Significant Predictors Of Recurrence Research Articles

Clinical Value of Lymph Node Ratio Integration with the 8th Edition of the UICC TNM Classification and 2015 ATA Risk Stratification Systems for Recurrence Prediction in Papillary Thyroid Cancer

Recently, the 2015 American Thyroid Association (ATA) risk stratification and the 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system were released. This study was conducted to assess the clinical value of the lymph node ratio (LNR) as a predictor of recurrence when integrated with these newly released stratification systems, and to compare the predictive accuracy of the modified systems with that of the newly released systems. The optimal LNR threshold value for predicting papillary thyroid cancer (PTC) recurrence was 0.17857 using the Contal and O’Quigley method. The 8th edition of the AJCC/UICC TNM staging system with the LNR and the 2015 ATA risk stratification system with the LNR were significant predictors of recurrence. Furthermore, calculation of the proportion of variance explained (PVE), the Akaike information criterion (AIC), Harrell’s c index, and the incremental area under the curve (iAUC) revealed that the 8th edition of the TNM staging system with the LNR, and the 2015 ATA risk stratification system with the LNR, showed the best predictive performance. Integration of the LNR with the TNM staging and the ATA risk stratification systems should improve prediction of recurrence in patients with PTC.

Association of fragmented QRS with left atrial scarring in patients with persistent atrial fibrillation undergoing radiofrequency catheter ablation

Fragmented QRS (fQRS) on 12-lead electrocardiography is a noninvasive marker of intramyocardial conduction delay due to ventricular scarring that has not previously been studied in atrial fibrillation. The purpose of this study was to assess the association of fQRS with left atrial (LA) scarring in patients with persistent atrial fibrillation (PsAF) undergoing first catheter ablation. A total of 376 patients with PsAF were enrolled. Severity of LA scarring was assessed using electroanatomic mapping. Narrow fQRS was defined by the presence of an additional R wave (R') or notching in the nadir of the S wave, or the presence of >1 R' in 2 contiguous leads corresponding to inferior, lateral, or anterior myocardial regions. Both any degree (97.3% vs 63.3%) and severe (42.2% vs 6.3%) LA scarring were higher in patients with fQRS. Age and fQRS were found to be independent predictors of severe LA scarring. At multiple ventricular regions, fQRS had diagnostic accuracy of 79.8% for prediction of severe LA scarring. Nonpulmonary vein triggers were more often detected and ablated in patients with fQRS and severe LA scarring (84.4% vs 70%; P = .001). Atrial tachyarrhythmia recurrence was observed in 131 patients (34.8%) during 18.9 ± 7.7 months of follow-up, which was significantly higher in patients with fQRS (53.2% vs 16.8%). In multivariate analysis, fQRS was found to be a significant predictor of recurrence (hazard ratio 4.65; 95% interval confidence 2.91-7.42; P <.001). The study results showed that fQRS is a simple, available, and noninvasive marker, and that fQRS at multiple ventricular regions is significantly associated with the severity of LA scarring in PsAF patients.

Long-term outcomes of cryoballoon-based left atrial appendage isolation in addition to pulmonary vein isolation in persistent atrial fibrillation.

Pulmonary vein isolation (PVI) alone in persistent atrial fibrillation (AF) is not as successful as in paroxysmal AF, and recent data indicate the key role of non-PV triggers. We aimed to assess the long-term safety and efficacy of left atrial appendage isolation (LAAi) as an adjunct to PVI using cryoballoon (CB) in persistent AF. We compared 144 persistent AF patients (59 ± 10 years, 51% females) who underwent PVI combined with LAAi with a propensity-score matched cohort of 138 persistent AF patients (59 ± 6 years, 52% female) in whom PVI-only was performed. Baseline and follow-up data including electrocardiography (ECG), 24-h Holter ECG's, and echocardiography were recorded for all patients. Atrial tachyarrhythmia (ATa) recurrence was defined as detection of AF, atrial flutter, or atrial tachycardia (≥30 s) after a 3-month blanking period. At a mean of 30.5 ± 5.6 months follow-up, 85 (61.6%) patients in the PVI-only group and 109 (75.7%) patients in the PVI+LAAi group were free of ATa after the index procedure (P = 0.008). Ischaemic stroke/transient ischaemic attack was detected in 4 (2.9%) patients in PVI-only group and in 5 (3.5%) patients in the PVI+LAAi group (P = 0.784). Cox regression analysis revealed that the PVI-only strategy was found as a significant predictor for recurrence (hazard ratio 3.01, 95% confidence interval 1.81-5.03; P < 0.001). Our findings indicated that CB-based LAAi+PVI was associated with a favourable efficacy compared to PVI-only strategy in patients with persistent AF. Although ischaemic event rates were similar between the groups, rigorous adherence to anticoagulation regime is paramount in order to prevent thrombo-embolic complications.

