrant localization and overexpression of Ezrin could be an independent effective biomarker for prognostic evaluation of cervical cancers. In this study, we identified Ezrin as a regulator of epithelial-mesenchymal transition (EMT) and metastasis in cervical cancer. Ezrin knock-down inhibited anchorage-independent growth, cell migration, and invasion of cervical cancer cell lines in vitro and in vivo. EMT was inhibited in Ezrin-depleted cells, with up-regulation of E-cadherin and Cytokeratin-18 (CK-18) and down-regulation of mesenchymal markers. Ezrin knock-down also induced Akt phosphorylation. These results implicate Ezrin as an EMT regulator and tumor promoter in cervical cancer, and down-regulation of Ezrin suppressed cervical cancer progression, possibly via the phosphoinositide 3-kinase/Akt pathway. Furthermore, the expression pattern of Ezrin protein was closely related with the lymphovascular invasion status of cervical cancer by immunohistochemistry, and the survival analysis revealed that the cervical cancer patients with the perinuclear Ezrin expression pattern had longer survival time than those with the cytoplasmic Ezrin expression pattern. Ezrin thus represents a promising target for the development of novel and effective strategies aimed at preventing the progression of cervical cancer.

Nodal Yield Threshold for Early-Stage Clinically Node-Negative Oral Cavity Cancer

A recently published randomized study demonstrated the superiority of an elective neck dissection over a therapeutic (salvage) neck dissection for patients with early-stage oral cavity cancer. Further data have suggested that resection of at least 18 lymph nodes improves outcomes for patients with head and neck cancer. We hypothesized that for early-stage oral cavity cancer, a lower threshold of resected nodes would be adequate to confer survival benefit. We retrospectively reviewed 551 consecutive patients treated at our institution from 1998 to 2013 for oral cavity squamous cell carcinoma with surgical resection followed by adjuvant therapy if indicated. Patients treated for recurrent disease and metastatic disease were not included. For this study, we included patients with T1 or T2 tumors who were clinically node-negative and underwent a neck dissection as part of their primary surgical treatment. We used iterative Kaplan-Meier modeling to determine the number of resected nodes that would confer a survival benefit in this cohort. We then used a Cox regression model to control for pathologic and demographic factors known to affect prognosis. A total of 81 patients met the inclusion criteria for this cohort study with the following breakdown by subsite: 68% oral tongue, 19% floor of mouth, 6% buccal mucosa, 5% alveolar ridge, 1% retromolar trigone, 1% lip, and 0% hard palate. Iterative modeling revealed a survival benefit in patients who had at least 10 lymph nodes resected (P=.006). Only 13 patients had fewer than 10 lymph nodes resected. Sixty-one percent of these patients were pathologically node-negative compared to 71% in those with more than 10 lymph nodes resected (P=NS). Locoregional failure at 2 years was 26% versus 40% in patients with 10 or more versus fewer than 10 lymph nodes resected, respectively (P=NS). When stratified by perineural invasion (PNI), patients with the best overall survival were those without PNI who had at least 10 nodes resected (2-year overall survival [OS] 91%). Patients with PNI who had at least 10 nodes resected (2-year OS 79%) did no better than those with fewer than 10 nodes resected regardless of PNI status (P=.01). After controlling for PNI, depth of invasion, poor differentiation, lymphovascular invasion, and active smoking status at diagnosis, the effect of fewer than 10 lymph nodes resected was still significant (hazard ratio 2.9, P=.05). Even for early-stage clinically node-negative oral cavity cancer, there may be a nodal yield threshold that defines an adequate neck dissection. Our data suggest that this threshold is 10 lymph nodes.

