Node Pathological Stage Research Articles

Reduced E-Cadherin and Aberrant β-Catenin Expression are Associated With Advanced Disease in Signet-Ring Cell Carcinomas.

Signet-ring cell carcinomas (SRCCs) tend to present at higher stages and thus are generally associated with a worse prognosis. It has been postulated that a deficiency of E-cadherin may be causal in the pathogenesis of SRCC in animal models. In this study, we systemically analyzed the expression of E-cadherin and β-catenin, a key component of the cadherin complex, in 137 consecutive SRCCs of various organ systems to explore the significance of these molecules in the pathogenesis and progression of SRCCs. Seventy-six percent of SRCCs showed loss or reduced E-cadherin expression. Aberrant β-catenin expression, defined as loss of membranous expression and nuclear/cytoplasmic subcellular localization, was observed in 60% of these cases, with the altered β-catenin expression observed most commonly in the breast (93%) and least in the lung (38%) primaries. Further, the aberrant β-catenin was significantly associated with pathologic nodal stage (P=0.002) and clinical stage (P=0.02). Our findings demonstrated that reduced membranous E-cadherin and aberrant β-catenin expression were frequent events in SRCCs of various organs, and that the altered β-catenin expression was significantly associated with advanced disease. The observations further support the importance of these molecules in the pathogenesis of SRCCs, and indicate the fundamental role of the Wnt/β-catenin signaling pathway in the progression of these tumors. Further investigations of the downstream molecules in this cascade may provide potential novel therapeutic targets for this aggressive tumor type.

Intraoperative identification and analysis of lymph nodes at laparoscopic colorectal cancer surgery using fluorescence imaging combined with rapid OSNA pathological assessment

BackgroundStandard surgical practice for colorectal cancer involves resection of the primary lesion and all draining lymph nodes. Accurate intraoperative assessment of nodal status could allow stratified resectional extent. One-step nucleic acid (OSNA) can provide a rapid method of interrogating nodal tissue, whilst near-infrared (NIR) laparoscopy together with indocyanine green (ICG) can identify relevant nodal tissue intraoperatively.MethodsICG was administered around the tumour endoscopically prior to the operation. Fluorescent nodes identified by NIR were marked and submitted for whole-node OSNA analysis. Further fresh lymph nodes dissected from the standard resection specimen were examined and analysed by both conventional histology and OSNA. In addition, the status of the fluorescent nodes was compared to that of non-ICG nodes to assess their predictive value.ResultsSixteen patients were recruited with a total final lymph node count of 287. 78 fresh lymph nodes were identified on fresh dissection for both histological and OSNA assessment with an analytical concordance rate of 98.7% (77/78). OSNA sensitivity was 1 (0.81–1, 95% CI) and specificity 0.98 (0.91–1, 95% CI). Six patients had a total of nine nodes identified intraoperatively by ICG fluorescence. Of these nine nodes, one was positive for metastasis on OSNA. OSNA analysis of the ICG-labelled node matched the final histological nodal stage in 3/6 patients (two being N0 and one N1). The final pathological nodal stage of the other three was N1 or N2, while the ICG nodes were negative.ConclusionOSNA is highly concordant with standard histology, although only a minority of nodes identifiable by full pathological analysis were found for OSNA on fresh dissection. OSNA can be combined with NIR and ICG lymphatic mapping to provide intraoperative assessment of nodal tissue in patients with colorectal cancer.

Revealing determinant factors for early breast cancer recurrence by decision tree

Early breast cancer recurrence is indicative of poor response to adjuvant therapy and poses threats to patients’ lives. Most existing prediction models for breast cancer recurrence are regression-based models and difficult to interpret. We apply a Decision Tree algorithm to the clinical information of a cohort of non-metastatic invasive breast cancer patients, to establish a classifier that categorizes patients based on whether they develop early recurrence and on similarities of their clinical and pathological diagnoses. The classifier predicts for whether a patient developed early disease recurrence; and is estimated to be about 70% accurate. For an independent validation cohort of 65 patients, the classifier predicts correctly for 55 patients. The classifier also groups patients based on intrinsic properties of their diseases; and for each subgroup lists the disease characteristics in a hierarchal order, according to their relevance to early relapse. Overall, it identifies pathological nodal stage, percentage of intra-tumor stroma and components of TGFβ-Smad signaling pathway as highly relevant factors for early breast cancer recurrence. Since most of the disease characteristics used by this classifier are results of standardized tests, routinely collected during breast cancer diagnosis, the classifier can easily be adopted in various research and clinical settings.

