Recurrence-free Survival Analysis Research Articles

Development and prognostic validation of a three-level NHG-like deep learning-based model for histological grading of breast cancer

BackgroundHistological grade is a well-known prognostic factor that is routinely assessed in breast tumours. However, manual assessment of Nottingham Histological Grade (NHG) has high inter-assessor and inter-laboratory variability, causing uncertainty in grade assignments. To address this challenge, we developed and validated a three-level NHG-like deep learning-based histological grade model (predGrade). The primary performance evaluation focuses on prognostic performance.MethodsThis observational study is based on two patient cohorts (SöS-BC-4, N = 2421 (training and internal test); SCAN-B-Lund, N = 1262 (test)) that include routine histological whole-slide images (WSIs) together with patient outcomes. A deep convolutional neural network (CNN) model with an attention mechanism was optimised for the classification of the three-level histological grading (NHG) from haematoxylin and eosin-stained WSIs. The prognostic performance was evaluated by time-to-event analysis of recurrence-free survival and compared to clinical NHG grade assignments in the internal test set as well as in the fully independent external test cohort.ResultsWe observed effect sizes (hazard ratio) for grade 3 versus 1, for the conventional NHG method (HR = 2.60 (1.18–5.70 95%CI, p-value = 0.017)) and the deep learning model (HR = 2.27, 95%CI 1.07–4.82, p-value = 0.033) on the internal test set after adjusting for established clinicopathological risk factors. In the external test set, the unadjusted HR for clinical NHG 2 versus 1 was estimated to be 2.59 (p-value = 0.004) and clinical NHG 3 versus 1 was estimated to be 3.58 (p-value < 0.001). For predGrade, the unadjusted HR for predGrade 2 versus 1 HR = 2.52 (p-value = 0.030), and 4.07 (p-value = 0.001) for preGrade 3 versus 1 was observed in the independent external test set. In multivariable analysis, HR estimates for neither clinical NHG nor predGrade were found to be significant (p-value > 0.05). We tested for differences in HR estimates between NHG and predGrade in the independent test set and found no significant difference between the two classification models (p-value > 0.05), confirming similar prognostic performance between conventional NHG and predGrade.ConclusionRoutine histopathology assessment of NHG has a high degree of inter-assessor variability, motivating the development of model-based decision support to improve reproducibility in histological grading. We found that the proposed model (predGrade) provides a similar prognostic performance as clinical NHG. The results indicate that deep CNN-based models can be applied for breast cancer histological grading.

The Effect of Renin-Angiotensin System Inhibitors in Patients Undergoing Pancreatic Cancer Resection.

The local renin-angiotensin system promotes angiogenesis and proliferation via vascular endothelial growth factor or epidermal growth factor receptor expression. In this study, we aimed to evaluate the impact of angiotensin system inhibitors (ASIs) on long-term outcomes in patients undergoing surgical resection of pancreatic ductal adenocarcinoma (PDAC). A single institutional retrospective analysis was performed using the medical records of patients who underwent pancreatic resection with curative intent for PDAC between January 2005 and December 2018. Patient characteristics and surgical outcomes were compared between patients taking ASIs and those who are not. A total of 272 patients were included in the study and classified into the ASI group (n = 121) and the non-ASI group (n = 151). The median overall survival times in the ASI group and non-ASI group were 38.0 and 34.0 months ( P = 0.250), and the median recurrence-free survival times were 24.0 and 15.0 months ( P = 0.025), respectively. Multivariate analysis for recurrence-free survival identified the use of ASIs ( P = 0.020), CA19-9 level >500 IU/L ( P = 0.010), positive lymph node metastasis ( P < 0.001), and no adjuvant chemotherapy ( P < 0.001) as independent prognostic factors. The use of ASI may improve long-term outcomes after surgery for PDAC.

The role of MAPK, notch and Wnt signaling pathways in papillary thyroid cancer: Evidence from a systematic review and meta-analyzing microarray datasets employing bioinformatics knowledge and literature

Papillary thyroid cancer (PTC) is a prevalent kind of thyroid cancer (TC), with the risk of metastasis increasing faster than any other malignancy. So, understanding the role of PTC in pathogenesis requires studying the various gene expressions to find out which particular molecular biomarkers will be helpful. The authors conducted a comprehensive search on the PubMed microarray database and a meta-analysis approach on the remaining ones to determine the differentially expressed genes between PTC and normal tissues, along with the analyses of overall survival (OS) and recurrence-free survival (RFS) rates in patients with PTC. We considered the associated genes with MAPK, Wnt, and Notch signaling pathways. Two GEO datasets have been included in this research, considering inclusion and exclusion criteria. Nineteen genes were found to have higher differences through the meta-analysis procedure. Among them, ten genes were upregulated, and nine genes were downregulated. The expression of 19 genes was examined using the GEPIA2 database, and the Kaplan-Meier plot statistics were used to analyze RFS and the OS rates. We discovered seven significant genes with the validation: PRICKLE1, KIT, RPS6KA5, GADD45B, FGFR2, FGF7, and DTX4. To further explain these findings, it was discovered that the mRNA expression levels of these seven genes and the remaining 12 genes were shown to be substantially linked with the results of the experimental literature investigations on the PTC. Our research found nineteen panels of genes that could be involved in the PTC progression and metastasis and the immune system infiltration of these cancers.

