Citations

Background: Histologic subtypes of appendiceal cancer vary in their propensity for metastases to regional lymph nodes (LN). A predictive model would help direct subsequent surgical therapy. Methods: The National Cancer Database was queried for patients with appendiceal cancer undergoing surgery between 1998 and 2012. Multivariable logistic regression was used to develop a predictive model of LN metastases which was internally validated using Brier score and Area under the Curve (AUC). Results: A total of 21,647 patients were identified, of whom 9079 (41.9%) had node negative disease, 4575 (21.1%) node positive disease, and 7993 (36.9%) unknown LN status. The strongest predictors of LN positivity were histology (carcinoid tumors OR 12.78, 95% CI 9.01–18.12), increasing T Stage (T3 OR 3.36, 95% CI 2.52–4.50, T4 OR 6.30, 95% CI 4.71–8.42), and tumor grade (G3 OR 5.55, 95% CI 4.78–6.45, G4 OR 5.98, 95% CI 4.30–8.31). The coefficients from the regression analysis were used to construct a calculator that generated predicted probabilities of LN metastases given certain inputs. Internal validation of the overall model showed an AUC of 0.75 (95% CI 0.74–0.76) and Brier score of 0.188. Histology-specific predictive models were also constructed with an AUC that varied from 0.669 for signet cell to 0.75 for goblet cell tumors. Conclusions: The risk for nodal metastases in patients with appendiceal cancers can be quantified with reasonable accuracy using a predictive model incorporating patient age, sex, tumor histology, T-stage, and grade. This can help inform clinical decision making regarding the need for a right hemicolectomy following appendectomy.

Abstract Tumor–stroma interactions significantly influence cancer cell metastasis and disease progression. These interactions are partly comprised of the cross-talk between tumor and stromal fibroblasts, but the key molecular mechanisms within the cross-talk that govern cancer invasion are still unclear. Here, we adapted our previously developed microfluidic device as a 3D in vitro organotypic model to mechanistically study tumor–stroma interactions by mimicking the spatial organization of the tumor microenvironment on a chip. We cocultured breast cancer and patient-derived fibroblast cells in 3D tumor and stroma regions, respectively, and combined functional assessments, including cancer cell migration, with transcriptome profiling to unveil the molecular influence of tumor–stroma cross-talk on invasion. This led to the observation that cancer-associated fibroblasts (CAF) enhanced invasion in 3D by inducing expression of a novel gene of interest, glycoprotein nonmetastatic B (GPNMB), in breast cancer cells, resulting in increased migration speed. Importantly, knockdown of GPNMB blunted the influence of CAF on enhanced cancer invasion. Overall, these results demonstrate the ability of our model to recapitulate patient-specific tumor microenvironments to investigate the cellular and molecular consequences of tumor–stroma interactions. Significance: An organotypic model of tumor–stroma interactions on a microfluidic chip reveals that CAFs promote invasion by enhancing expression of GPNMB in breast cancer cells.

AbstractBackgroundCompletion lymph node dissection (CLND) for sentinel lymph node (SLN) disease in melanoma patients is debated. We evaluated the impact of CLND on survival and assessed for predictors of nonsentinel node metastasis (positive CLND).MethodsPositive SLN melanoma patients were retrospectively identified in the Sentinel Lymph Node Working Group database. Clinicopathological factors were correlated with CLND status, overall survival (OS), and melanoma‐specific survival (MSS).ResultsThere were 953 positive SLN patients of whom 831 (87%) had CLND. Positive CLND was seen in 141 (17%) cases and was associated with worse OS and MSS (both P < 0.001). CLND was not performed (No‐CLND) in 122 of 953 positive SLN cases (13%), of whom 100 had follow‐up and 18 (18%) developed a nodal recurrence (NR). No significant differences in OS and MSS were seen comparing CLND with No‐CLND (P = 0.084, P = 0.161, respectively) and comparing positive CLND with No‐CLND NR patients (P = 0.565, P = 0.998, respectively). Gender, primary site, ulceration, and number of positive SLNs were correlated with nonsentinel node metastasis.ConclusionsPerformance of CLND provides prognostic information but is not associated with a survival benefit. Clinical variables can predict a positive CLND in patients who may be at high risk of recurrence.

Abstract OBJECTIVE: Currently, no study has assessed the performance of contrast-enhanced spectral mammography (CESM) in evaluating tumor response in breast cancer patients undergoing neoadjuvant systemic therapy (NST). This study aims to evaluate whether the accuracy of CESM is comparable to MRI in detection of residual breast cancer following NST. MATERIALS AND METHODS: Retrospective review of CESM cases at our institution between September 2014 and June 2016 identified patients who had both CESM and MRI pre- and post-NST with pathologic assessment after surgical management. Size of residual malignancy (if any) on post-neoadjuvant CESM and MRI was compared to surgical pathology (reference standard). Pathologic complete response (pCR) was documented and compared to Residual Cancer Burden (RCB) score for confirmation. Bland-Altman plots were used to visualize the differences between CESM/MRI and pathologic tumor size. RESULTS: Forty female patients met inclusion criteria. Mean age was 52.3 years (range 35-73). Type of NST included: 34 (85%) chemotherapy and 6 (15%) endocrine therapy. Histological analysis showed invasive ductal carcinoma in 38 (95%), the remaining cases consisted of one invasive lobular carcinoma, and one mixed invasive carcinoma. Mean tumor size after NST was 10.3 mm (range 0-75 mm) for CESM and 9.7 mm (range 0-60 mm) for MRI compared to 15.7 mm (range 0-100 mm) on final surgical pathology. Equivalence tests demonstrated that the mean tumor size measured by CESM or by MRI is equivalent to the mean tumor size measured by pathology within -1 and 1 cm range (p=0.0132 for CESM and p=0.0194 for MRI). Difference in Measurement Post-NST Compared to Pathology Path Tumor Size (mm)CESM Tumor Size (mm)MRI Tumor Size (mm)Mean (SD)15.7 (24.5)10.3 (18.9)9.7 (16.3)Difference Compared with Path (SD); P value -5.4 (12.6); 0.0132-6.0 (11.7); 0.0194 A complete radiologic response was seen in 25 CESM and 22 MRI cases which was confirmed by pathology in 17 and 14, respectively. Alternatively, CESM and MRI demonstrated residual disease in 15 patients and 18 patients respectively and this was confirmed on pathology in 15 and 15, respectively. Accuracy of CESM vs. MRIModalityResidual Disease by Pathology (N=23)Complete Response by Pathology (N=17)SensitivitySpecificityPPVNPVResidual Disease by CESM (N=15)150Complete Response by CESM (N=25)81765.2%100%100%68%Residual Disease by MRI (N=18)153Complete Response by MRI (N=22)81465.2%82.4%83.3%63.6% All patients who achieved a pCR had an RCB score of 0 indicating no residual cancer in lymph nodes. Among patients with residual disease, their mean RCB score was 2.6 (range 0.8-4.18). CONCLUSION: In this study, CESM was comparable to MRI in assessing residual malignancy after completion of NST, thereby offering a potentially faster and less expensive alternative to MRI for monitoring treatment response in the neoadjuvant setting. Citation Format: Hilal T, Covington M, Sugi M, Zhang N, Pockaj B, Northfelt D, Ocal IT, Patel BK. Contrast-enhanced spectral mammography is comparable to MRI in the assessment of residual breast cancer following neoadjuvant systemic therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-11.