Independent Predictor Of Disease Recurrence Research Articles

Neutrophil–Lymphocyte Ratio and Absolute Lymphocyte Count as Prognostic Markers in Patients Treated with Curative-intent Radiotherapy for Non-small Cell Lung Cancer

AimsThe neutrophil–lymphocyte ratio (NLR) and the absolute lymphocyte count (ALC) have been proposed as prognostic markers in non-small cell lung cancer (NSCLC). The objective of this study was to examine the association of NLR/ALC before and after curative-intent radiotherapy for NSCLC on disease recurrence and overall survival. Materials and methodsA retrospective study of consecutive patients who underwent curative-intent radiotherapy for NSCLC across nine sites in the UK from 1 October 2014 to 1 October 2016. A multivariate analysis was carried out to assess the ability of pre-treatment NLR/ALC, post-treatment NLR/ALC and change in NLR/ALC, adjusted for confounding factors using the Cox proportional hazards model, to predict disease recurrence and overall survival within 2 years of treatment. ResultsIn total, 425 patients were identified with complete blood parameter values. None of the NLR/ALC parameters were independent predictors of disease recurrence. Higher pre-NLR, post-NLR and change in NLR plus lower post-ALC were all independent predictors of worse survival. Receiver operator curve analysis found a pre-NLR > 2.5 (odds ratio 1.71, 95% confidence interval 1.06–2.79, P < 0.05), a post-NLR > 5.5 (odds ratio 2.36, 95% confidence interval 1.49–3.76, P < 0.001), a change in NLR >3.6 (odds ratio 2.41, 95% confidence interval 1.5–3.91, P < 0.001) and a post-ALC < 0.8 (odds ratio 2.86, 95% confidence interval 1.76–4.69, P < 0.001) optimally predicted poor overall survival on both univariate and multivariate analysis when adjusted for confounding factors. Median overall survival for the high-versus low-risk groups were: pre-NLR 770 versus 1009 days (P = 0.34), post-NLR 596 versus 1287 days (P ≤ 0.001), change in NLR 553 versus 1214 days (P ≤ 0.001) and post-ALC 594 versus 1287 days (P ≤ 0.001). ConclusionNLR and ALC, surrogate markers for systemic inflammation, have prognostic value in NSCLC patients treated with curative-intent radiotherapy. These simple and readily available parameters may have a future role in risk stratification post-treatment to inform the intensity of surveillance protocols.

Recurrence after surgical resection of pancreatic cancer: the importance of postoperative complications beyond tumor biology.

Current treatment of potentially resectable pancreatic ductal adenocarcinoma (PDAC) includes pancreatic resection followed by adjuvant therapy. Aim of this study is to identify factors that are related with overall and early recurrence after pancreatectomy for PDAC. Retrospective analysis of patients with histologically confirmed PDAC who underwent pancreatectomy between September 2009 and December 2014. Early relapse was defined as recurrence within 12 months after surgery. Univariate/multivariate analysis was performed to identify prognostic factors for recurrence. 261 patients were included (54% males, mean age 67 years). Neoadjuvant and adjuvant treatments were performed in 55 (21%) and 243 (93%) patients. Overall morbidity was 56% with a rate of grade 3-4 Clavien-Dindo complications of 25%. Median disease-free survival was 18 months. Multivariate analysis identified nodal metastases (OR: 3.6) and perineural invasion (OR: 2.14) as independent predictors of disease recurrence in the entire cohort. 76 patients (29%) had an early recurrence. Poorly differentiated tumors (OR: 3.019) and grade 3-4 Clavien-Dindo complications (OR: 3.05) were independent risk factors for early recurrence. Although overall recurrence is associated with tumor-related factors, severe postoperative complications represent an independent predictor of early recurrence. Patients at increased risk of severe postoperative complications may benefit from neoadjuvant therapy.

Impact of lymph node density on prognosis of advanced laryngeal carcinoma with nodal metastasis

Objective: To determine the prognostic value of lymph node density (LND) as a predictor for tumor recurrence in patients with advanced laryngeal carcinoma undergoing curative surgery. Patients and methods: This is a prospective study, included 87 patients, diagnosed with locally advanced laryngeal carcinoma (T3 & T4a) and carried out total laryngectomy with neck dissection, presented to otorhinolaryngology outpatient clinic at faculty of medicine, Cairo university, Egypt, between June 2018 and May 2019. LND was determined by calculating the ratio between number of resected lymph nodes (LNs) positive for malignancy and total number of resected LNs. The mean follow up duration for tumor recurrence was 24 months (range 17 – 29 months).Results: LND, number of positive LNs, involved surgical margins, presence of metastatic LNs and adjuvant chemoradiation were statistically significant predictors for disease recurrence in univariate analysis. LND was the only independent predictor of recurrence in pathologically positive neck node (pN+) patients in multivariate analysis. In patients with LND > 0.066, hazard ratio for disease recurrence was 3.887 (P=0.021), and for nodal recurrence was 6.453 (P=0.008), reaching LND > 0.25 significantly increased hazard ratio for recurrence to 5.838 (P=0.001), and for nodal recurrence to 9.329 (P=0.001) compared with pN0 cases.Conclusion: LND was found to be the only independent predictor for disease recurrence in pN+ laryngeal cancer. LND should be used complementary to the conventional TNM staging to assess the precise risk of treatment failure and planning of possible postoperative adjuvant treatment.