Sellar Remodeling after Surgery for Nonfunctioning Pituitary Adenoma: Intercarotid Distance as a Predictor of Recurrence.

Introduction As they grow, pituitary adenoma can remodel the sella turcica and alter anatomical relationships with adjacent structures. The intercarotid distance (ICD) at the level of the sella is a measure of sella width. The purpose of this study was to (1) assess how ICD changes after transsphenoidal surgery and (2) explore whether the extent of ICD change is associated with tumor recurrence. Methods A retrospective analysis of preoperative and postoperative coronal magnetic resonance imaging (MRI) scans was carried out by two independent assessors on patients who underwent transsphenoidal surgery for nonfunctioning pituitary macroadenomas. Preoperative tumor volume and any change in ICD following surgery were recorded and compared between groups. Logistic regression models of recurrence were generated. Results In 36 of 42 patients, ICD fell after surgery (mean = 1.8 mm) and six cases were static. At time of follow-up (mean = 77 months), 25 had not required further intervention and 17 had undergone second surgery or radiosurgery. In patients in whom no further intervention has yet been necessary, the postoperative reduction in ICD was significantly smaller than in those who required repeat intervention (1.1 vs. 2.7 mm respectively, p < 0.01). ICD decrease was weakly correlated with tumor volume ( r = 0.35). ICD decrease was a significant predictor of recurrence (odds ratio [OR] = 3.15; 95% confidence interval [CI]: 1.44-6.87), largely independent of tumor volume. Conclusion For most patients, ICD falls following surgical excision of a nonfunctioning pituitary macroadenoma. A greater reduction in ICD postsurgery appears to predict recurrence. Change in ICD shows promise as a radiographic tool for prognosticating clinical course after surgery.

Recurrence and Long-Term Survival Following Segmental Colectomy for Right-Sided Colon Cancer in 813 Patients: a Single-Institution Study

BackgroundControversy exists regarding optimal surgical approach to right-sided colon cancer due to increasing complete mesocolic excision outcome data; yet, scarce long-term surgical and oncologic outcome data from high-volume centers following right segmental resections without complete mesocolic excision make comparisons difficult to interpret. We report long-term outcomes following standard mesocolic excision for right-sided colon adenocarcinoma. MethodsA retrospective review of a prospective database was conducted of all consecutive adult patients undergoing surgery for a right-sided colon adenocarcinoma between 2000 and 2007. Demographics, oncologic, operative, and pathologic details are reported. Primary endpoints consisted of overall survival and recurrence. Patients with stage IV and recurrent disease were excluded. ResultsEight hundred thirteen patients were identified. Majority of tumors were stage II (n = 318, 39%). Adjuvant chemotherapy was administered to 228 patients (28%). Recurrence was observed in 97 patients (12%), at median 1.3 years. Recurrence was most commonly distant (n = 73, 9%). At median follow-up 7.3 years, 5- and 10-year overall survival was 72.4%, and 48.6%, respectively. Five- and 10-year disease-free survival was 67% and 45.8%, respectively. Multivariable analysis demonstrated that TNM stage was a significant predictor of recurrence. For disease-free survival, T stage, and N stage were significant on multivariate analysis. Multivariable predictors of overall survival included age, number of lymph nodes removed, N stage, and adjuvant chemotherapy use. ConclusionsExcellent long-term outcomes from a large cohort of patients with non-metastatic, right colon adenocarcinoma treated by segmental colectomy without complete mesocolic excision are reported. The majority of recurrences were distant.

Predictive Value of MRI in Diagnosing Brain AVM Recurrence after Angiographically Documented Exclusion in Children.