How many lymph nodes is enough? Defining the optimal lymph node dissection in stage I-III gastric cancer using the National Cancer Database.

4034 Background: Gastric cancer is one of the most causes of cancer-related death worldwide. Surgical resection with lymph node dissection is the primary therapeutic modality. However, the appropriate extent of lymph node dissection remains controversial. Herein, the National Cancer Database (NCDB) was used to determine the optimal number of lymph nodes (LNs) to be dissected for resectable gastric cancer. Methods: The NCDB was queried from 2004-2013 for patients with invasive gastric cancer who underwent surgical resection with negative margins. The optimal number of LNs dissected was determined using a univariate χ2 cut-point analysis. Actuarial survival was determined using the Kaplan Meier method, and comparisons of survival estimates were completed with log-rank tests. Multiple sensitivity analyses were utilized to decrease bias. Results: 17,851 patients were included. The mean (±SD) number of LNs examined was 16 ± 11. For all patients, the optimal number of LNs needed to be examined was 20+ nodes. When correcting for stage migration ( < 7 LNs removed), the optimal cut-off value was 20+ LNs. When stratifying by pathologic nodal stage, the cutpoint was 10+ LNs for pN1 and pN2. The 5-year survival was 30.6 ± 1.6% for 0-9 removed LNs compared to 48.2 ± 1.2% for 10+ removed LNs (p < 0.001) in pN1 disease and 18.3 ± 1.7% for 0-9 removed LNs compared to 32.6 ± 1.2% for 10+ removed LNs (p < 0.001) in pN2 disease. For pN3 disease, the optimal cut-off point was 20+ LNs; the 5-year survival was 17.2 ± 1.3% for 0-19 removed LNs compared to 28.5 ± 1.7% for 20+ removed LNs (p < 0.001). Moreover, the outcome was inferior among patients who had > 10% positive dissected LNs (p < 0.05). Conclusions: The optimal number of dissected LNs of 20+ LNs was associated with superior survival. Extended LN dissection is to be considered especially in patients with > 10% positive dissected LNs.

Clinicopathological Factors of Cervical Nodal Metastasis and the Concept of Selective Lateral Neck Dissection in the Surgical Management of Carcinoma Larynx and Hypopharynx and Its Outcome.

To study the clinicopathological and molecular factors which correlate with nodal metastasis in laryngeal and hypopharyngeal carcinoma, a retrospective analysis of 170 patients who underwent surgery for laryngeal and hypopharyngeal carcinoma at RCC, Trivandrum from 2006 to 2010 was done. The pathological nodal stage and levels of involvement were correlated with the clinicopathologic features of the primary disease. Neck node positivity was significantly more for lesions of pyriform sinus lesion (61%), with thyroid cartilage erosion (56%) and with base tongue involvement (88%). Other clinicopathological factors have no impact on the disease-free survival and overall survival for patients with pathologically N0 status. Elective lateral neck dissection is advisable in cases with laryngeal cartilage erosion, pyriform sinus, supraglottis and base tongue involvement.

The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study.

This retrospective cohort study aimed to discuss the prognostic value of p53 positive in colorectal cancer. A total of 124 consecutive patients diagnosed with colorectal cancer were evaluated at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 1 January 2009 to 31 December 2010. The expression of p53 in colorectal cancer was examined by immunohistochemistry. Based on the expression levels of p53, the 124 patients were divided into a p53 positive group and a p53 negative group. In this study, 72 patients were in the p53 positive group and 52 in the p53 negative group. The two groups were well balanced in gender, age, body mass index, American Society of Anesthesiologists scores, and number of lymph nodes harvested. p53 positive was associated with carcinoembryonic antigen ≥5 ng/mL ( p = 0.036), gross type ( p = 0.037), degree of tumor differentiation ( p = 0.026), pathological tumor stage ( p = 0.019), pathological node stage ( p = 0.004), pathological tumor-node-metastasis stage ( p = 0.017), nerve invasion ( p = 0.008), and vessel invasion ( p = 0.018). Tumor site, tumor size, and pathological pattern were not significantly different between these two groups. Disease-free survival and overall survival in the p53 positive group were significantly shorter than the p53 negative group ( p = 0.021 and 0.025, respectively). Colorectal cancer patients with p53 positive tended to be related to a higher degree of malignancy, advanced tumor-node-metastasis stage, and shorter disease-free survival and overall survival. p53 positive was independently an unfavorable prognostic marker for colorectal cancer patients.