Elevated neutrophil-to-lymphocyte ratio and predominance of intrahepatic cholangiocarcinoma prediction of poor hepatectomy outcomes in patients with combined hepatocellular-cholangiocarcinoma.

Although elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in some liver cancers, its prognostic relevance has not been studied in the context of combined hepatocellular cholangiocarcinoma CHCC-CC, a rare primary liver cancer. We investigated whether elevated NLR and a predominance of cholangiocarcinoma might predict poor prognosis in patients with resectable CHCC-CC. We retrospectively reviewed the clinicopathologic data of forty-two patients with CHCC-CC receiving hepatectomies at our hospital. We used Kaplan-Meier and Cox regression to analyze survival. Two-year disease-free survival and five-year overall survival rates were 43.2% and 32.9%, respectively. Univariate analyses showed that patients with NLR ≥3 had significantly worse 2-year DFS and 5-year OS rates. Univariant Kaplan-Meier survival analysis also associated these rates with a predominance in intrahepatic cholangiocarcinoma, AJCC tumor stage, pathological T stage and lymph-vascular invasion. However, our multivariate analysis found NLR ≥3 to be the only independent predictor of disease recurrence and poorer survival. Neutrophil-to-lymphocyte ratio was the most important independent predictor of poorer survival in patients with resectable CHCC-CC. Predominance of intrahepatic cholangiocarcinoma, advanced AJCC tumor stage and pathological T stage, and lymph-vascular invasion also may affect poor prognosis in patients receiving complete tumor resections.

A model based on tumor-infiltrating immune cells for predicting the relapse rates of patients with testicular germ cell tumors

ObjectiveThe activities of tumor-infiltrating immune cells (TIICs) play an important role in the outcomes of many types of cancers. Here, we sought to describe the landscape of TIICs in testicular germ cell tumors (TGCT) and to develop a prognostic model based on this information. MethodsThe Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to determine the proportions of 22 types of TIICs in a TGCT dataset (n = 74). Univariate and multivariate Cox regression analysis were used to develop an immune risk score (IRS) based on the association between TIICs and disease-free survival (DFS). The predictive accuracy of the IRS was evaluated using receiver operating characteristic curves, and the predictive accuracy of a prognostic nomogram was assessed using C-index and calibration curves. The biological functions of IRS-associated genes were evaluated by gene set enrichment analysis. ResultsThe relative abundances of three TIICs (plasma cells, M2 macrophages, and resting mast cells) were significantly associated with DFS in TGCT patients. In receiver operating characteristic curve analysis, the resulting IRS had areas under the curve of 0.70, 0.793, and 0.827, for predicting 1-, 2-, and 3-year DFS, respectively. Kaplan–Meier analysis confirmed that DFS was shorter for patients with high IRS compared with low IRS. IRS was an independent predictor of disease recurrence (hazard ratio 1.306, 95% confidence interval 1.022–1.668; P = 0.033). The C-index for the nomogram was 0.733. Genes involved in cancer-associated and immunity-associated pathways were enriched in TGCT samples from patients in the high- and low-risk groups, respectively, and expression of four immune checkpoint regulators was significantly lower in the high IRS group compared with the low IRS group. ConclusionsA TIIC-based IRS may have utility as a complementary tool to predict relapse in patients with TGCT.

MP50-10 LONG-TERM RISK OF RECURRENCE IN SURGICALLY TREATED RENAL CELL CARCINOMA: A POST-HOC ANALYSIS OF THE EASTERN COOPERATIVE ONCOLOGY GROUP - AMERICAN COLLEGE OF RADIOLOGY IMAGING NETWORK (ECOG-ACRIN) E2805 TRIAL COHORT