MRI is routinely performed following brain AVM after treatment in children. Our aim was to determine the predictive values of contrast-enhanced MR imaging and TOF-MRA for brain AVM recurrence in children, compared with conventional angiography and the role of 3D rotational angiography-MR imaging fusion in these cases. We included all pediatric patients with brain AVMs during an 18-year period with angiographically documented obliteration after treatment. Patients underwent 3T MR imaging, including contrast-enhanced MR imaging, TOF-MRA, and conventional angiography, with a subset undergoing 3D rotational angiography. The predictive values of contrast-enhanced MR imaging and TOF-MRA for brain AVM recurrence were determined. CTA sections reconstructed from 3D rotational angiography were coregistered with and fused to 3D-T1WI for analysis. Thirty-nine children (10.8 ± 3.9 years of age; range, 2-17 years; male/female ratio, 19:20; mean Spetzler-Martin grade, 1.9 ± 0.6) met the inclusion criteria. Of these, 13 had angiographically confirmed brain AVM recurrence, 8 following surgery and 5 following embolization. Sensitivity, specificity, and positive and negative predictive values for recurrence were the following: contrast-enhanced MR imaging: 84.6%, 38.5%, 40.7%, 81.8%; TOF-MRA: 50.0%, 96.1%, 85.7%, 79.3%; both: 75.0%, 90.9%, 85.7%, 83.3%. 3D rotational angiography-MR imaging fused images confirmed or excluded recurrence in all available cases (13/13). Embolization-only treatment was a significant predictor of recurrence (OR = 32.4, P = .006). MR imaging features predictive of recurrence included a tuft of vessels on TOF-MRA and nodular juxtamural/linear enhancement with a draining vein on contrast-enhanced MR imaging. MR imaging is useful for surveillance after brain AVM treatment in children, but conventional angiography is required for definitive diagnosis of recurrence. TOF-MRA and contrast-enhanced MR imaging provide complementary information for determining brain AVM recurrence and should be interpreted in conjunction. 3D rotational angiography-MR imaging fusion increases the diagnostic confidence regarding brain AVM recurrence and is therefore suited for intraoperative neuronavigation.

Tumor-Infiltrating Lymphocytes in a Contemporary Cohort of Women with Ductal Carcinoma In Situ (DCIS).

Growing evidence suggests that the tumor immune microenvironment influences breast cancer development and prognosis. Density of tumor-infiltrating lymphocytes (TILs) within invasive breast cancer is correlated with response to therapy, especially in triple-negative disease. The clinical relevance and outcomes of TILs within ductal carcinoma in situ (DCIS) are less understood. Our institutional database of 668 patients with pure DCIS from 2010 to 2018 was queried. TILs were evaluated by International TILs Working Group guidelines. Percentage of TILs was assessed from the densest focus (hotspot) in one high-power field of stroma touching the basement membrane. Statistical methods included cluster analyses (to define sparse versus dense TILs), logistic, and Cox regression models. Sixty-nine patients with DCIS and TILs were evaluated, of whom 54 (78%) were treated by breast-conserving surgery. Thirteen (19%) patients had ipsilateral recurrence. Each recurrence (n = 13) was matched to four controls (n = 56) based on date of surgery. Median follow-up was 6.7years. TILs were defined as sparse (< 45%) or dense (≥ 45%). Dense TILs were associated with younger age (p = 0.045), larger tumor size (p < 0.001), high nuclear grade (p = 0.010), comedo histology (p = 0.033), necrosis (p = 0.027), estrogen receptor (ER) negativity (p = 0.037), and ipsilateral recurrence (p = 0.001). Nine patients with dense TILs had mean time to recurrence of 73.5months compared with four patients with sparse TILs with mean time to recurrence of 97.9months (p = 0.003). Dense TILs were significantly associated with age, tumor size, nuclear grade, comedo histology, necrosis, and ER status and was a significant predictor of recurrence in patients with pure DCIS.

Composite criteria using clinical and FDG PET/CT factors for predicting recurrence of hepatocellular carcinoma after living donor liver transplantation.

