Independent Predictors Of Poor Recurrence-free Survival Research Articles

Intrahepatic Mass-Forming Cholangiocarcinoma: Is There Additional Prognostic Value in Using Gd-EOB Enhanced MRI?

To investigate the prognostic value of enhancement patterns of intrahepatic mass-forming cholangiocarcinomas (IMCCs) during the hepatobiliary phase (HBP) in gadoxetic acid (Gd-EOB)-enhanced MRI. We retrospectively identified 66 consecutive patients with histopathologically proven IMCCs (reference standard: resection) and preoperative Gd-EOB-enhanced MRI. Gd-EOB retention area was subjectively rated based on areas of intermediate signal intensity. Lesions were classified as either hypointense (0-25% retention area) or significantly-retaining (>25% retention area). Clinical, radiological, and prognostic features were compared between these groups. The primary endpoints were recurrence-free survival (RFS) and overall survival (OS) after primary surgical resection. 73% (48/66) of lesions were rated as hypointense and 29% (19/66) as significantly-retaining. While the hypointense subgroup more frequently featured local and distant intrahepatic metastases (p = 0.039 and p = 0.022) and an infiltrative growth pattern (p = 0.005), RFS, OS, and clinical features did not differ significantly with estimated Gd-EOB retention area or quantitatively measured HBP enhancement ratios. Lymph node metastasis was an independent predictor of poor RFS (p = 0.001). Gd-EOB-enhanced MRI revealed two subtypes of IMCC in the HBP: hypointense and signal-retaining. The hypointense subtype is associated with more frequent intrahepatic metastases and an infiltrative growth pattern, indicating potential tumor aggressiveness. However, this did not result in a significant difference in survival after the primary resection of IMCC.

Long-term outcomes and early recurrence after resection for metachronous pulmonary metastases from colorectal cancer.

Properly selecting patients for aggressive curative resection for pulmonary metastases (PMs) from colorectal cancer (CRC) is desirable. We purposed to clarify prognostic factors and risk factors for early recurrence after metachronous PM resection. Clinical data of 151 patients who underwent R0 resection for metachronous PMs from CRC at two institutions between 2008 and 2021 were reviewed. Seventy-six patients (50.3%) were male, and the median age was 71 (42-91) years. The numbers of colon/rectal cancers were 76/75, with pStage I/II/III/IV/unknown in 15/34/86/13/3. The duration from primary surgery to PM was 19.7 (1.0-106.4) months. The follow-up period was 41.9 (0.3-156.2) months. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 75.1%, 53.7%, and 51.1%, and the 1-, 3-, and 5-year overall survival (OS) rates were 97.7%, 87.5%, and 68.2%. On multivariate analysis, lymph node metastasis of the primary lesion (HR 1.683, 95%CI 1.003-2.824, p = 0.049) was an independent predictor of poor RFS, and history of resection for extrapulmonary metastasis (e-PM) (HR 2.328, 95%CI 1.139-4.761, p = 0.021) was an independent predictor of poor OS. Patients who experienced early recurrence (< 6months) after PM resection showed poorer OS than others (3-year OS 50.8% vs. 90.2%, p = 0.002). On multivariate analysis, e-PM was an independent predictor of early recurrence after PM resection (OR 3.989, 95%CI 1.002-15.885, p = 0.049). Since a history of e-PM was a predictor of early recurrence and poor OS after R0 resection for PM, surgical treatment of patients with a history of e-PM should be considered carefully.

Prognostic impact of perioperative change in serum p53 antibody titers in esophageal squamous cell carcinoma.