AURKA mRNA expression is an independent predictor of poor prognosis in patients with non-small cell lung cancer.

Deregulation of mitotic spindle genes has been reported to contribute to the development and progression of malignant tumours. The aim of the present study was to explore the association between the expression profiles of Aurora kinases (AURKA, AURKB and AURKC), cytoskeleton-associated protein 5 (CKAP5), discs large-associated protein 5 (DLGAP5), kinesin-like protein 11 (KIF11), microtubule nucleation factor (TPX2), monopolar spindle 1 kinase (TTK), and β-tubulins (TUBB) and (TUBB3) genes and clinicopathological characteristics in human non-small cell lung carcinoma (NSCLC). Reverse transcription-quantitative polymerase chain reaction-based RNA gene expression profiles of 132 NSCLC and 44 adjacent wild-type tissues were generated, and Cox's proportional hazard regression was used to examine associations. With the exception of AURKC, all genes exhibited increased expression in NSCLC tissues. Of the 10 genes examined, only AURKA was significantly associated with prognosis in NSCLC. Multivariate Cox's regression analysis demonstrated that AURKA mRNA expression [hazard ratio (HR), 1.81; 95% confidence interval (CI), 1.16-2.84; P=0.009], age (HR, 1.03; 95% CI, 1.00-1.06; P=0.020), pathological tumour stage 2 (HR, 2.43; 95% CI, 1.16-5.10; P=0.019) and involvement of distal nodes (pathological node stage 2) (HR, 3.14; 95% CI, 1.24-7.99; P=0.016) were independent predictors of poor prognosis in patients with NSCLC. Poor prognosis of patients with increased AURKA expression suggests that those patients may benefit from surrogate therapy with AURKA inhibitors.

Poorer prognosis associated with simultaneous lymphatic and vascular invasion in patients with squamous carcinoma of the thoracic oesophagus.

The objective of this study was to demonstrate the cumulative influence of simultaneous lymphatic and vascular invasion in thoracic oesophageal squamous carcinoma after radical operation. A total of 598 cases with thoracic oesophageal squamous carcinoma that were cured by radical open oesophagectomy and extensive lymphadenectomy in the period of 2002 to 2014 were included. An association of the status of lymphovascular invasion with clinicopathological factors and a recurrent pattern was illustrated. Overall survival and disease-free survival were calculated, and the risk factors for decreased disease-free survival were determined with Kaplan-Meier subset analyses and Cox regression analysis. The status of lymphovascular invasion was significantly associated with tumour differentiation ( P = 0.045) and the pathological tumour, node and metastasis stage ( P < 0.001), which includes the tumour intramural invasive depth (T parameter) as well as regional (N parameter) and distant (M parameter) lymph node involvement. The 1-, 3- and 5-year overall survival and postoperative disease-free survival were significantly decreased by lymphatic or vascular invasion alone ( P < 0.001) and were further decreased by simultaneous lymphatic and vascular invasion ( P < 0.001). The independent risk factors that predicted reduced disease-free survival were the following: T parameter ( P < 0.001, odds ratio: 1.436), N parameter ( P < 0.001, odds ratio: 1.838) and the status of lymphovascular invasion ( P < 0.001, odds ratio: 1.568). Simultaneous lymphatic and vascular invasion were significantly correlated with postoperative early recurrence ( P = 0.037). Simultaneous lymphatic and vascular invasion independently has a more adverse effect on prognosis than lymphatic or vascular invasion alone. Differentiating between lymphatic and vascular invasion is recommended in order to further study the role of lymphovascular invasion in cancer staging and prognostication in multicentre prospective studies.

Evaluation of Diagnostic Performance of Screening Thyroid Ultrasonography and Imaging Findings of Screening-Detected Thyroid Cancer.