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging/Surveillance I (MP50)1 Apr 2020MP50-10 LONG-TERM RISK OF RECURRENCE IN SURGICALLY TREATED RENAL CELL CARCINOMA: A POST-HOC ANALYSIS OF THE EASTERN COOPERATIVE ONCOLOGY GROUP - AMERICAN COLLEGE OF RADIOLOGY IMAGING NETWORK (ECOG-ACRIN) E2805 TRIAL COHORT Marcus Jamil*, Jacob Keeley, Akshay Sood, Deepansh Dalela, Sohrab Arora, James Peabody, Quoc-Dien Trinh, Mani Menon, Craig Rogers, and Firas Abdollah Marcus Jamil*Marcus Jamil* More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Akshay SoodAkshay Sood More articles by this author , Deepansh DalelaDeepansh Dalela More articles by this author , Sohrab AroraSohrab Arora More articles by this author , James PeabodyJames Peabody More articles by this author , Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author , Mani MenonMani Menon More articles by this author , Craig RogersCraig Rogers More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000912.010AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Optimal post-operative surveillance for surgically resected renal cell carcinoma (RCC) remain unclear. Our primary objective was to revisit the recurrence rates of surgically treated RCC using randomized clinical trial data to determine recurrence rates. Secondary objective aimed to assess the long-term durability in clinical and pathological features in predicting disease recurrence at 0 and 60-months. METHODS: A post-hoc analysis of patients in the ECOG-ACRIN E2805 Trial was performed. Primary objective was assessed using 36-month cumulative incidence of recurrence at set intervals following surgery. Secondary objective was assessed by preforming multivariable competing risks analysis between all available covariables in the entire cohort at entry and in patients who did not have recurrence at 60-months from surgery. RESULTS: Total of 1943 patients, all with intermediate- or high-risk disease, of which 730 developed recurrence. Median follow-up 67.9 months. 36-month cumulative incidence of recurrence was found to be 31.1%, 26.0%, 18.8%, 16.1%, 18.9% and 20.3 for patients who did not have recurrence at 0, 12-, 24-, 36-, 48- and 60-months from surgery, respectively (Figure 1). At 0-months from surgery; age (hazard ratio (HR): 1.01, 95% confidence interval [CI]: 0.99 – 1.03), pathologic T3/4 stage (HR: 1.74 95%CI: 1.3 - 2.31), pathologic N1/2 stage (HR: 2.38, 95%CI: 1.85 - 3.07), Fuhrman grade 3 (HR: 1.36, 95%CI: 1.14 - 1.62), and Fuhrman grade 4 (HR: 2.36, 95%CI: 1.92 - 2.9) were independent predictors of disease recurrence. Conversely, none of the aforementioned covariables were predictors of recurrence at 60-months following surgery (Table 1). CONCLUSIONS: These findings support surveillance imaging be performed beyond 5-years following surgical resection of intermediate- to high-risk RCC. Also the usual predictors of recurrence early in the surveillance period lose their predictive capacity at 5-years. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e756-e757 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marcus Jamil* More articles by this author Jacob Keeley More articles by this author Akshay Sood More articles by this author Deepansh Dalela More articles by this author Sohrab Arora More articles by this author James Peabody More articles by this author Quoc-Dien Trinh More articles by this author Mani Menon More articles by this author Craig Rogers More articles by this author Firas Abdollah More articles by this author Expand All Advertisement PDF downloadLoading ...

PD08-10 LOCAL ABLATION OF RENAL TUMORS: REAL COMPETITOR OF PARTIAL NEPHRECTOMY? A PROPENSITY-SCORE MATCHING ANALYSIS

You have accessJournal of UrologyKidney Cancer: Localized: Ablative Therapy (PD08)1 Apr 2020PD08-10 LOCAL ABLATION OF RENAL TUMORS: REAL COMPETITOR OF PARTIAL NEPHRECTOMY? A PROPENSITY-SCORE MATCHING ANALYSIS Lorenzo Bianchi, Pietro Piazza*, Riccardo Schiavina, Francesco Chessa, Amelio Ercolino, Matteo Droghetti, Alessandro Colella, Angelo Mottaran, Martina Masetti, Carla Serra, Caterina Gaudiano, Bernardino De Concilio, Antonio Celia, and Eugenio Brunocilla Lorenzo BianchiLorenzo Bianchi More articles by this author , Pietro Piazza*Pietro Piazza* More articles by this author , Riccardo SchiavinaRiccardo Schiavina More articles by this author , Francesco ChessaFrancesco Chessa More articles by this author , Amelio ErcolinoAmelio Ercolino More articles by this author , Matteo DroghettiMatteo Droghetti More articles by this author , Alessandro ColellaAlessandro Colella More articles by this author , Angelo MottaranAngelo Mottaran More articles by this author , Martina MasettiMartina Masetti More articles by this author , Carla SerraCarla Serra More articles by this author , Caterina GaudianoCaterina Gaudiano More articles by this author , Bernardino De ConcilioBernardino De Concilio More articles by this author , Antonio CeliaAntonio Celia More articles by this author , and Eugenio BrunocillaEugenio Brunocilla More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000835.010AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Due to the low morbidity, local tumor ablation (LTA) like Cryoablation (Cryo) and Radiofrequency ablation (RFA), are gaining popularity as alternative to PN. The aim of our study is to compare oncologic outcomes in patients treated with PN and LTA in a matched cohort of patients with T1 renal mass. METHODS: We identified a retrospective population of patients underwent LTA (percutaneous Cryo or RFA n=146) or PN (open, laparoscopic or robotic; n=594) in two tertiary centers. A propensity score 1:1 match (adjusting for age, Charlson Comorbidity Index [CCI], clinical size of tumor, PADUA score and preop eGFR) analysis was performed between the two groups (LTA n=146 and PN n=146). Clinicopathologic, perioperative and oncologic outcomes were compared. Finally, cumulative-incidence plots were generated for cancer specific mortality (CSM) and other causes mortality (OCM) according to the competing-risks method, after stratifying patients by treatments (LTA vs PN) and age (≤70 yrs vs >70 yrs). RESULTS: No significant differences were found between the two groups concerning preoperative patients’ and tumor’s characteristics. Post-operative complications rate was higher in the PN group compared to LTA group (26% vs 11% p=0.001). The median hospital stay was lower in the LTA group compared to PN group (2 vs 5 days p<0.001). The 8-yrs disease free survival (DFS) rates were 72% and 89% in LTA group and PN group (p=0,001). After stratifying according to technique (RFA vs Cryo vs PN), the 8-yrs DFS rates were 67% vs 76% vs 89% (RFA vs PN p<0.001; RFA vs Cryo p=0.3; Cryo vs PN p=0.1). At multivariate analysis CCI (Hazard ratio [HR] 1.58), number of synchronous tumors (HR 5.18) and LTA (HR 5.33) were independent predictors of disease recurrence (all p≤0.002). The 10-yr CSM rates were 6.7% vs 6.2% for patients aged ≤70 years and 2.2% vs 6.5% for patients aged >70 years treated with PN and PCA. The 10-yr OCM rates was 0% and 2.7% for patients treated with PN and ablative techniques aged ≤70 years and 9.1% vs 39% for patients aged >70 year treated with PN and ablative techniques, respectively. CONCLUSIONS: LTA are affected by higher rates of cancer recurrence compared to PN. However, due to reduced risk of complications, PCA are attractive alternative to PN in patients unfit for surgery or when the preservation of renal function is essential. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e172-e172 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lorenzo Bianchi More articles by this author Pietro Piazza* More articles by this author Riccardo Schiavina More articles by this author Francesco Chessa More articles by this author Amelio Ercolino More articles by this author Matteo Droghetti More articles by this author Alessandro Colella More articles by this author Angelo Mottaran More articles by this author Martina Masetti More articles by this author Carla Serra More articles by this author Caterina Gaudiano More articles by this author Bernardino De Concilio More articles by this author Antonio Celia More articles by this author Eugenio Brunocilla More articles by this author Expand All Advertisement PDF downloadLoading ...