Fluorodeoxyglucose (FDG) PET/CT is effective for predicting recurrence of hepatocellular carcinoma after liver transplantation. This study aimed to design composite criteria for predicting post-transplantation recurrence using clinical and FDG PET/CT factors. We retrospectively enrolled 239 patients who underwent living donor transplantation in two independent centers between 2005 and 2013. On PET, maximum tumor-to-background ratio (TBRmax) was measured. Significant predictors for recurrence were selected by logistic regression and survival analyses. With varying cutoff values for the selected factors, composite criteria were designed to maximize the predictive performance for recurrence, and tenfold cross-validation was performed. Predictive values were compared between the composite criteria and the conventional recipient selection criteria. Tumor size, number, alpha-fetoprotein, and TBRmax were selected as significant predictors in both logistic regression and multivariate survival analyses. In combination of these factors, the highest diagnostic performance was sensitivity of 75.7% and specificity of 88.5% with cutoff values of tumor size < 6.0cm, tumor number < 8, alpha-fetoprotein < 465ng/mL, and TBRmax < 2.8. The composite criteria exhibited the highest performance for predicting recurrence and recurrence-free survival among the tested criteria including conventional ones. The composite criteria adding FDG PET findings to clinical factors are effective in selecting appropriate liver cancer patients who are candidates for liver transplantation. • In patients with HCC, tumor uptake on FDG PET/CT, tumor size, number, and serum AFP level are recognized individual predictors for tumor recurrence after LT. • A composite criterion set, combining tumor size, number, serum AFP level, and maximum tumor-to-background ratio (TBR max ), predicts post-LT recurrence most effectively when compared with conventional criteria sets in selecting candidates for living donor LT.

Performance comparison of the methylated BCAT1/IKZF1 ctDNA test (COLVERA) with the CEA assay for detection of recurrent colorectal cancer.

3589 Background: Early detection of recurrent colorectal cancer (CRC) will improve treatment options, but the current standard blood test of carcinoembryonic-antigen (CEA) has suboptimal sensitivity for recurrence. This study compared performance of a quantitative circulating tumor DNA (ctDNA) assay for methylated BCAT1 and IKZF1 (COLVERA) with that of CEA. Methods: 301 patients were monitored for recurrence after clearance of primary CRC. Blood was collected at scheduled intervals and concentrations of CEA and ctDNA were measured using the LIAISON CEA test (Diasorin) and the COLVERA ctDNA test (Clinical Genomics). Surveillance for recurrent disease was examined using regular CT scans. Sensitivity of each blood test for recurrence was assessed in the sample collected closest to the time of imaging confirming recurrence status. Absence of recurrence was defined as at least two consecutive clear CT scans. Receiver operator characteristic (ROC) analyses were used to determine optimal positivity threshold for Colvera. Results: 131 patients underwent satisfactory assessment for recurrence and had blood testing performed within 12 months of determining recurrence status (61.8% male, mean age 62.6 ±.12.2(SD)y). Of the 47 recurrence cases, 37 (74%) were distant. The areas under the ROC curves were 0.7761 and 0.8188 for CEA and COLVERA, respectively (each p &lt; 0.001). An optimal cut-off of 12.8pg/sample was determined for COLVERA and the standard 5ng/mL cut-off was selected for CEA. COLVERA had a significantly higher sensitivity for detecting recurrence as compared to CEA (68.1% vs 31.9%, p &lt; 0.001) with a similar specificity (97.6% Vs 96.4%, p = 0.6547). A multivariate analysis determined COLVERA to be a predictor of recurrence independent of CEA with positive COLVERA samples being 66.4 times (95%CI 14.0-315.8) more likely to have recurrence confirmed within the study timeframe, whereas CEA was not a significant predictor of recurrence (p = 0.228). Conclusions: These findings indicate that COLVERA, reporting in quantitative mode, is a more sensitive test than CEA. It provides a viable alternative for sensitive and early detection of recurrent CRC. Clinical trial information: 12611000318987.

18F-FDG-PET/CT imaging of uterine cervical cancer recurrence in women with and without HIV infection.

To compare the rate, time and, pattern of recurrence of cervical cancer between patients with and without HIV infection and to determine factors predicting cervical cancer recurrence in patients evaluated by 18F-FDG-PET/CT. We reviewed the 18F-FDG-PET/CT images of patients with histologically proven cervical carcinoma who were presenting with suspected recurrence. We extracted epidemiologic data, previous treatment, histologic subtype, HIV status, viral load and CD4 counts from the electronic laboratory database and the referral form for the 18F-FDG-PET/CT study. We studied 303 women including 112 HIV-infected patients. FIGO stage III disease was present in 131 patients. Of 198 patients with recurrence, 74 were HIV-infected while 124 were not (P=0.849). HIV infected patients were younger (41.99±9.30 years) compared to HIV-uninfected (50.19±11.09), P<0.001. Local recurrence was present in 125 patients while 100 patients had a distant recurrence. Recurrence occurred at a single site in 88 patients and two or more sites in 110 patients. No significant difference in the recurrent patterns between HIV-infected and uninfected patients. Median time to recurrence was 10.50 months (range: 6.00-156.00) among HIV-infected versus 12.00 months (IQR:7.00-312.00) among the uninfected, P=0.065. FIGO stage III (P=0.042) and the presence of histological sub-types other than SCC (P=0.005) were significant predictors of recurrence. HIV infection by itself was not significant in predicting recurrence (P=0.843). HIV infection has no significant impact on the rate, time or pattern of recurrence in women with suspected cervical carcinoma recurrence. Advanced disease and histological variant other than SCC are predictive of recurrence.