PurposeThe purpose of this study was to evaluate the diagnostic performance and cost of screening thyroid ultrasonography (US) in an asymptomatic population and determine the US features of screening-detected thyroid cancer.Materials and MethodsThis study included 1,845 asymptomatic participants who underwent screening thyroid US between March and August 2012 at the screening center in our hospital. We evaluated the diagnostic performance of screening thyroid US for thyroid cancer and the average cost of diagnosis for each patient. We also determined the characteristic US features of screening-detected thyroid cancer.ResultsOf the 1,845 subjects, 661 showed no abnormalities, 1,155 exhibited benign thyroid nodules, and 29 exhibited thyroid cancer. Imaging features such as solid composition, hypoechogenicity, taller-than-wide axis, and ill-defined or spiculated margins of nodules were suggestive of malignancy. The rate of detection of cancer was 1.6% (29/1,845), and the sensitivity, specificity, and positive and negative predictive values were 100% (18/18), 98.7% (1,051/1,065), 56.3% (18/32), and 100% (1,051/1,051), respectively. Of 18 patients who underwent thyroidectomy, three (16.7%) had a pathological tumor staging of T3, and four (22.2%) had a pathological nodal staging of N1a. The average cost of diagnosis for each patient with cancer was $7,319.ConclusionScreening thyroid US exhibited a good diagnostic performance, with a feasible social cost of use. This modality demonstrated significant differences in sonographic features between screening-detected cancer and benign nodules.

Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma

Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11months, respectively (P<.001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P<.001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P<.001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging.

Abstract P2-01-39: Axillary reverse mapping using fluorescence imaging in the surgical treatment for breast cancer patients

Abstract Background: Axillary lymph node dissection (ALND) is the standard surgical treatment for breast cancer patients who have axillary nodal metastasis but do not meet the criteria of Z0011 trial. Arm lymphedema is one of the most common and serious complications of ALND. Based on the hypothesis that the lymphatic system of the upper extremity may be separate from that of the breast, the axillary reverse mapping (ARM) technique has been developed to identify the axillary lymph nodes and lymphatics that receive the lymph from the upper limb, and to preserve them during ALND in order to prevent arm lymphedema. However, it is difficult to keep the arm lymphatic system intact because of the lack of full understanding of anatomical variations of the ARM nodes and lymphatics in the axilla, the inconsistency of different ARM techniques in identifying the axillary ARM nodes, and the potentially high rate of ARM nodal metastases in breast cancer patients. The aims of this study was to know (1) the identification rate of ARM with fluorescence imaging (2) the distribution of these ARM nodes and (3) whether it's safe to spare the ARM nodes in breast cancer patients during SLNB or ALND. Method: Forty female patients of primary invasive breast cancer between 28 to 69 years old were included in the prospective study. Patients who had bilateral breast cancer, the history of axillary surgery, or the history of neoadjuvant chemotherapy were excluded. Methylene blue dye was used in the SLNB procedure. The ARM procedure was carried out to all the patients with a subcutaneous injection of the fluorescent dye indocyanine green into the medial bicipital sulcus in the upper arm about 15 minutes before SLNB or ALND. During surgery, photodynamic eye was used to detect the fluorescent nodes in the axilla. The fluorescent ARM nodes in the surgical region were removed and sent for pathological examination of node metastasis. Results: ARM was successful in 8 out of the 35 patients who underwent SLNB + ARM, in 3 out of the 5 patients who underwent ALND + ARM and in 25 out of the 35 patients who underwent ALND following SLNB + ARM. The ARM identification rate was 22.9%(8/35) in SLNB, and was 93.3%(28/30) in ALND. Totally, 119 fluorescent ARM nodes were detected, and 57.1 % (68/119) of them were located under the axillary vein, above the 2nd intercostobrachial nerve, and in the lateral of thoracic dorsal neurovascular bundle. Six out of 35 patients were found to have ARM-SLN crossover during SLNB+ARM procedure. Two out of 24 patients were found to have the ARM nodal metastases, with the pathological node stage being pN2, pN3 respectively. Conclusion: ARM with fluorescence imaging using indocyanine green was sensitive for identification of ARM nodes in ALND with a high success rate; ARM nodes had a certain distribution pattern in the axilla; ARM should not be performed to the patients with multiple nodal metastases in the axilla. Citation Format: Liu J, Li J, Zhou J, Cui H, Xiang J, Jia P, Xiang A, Chen H. Axillary reverse mapping using fluorescence imaging in the surgical treatment for breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-39.