Overall tumor genomic instability: an important predictor of recurrence-free survival in patients with localized clear cell renal cell carcinoma

ABSTRACTMeasurement of a tumor’s overall genomic instability has gathered recent interest over the identification of specific genomic imbalances, as it may provide a more robust measure of tumor aggressiveness. Here we demonstrate the association of tumor genomic instability in the prediction of disease recurrence in patients with clinically localized clear cell renal cell carcinoma (ccRCC). Genomic copy number analysis was performed using SNP-based microarrays on tumors from 103 ccRCC patients. The number of copy number alterations (CNAs) for each tumor was calculated, and a genomic imbalance threshold (GIT) associated with high stage and high-grade disease was determined. Cox proportional hazards regression analyzes were performed to assess the effect of GIT on recurrence-free survival adjusting for known confounders. In the cohort, copy number losses in chromosome arms 3p, 14q, 6q, 9p, and 1p and gains of 5q and 7p/q were common. CNA burden significantly increased with increasing stage (p < .001) and grade (p < .001). The median CNA burden associated with patients presenting with advanced stage (IV) and high-grade (III/IV) tumors was ≥9, defining the GIT. On regression analysis, GIT was a superior predictor of recurrence (Hazard Ratio 4.44 [CI 1.36–14.48], p = .01) independent of stage, with similar results adjusting for grade. These findings were confirmed using an alternative measure of genomic instability, weighted Genomic Integrity Index. Our data support a key role for genomic instability in ccRCC progression. More importantly, we have identified a GIT (≥ 9 CNAs) that is a superior and independent predictor of disease recurrence in high-risk ccRCC patients.

Abstract GS5-02: Detection of circulating tumor DNA (ctDNA) after neoadjuvant chemotherapy is significantly associated with disease recurrence in early-stage triple-negative breast cancer (TNBC): Preplanned correlative results from clinical trial BRE12-158