Elective Laparoscopic Sigmoid Colectomy for Diverticulitis—an Updated Look at Recurrence After Surgery

BackgroundSurgical management of diverticulitis is evolving and the decision to offer elective sigmoidectomy for diverticulitis has become more individualized. However, preoperative variables that may predict recurrent diverticulitis after resection and guide surgical decision-making were not well studied. MethodsThis was a retrospective chart review with a prospective questionnaire follow-up of patients. Patients who underwent elective sigmoidectomy for diverticulitis from 2002 to 2016 at a tertiary academic colorectal surgery practice were included and their medical records reviewed. They were then contacted with a questionnaire to inquire about recurrence of diverticulitis since resection. The primary outcome was rate of recurrent diverticulitis after elective sigmoidectomy. The secondary outcome was risk factors for recurrence after sigmoidectomy. ResultsOf 662 patients who underwent elective sigmoidectomy for diverticulitis, 361 had long-term follow-up data available. Mean follow-up was 86 months. Indication for surgery was uncomplicated recurrent diverticulitis in 50%. Recurrent diverticulitis developed in 15 (4.2%) patients. Mean time to recurrence was 55 (range, 6–109) months. All recurrences were confirmed by CT scan. Univariate analysis showed that preoperative diagnosis of irritable bowel syndrome and uncomplicated recurrent diverticulitis was significantly more prevalent in patients who experienced recurrent diverticulitis after sigmoidectomy (p = 0.049 and p = 0.02); however, these variables did not predict recurrence after resection. ConclusionsOverall rate of recurrent diverticulitis after elective sigmoidectomy was 4.2%. Preoperative diagnosis of irritable bowel syndrome and uncomplicated recurrent diverticulitis was associated with but not significant predictor of recurrence after elective resection.

Usefulness of Failed Electrical Cardioversion for Early Recurrence After Catheter Ablation for Atrial Fibrillation as a Predictor of Future Recurrence

Early recurrence of atrial arrhythmia (ERAA) during a blanking period after catheter ablation (CA) for atrial fibrillation (AF) does not always result in subsequent AF recurrence. We investigated whether failed electrical cardioversion (ECV) during the blanking period was associated with recurrence. A total of 1,240 consecutive patients who underwent first-time CA for AF at our institution between March 2012 and March 2016 were investigated. Among the 517 patients (42%) who experienced ERAA, 262 underwent ECV. Failure or success of ECV was defined according to the current expert consensus statement. Failed ECV was defined as failure to terminate AF and/or relapse into AF within 30 seconds after transient sinus rhythm conversion by ECV with a shock energy of 270 J in this study. Of the patients, 254 (97%) with restored sinus rhythm were included, and 8 who experienced sustained AF afterward and discontinued the rhythm-control strategy were excluded. We divided the 254 patients into the following 2 groups on the basis of failed or successful ECV: failed-ECV (n = 105; at least 1 failed ECV but experienced successful ECV at a later date nevertheless) and successful-ECV (n = 149, no failed ECV) groups. At the median follow-up period of 610 days after CA, the recurrence rate was higher in the failed-ECV group than in the successful-ECV group (76.2% vs 45.6%, log-rank p < 0.001). After adjustment for baseline differences, failed ECV was found to be a significant predictor of recurrence in the multivariate model (p < 0.001). In conclusion, failed ECV for ERAA was an independent predictor of future recurrence.

