Predictors Of Invasive Disease Research Articles

Predictors of invasive disease in patients preoperatively diagnosed with ductal carcinoma without stromal invasion, with breast magnetic resonance imaging (MRI) and ultrasound (US).

A preoperative diagnosis of ductal carcinoma in situ (DCIS) is sometimes upstaged to invasive disease postoperatively. Our objective was to clarify the predictive factors of invasive disease using preoperative imaging and to investigate the positive ratio of sentinel lymph nodes (SLN) and the incidence of invasive disease. The subjects were 402 patients with preoperatively diagnosed ductal carcinoma without stromal invasion who underwent breast surgery with concomitant SLN surgery in January 2007 to December 2016. Of the 306 included patients, all 306 patients underwent preoperative MRI and US assessment. Outcomes were analyzed for significance using univariate and multivariate analyses. Of the 306 patients, 115 (37.6%) had invasive disease and 191 (62.4%) had DCIS only. Of the 115 patients with invasive disease, 5 (4.4%) and 4 (3.5%) had macro- and micrometastases in SLN. On the other hand, of the 191 patients with DCIS, only 1 (0.5%) had a micrometastasis. Predictors of invasive disease in the univariate analysis included having a palpable mass, were varied by biopsy method, having a US hypoechoic mass, MRI enhancement, or MRI large enhanced lesion; the size of the mass enhancement ≥ 1.1cm or a spread of non-mass enhancement ≥ 3.1cm (P = 0.003). Predictors of invasive disease in the multivariate analysis included US hypoechoic mass and MRI large enhanced lesion. We need to perform SLN biopsy for preoperatively diagnosed DCIS when patients have predictors of invasive disease, but SLN biopsy will no longer be essential for patients when they have no predictors of invasive disease.

P291 - Predictors of invasive disease and nodal involvement in patients with an initial diagnosis of DCIS obtained by core needle biopsy or vacuum-assisted biopsy

P291 - Predictors of invasive disease and nodal involvement in patients with an initial diagnosis of DCIS obtained by core needle biopsy or vacuum-assisted biopsy

Abstract 4048: Histological image profiling identifies aggressive glioblastoma phenotype with poorer survival

Abstract The stratification of glioblastoma (GBM) patients into clinically relevant subtypes is an essential step in the direction of personalized genomic medicine. In contrast to currently employed time- and cost-intensive genomic methodologies, we describe here a novel cost-effective approach capable of detecting predictors of invasive disease in GBM based on profiling of histological images. Unsupervised statistical analysis of imaging feature data first distinguishes two major clusters with strikingly different phenotypes. The subsequent Kaplan-Meier survival analysis of these two clusters shows that patients who had tumors in cluster 2 (which we refer to as aggressive subtype for the purpose of clarity) had poorer overall survival. Among the differentially varied features, the aspect ratio parameter, which is a strong indicator of cell movement, exhibits larger values in the aggressive subtype, suggesting greater invasiveness of this subset. Based on the initial dataset, a predictive model comprised of informative features was constructed using a weighted voting algorithm. Cross-validation of this sample set revealed a predictive accuracy of over 90% in correctly classifying these two groups, with specificity of ∼94% and sensitivity of ∼90% as determined by the receiver operating characteristic curves method. In a manner similar to gene biomarkers, some of imaging features can be used as diagnostic and prognostic factors in GBM. To identify the molecular events underlying the identified phenotypes, we performed genome-wide expression data analysis of the same sample set. Among the marker genes identified as overexpressed in the aggressive subtype were CHI3L1, CD44 and TNFRSF1A, which have been previously associated with poorer survival in GBM. In addition, pathway analysis of differentially-expressed genes indicates significant activation of the glioma invasiveness signaling and NF-κB signaling pathways; most of the altered genes in both pathways are more highly expressed in the aggressive GBM subtype and are thus potentially linked to the poorer survival of this group. Our novel approach has the potential to unify the imaging and genomic dimensions of GBM for clinical stratification. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4048. doi:10.1158/1538-7445.AM2011-4048

Multicenter, Prospective Surveillance Study of Staphylococcus aureus Nasal Colonization in 28 Italian Intensive Care Units: The ISABEL Study

The role of methicillin-resistant Staphylococcus aureus (MRSA) colonization as a predictor of invasive disease in intensive care unit (ICU) patients was established many years ago. The role of mefhicillin-susceptible Staphylococcus aureus (MSSA) colonization is more debated, although in a recent report patients who were carriers of MRSA or MSSA at ICU admission were found to be at increased risk. Whether carriage at ICU admission involves a higher risk of invasive infection than carriage acquired during an ICU stay has not been established. We report the results of a study aimed at estimating the frequency of S. aureus (MRSA and MSSA) colonization at admission and at discharge in patients admitted to several ICUs in Italy and at estimating the relationship between colonization status and infection by S. aureus.