Abstract Background: A significant proportion of patients with early-stage TNBC are treated with neoadjuvant chemotherapy (NAC). Sequencing of ctDNA after surgery can be used to detect minimal residual disease and predict which patients may experience clinical recurrence. Methods: BRE12-158 is a recently completed Phase II clinical trial which randomized early-stage TNBC patients with residual disease after NAC to post-neoadjuvant genomically-directed therapy vs treatment of physician choice. 151 patients had a plasma sample collected at the time of treatment assignment (after surgery and radiation). ctDNA was successfully sequenced in 150 patients. 148 of the 150 sequenced patients had clinical follow-up. Sequencing was performed by Foundation Medicine using the FoundationOne Liquid assay which profiles for 70 commonly mutated oncogenes. Presence of mutated ctDNA was associated with distant disease free survival (DDFS) and overall survival (OS) in univariate analysis using the Log-Rank test, and in multi-variate analysis using Cox proportional hazards model. Results: Mutated ctDNA was detected in 94 of 148 sequenced patients (64%). TP53 was the most commonly mutated gene consistent with prior genomic studies of TNBC. At 16.7 months of median follow-up, detection of ctDNA was significantly associated with an inferior DDFS (median DDFS 32.5 months vs. Not Reached, p=0.0030). At 24 months, the DDFS probability was 53% in ctDNA-positive patients as compared to 81% in ctDNA-negative patients. In multi-variate analysis, when considering significant covariates, including: residual cancer burden (RCB); number of positive lymph nodes; tumor size; stage; grade; age; and race; detection of ctDNA remained independently associated with inferior DDFS (HR=3.1, CI: 1.4-6.8, p=0.0048). Similarly, detection of ctDNA was associated with inferior OS in univariate (p=0.021) and multi-variate analysis (HR=2.7, CI:1.1-6.2, p=0.022). Lastly, we observed a correlation between higher maximum somatic allele frequency and a shorter DDFS interval in multivariate analysis (HR=4.7, CI: 1.04-21.1, p=0.044) and shorter OS (HR=4.9, CI:1.06-22.4, p=0.041), suggesting that the quantitative degree of ctDNA burden is associated with clinical outcome. Conclusions: Detection of ctDNA in early-stage TNBC after neoadjuvant chemotherapy is an independent predictor of disease recurrence, and represents an important novel stratification factor for future post-neoadjuvant trials. Citation Format: Milan Radovich, Guanglong Jiang, Christopher Chitambar, Rita Nanda, Carla Falkson, Filipa C. Lynce, Christopher Gallagher, Claudine Isaacs, Marcelo Blaya, Elisavet Paplomata, Radhika Walling, Karen Daily, Reshma Mahtani, Michael A. Thompson, Robert Graham, Maureen E. Cooper, Dean C. Pavlick, Lee Albacker, Jeff Gregg, Casey L. Bales, Bradley A. Hancock, Erica Cantor, Fei Shen, Anna Maria V. Storniolo, Sunil Badve, Tarah Ballinger, Kathy D. Miller, Bryan P. Schneider. Detection of circulating tumor DNA (ctDNA) after neoadjuvant chemotherapy is significantly associated with disease recurrence in early-stage triple-negative breast cancer (TNBC): Preplanned correlative results from clinical trial BRE12-158 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS5-02.

Microscopic Positive Tumor Margin Increases Risk for Disease Persistence but Not Recurrence in Patients with Stage T1-T2 Differentiated Thyroid Cancer.

Introduction Differentiated thyroid cancer (DTC) has an overall excellent prognosis. Patients who develop recurrent disease have a more unfavorable disease course than those with no recurrence. Higher recurrence rates are seen with incomplete surgical resection and gross positive margins. It is unclear whether microscopic positive margin affects disease recurrence rates as much as grossly positive margin. Aim of the Study. To assess whether microscopic positive margin is an independent predictor of disease recurrence in patients with overall low-risk DTC. Patients and Methods. We conducted a retrospective single-center institutional review of 1,583 consecutive patients' charts from 1995–2013 using the Canadian Thyroid Cancer Consortium Registry. We included adult patients with nonmetastasizing T1 and T2 DTC with a minimum of three years follow-up. Univariate and multivariate analyses were used to study factors that may influence the risk of persistent/recurrent disease. Strict definitions of persistent versus recurrent disease were applied. Results 963 patients (152 men and 811 women) were included in the study with a mean age of 46 years. Microscopic positive margins were present in 12% of the specimens and were associated with an increased rate of persistent disease (8% versus 2% in the controls) but not with an increased risk of recurrent disease (1% in both groups). T2 tumors had a significantly higher incidence of positive margins than T1 tumors (48% versus 36%) and significantly higher nodal staging. Conclusions Microscopic positive margin in the histopathology report in patients with low-risk DTC was associated with a higher rate of persistent disease but did not increase the risk of disease recurrence. A close follow-up of biomarkers and occult residual cancerous lesions is needed, especially in the first year. Further studies are needed to determine whether additional therapeutic measures to prevent recurrence are indicated in T1 and T2 DTC with positive microscopic surgical margins.

Prognostic Significance of Neoadjuvant Rectal Score and Indication for Postoperative Adjuvant Therapy in Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy.

Neoadjuvant chemoradiotherapy (CRT) is a standard treatment for patients with clinical Stage II/III rectal cancer. However, the benefit of postoperative adjuvant chemotherapy for patients after neoadjuvant CRT is uncertain. Recently, neoadjuvant rectal (NAR) score was suggested as an independent prognostic factor for patients with rectal cancer after neoadjuvant CRT. The aim of this study was to examine the prognostic significance of NAR score in rectal cancer patients who underwent neoadjuvant CRT followed by surgery, and to investigate which patients may benefit from postoperative adjuvant therapy. A total of 72 patients who underwent neoadjuvant CRT followed by R0 resection for clinical stage II /III rectal cancer were evaluated. The correlation between NAR score, various clinicopathological factors and disease recurrence were evaluated. Disease recurrence was significantly more often observed in patients with incomplete neoadjuvant CRT, tumor regression grade (TRG) 3-4, and high NAR score. Multivariate analysis revealed that NAR score was an independent predictor of disease recurrence. NAR score may be one of the predictive markers for disease recurrence in patients who underwent neoadjuvant CRT followed by surgery for rectal cancer. Patients with a low NAR score may benefit form postoperative adjuvant chemotherapy.

Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder

ObjectivesCheckpoint inhibitors are approved for the treatment of urothelial bladder cancer. However, there have been no reports on the prognostic value of programmed-death receptor ligand 1 (PD-L1) expression in squamous cell carcinoma (SCC) of the bladder. We assessed the relationship between PD-L1 expression, clinicopathological features, and oncologic outcomes in bladder SCC. Methods and materialsImmunohistochemistry of PD-L1 was performed on 151 radical cystectomy specimens with pure SCC treated in Mansoura, Egypt from 1997 to 2004. ResultsMedian patient age was 52 years (range: 36–74 years) and median length of follow up was 63 months (range: 1–100 months). Schistosomiasis was present in 81% of the specimens and 93% had muscle-invasive disease on pathologic staging. PD-L1 expression was negative in 50 (33%) of the specimens. Negative PD-L1 expression was associated with higher pathologic tumor stage (P = 0.04), higher grade lesions (P = 0.01), and the presence of lymphovascular invasion (P < 0.01). Kaplan-Meier analyses showed that negative PD-L1 expression is associated with worse recurrence-free (P = 0.01) and worse cancer-specific survival (P = 0.01). Multivariable Cox regression analyses showed negative PD-L1 expression was an independent predictor of disease recurrence (hazards ratio 2.05, 95% confidence interval 1.06–3.96, P = 0.03) and cancer-specific mortality (hazards ratio 2.89, 95% confidence interval 1.22–6.82, P = 0.02). ConclusionsNegative PD-L1 expression is associated with higher pathologic tumor stage, higher grade lesions, presence of lymphovascular invasion, and worse oncologic outcomes after radical cystectomy for SCC. These findings support the need for the inclusion of patients with bladder SCC into immunotherapy clinical trials.

Stanniocalcin-2 May Be a Potentially Valuable Prognostic Marker in Endometrial Cancer: a Preliminary Study.

In the current study, we primarily aimed to investigate stanniocalcin-2 (STC2) protein expression pattern in hysterectomy specimens from patients with endometrioid type endometrial cancer (EC) using immunohistochemistry. Secondly, in order to clarify its prognostic impact, we examined relationships of the expression levels of STC2 with clinicopathologic features and outcome of patients. Histopathology slides of 49 patients were stained with the monoclonal mouse antibody targeting STC2 protein. The expression levels of STC2 were classified based on three-tiered semiquantitative scheme: negative expression, expression level of 0; low-expression, expression level of 1+; and high-expression, expression levels of 2+ and 3+. Recurrence-free survival (RFS) was used as the primary prognostic outcome. Immunohistochemical analysis revealed that 73.5% of tissue samples exhibited positive staining with STC2. The intensity of staining with STC2 was weak in 40.8%, moderate in 22.4%, and strong in 10.2%. Thirty-eight percent of samples showed negative expression; 18.4%, low-expression (1+); and 42.8%, high-expression (2 to 3+). High-expression of STC2 was significantly associated with grade 2-3 tumors (p = 0.026) and disease recurrence (p = 0.013). Multivariate analysis revealed that both the tumor grade and STC2 were independent predictors of disease recurrence. Kaplan-Meier analyses confirmed that patients with high-expression of STC2 had a significantly poorer RFS than those with negative or low STC2 expression (p = 0.037); although overall survival did not differ with respect to expression levels of STC2 (p = 0.148). In conclusion, high-expression of STC2 is a negative prognostic factor, associated with increased risk of recurrence in endometrioid EC.

Differential outcomes in triple negative breast cancer observed among the major ethnic groups in Singapore

Objectives: Although Triple Negative Breast Cancers (TNBCs) are known as a particularly aggressive subtype, some women have a favorable prognosis and recurrence after the initial few years is uncommon. In this study, we reviewed the outcome of women with TNBC and evaluated factors potentially useful for risk stratification. Methods: Retrospective review was performed of 345 patients diagnosed with TNBC at two local institutes from 2006 to 2011. Detailed analyses focused on 315 women without metastasis. Results: TNBC accounted for 11.3% of cancers diagnosed and was most prevalent among Indian women. Disease recurrence was a significant determinant of overall survival (P<0.001) and apart from the disease stage (P<0.001), it was independently associated with ethnicity (P=0.011). Recurrence was two-fold higher among Malay and Indian women compared to Chinese women (P=0.027) and 5-year recurrence-free survival was significantly shorter compared to Chinese women (P=0.031, HR 2.575, 95% CI 0.165 to 0.915; P=0.034, HR 2.090, 95% CI 0.514 to 0.929). On the other hand, 5-year recurrence-free survival was similar between Malay and Indian women (P=0.987). This survival difference could not be attributed to differences in disease factors or stage at presentation, and apart from more Malay women receiving radiation (P=0.020), due to higher rates of breast conservation in this group, the women all received similar treatments. Conclusions: Ethnicity and disease stage were identified as independent predictors of disease recurrence in women with TNBC, with Chinese women having better survival outcomes.

Do Stage I Colorectal Cancers with Lymphatic Invasion Require a Different Postoperative Approach?