The clinical effectiveness of tumor markers for estimating prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. We assessed the clinical impact of changes in perioperative serum p53 antibodies (s-p53-Abs) titers in ESCC. From January 2011 to March 2021, 249 patients were enrolled in this study. Titers of s-p53-Abs were measured before the initial treatment and 3months after esophagectomy. Patients were divided into a s-p53-Abs decreased or unchanged group (Group D, n = 217) and an increased group (Group I, n = 32). Short- and long-term outcomes were compared between the groups. There was no correlation between the changes in squamous cell carcinoma antigen and carcinoembryonic antigen titers and recurrence site, number of recurrent lesions, and prognosis. However, the recurrence rate was significantly higher in Group I than in Group D (53.1% vs. 28.6%, p = 0.008), especially for distant organ recurrence (37.5% vs. 18.4%, p = 0.019). Furthermore, the rate of polyrecurrence was higher in Group I than in Group D (34.4% vs. 14.3%, p = 0.009). Recurrence-free survival (RFS) was significantly worse in Group I than in Group D (median survival time, 21.2months vs. 36.7months, p = 0.015). Multivariate analysis revealed that lymphatic vessel infiltration (hazard ratio [HR], 1.721; 95% CI 1.069-2.772; p = 0.026), blood vessel infiltration (HR, 2.348; 95% CI 1.385-3.982; p = 0.002), advanced pathological stage (≥ III) (HR, 3.937; 95% CI 2.295-6.754; p < 0.001), and increased s-p53-Abs titers (HR, 2.635; 95% CI 1.488-4.667; p = 0.001) were independent predictors of poor RFS. Elevation of s-p53-Abs titers after esophagectomy can predict polyrecurrence in distant organs and poor prognosis.

Prognostic significance of extra-nodal extension and positive surgical margins in HPV positive oropharyngeal squamous cell carcinoma

BackgroundWhether extra-nodal extension (ENE+) and surgical margin positivity (margin+) are poor prognostic factors in HPV-associated (HPV+) oropharyngeal carcinoma (OPC) remains uncertain. ResultsOur study evaluated if microscopic ENE+ and/or margin+ are associated poorer recurrence free survival (RFS) and overall survival (OS) in HPV+ OPC. Patients were classified as high risk (ENE+ and/or margin+) or low risk (ENE- and margins-). Of a total of 176 patients HPV+ OPC, 81 underwent primary surgery and dad data on ENE and margin status. There was no statistically significant difference in RFS (p = 0.35) or OS (p = 0.13) for high-risk versus low-risk groups. Ongoing smoking (p = 0.023), alcohol use (p = 0.044) and advanced stage (p = 0.019) were associated with higher risk of recurrence. Only advanced stage (p-value <0.0001) was associated poorer overall survival. ConclusionsThe presence of ENE+ and/or margin+ was not an independent predictor of poor RFS or OS in HPV+ OPC.

Differences in the clinical characteristics of papillary thyroid microcarcinoma located in the isthmus ≤5 mm and >5mm in diameter.

BackgroundThe optimal treatment of papillary thyroid microcarcinomas (PTMCs) located in the isthmus (iPTMCs) is still controversial. The purpose of this study was to compare the clinicopathologic features of patients with iPTMCs ≤5 mm and >5 mm in diameter after total thyroidectomy, and to identify the risk factors for recurrence in patients with iPTMCs.MethodsA total of 102 iPTMC patients who underwent total thyroidectomy were reviewed retrospectively. The clinicopathologic characteristics of iPTMCs ≤5 mm group (n = 29) have been compared with a group >5 mm (n = 73). Univariate and multivariate Cox proportional hazard models served to identify risk factors associated with recurrence-free survival (RFS).ResultsGender (p = 0.033), multifocality (p = 0.041), and central lymph node metastasis (CLNM) (p = 0.009) of patients in the ≤5 mm and >5 mm groups differed significantly. iPTMC patients with age <55 years, male, multiple tumor, and extrathyroidal extension showed comparatively more frequent of CLNM in >5 mm groups. Of the 102 patients, nine (8.8%) developed recurrence during follow-up (median: 49.5 months). The patients with recurrences had comparatively high rates of CLNM (p = 0.038), extranodal invasion (p = 0.018), and more MNCND (Metastasis Nodes for Central Neck dissection) (p = 0.020). A cutoff of MNCND >2.46 was established as the most sensitive and specific level for the prediction of recurrence based on receiver operating characteristic (ROC) curve analyses. Multivariate analysis showed that the number of MNCND ≥3 was an independent predictor of poor RFS (p = 0.028).ConclusionWe have found that the recurrence rates are similar in patients with iPTMCs ≤5 mm and >5 mm. The iPTMCs >5 mm were more likely to be associated with pathological features such as multifocality and CLNM. The male gender, extrathyroidal extension, and CLNM were associated with recurrence of iPTMCs except for tumor size and multifocality. Higher risk of CLNM should be considered in iPTMC >5 mm when it reaches some risk factors. The numbers of MNCND ≥3 may be an independent predictor for recurrence, which could help clinicians for the decision of radioiodine administration and the modulation of follow-up modalities.