Abstract P1-15-08: Comparison of Core Needle Biopsy and Surgical Specimens To Investigate the Percentage of Pre-Operative Ductal Carcinoma In Situ Diagnosis Who Were Found To Have Invasive Breast Cancer after Surgery at University Hospitals of Leicester (UHL)

Abstract Introduction: Ductal carcinoma in situ (DCIS) accounts for 25% of all breast cancer diagnosis. This study was carried out to investigate the percentage of patients at UHL who are diagnosed to have DCIS on core needle biopsy but found to have invasive cancer from the surgical specimen. In addition, we analysed how many of these patient went on to have further surgery for removal of residual invasive cancer and axillary staging. Method: Data of all patients who presented between 2008 and 2010 was retrospectively analysed. Clinical presentation, histology pre-and post-procedure, cancer grade, treatment methods, axillary node involvement and calcification were recorded. Results: A total of 177 patients with DCIS were recorded. The mean age was 61.1 years (range 31 — 102). The most common site of cancer was upper outer quadrant (28.2%). Majority of patients were identified through the screening programme (67.2%) as opposed to symptomatic presentation (32.8%). The most common procedure was Wide Local Excision (59.3%) followed by Mastectomy (31.7%). 9% of patients who had positive histology did not have any surgery. Post-procedure histology proved that the mean size of DCIS was 25.4mm and 62.7% was high grade. Most patients had no axillary node involvement and no malignant calcification (91.5% and 74.6% respectively). In 54 of 177 (30.5%) patients who were histopathologically diagnosed as DCIS by core needle biopsy, final diagnosis was changed to invasive carcinoma in surgical specimens The mean size of the invasive tumour in these patients was 13.4 mm and majority of the patients had grade 2 invasion (46.2%). Out of these 54 patients with new invasion, core biopsy results showed 31 patients (57.4%) had high grade DCIS, 10 patients (18.5%) had intermediate grade DCIS, 5 patients (9.2%) had low grade DCIS and 8 patients (14.8%) had unknown DCIS grade. Nineteen out of 54 patients (35.2%) went on to have further surgery after invasion was detected. Conclusion: The most common site was upper outer quadrant and majority of patients have been identified through the screening programme. Wide local excision was the most common surgical intervention. Our study showed almost 1/3 patients who were originally diagnosed with DCIS were found to have invasion post surgery at UHL and majority had high grade DCIS on core needle biopsy. This value is in keeping with the findings from previous studies[1]. However, only a small percentage of these patients went on to have further surgery. [1] Predictors of invasive disease in breast cancer when core biopsy demonstrates DCIS only. Dillon MF, McDermott EW, Quinn CM, O'Doherty A, O'Higgins N, Hill AD. Department of Surgery, St Vincent's University Hospital, Dublin, Ireland. J Surg Oncol. 2006 Jun 1;93(7):559- 63. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-15-08.

Population-based surveillance for scedosporiosis in Australia: epidemiology, disease manifestations and emergence of Scedosporium aurantiacum infection

Australia-wide population-based surveillance for scedosporiosis identified 180 cases, with 118 (65.6%) cases of colonization and 62 (34.4%) cases of infection. Predisposing factors for isolation of Scedosporium spp. included chronic lung disease in 37.8% and malignancy in 21.7% of cases. Predictors of invasive disease (n=62) included haematological stem cell transplantation (n=7), leukaemia (n=16) and diabetes mellitus (n=8). Of 183 phenotypically-speciated isolates, 75 (41%) were Scedosporium prolificans (risk factors: haematologic cancer (n=17), neutropaenia (n=14)) and 108 (59%) had Scedosporium apiospermum/Pseudallescheria boydii phenotype [risk factor: diabetes (n=15)]. Scedosporium prolificans (p 0.01) and leukaemia (p 0.03) independently predicted death. Epidemiological and antifungal susceptibility profiles of Scedosporium aurantiacum (prevalence>or=15.8%) and S. apiospermum were similar. No patient with S. aurantiacum infection (n=6) died. This is the first description of clinical features associated with S. aurantiacum.

BS06 INDICATIONS FOR SENTINEL LYMPH NODE BIOPSY IN PATIENTS WITH A PRE‐OPERATIVE DIAGNOSIS OF DUCTAL CARCINOMA IN SITU

Purpose: Ductal carcinoma in situ (DCIS) is non‐invasive so the use of sentinel lymph node biopsy (SLNB) in patients diagnosed with DCIS is questionable. DCIS has the potential to progress to invasive cancer, so SLNB would be useful in staging disease in patients at higher risk of invasion. This study aims to identify pre‐operative characteristics of DCIS that are predictors of invasive disease and thus provide a guide as to when to use SLNB.Methodology: This study is a consecutive series of 374 patients that underwent SLNB, of whom 37 patients had a preoperative diagnosis of DCIS, treated by one surgeon between July 2001 and February 2008. The association between pre‐ operative clinical and pathological factors and a post‐operative diagnosis of invasive disease were analysed. Associations between final pathological diagnosis of DCIS or invasive disease and treatment parameters were also analysed.Results: Of the 37 patients, 13 (35%) were found to have invasive disease post‐operatively. Analysis revealed that an initial suspicion of microinvasion, larger mammographic size, younger age, diagnosis with core biopsy, nipple discharge and presence of necrosis had statistically significant association with a post‐operative diagnosis of invasive cancer. Only patients with invasive disease had positive SLNs. Analysis of treatment with mastectomy or conservative surgery showed a link between mastectomy and a palpable lump.Conclusion: SLNB is recommended for staging disease in patients with a pre‐operative diagnosis of DCIS who also have characteristics suggestive of invasive disease

Are there preoperative predictors for invasive disease in DCIS?.