BackgroundAlthough stage I colorectal cancer has an excellent prognosis after complete surgical resection, disease recurrence still occurs. This study aimed to assess prognostic risk factors in this early stage of disease. MethodsAll non-neoadjuvantly treated stage I colon (CC) and rectal (RC) patients who underwent a surgical resection between 2004 and 2015 were identified. Clinicopathological differences and long-term oncological outcomes were compared. ResultsCC patients (n = 433) were older and had more pre-existing comorbidities. RC patients (n = 86) were associated with more T2 tumors, venous invasion, and higher rates of 30-day morbidity. In multivariate analysis, lymphatic invasion was found to be an independent predictor for disease recurrence (OR 4.57, P = 0.010) and worse disease-free survival (HR 4.26, P = 0.012). This was particularly true for distant recurrence, with eight times higher hazard ratios when lymphatic invasion was present (HR 8.02, P < 0.001). T2 tumors were at risk, though no significant association was found (OR 3.86, P = 0.051; HR 3.61, P = 0.065, respectively). ConclusionsLymphatic invasion was strongly associated with worse DFS, in particular distant recurrence. This subgroup of stage I patients might benefit from a more intensive follow-up and maybe should be considered for adjuvant therapy.

Epidermal growth factor expression as a predictor of chemotherapeutic resistance in muscle-invasive bladder cancer

BackgroundEpidermal growth factor receptor (EGFR) overexpression is believed to be associated with bladder cancer (BC) progression and poor clinical outcomes. In vivo studies have linked EGFR subcellular trafficking and chemo-resistance to cisplatin-based chemotherapies. This has not been studied in the clinical adjuvant setting. We aimed to investigate the prognostic significance of EGFR expression in patients receiving cisplatin-based adjuvant chemotherapy following radical cystectomy for advanced BC.MethodsThe database from the Urology and Nephrology Center at Mansoura University was reviewed. BC patients who were treated with radical cystectomy and adjuvant chemotherapy for adverse pathological features or node positive disease were identified. Patients who underwent palliative cystectomy, had histological diagnoses other than pure urothelial carcinoma, or received adjuvant radiotherapy were excluded from the study. Immunohistochemical staining for EGFR expression was performed on archived bladder specimens. The following in vitro functional analyses were performed to study the relationship of EGFR expression and chemoresponse.ResultsThe study included 58 patients, among which the mean age was 57 years old. Majority of patients had node positive disease (n = 53, 91%). Mean follow up was 26.61 months. EGFR was overexpressed in 25 cystectomy specimens (43%). Kaplan-Meier analysis revealed that EGFR over-expression significantly correlated with disease recurrence (p = 0.021). Cox proportional hazard modeling identified EGFR overexpression as an independent predictor for disease recurrence (p = 0.04). Furthermore, in vitro experiments demonstrated that inhibition of EGFR may sensitize cellular responses to cisplatin.ConclusionsOur findings suggest that EGFR overexpression is associated with disease recurrence following adjuvant chemotherapy for advanced BC. This may aid in patient prognostication and selection prior to chemotherapeutic treatment for BC.

FA03.01: LONG-TERM OUTCOMES OF PATIENTS WITH RECURRENT SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS UNDERGOING SALVAGE ENDOSCOPIC RESECTION

Abstract Background introduction: Definitive chemoradiotherapy (dCRT) is a treatment option for esophageal squamous cell carcinoma (ESCC). Salvage endoscopic resection (ER) has a potential of cure for patients with local recurrence or residual tumor after dCRT, which is less invasive compared with salvage esophagectomy. Aim: To evaluate the long-term outcomes of patients with recurrence ESCC undergoing salvage ER and to identify risk factors associated with disease recurrence after salvage ER. Methods Retrospective analysis of 42 patients with ESCC treated with salvage ER for either local failure or recurrent disease after dCRT between January 2000 and December 2017. Salvage ER was indicated for clinically diagnosed T1N0M0 post dCRT in our hospital. Cox hazard model analysis was used to identify risk factors for recurrence after post-salvage ER. Results A total of 42 patients (35 males, 5 females), mean age 65 years (39–85), TNM stage before dCRT (I, II, III) 22/13/6, complete response (35 [85%]) were evaluated. The median time to salvage ER from the initiation of dCRT was 18.3months (2–130). ESD, EMR-C, and SB were performed for 4, 26, 11 patients. En-bloc resection rates were 100% (4/4), 61% (16/26) and 18% (2/11) for ESD, EMR-C, SB, respectively. There were no severe adverse event. Histological findings in the ER specimen was as follows; depth of invasion: T1a/T1b = 27/14(65/35%), lymphovascular invasion +/− = 7/34 (17/83%), vertical margin: 0/1/X = 34/4/3, and horizontal margin: 0/1/X = 25/5/11. A total of 19 patients (46%) developed recurrence after salvage ER. Recurrence sites were local/lymph node/local + lymph node/lymph nodes + distant metastasis in 9/8/2. For recurrent disease after ER, esophagectomy, lymphadenectomy and chemotherapy and best supportive care were performed for 8, 2, 4, 4 and 2, respectively, resulting in 6 death from ESCC. Three-year recurrence free survival rate, overall survival rate, and disease specific survival rate were 53.9%, 84.2%, and 88.4%, respectively. Multivariate analysis revealed that lymphovascular invasion was independent predictor of disease recurrence after salvage ER (HR = 2.96, 95%C. I 1.05–8.38, P = 0.04). Conclusion Salvage ER is clinically safe and effective in patients with local recurrence of ESCC after dCRT. Careful follow-up might be recommended for the patients with lymphovascular invasion. Disclosure All authors have declared no conflicts of interest.