High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival

BackgroundATP-binding cassette transporter G1 (ABCG1) regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity. But, for hepatocellular carcinoma (HCC), the role of ABCG1 has not been investigated. Thus, the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC. MethodsOne hundred and four adult patients with HCC were enrolled, and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry. All these patients were stratified by ABCG1 expression, Kaplan-Meier analysis was used to compare the overall survival (OS) and recurrence-free survival (RFS), and Cox regression analysis was used to determine independent predictors of tumor recurrence. ResultsUpregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues. Patients with high nuclear ABCG1 expression had lower OS and RFS (P = 0.012 and P = 0.020, respectively). High nuclear ABCG1 expression was related to larger tumor size (P = 0.004) and tumor recurrence (P = 0.027). Although ABCG1 was expressed in the cytoplasm, cytosolic expression could not predict the outcome in patients with HCC. A new stratification pattern was established based on the heterogenous ABCG1 expression pattern: high risk (Highnucleus/Lowcytosol), moderate risk (Highnucleus/Highcytosol or Lownucleus/Lowcytosol), and low risk (Lownucleus/Highcytosol). This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with HCC. Multivariate Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS (P = 0.015). ConclusionsHigh nuclear ABCG1 expression indicates poor prognosis in patients with HCC. Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence.

Quantitative Dynamic-Enhanced MRI and Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Prediction of the Pathological Response to Neoadjuvant Chemotherapy and the Prognosis in Locally Advanced Gastric Cancer.

BackgroundThis study aimed to explore the predictive value of quantitative dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) quantitative parameters for the response to neoadjuvant chemotherapy (NCT) in locally advanced gastric cancer (LAGC) patients, and the relationship between the prediction results and patients’ prognosis, so as to provide a basis for clinical individualized precision treatment.MethodsOne hundred twenty-nine newly diagnosed LAGC patients who underwent IVIM-DWI and DCE-MRI pretreatment were enrolled in this study. Pathological tumor regression grade (TRG) served as the reference standard of NCT response evaluation. The differences in DCE-MRI and IVIM-DWI parameters between pathological responders (pR) and pathological non-responders (pNR) groups were analyzed. Univariate and multivariate logistic regressions were used to identify independent predictive parameters for NCT response. Prediction models were built with statistically significant quantitative parameters and their combinations. The performance of these quantitative parameters and models was evaluated using receiver operating characteristic (ROC) analysis. Clinicopathological variables, DCE-MRI and IVIM-DWI derived parameters, as well as the prediction model were analyzed in relation to 2-year recurrence-free survival (RFS) by using Cox proportional hazards model. RFS was compared using the Kaplan–Meier method and the log-rank test.ResultsSixty-nine patients were classified as pR and 60 were pNR. Ktrans, kep, and ve values in the pR group were significantly higher, while ADCstandard and D values were significantly lower than those in the pNR group. Multivariate logistic regression analysis demonstrated that Ktrans, kep, ve, and D values were independent predictors for NCT response. The combined predictive model, which consisted of DCE-MRI and IVIM-DWI, showed the best prediction performance with an area under the curve (AUC) of 0.922. Multivariate Cox regression analysis showed that ypStage III and NCT response predicted by the IVIM-DWI model were independent predictors of poor RFS. The IVIM-DWI model could significantly stratify median RFS (52 vs. 15 months) and 2-year RFS rate (72.3% vs. 21.8%) of LAGC.ConclusionPretreatment DCE-MRI quantitative parameters Ktrans, kep, ve, and IVIM-DWI parameter D value were independent predictors of NCT response for LAGC patients. The regression model based on baseline DCE-MRI, IVIM-DWI, and their combination could help RFS stratification of LAGC patients.