Predictive factors for long-term survival after conversion surgery for unresectable gastric cancer: A retrospective analysis.

205 Background: Chemotherapy occasionally converts an initially unresectable gastric cancer to a resectable cancer. However, the association between clinical factors and long-term prognosis after conversion surgery for unresectable gastric cancer has not been investigated. Methods: We retrospective reviewed 36 gastric cancer patients who underwent conversion surgery at our institute between 2005 and 2015. Clinicopathologic characteristics and patient outcomes were analyzed, with particular focus on the potential to predict long-term survival. Results: The number of incurable factors was one in 31 patients and two in 5, including metastases to non-regional lymph node in 22, peritoneum in 10, liver in 6, and lung in 3. The regimen of chemotherapy was Docetaxel/CDDP/S-1 in 23 patients, Docetaxel/CDDP/S-1+Trastuzmab in 7, S-1/CDDP in 2, Docetaxel/S-1 in 1, CPT/CDDP in 1, and S-1 monotherapy in 1. Complete resection with no residual tumor (R0) was achieved in 25 of 36 patients, microscopic residual tumor status (R1) in 10, and macroscopic residual tumor (R2) in 1. The 3-year overall survival (OS) rate among the 36 patients who underwent conversion surgery was 60.3 % (median survival time, 1200 days). The 3-year OS rate among patients who underwent R0 resection was 70.8 % (median survival time, 1503 days). Patients who underwent R0 resection had significantly longer OS times than those who underwent R1 and R2 resection ( p=0.0124). We selected 16 variables in addition to residual tumor for Kaplan–Meier analysis. According to the log rank test, the following four variables were significantly associated with a better OS: clinical response to 1st line therapy (CR or PR vs. SD or PD)( p=0.0283), pathological response grade (1b-3 vs. 0-1a) ( p=0.0304), pathological tumor depth (CR or T1~T3 vs. T4) ( p=0.0261), and pathological nodal stage (N0〜2 vs. N3) ( p=0.0086). Conclusions: Our data indicates that clinical response to 1st line therapy in preoperative characteristics, R0 resection, pathological response grade, pathological tumor depth, pathological nodal stage in postoperative characteristics are predictive factors that can be expected to long-term survival.

Positive radial resection margin after esophagectomy for esophageal cancer patients treated at a tertiary center and its impact on survival.

162 Background: Although residual tumor at the radial margin can be expected to have a significant impact on the recurrence or overall survival of patient with node negative esophageal cancer (EC), its impact on recurrence and overall survival of patients with node positive EC has not been well characterized. Methods: A retrospective review of patients who underwent esophagectomy for EC at a single institution over a 16 year period (1999-2015) was performed. Pre-operative clinical parameters, stage as well as oncologic management were reviewed as well as the impact of positive radial margin on overall survival of pre-treatment node positive tumors was analyzed using descriptive statistics. Results: The study group consisted of 437 patients (46%) with pre-treatment stage IIB or III out of 945 patients with EC undergoing esophagectomy. The mean age of patients was 63 years with male predominance (85%). Neoadjuvant therapy (NAT) was administered to 87% of patients. Trans-thoracic surgery was performed in 86% of patients and trans-hiatal in 14%. Positive radial margin on final pathology was identified in 14 patients (3.2%); none of these had squamous histology. Neither the surgical approach nor the use of NAT was associated with radial margin positivity (p = 0.6). The median overall survival was significantly lower in the patients with positive radial margin when compared to the rest of the cohort (13.6 months v/s 41.2 months, p = 0.004). Moreover, when focused only on patients with post treatment pathologic T3 and T4 disease, margin positive disease remained associated with worse survival (p = 0.04). However, when final N status is included in multivariate analysis margin positivity loses significance. Conclusions: Radial margin positive disease after surgical resection for EC is associated with worse overall survival. This finding was significant regardless of the pathologic T stage; however, pathologic nodal staging was the most important factor for prognostication in locally advanced EC. Adenocarcinoma is the predominant pathology identified in patients with positive radial margin and concurrent node positivity.

Pathologic nodal response in gastric cancer: Do all patients need adjuvant therapy?