MIB Index as Predictor of Recurrence in Sporadic Vestibular Schwannomas

Nearly 9.2% of vestibular schwannomas (VS) recur. We evaluate the association of cell proliferative markers like MIB with recurrence in VS. Retrospective data of 144 consecutive patients who underwent surgical excision for sporadic VS between January 2010 and July 2015 were collected. Comparison between groups based on recurrence of VS was done. The average age of the study population was 43.95 ± 12.86 years with 77 (53.5%) men. The average maximal diameter of VS was 40.25 ± 7.23 mm. Gross total resection was done in 52 (36.1%) patients. While near total resection was performed in 81 (56.3%) patients, the remaining 11 (7.6%) patients underwent a subtotal resection. The mean follow-up period was 37.99 ± 10.09 months (24-60). Recurrence of VS was observed in 18 (12.5%) patients. There was no difference between the groups for diameter of the tumor (42.22 ± 8.04 vs. 39.64 ± 7.00 mm; P= 0.191). The average MIB index value was higher in patients with recurrence of tumor at follow-up (4.78 ± 5.77 vs. 1.89 ± 1.48 mm; P < 0.001). There was no difference between the groups for extent of resection or postoperative complications. MIB was the only significant predictor for recurrence (β= 1.355 (1.07-1.78; confidence interval 95%); P= 0.031). On receiver operating characteristic curves, a cutoff value of 3.5% for MIB showed a specificity of 84.1%. MIB index ≥3.5% is associated with recurrence in VS. Maximal diameter of the tumor and extent of resection are perhaps not associated with recurrence of VS.

AROS is a significant biomarker for both short- and long-term prognosis in non-cirrhotic HCC

Purpose: Despite a low risk of liver failure and preserved liver function, non-cirrhotic HCC has poor prognosis. To improve clinical outcomes of the curative-intent treatment in non-cirrhotic HCC, identification of prognostic factors accompanied by new treatment strategies are needed. In the current study, we evaluated AROS as a prognostic biomarker in non-cirrhotic HCC. Methods: mRNA levels of AROS was measured in tumor and non-tumor tissues derived from 283 non-cirrhotic HCC patients. Relationships between clinical characteristics and AROS expression were analyzed using Chi square and Fisher's exact test. The prognostic significance of AROS expression was analyzed using Kaplan-Meier curves and Cox regression models. Results: AROS was significantly up-regulated in tumors irrespective of tumor stage and BCLC stage. Additionally, recurrent tissues revealed higher average levels of AROS than non-recurrent tissues for follow-up times of 2 years and 5 years and the differences were statistically significant. High mRNA levels of AROS were associated with tumor stage, BCLC stage, AFP level, vascular invasion, tumor size, and portal vein invasion. HCC patients with higher AROS levels showed higher recurrence and shorter DFS for both short-term and long-term compared to those with AROS-low group. Cox regression analysis demonstrated that AROS is a significant predictor for recurrence and DFS along with large tumor size, tumor multiplicity, vascular invasion, and poor tumor differentiation which are the known prognostic factors. Conclusions: Our findings on AROS as a prognostic biomarker could be helpful for designing a strategy for the effective treatment and management of non-cirrhotic HCC.

Analysis of recurrence after the resection of pancreatic neuroendocrine tumors.

Outcomes after recurrence of resected pancreatic neuroendocrine tumors (PNETs) are not well described. We aim to assess the rate and sites of recurrence, and its effect on clinical outcomes. Retrospective chart review of patients (n = 83) who underwent surgical resection of PNETs at 2 institutions. Patients were treated from September2002 to July2010. There were 13 (16%) recurrences. The most common site of recurrence was the liver (9 patients, 9.6%). The most common treatment of recurrences was chemotherapy (5 patients, 36%). The 1-, 3-, and 5-year disease-free survival was 90.9%, 82.7%, and 72.5%, respectively. Median recurrence-free survival was 127 months. The median follow-up for all PNET patients was 25.8 months (range, 1-140 months). The 3-year survival was 97%. The median follow-up of patients after the diagnosis of a recurrence was 13.8 months. The overall survival for those with and without recurrence was 96.3% and 100%, respectively (P = .36). The age ( P = .002) and lymph node ratio ( P < .001) were predictors of recurrence on multivariate analysis. Age and lymph node ratio are significant predictors of recurrence after the resection of PNETs with hepatic metastases being the most common. Survival of patients with recurrence is not significantly different from patients without recurrence.