Combined hepatocellular carcinoma-cholangiocarcinoma: MRI features correlated with tumor biomarkers and prognosis.

To determine how MRI features are correlated to biomarkers, and to the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) in combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) patients. The study enrolled 160 cHCC-CCA patients pathologically confirmed according to the 2019 WHO classification. The preoperative MRI features and clinical data were retrospectively evaluated and compared between patients grouped by AFP or CA19-9 level and with pathological findings. The RFS and OS of cHCC-CCA patients were estimated using Kaplan-Meier survival curves and compared using the log-rank test. Moreover, predictors of RFS and OS were investigated using Cox regression analyses. One hundred and sixty patients (mean age, males vs. females: 55.7 ± 10.2 years vs. 54.9 ± 14.0 years) were evaluated. The incidence of nodule-in-nodule architecture, mosaic architecture, intratumoral hemorrhage, hepatic capsule retraction, arterial phase peritumoral enhancement, and portal vein thrombus was significantly higher in patients with AFP > 20 ng/ml (all p < 0.05). Multivariate Cox regression analysis indicated that age (HR 1.031, p = 0.03), CA19-9 > 37 U/ml (HR 1.880, p = 0.04), arterial phase peritumoral enhancement (HR 2.287, p = 0.01), and delayed enhancement (HR 0.377, p = 0.02) were independent predictors of poor RFS, while arterial phase peripheral enhancement (HR 2.391, p = 0.04) was an independent predictor of poor OS. cHCC-CCA imaging features are complex and not correlated with AFP or CA19-9. Age, CA19-9 > 37 U/ml, arterial phase peritumoral enhancement, and delayed enhancement are independent predictors of poor RFS. Arterial phase peripheral enhancement is an independent predictor of poor OS. • The imaging features of combined hepatocellular carcinoma-cholangiocarcinoma are complex and are not correlated with the alpha fetoprotein or CA19-9 levels. • Age, CA19-9 > 37 U/ml, arterial phase peritumoral enhancement, and delayed enhancement are independent predictors of poor recurrence-free survival in combined hepatocellular carcinoma-cholangiocarcinoma patients. • Arterial phase peripheral enhancement is an independent predictor of poor overall survival in patients with combined hepatocellular carcinoma-cholangiocarcinoma.

Prognostic value of radiologic extranodal extension in patients with hypopharyngeal cancer treated with primary chemoradiation