107 Background: Recent data from the MAGIC trial show that pathologically positive lymph nodes (ypN+) despite neoadjuvant (NA) chemotherapy are associated with poorer survival. Although the use of NA therapy has increased, pathologic disease response to multimodality therapy (MMT) and its impact on outcome have not been well-defined. Methods: This retrospective cohort study of the National Cancer Database included patients with cN+ gastric cancer who underwent NA therapy followed by surgical resection between 2006 and 2012. Patients were categorized by NA treatment (chemotherapy or concurrent chemoradiation). Pre-treatment clinical (cN) and pathologic nodal staging (ypN) were used to determine downstaging rates from cN+ to ypN0. The association between overall risk of death and NA treatment, nodal response, and the use of adjuvant therapy was evaluated with multivariable Cox regression. Results: Among 1,489 patients with cN+ gastric cancer receiving NA therapy, 45.5% were treated with chemotherapy and 54.5% with chemoradiation. Rates of nodal downstaging were 29.9% for chemotherapy and 45.4% for chemoradiation. On multivariable analysis, treatment sequence and type were not associated with risk of death. Median survival was significantly lower in patients with ypN+ compared to those with ypN0 disease (27.7 vs 79.7 months; log-rank, p &lt; 0.001).Among patients with ypN+ disease (n = 918), median survival was greater if adjuvant therapy was received (32.6 months vs. 25.3 months, log-rank, p &lt; 0.001); adjuvant therapy was associated with a 19% decreased risk of death (Hazard Ratio [HR] 0.81; 95% CI 0.66-0.99), with further reduction among those who underwent a margin negative resection (HR 0.73; 95% CI 0.58-0.92). In patients with ypN0, adjuvant therapy was not associated with a lower risk of death. Conclusions: Over one third of node-positive gastric cancers demonstrated pathologic nodal downstaging with NA treatment, with chemoradiation yielding a higher response than chemotherapy. Patients with ypN+ had worse survival, and appeared to benefit from adjuvant therapy. Future gastric cancer trials should better define the role for NA chemoradiation and help individualize the use of adjuvant therapy based on nodal response.

Local Excision Versus Total Mesorectal Excision for Clinical Stage I (cT1–cT2) Rectal Cancer

Early rectal cancer (cT1 and cT2) has been increasingly detected due to the wide application of colorectal cancer screening program. Total mesorectal excision (TME) is a gold standard for the treatment of this early stage disease. However, postoperative complications, unfavorable functional outcomes, and risk of permanent stoma following TME are not uncommon. In contrast, local excision (LE) is less invasive and more tolerable to frail patients and those with severe co-morbidities. Simultaneously, both functional and sexual outcomes following LE were not disturbed and the patient could avoid abdominoperineal resection. The drawback of LE is leaving perirectal lymph node yielding unknown actual pathological nodal staging—which partly leads to more recurrence comparing to TME. This article aimed to review the current evidence of TME and LE in early rectal cancer, to critically review the role and consequence of chemoradiation in LE, and to update ongoing trials on this subject.

Trends in multimodality therapy for gastric cancer post-MAGIC.

148 Background: Althoughmultimodality therapy (MMT) is recommended for most patients with resectable gastric cancer, no single approach has been established as standard. As such, little is known about current national practice patterns and MMT treatment sequencing for patients with gastric cancer. Methods: This was a retrospective cohort study of ≥ T2 and/or node positive gastric cancer patients treated with MMT using the National Cancer Database (2006-2012). Patients were categorized based on type of MMT (chemotherapy, concurrent chemoradiation (cXRT), or both chemotherapy and cXRT) and treatment sequence (preoperative, postoperative, or perioperative). Accuracy of pre-treatment clinical nodal staging was ascertained by comparison to pathologic nodal staging in patients treated with upfront surgery. Multivariable Cox regression was used to evaluate the association between overall risk of death and MMT type and sequence. Results: Among 4,857 patients, 14.1% were treated perioperatively, 48.0% preoperatively, and 37.9% postoperatively. Rates of chemotherapy, cXRT, and both chemotherapy and cXRT were 32.1%, 53.4%, and 14.5%. Among patients treated with upfront surgery, sensitivity, specificity, PPV, and NPV of clinical nodal staging were 70.7%, 88.8%, 92.1%, and 62.2%, respectively. Over the study period, use of cXRT decreased (61.8% 2006 vs 52.0% 2012; trend test, p &lt; 0.001) while use of chemotherapy increased (23.6% vs 35.7%; trend test, p &lt; 0.001) and use of both chemotherapy and cXRT did not change. There was an increase in the use of perioperative treatment (8.1% vs 17.4%; trend test, p &lt; 0.001) while postoperative treatment decreased (44.4% vs 31.1%; trend test, p &lt; 0.001). After multivariable modeling, neither type of MMT nor treatment sequence was associated with risk of death. Conclusions: Although current national practice patterns favor pre- and perioperative treatment, one third of patients were treated with upfront surgery. Survival was not associated with MMT type or sequence. However, given the high false negative rate of clinical nodal staging and high non-completion rate of postoperative treatment (50% in MAGIC trial), efforts to improve gastric cancer outcomes should focus on increasing use of preoperative therapy.