Abstract 1558: STAG2 as a biomarker for prediction of recurrence in papillary non-muscle invasive bladder cancer

Abstract Purpose: Bladder cancer is the sixth most common human cancer. Most cases are early-stage tumors known as papillary non-muscle invasive bladder cancer (NMIBC). After resection, 60-70% of NMIBCs recur locally, and ~15% progress to muscle invasion and metastasis. There is an unmet need for a biomarker to stratify tumors on their likelihood of recurrence. Such a biomarker could make it possible to identify those patients most likely to benefit from adjuvant intravesical therapy such as BCG. Furthermore, lower-risk patients could become eligible for less frequent post-resection surveillance by cystoscopy than the extremely intensive current standard of care. We recently identified STAG2 as among the most commonly mutated genes in NMIBC and provided initial evidence that STAG2 mutant tumors may recur less frequently than STAG2 wild-type tumors. Here we report a STAG2 biomarker study using an independent cohort of clinically annotated papillary NMIBC tumors. Experimental Design: We identified all cases of papillary NMIBC treated at the Lombardi Comprehensive Cancer Center prior to 2013. STAG2 immunohistochemistry was performed and correlated with time to recurrence. This assay is particularly robust because (i) it utilizes a monoclonal antibody whose epitope is in the extreme carboxyl-terminus of STAG2, and ~85% of tumor-derived mutations of STAG2 are truncating; (ii) STAG2 is on the X-chromosome, so only a single mutation is required for complete gene inactivation; and (iii) STAG2 is among the most abundant proteins in the human proteome. Results: 52% of NMIBC tumors with STAG2 expression recurred, whereas only 25% of NMIBC tumors with loss of STAG2 expression recurred (p=0.017). Multivariate analysis identified STAG2 as the only significant independent predictor of recurrence (p=0.050). The relative risk of recurrence for patients with STAG2-expressing tumors was 2.408 times the risk for patients with STAG2-negative tumors. Conclusions: Here we demonstrate that a simple, robust assay for identifying STAG2-mutant tumors stratifies patients into two groups: (i) patients with retention of STAG2 expression (wild-type), ~52% of whom will recur; and (ii) patients with loss of STAG2 expression, of whom only ~25% will recur. Of note, STAG2 expression status, unlike pathologic grade–the current standard–was a significant predictor of recurrence. This information could help physicians make more informed decisions about the need for adjuvant immunotherapy/chemotherapy and also help inform the frequency of post-resection surveillance needed for individual patients. In conclusion, STAG2 is a simple, powerful, and potentially useful biomarker for prediction of recurrence in papillary NMIBC. Citation Format: Alana Lelo, Brent T. Harris, Deborah L. Berry, Krysta Chaldekas, Anagha Kumar, David Solomon, Jeffry Simko, Pritish Bhattacharyya, Ciaran Mannion, Jung-Sik Kim, George Philips, Todd Waldman. STAG2 as a biomarker for prediction of recurrence in papillary non-muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1558.

Incidence of Atrial Fibrosis in Non-Valvular Atrial Fibrillation Patients and its Impact on Recurrence after Pulmonary Vein Antral Isolation.

Atrial fibrillation (AF) is the most common sustained arrhythmia; it affects 1%-2% of the general population [1]. Many studies demonstrated an association between atrial fibrosis and AF [2]. There is increasing evidence that even in patients with lone AF; the AF is an arrhythmic manifestation of a structural atrial disease which has been described as fibrotic atrial cardiomyopathy [3]. It is unknown whether the presence of atrial fibrosis has any impact on post pulmonary vein antrum isolation outcome. This study aims to determine the incidence of atrial fibrosis in patients with non-valvular AF and its impact on recurrence after pulmonary vein antrum isolation. This study included twenty eight consecutive patients referred for first-time pulmonary vein antrum isolation for the treatment of symptomatic recurrent non-valvular AF not responding to medical treatment, Isolation of the pulmonary veins antra was performed using three dimensional electroanatomical mapping, detailed voltage map was done in the right and left atrium, before ablation and Low-voltage zones were identified. Follow up of the patients was done for 6 months after the procedure to detect recurrence of AF. Left atrium fibrosis was present in 6 (21.4%) cases, right atrium fibrosis was present only in 1 (3.6%) case and recurrence of atrial fibrillation after 6 months occurred in 12 (42.9%) cases. AF burden was significantly higher in the recurrence group [50.33 ±19.7 (48) (hour/month)] as compared to no recurrence group [29.5 ± 6.99 (32) (hour/month)] with P-value 0.002 and the incidence of left atrium fibrosis was significantly higher in the recurrence group as compared to no recurrence group with P-value 0.024. The only significant predictors of recurrence were the presence of left atrium fibrosis (OR 10.71, 95% CI 1.05 to 109.78; P=0.046) and AF burden (OR 1.14, 95% CI 1.02 to 1.27; P=0.023). The only significant predictor of the presence of left atrium fibrosis was AF burden (OR 1.06, 95% CI 1.01 to 1.13; P=0.031). The presence of the atrial fibrosis in the left atrium is an independent predictor of atrial fibrillation recurrence after pulmonary vein antrum isolation after 6 months without left atium substrate modification.