Background and purposeWe aimed to evaluate the prognostic value of radiologic extranodal extension (rENE) in patients with hypopharyngeal cancer (HPC) treated with primary chemoradiation. Materials and methodsCancer registry data were reviewed from 2005 to 2014. Inclusion criteria included HPC, clinical N1–3 disease (AJCC staging system, 7th edition), and receiving radiotherapy. Patients with M1 diseaseor with synchronous/metachronous cancer were excluded. Staging images were reviewed by two radiologists. rENE was defined as infiltration of adjacent fat/muscles, irregular nodal surface, or irregular capsular enhancement. Clinical stage, rENE status, and clinical outcome were analyzed. ResultsOverall, 355 patients were included. Patients with rENE had lower 3-year overall survival (OS) and recurrence-free survival (RFS) rates. Univariate analysis showed that clinical T4 or N3 stage, overall stage IV, and rENE correlated with OS and RFS. In multivariate analysis, clinical T4 or N3 stage correlated with poor OS, while clinical T4 or N3 stage and rENE were independent predictors of poor RFS. N1/2 without rENE was designated as Group 1, N1/2 with rENE as Group 2, and N3 with/without rENE as Group 3. The 3-year RFS rates in Groups 1, 2, and 3 were 55.8%, 41.0%, and 29.3%, respectively. The 3-year RFS rate in Group 1 was significantly higher than that in the other two groups. ConclusionsrENE is an adverse prognostic factor for survival in patients with HPC treated with primary chemoradiation. It correlated with inferior RFS regardless of N stage. rENE may be used as a criterion for clinical ENE in future staging systems.

Prognostic value of radiologically enlarged lymph nodes in node-negative colon cancer.

Assessment of lymph node (LN) involvement is of crucial importance in the estimation of prognosis and choice of therapeutic options for patients with colon cancer. The relationship between the radiological size of LNs and prognosis in node-negative colon cancer remains uncertain. This study aims to investigate the prognostic impact of radiologically enlarged LNs on the survival of patients with node-negative colon cancer. This retrospective study recruited 395 patients with Stages I and II colon cancer diagnosed between January 2012 and March 2016. Preoperative computed tomography was reviewed for the maximum short-axis diameter of regional LNs, the optimal cutoff value of which was set to 8mm. The prognostic relevance was analysed in Kaplan-Meier and multivariable Cox proportional hazard regressions. Patients with tumour in the left colon, TNM Stage II and 12 or more retrieved LNs tended to have radiologically enlarged LNs. Our results suggest that 3-year recurrence-free survival (RFS) and overall survival (OS) were significantly worse in patients with enlarged LNs than those without (RFS 82.8% vs 92.4%, P=0.026; OS 87.1% vs 95.2%, P=0.017), which was also confirmed in multivariable analysis [RFS hazard ratio (HR)=2.192, P=0.018; OS HR=3.305, P=0.010]. Subgroup analysis revealed that in patients with Stage II disease or at least 12 retrieved LNs, radiologically enlarged LN remained an independent predictor of poor RFS and OS. The presence of radiologically enlarged LNs in patients with node-negative colon cancer had an adverse prognosis.

Preoperative inflammatory response as prognostic factor of patients with colon cancer.

This study aimed to investigate the abilities of the modified Glasgow prognostic score (mGPS) and other inflammatory scores to predict recurrence-free survival (RFS) among patients with colon cancer (CC). In addition, we evaluated the abilities of the mGPS to predict recurrence of stage II disease and the efficacy of adjuvant chemotherapy (AC) for stage III disease. This retrospective study evaluated 477 patients with stage I-III CC who underwent curative surgery. These patients were categorized as having a low mGPS (mGPS 0) or a high mGPS (mGPS 1-2). Patients in the high mGPS group had significantly poorer RFS than patients in the low mGPS group (p < 0.01). Multivariate analysis revealed that a high mGPS independently predicted poor RFS (p < 0.01). Among patients with stage II CC, multivariate analysis revealed that the independent predictors of poor RFS were pT4 status (p < 0.01) and a high mGPS (p = 0.04). Among patients with stage III CC, AC was not significantly associated with the 5-year RFS for patients with a low mGPS (p = 0.38), although AC significantly improved the 5-year RFS for patients with a high mGPS (p < 0.01). The preoperative mGPS significantly predicted recurrence among patients with CC, even among patients with stage II CC. In addition, mGPS may provide valuable information regarding subgroups of patients with stage III CC who might benefit from AC.