Lymph node pooling: a feasible and efficient method of lymph node molecular staging in colorectal carcinoma

Background Pathologic lymph node staging is becoming a deficient method in the demanding molecular era. Nevertheless, the use of more sensitive molecular analysis for nodal staging is hampered by its high costs and extensive time requirements. Our aim is to take a step forward in colon cancer (CC) lymph node (LN) pathology diagnosis by proposing a feasible and efficient molecular method in routine practice using reverse transcription loop-mediated isothermal amplification (RT-LAMP).ResultsMolecular detection of tumor cytokeratin 19 (CK19) mRNA with RT-LAMP was performed in 3206 LNs from 188 CC patients using two methods: individual analysis of 1449 LNs from 102 patients (individual cohort), and pooled LN analysis of 1757 LNs from 86 patients (pooling cohort). A median of 13 LNs (IQR 10–18) per patient were harvested in the individual cohort, and 18 LNs (IQR 13–25) per patient in the pooling cohort (p ≤ 0.001). The median of molecular assays performed in the pooling cohort was 2 per patient (IQR 1–3), saving a median of 16 assays/patient. The number of molecular assays performed in the individual cohort was 13 (IQR 10–18), corresponding to the number of LNs to be analyzed. The sensitivity and specificity of the pooling method for LN involvement (assessed by hematoxylin and eosin) were 88.9% (95% CI 56.5–98.0) and 79.2% (95% CI 68.9–86.8), respectively; concordance, 80.2%; PPV, 33.3%; NPV, 98.4%. The individual method had 100% sensitivity (95% CI 72.2–100), 44.6% specificity (95% CI 34.8–54.7), 50% concordance, 16.4% PPV, and 100% NPV. The amount of tumor burden detected in all LNs of a case, or total tumor load (TTL) was similar in both cohorts (p = 0.228).ConclusionsLN pooling makes it possible to analyze a high number of LNs from surgical colectomies with few molecular tests per patient. This approach enables a feasible means to integrate LN molecular analysis from CC specimens into pathology diagnosis and provides a more accurate LN pathological staging with potential prognostic implications.

Long-term outcome of breast cancer patients with pathologic N3a lymph node stage

PurposeTo evaluate factors influencing the long-term outcome of patients presenting with 10 or more metastatic axillary lymph nodes (pN3a) after surgery for primary breast cancer. MethodBetween January 1990 and December 2015, a total of 130 patients with pN3a breast cancer at surgery were identified in our Institutions and included in the study. Twenty-nine of them (22.3%) received neoadjuvant chemotherapy. The Multivariate Cox proportional hazards model was used to determine independent prognostic factors associated with DFS and OS. ResultsAfter a median follow-up of 6.4 years (range 0.87–25 years), 2 patients had a local relapse, 59 distant metastases (1 with local relapse) and 52 patients died. The 5-year DFS and OS rates were 61.8% and 71.5%, respectively. At multivariate analysis, pN3a stage after neoadjuvant chemotherapy (ypN3a) was significantly associated with increased risk of recurrence (HR 1.92, p = 0.02) and death (HR 2.05, p = 0.029). Absence of progesterone receptor (PR) expression was the most important tumor characteristic associated with poor prognosis, both in terms of recurrence (HR 2.55, p < 0.001) and death (HR 2.23, p = 0.019). High levels of Ki-67 index (≥20%) were significantly associated with a shorter OS (HR 2.03, p = 0.027), but not with DFS. ConclusionsThe results of this study indicate that ypN3a stage, lack of expression of PR, and Ki-67 ≥ 20% negatively affect long-term outcome of patients with pN3a breast cancer.