Abstract Abstract #3014 Introduction: Ductal carcinoma in situ (DCIS) of the breast is defined as a proliferation of malignant epithelial cells within breast ducts without evidence of invasion through the basement membrane. Core needle biopsy (CNB) is used to sample both symptomatic and screen detected breast lesions preoperatively. However in a proportion of patients invasive disease is identified following surgical excision and as a result an upstaged patient may need to undergo additional surgery for axillary nodal evaluation such as sentinel lymph node biopsy (SLNB). Our aim was to evaluate predictive factors for invasive disease in this group.
 Method: Data from all patients with preoperative diagnosis of DCIS on core biopsy between February 2006 and December 2007 were analysed. Demographic data, screening /symptomatic presentation, palpability, size and histological features of DCIS on core biopsy including presence/absence of comedo necrosis, size of post operative invasion when present and result of axillary staging in this group was recorded. All patients with invasive disease had axillary staging.
 Results: A total of 75 patients were identified (all female), median age 63 (range 38-77). 72% (54/75) were screen detected. All palpable lesions were in the symptomatic group (13/19). Invasive disease was identified in 18 (24%) on post operative histology (2 micro-invasions). Only one patient with invasive disease had axillary involvement.
 
 Invasive disease was significantly higher in symptomatic and palpable lesions (P=0.04). Size of the lesion was significantly larger in the invasive group (P=0.04). High grade histology or presence of comedo necrosis was not a predictor of invasive disease in our series.
 Conclusion: A quarter of patients were upstaged and required axillary staging. 50% of symptomatic, palpable lesions larger than 20mm were found to be invasive on final histology, this group accounted for the only positive axilla. Symptomatic patients presenting with large, palpable areas of DCIS should be considered for axillary ultrasound scan and/or SLNB. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3014.

Predictors of invasive disease in breast cancer when core biopsy demonstrates DCIS only

Ductal carcinoma in-situ on core biopsy does not preclude invasive disease within the excision specimen, resulting in the need for further axillary surgery. We sought to identify predictors of invasion when DCIS is present on core biopsy. From a database of 895 breast cancer patients, patients with DCIS on core biopsy who had subsequent surgical excision were identified. Their excision pathology and preoperative mammography were correlated with risk of invasion. Patients (93) with a preoperative diagnosis of DCIS on core biopsy were identified. On excision, 31 patients (33%) had invasive carcinoma and 13 patients (14%) had microinvasion. A preoperative finding of calcification only on mammogram was associated with DCIS on excision (P = 0.014), whereas the presence of other mammographic features increased the risk of invasion. Size > or =5 cm on excision pathology was associated with increased risk of invasion (P = 0.002). Forty-eight percent (n = 11/23) of those diagnosed by ultrasound-guided core biopsy had frank invasion on excision compared to 21% (n = 12/57) diagnosed by stereotactic techniques (P = 0.017). Mammographic features and tumor size can help predict invasion in patients who have DCIS on core biopsy. Patients who have features other than calcification on mammography or have tumor size > or =5 cm should be considered for a sentinel node biopsy.

Epigenetic Inactivation of SFRP Genes and TP53 Alteration Act Jointly as Markers of Invasive Bladder Cancer

In the United States each year, almost 13,000 deaths are attributable to bladder cancer, with the majority of these deaths related to higher stage, muscle-invasive solid tumors. Epigenetic silencing of the secreted frizzled receptor proteins (SFRP), antagonists of the WNT pathway, leads to constitutive WNT signaling, altering cell morphology and motility. Identifying alterations in this pathway in bladder cancer may prove useful for defining the invasive phenotype and provide targets for guiding therapy. Using a population-based study of bladder cancer (n = 355), we examined epigenetic alterations, specifically gene promoter hypermethylation, of four SFRP genes in addition to immunohistochemical staining of TP53, which has been previously shown to be a predictor of invasive disease. We observed a significant linear trend (P < 0.0004) in the magnitude of the risk of invasive disease with the number of SFRP genes methylated. Both TP53 alteration and SFRP gene methylation showed significant independent associations with invasive bladder cancer. Strikingly, in examining the joint effect of these alterations, we observed a >30-fold risk of invasive disease for patients with both altered SFRP gene methylation and intense TP53 staining (odds ratio, 32.1; P < 10(-13)). Overall patient survival was significantly poorer in patients with any SFRP genes methylated (P < 0.0003) and in proportional hazards modeling, patients with methylation of any SFRP gene had significantly poorer overall survival (hazard ratio, 1.78; P < 0.02) controlled for TP53 staining intensity and other survival-associated factors. Classifying tumors based on SFRP methylation status and TP53 protein staining intensity may be a clinically powerful predictor of invasive, deadly disease.