Prognostic significance of preoperative CT findings in patients with advanced gastric cancer who underwent curative gastrectomy.

BackgroundPreoperative therapy has gained wide interest in advanced gastric cancer patients due to its potential advantages of improved disease control. Selection of high risk patients based on preoperative staging is crucial to choose the candidates for neoadjuvant therapy.MethodsOur institutional review board approved this retrospective study and waived the requirement for patient consent. We searched 394 advanced gastric cancer patients (pT2-4) who underwent curative resection in 2010 without neoadjuvant therapies. Two abdominal radiologists independently reviewed the preoperative CT including tumor depth on CT (CT-tumor depth), which was categorized as follows: intramural, minimal extramural(<1mm), spiculated extramural(≥1mm) and nodular extramural infiltration. The impact of clinicoradiologic factors on disease recurrence and disease free survival (DFS) was evaluated. Recursive partitioning analysis was performed to suggest prediction models for recurrence.ResultsOf total 394 patients, 86 patients (21.8%) experienced recurrence. Spiculated (≥1mm) and nodular extramural tumor infiltration and CT size of 5-10cm were independent predictors of disease recurrence and significantly associated with worse DFS. Lymph node involvement on CT was not significantly associated with patient outcome. Among patients with same pT4a stage, the recurrence rate rises and DFS gets worse as the extramural tumor infiltration progresses (P < 0.001). The prediction model for recurrence revealed that size and CT-tumor depth were the two major discriminating factors.ConclusionCT-tumor depth and size could be used as independent predictors for prognosis. Preoperative CT can be used for prognostic stratification to select high risk patients for whom neoadjuvant therapies might be considered.

Commentary on “Detection and oncological effect of circulating tumor cells in patients with variant urothelial carcinoma histology treated with radical cystectomy.”

ObjectivesTo investigate for the presence of circulating tumor cells (CTC) in patients with variant urothelial carcinoma of the bladder (UCB) histology treated with radical cystectomy (RC), and to determine their impact on oncological outcomes. Patients and methodsWe, prospectively, collected data of 188 patients with UCB treated with RC without neoadjuvant chemotherapy. Pathological specimens were meticulously reviewed for pure and variant UCB histology. Preoperatively collected blood samples (7.5ml) were analyzed for CTC using the CellSearch system (Janssen, Raritan, NJ). ResultsVariant UCB histology was found in 47 patients (25.0%), most frequently of squamous cell differentiation (16.5%). CTC were present in 30 patients (21.3%) and 12 patients (25.5%) with pure and variant UCB histology, respectively. At a median follow-up of 25 months, the presence of CTC and nonsquamous cell differentiation were associated with reduced recurrence-free survival (RFS) and cancer-specific survival (pairwise P ≤ 0.016). Patients without CTC had better RFS, independent of UCB histology, than patients with CTC with any UCB histology (pairwise P<0.05). In multivariable analyses, the presence of CTC, but not variant UCB histology, was an independent predictor for disease recurrence (hazard ratio = 3.45, P<0.001) and cancer-specific mortality (hazard ratio = 2.62, P = 0.002). ConclusionCTC are detectable in about a quarter of patients with pure or variant UCB histology before RC, and represent an independent predictor for outcomes, when adjusting for histological subtype. In addition, our prospective data confirm the unfavorable influence of nonsquamous cell-differentiated UCB on outcomes.

Altered DNA methyltransferases promoter methylation and mRNA expression are associated with tamoxifen response in breast tumors.

Tamoxifen is a standard anti-hormone treatment in estrogen receptor positive breast carcinoma patients. Unfortunately, about 50% of patients relapse during treatment. Promoter hypermethylation contributes to the epigenetic modulation of tamoxifen resistance-related genes. To evaluate the contribution of DNMTs expression and their promoter methylation as diagnostic biomarkers in development of breast malignancy and tamoxifen resistance, the present study was designed and 107 breast tumors and normal breast tissues were recruited. Methylation-specific high-resolution melt curve analysis and quantitative RT-PCR were performed to evaluate DNMTs promoter methylation and mRNA expression, respectively. Our results indicated that DNMT3A and DNMT3B promoters were demethylated in breast tumors as compared to control tissues. The mRNA expression levels of all three DNMTs were significantly increased in tumor specimens in comparison to control tissues (p < 0.05). Among tumor tissues, DNMT3A promoter methylation was significantly higher in tamoxifen sensitive patients (p = 0.001). Overexpression of DNMT3A (p = 0.037) and DNMT3B (p < 0.001) mRNA were observed in tamoxifen resistance group. Multivariate logistic regression analysis indicated that low methylation status of DNMT3A and overexpression of DNMT3B could be as independent predictors of disease recurrence. Multivariate Cox regression analysis, revealed that high methylation status of DNMT3A could be an independent and favorable predictor for disease free survival (p = 0.002) and overall survival (p = 0.026); high expression of DNMT1 (p = 0.03) remained significant and unfavorable predictive factor for overall survival. In conclusion, our data for the first time indicated that low methylation status of DNMT3A promoter and overexpression of DNMT3B could contribute to disease recurrence in tamoxifen-treated breast cancer patients.