Neoadjuvant and adjuvant chemotherapy use in upper tract urothelial carcinoma

ObjectiveTo determine trends in neoadjuvant and adjuvant chemotherapy use for upper tract urothelial cancer and assess its effects on survival. Materials and methodsWe identified all patients diagnosed with upper tract urothelial cancer who underwent surgical treatment in the SEER-Medicare database from 2002 to 2011. We collected and analyzed patient demographic, clinical, and pathologic characteristics. We strictly defined neoadjuvant and adjuvant chemotherapy and studied patients who met such criteria. Multivariable Cox proportional hazards models identified were used to identify independent predictors of overall and cancer-specific survival. ResultsA total of 3,432 patients met inclusion criteria, and their median age was 77 years. Overall, 86.4% of patients underwent surgery alone, 1.8% received neoadjuvant chemotherapy plus surgery, and 11.8% underwent surgery and adjuvant chemotherapy. Neoadjuvant chemotherapy use increased during the study period. Gemcitabine, carboplatin, cisplatin, and paclitaxel were the most commonly used agents. Cancer-specific survival at 5 years was 65.0% (95% CI: 63.2%–66.8%). Cox proportional hazards modeling controlling for sex, race, year of diagnosis, location, and pathologic stage revealed that higher pathologic nodal stage, tumor size>3cm, increased age, and carcinoma in situ predicted for worse survival. ConclusionAge, nodal stage, and tumor size>3cm predict for worse cancer-specific survival. Neoajduvant chemotherapy is underused.

OA01.01 Institutional-Based Differences in the Quality and Outcomes of US Lung Cancer Resections

Institutional-level differences in NSCLC survival are associated with differences in the quality of oncologic care. We examined stage-stratified and overall survival of patients in different categories of US Commission-on-Cancer (CoC)-accredited institutions, to quantify inter-institutional differences in survival-impactful quality measures and estimate their relative survival impact, in order to identify the most impactful targets for improvement efforts. National Cancer Data Base (NCDB) institutions were grouped according to CoC category into: Community Cancer Program (CCP), Comprehensive Community Cancer Program (CCCP), Teaching Research Program (TRP), and NCI Program/Network (NCIP). Resections for stage I-IIIA NSCLC in the National Cancer Data Base from 2004-2013 performed within each category of institution were examined for specific quality parameters. Survival was estimated by the Kaplan-Meier method and compared with the log-rank test. Of 125,408 NSCLC eligible patients, 8% received surgery at CCP, 52% at CCCP, 28% at TRP, and 12% at NCIP. The pNX rate was 8%, 5.7%, 5.5%, and 3.2% respectively (p<.0001); the median (IQR) nodal count for pN0/1 patients was 6 (7), 7 (7), 8 (9), and 10 (10) respectively, and the CoC quality criterion attainment rate (examination of >10 nodes for stage I/II patents) was 25.5%, 30.2%, 38.7%, and 51.4% (p<.0001). The nodal upstaging rate from clinical (c) N0 to pathologic N-positive was 10.4%, 10.8%, 10.7% and 13.1% (p<.0001); for cN1, nodal upstaging rate was 9.4%, 10.5%, 10.4% and 15.5% (p<.0001). There was no significant inter-institutional difference in 5-year OS for stage I/II patients with pNX resections: 0.47 v 0.50 v 0.51 v 0.54 (log-rank p=.27), whereas stage I/II patients with resections meeting or failing the CoC quality standard had persistent inter-institutional survival differences. For those with <10 nodes, 5-year survival was 0.59 v 0.63 v 0.65 v 0.69 (log-rank p<.0001) and for those with >10 nodes, it was 0.62 v 0.64 v 0.67 v 0.69 (log-rank p<.0001). Striking differences in the quality and accuracy of NSCLC pathologic nodal staging exist between the different categories of CoC-accredited facilities. Institutions with higher quality staging have significantly better stage-stratified OS. This inter-institutional survival difference disappears in the patients without examination of any lymph nodes, who arguably have similarly bad quality pathologic nodal staging. However, adjustment for other measures of pathologic nodal staging quality failed to eliminate the inter-institutional survival disparity. Further investigation of inter-institutional practice differences is needed to understand the institutional-level difference in survival after lung cancer surgery.