A 5-year follow-up study of 633 cutaneous SCC excisions: Rates of local recurrence and lymph node metastasis

A 5-year follow-up study of 633 cutaneous squamous cell cancer (SCC) excisions was performed by collecting data on rates of local recurrence (LR) and lymph node (LN) metastasis. A retrospective analysis of patients was performed across four regional plastic surgery centres (Stoke Mandeville Hospital, Aylesbury; John Radcliffe Hospital, Oxford; Salisbury District Hospital, Salisbury and Queen Alexandra Hospital, Portsmouth) assessing rates of LR and LN metastasis. We report 5-year outcomes from 598 SCCs (95% follow-up rate). The total recurrence rate (LR and LN metastasis) was 6.7% (n = 40) at 5 years, with 96% of these occurring within 2 years. Median time to LR was 9 months (1-57), with 76.9% (n = 20) undergoing further wide local excision. Median time to LN metastasis was 5.5 months (1-18 months). There were two cases of disease-related death. Only 15% (n = 6) of incomplete excisions recurred. Interestingly, 19.1% (n = 9) of 47 SCCs with perineural invasion on original histopathology recurred versus only 5.6% (n = 31) of the 551 SCCs without perineural invasion (p = 0.005). This study is one of the largest studies to date following up 598 SCC excisions at 5 years with total recurrence rates comparable to those in current published literature. We report perineural invasion as a significant predictor of recurrence and that 96% of total recurrence occurred within 2 years. This is in contrast to current UK guidelines (75% at 2 years, 95% at 5 years), thus suggesting that shorter length of hospital follow-up may be reasonable.

Predicting neo-adjuvant chemotherapy response and progression-free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F-18 FDG PET/CT and diffusion-weighted MR imaging.

Predicting response to neo-adjuvant chemotherapy (NAC) and survival in locally advanced breast cancer (LABC) is important. This study investigated the prognostic value of tumor heterogeneity evaluated with textural analysis through F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion-weighted imaging (DWI). We enrolled 83 patients with LABC who had completed NAC and curative surgery. Tumor texture indices from pretreatment FDG PET and DWI were extracted from histogram analysis and 7 different parent matrices: co-occurrence matrix, the voxel-alignment matrix, neighborhood intensity difference matrix, intensity size-zone matrix (ISZM), normalized gray-level co-occurrence matrix (NGLCM), neighboring gray-level dependence matrix (NGLDM), and texture spectrum matrix. The predictive values of textural features were tested regarding both pathologic NAC response and progression-free survival. Among 83 patients, 46 were pathologic responders, while 37 were nonresponders. The PET texture indices from 7 parent matrices, DWI texture indices from histogram, and 1 parent matrix (NGLCM) showed significant differences according to NAC response. On multivariable analysis, number nonuniformity of PET extracted from the NGLDM was an independent predictor of pathologic response (P = .009). During a median follow-up period of 17.3 months, 14 patients experienced recurrence. High-intensity zone emphasis (HIZE) and high-intensity short-zone emphasis (HISZE) from PET extracted from ISZM were significant textural predictors (P = .011 and P = .033). On Cox regression analysis, only HIZE was a significant predictor of recurrence (P = .027), while HISZE showed borderline significance (P = .107). Tumor texture indices are useful for NAC response prediction in LABC. Moreover, PET texture indices can help to predict disease recurrence.

Prognostic markers of recurrence and survival in rectal cancer treated with neoadjuvant chemoradiotherapy and surgery

Aim: To identify markers of recurrence and survival in patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy and surgery. Materials &amp; methods: A total of 280 patients were identified in Manitoba between 2007 and 2012. Demographics and clinical data were collected. Cox regression models were used to identify outcome predictors. Results: A total of 53 patients achieved pathological complete response (pCR) and 160 patients received adjuvant chemotherapy (ACT). The median follow-up duration was 2.06 years. Recurrence and survival rates at 5 years were 33.2 and 77.0%, respectively. pCR and lymphovascular invasion predicted recurrence. pCR and ACT predicted better survival. Conclusion: pCR is a significant predictor of recurrence and survival and may be considered as an oncological end point. The patients who achieve pCR may not derive additional survival benefit from ACT.