Systematic assessment of the clinicopathological prognostic significance of tissue cytokine expression for lung adenocarcinoma based on integrative analysis of TCGA data

Dysregulated intratumoral immune reactions are shaped by complex networks of cytokines, which coordinate with tumor cells to determine tumor progression and aggressiveness. In lung adenocarcinoma (LUAD), the role of intratumoral cytokine gene expression for stratifying prognosis has not been systematically investigated. Using high-dimensional datasets of cancer specimens from clinical patients in The Cancer Genome Atlas (TCGA), we explored the transcript abundance and prognostic impact of 27 clinically evaluable cytokines in 500 LUAD tumor samples according to clinicopathological features and two common driver mutations (EGFR and KRAS). We found that reduced expression of IL12B presented as the single prognostic factor for both poor overall survival (OS) and recurrence free survival (RFS) with high hazard ratios. Moreover, we identified that elevated expression of IL6, CXCL8 and CSF3 were additional independent predictors of poor RFS in LUAD patients. Their prognostic significance was further strengthened by their ability to stratify within clinicopathological factors. Notably, we prioritized high risk cytokines for patients with or without mutations in EGFR and KRAS. Our results provide integrative associations of cytokine gene expression with patient survival and tumor recurrence and demonstrate the necessity and validity of relating clinicopathological and genetic disposition factors for precise and personalized disease prognosis.

Overexpression of cysteine-glutamate transporter and CD44 for prediction of recurrence and survival in patients with oral cavity squamous cell carcinoma.

This study analyzed the expression of CD44 and cystine-glutamate transporter SLC7A11 (xCT) in primary oral cavity squamous cell carcinoma (SCC) and the relationships of expression to tumor recurrence and patient survival. Associations between CD44 and xCT expression and clinicopathologic results were analyzed in 231 patients with oral cavity SCC. Cox proportional hazard analyses were used to identify factors associated with recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Overexpression of CD44 and/or xCT was associated with advanced T classification, perineural invasion, and lymphovascular invasion (P < .05 each). High expression of xCT was also associated with nodal metastasis and depth of invasion (P < .01 each). Multivariate analysis indicated that high expression of xCT and both xCT and CD44 were independent predictors of poor RFS, DSS, and OS (P < .05 each). Overexpression of xCT or xCT plus CD44 may predict posttreatment recurrence and survival in patients with oral cavity SCC.

Combined use of preoperative lymphocyte counts and the post/preoperative lymphocyte count ratio as a prognostic marker of recurrence after curative resection of stage II colon cancer.

PurposeDiagnostic markers for recurrence of colorectal cancer have not been established. The aim of the present study was to identify new diagnostic markers for recurrence after curative surgery of stage II colon cancer.Materials and MethodsIn this study, the prognostic values of the preoperative lymphocyte count and the post/preoperative lymphocyte count ratio (PPLR) were evaluated in 142 patients with localized colon cancer treated with surgery at a single medical center. The associations of patient demographics, blood chemistry, and serum biochemical indices with recurrence-free survival (RFS) and cancer-specific survival (CSS) were examined by univariate and multivariate analyses.ResultsReceiver operating characteristic (ROC) curve analysis showed that the optimal cut-off values of the lymphocyte count and PPLR were, respectively, 1555.2/μl and 1.151 for RFS. On univariate analysis, tumor depth of invasion, carbohydrate antigen 19-9 (CA19-9), and preoperative low lymphocyte count (≤1555.2/μl) were all correlated with poorer RFS (p < 0.05). On multivariate analysis, T4, low lymphocyte count, and low PPLR were independent predictors of poor RFS. Furthermore, the patients were categorized into four categories based on preoperative lymphocyte count high/low and PPLR high/low. Patients with a low preoperative lymphocyte count and low PPLR had the poorest RFS and CSS compared to the other patients.ConclusionThe combination of the preoperative lymphocyte count and the PPLR appears to be a potential marker for predicting recurrence of stage II colon cancer.