Upper Tract Urothelial Carcinomas Accompanied by Previous or Synchronous Nonmuscle-Invasive Bladder Cancer and Preoperative Hydronephrosis Might Have Worse Oncologic Outcomes After Radical Nephroureterectomy

BackgroundThe purpose of the study was to identify predictors of clinicopathologic features and oncologic outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy (RNU). Patients and MethodsThe medical records of 172 patients treated with RNU from January 2001 to September 2014 were retrospectively reviewed. Logistic regression and survival analysis methodology were respectively used to evaluate predictors of clinicopathologic features and oncologic outcomes. ResultsOf the enrolled 172 patients, 80 (46.5%) had renal pelvic tumors, 67 (39%) had ureteral tumors, and the remaining 25 (14.5%) patients had multifocal tumors. Compared with patients with renal pelvic tumors, those with ureteral and multifocal tumors were more likely to have previous or synchronous nonmuscle-invasive bladder cancer (NMIBC) and severe hydronephrosis (P = .001 and P < .001, respectively). Logistic regression analysis showed that previous or synchronous NMIBC was significantly associated with worse renal function and high grade (P = .034 and P = .014, respectively), and severe hydronephrosis independently predicted worse renal function and positive lymph node or lymphovascular invasion status (P = .001 and P = .007, respectively). Moreover, severe hydronephrosis was an independent risk factor for overall survival and cancer-specific survival in multivariate analysis (P = .025 and P = .045, respectively). Multifocality and previous or synchronous NMIBC were significantly associated with bladder-recurrence-free survival (P = .023 and P = .001, respectively). ConclusionUpper tract urothelial carcinoma accompanied by previous or synchronous NMIBC and preoperative severe hydronephrosis could have worse oncologic outcomes after RNU. These common accompanied diagnoses could be valuable for guiding preoperative planning and postoperative adjuvant therapy.

Abstract P1-14-18: Postmastectomy radiotherapy improves the outcomes of stage III breast cancer patients with negative lymph nodes after neoadjuvant chemotherapy

Abstract Purpose: The aim of this study is to evaluate the role of postmastectomy radiotherapy (PMRT) in clinical stage II and III breast cancer patients who achieved negative node status (pN0) after neoadjuvant chemotherapy (NAC). Material and methods: We retrospectively analyzed the outcomes of 143 patients with pN0 after NAC and mastectomy at Fudan University Shanghai Cancer Center. In total, 103 (72%) patients received PMRT, and 40 (28%) patients did not. Univariate and multivariate survival analyses were performed to evaluate the effect of PMRT on locoregional recurrence-free survival (LRRFS) and overall survival (OS) of the two groups. Results: There were no differences between the two groups with respect to age, nuclear grade, estrogen receptor (ER) status, HER2/neu receptor status, lymphovascular space invasion (LVSI) status or pathological tumor size. However, a significantly higher proportion of patients in the irradiated group (64%) had clinical lymph node involvement than in the nonirradiated group (45%). After a median follow-up time of 49 months, 10 locoregional recurrence events occurred. For the entire cohort of patients, use of radiation therapy improved the 5-year LRRFS rate (94.5% vs. 80.2%; P =0.032) but not the 5-year OS rate (92.2% vs. 88.7%; P =0.617). In the subset of patients who presented with clinically stage II disease, the 5-year LRRFS and 5-year OS did not differ significantly between the PMRT and no-PMRT group (96.3% vs. 91.3%; P = 0.190 and 96.2% vs. 91.3%; P = 0.199, respectively). For patients with stage III disease at diagnosis, a trend was seen toward better local regional control with PMRT (the 5-year LRRFS rate was 92.7% vs. 64.2%; P = 0.063), although the benefit from radiation with respect to OS was not significant (5-year OS rate was 88.1% vs. 85.2%; P = 0.657). On multivariate Cox regression analyses, the clinical tumor size (hazard ratio [HR], 3.27; 95% confidence interval [CI], 1.05-10.18; P = 0.041), pathologic breast tumor response (HR, 1.82; 95% CI, 1,11-3.77; P = 0.046) and delivery of radiation therapy (HR, 1.27; 95% CI, 1.08-9.25; P = 0.047) were independent predictors of locoregional recurrence. Conclusions: For patients who achieved pN0 after NAC, PMRT seemed to provide a clinical benefit for breast cancer patients with stage III disease. Omission of PMRT in patients with stage II disease did not increase the risk of locoregional recurrence and death. Citation Format: He M, Li J, Ni X-J, Chen S, Jiang Y-Z, Di G-H, Shao Z-M. Postmastectomy radiotherapy improves the outcomes of stage III breast cancer patients with negative lymph nodes after neoadjuvant chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-18.