Treatment Outcomes and Risk Factors for Recurrence After Definitive Surgery of Locally Invasive Well-Differentiated Papillary Thyroid Carcinoma

Papillary thyroid carcinoma (PTC) is generally an indolent tumor that has a favorable prognosis. However, locally invasive PTC can recur after treatment, and its optimal treatment is still controversial. This study aimed to evaluate treatment outcomes and identify risk factors for recurrence and survival in patients with locally invasive PTC. All consecutive patients who underwent definitive surgery and radioactive iodine therapy for non-distant metastatic invasive PTC were included. Clinical factors, operative and pathological findings, surgical morbidity, and recurrences were recorded. Univariate and multivariate Cox proportional hazard models served to identify factors associated with recurrence-free survival (RFS) and overall survival. Of the 96 patients, 74 (77%), 52 (55%), 4 (4%), and 14 (15%) had invasion to the recurrent laryngeal nerve (RLN), trachea, larynx, and esophagus, respectively; 39 (41%) had preoperative vocal cord paresis or paralysis; and 24 (25%) developed recurrence during follow-up (median 77 months). The patients with single and multiple organ invasion did not differ significantly in terms of recurrence-free or overall survival (p > 0.05). The patients with and without recurrences did not differ in terms of surgical extent and involving nerve preservation. Multivariate analysis showed that high (≥1 ng/mL) post-ablation stimulated serum thyroglobulin concentration was an independent predictor of poor RFS (p = 0.013). Disease extent, surgical extent, and involving nerve preservation did not associate with recurrence or overall survival outcomes. The post-ablation stimulated thyroglobulin level may be an independent predictor for recurrence. Careful follow-up of patients with this risk factor is recommended.

Tumor-associated CD66b+ neutrophil and CD8+ lymphocyte densities as independent prognostic factors for recurrence in localized cervical cancer: Automated digital image analysis and observer-assisted stereological assessments.

5532 Background: The prognostic impact of tumor-associated immune cells in cervical cancer is unclear. Methods: Automated digital image analysis (DIA) software and observer-assisted stereological (OAS) assessments were used to obtain densities of immunostains for CD66b+ neutrophils, CD163+ macrophages, and CD8+lymphocytes in scanned whole slide images of tumor sections from 101 patients with FIGO stage IB and IIA cervical cancer. Primary end-point was recurrence-free survival (RFS). Results: The highest densities of CD66b+ neutrophils and CD163+ macrophages were observed by OAS in the peritumoral compartment (median 53.1 cells/mm2 and 1.3% area fraction, respectively). DIA required far less human resources than OAS assessments. We observed high correlations between DIA and OAS variables of corresponding parameters; spearman ρ was 0.79 for CD8+ lymphocytes , 0.85 for CD66b+ neutrophils, and 0.92 for CD163+ macrophages (all p &lt;0.0001). Hazard rates for DIA assessments in the global tumor area were comparable with the prognostically strongest OAS assessments in the peritumoral compartment. In multivariate analysis, high density of CD66b+ neutrophils (HR 2.6; 95% CI 1.2–5.7; p = 0.02), low density of CD8+ lymphocytes (HR 2.3; 95% CI 1.1–4.9; p = 0.03), and presence of lymph node metastases (HR 2.6; 95% CI 1.2–5.5; p = 0.02) were independent predictors of poor RFS, whereas FIGO stage and CD163+macrophage density were not. The CD66b/CD8 immunostain index obtained by DIA had excellent discriminatory power for each quartile with 5-year RFS of 92%, 80%, 65%, and 48% for quartile I (&lt;0.019), II (0.02-0.05), III (0.06-0.24), and IV (&gt;0.25), respectively (p = 0.001). Conclusions: High tumor-associated CD66b+ neutrophil and low CD8+ lymphocyte densities are independent prognostic factors for short recurrence-free survival in cervical cancer assessed by DIA and OAS. Combined CD66b+ neutrophil/CD8+ lymphocyte immunostain index obtained by DIA is a strong and cost-efficient prognostic variable with potential for routine application.