Predictors and outcomes of recurrent retroperitoneal liposarcoma: new insights into its recurrence patterns

BackgroundThe clinical profiles of recurrent retroperitoneal liposarcoma (RLS) need to be explored. The recurrence patterns of RLS are controversial and ambiguous.MethodsA total of 138 patients with recurrent RLS were finally recruited in the study. The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed by Kaplan‒Meier analysis. To identify independent prognostic factors, all significant variables on univariate Cox regression analysis (P ≤ 0.05) were subjected to multivariate Cox regression analysis. The corresponding nomogram model was further built to predict the survival status of patients.ResultsAmong patients, the 1-, 3-, and 5-year OS rates were 70.7%, 35.9% and 30.9%, respectively. The 1-, 3- and 5-year RFS rates of the 55 patients who underwent R0 resection were 76.1%, 50.8% and 34.4%, respectively. The multivariate analysis revealed that resection method, tumor size, status of pathological differentiation, pathological subtypes and recurrence pattern were independent risk factors for OS or RFS. Patients with distant recurrence (DR) pattern usually had multifocal tumors (90.5% vs. 74.7%, P < 0.05); they were prone to experience changes of pathological differentiation (69.9% vs. 33.3%, P < 0.05) and had a better prognosis than those with local recurrence (LR) pattern. R0 resection and combined organ resection favored the survival of patients with DR pattern in some cases.ConclusionsPatients with DR pattern had better prognosis, and they may benefit more from aggressive combined resection than those with LR pattern. Classifying the recurrence patterns of RLS provides guidance for individualized clinical management of recurrent RLS.

Increased plasma miR-370-3p expression in poor-outcome patients with pancreatic ductal adenocarcinoma

ObjectiveTo determine whether circulating microRNAs (miRNAs) can be used as prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC). MethodsPatients with PDAC (N = 120) who underwent surgical resection at Hiroshima University Hospital between November 2006 and January 2020 were enrolled in this study and grouped based on their overall survival (OS) into two groups: favorable prognosis group (F group; OS ≥ 18 months) and unfavorable prognosis group (U group; OS < 18 months). Blood plasma samples were collected prior to surgery. To identify candidate prognostic miRNAs, next-generation sequencing (NGS) analysis was used to evaluate the expression levels of miRNAs in seven of the plasma samples. Using quantitative real-time PCR (qRT-PCR), the expression levels of the selected miRNAs were determined in the remaining 113 patient plasma samples, and the relationship between miRNA expression and survival was statistically evaluated. ResultsNGS analysis and qRT-PCR revealed significantly upregulated plasma miR-370-3p expression in the U group compared to that in the F group (p = 0.028 and p = 0.005, respectively). Moreover, miR-370-3p expression and lymph node metastasis showed a statistically significant association (p = 0.028). In a multivariate analysis of OS and recurrence-free survival (RFS), the upregulation of miR-370-3p expression in plasma was identified as an independent risk factor for poor OS (HR2.13, p = 0.004) and RFS (HR1.84, p = 0.015). ConclusionsPlasma miR-370-3p expression upregulation correlates with poor prognosis in patients with PDAC.

A Multi-Decade, Multi-institutional Propensity Score Matched Analysis of Recurrence-Free Survival and Mortality in Post-mastectomy Patients with and without Immediate Breast Reconstruction

A Multi-Decade, Multi-institutional Propensity Score Matched Analysis of Recurrence-Free Survival and Mortality in Post-mastectomy Patients with and without Immediate Breast Reconstruction

Impact of media compositions and culture systems on the immunophenotypes of patient-derived breast cancer cells

BackgroundHeterogeneous tumor cells are thought to be a significant factor in the failure of endocrine therapy in estrogen receptor-positive (ER+) cancers. Culturing patient-derived breast cancer cells (PDBCCs) provides an invaluable tool in pre-clinical and translational research for the heterogeneity of cancer cells. This study aimed to investigate the effects of different media components and culture methods on the BCSC-associated immunophenotypes and gene expression in ER + PDBCCs.MethodsTen patients with ER + breast cancer were employed in this study, six of whom had neoadjuvant chemotherapy and four of whom did not. PDBCCs were isolated by enzymatic methods using collagen I and hyaluronidase. PDBCCs were grown as monolayers in mediums with different compositions and as multicellular spheroid in a suspended condition. Collagen I-coated plate and ultralow attachment plate coated with polymer-X were used for monolayer and spheroid culture. Flow cytometry, immunofluorescent staining, RT-PCR, and RNA-sequencing were employed to examine the immunophenotype and genetic profile of PDBCCs.ResultsMore than 95% of PDBCCs sustain EpCAM high/+/fibroblast marker- phenotypes in monolayer conditions by subculturing 3–4 times. A83-01 removal induced senescent cells with high β-galactosidase activity. PDBCCs grown as monolayers were characterized by the majority of cells having an EpCAM+/CD49f + phenotype. Compared to full media in monolayer culture, EGF removal increased EpCAM+/CD49f − phenotype (13.8-fold, p = 0.028), whereas R-spondin removal reduced it (0.8-fold, p = 0.02). A83-01 removal increased EpCAM+/CD24 + phenotype (1.82-fold, p = 0.023) and decreased EpCAM low/-/CD44+/CD24- phenotype (0.45-fold, p = 0.026). Compared to monolayer, spheroid resulted in a significant increase in the population with EpCAM-/CD49+ (14.6-fold, p = 0.006) and EpCAM low/-/CD44+/CD24- phenotypes (4.16-fold, p = 0.022) and ALDH high activity (9.66-fold, p = 0.037). ALDH1A and EMT-related genes were upregulated. In RNA-sequencing analysis between spheroids and monolayers, a total of 561 differentially expressed genes (2-fold change, p < 0.05) were enriched in 27 KEGG pathways including signaling pathways regulating pluripotency of stem cells. In a recurrence-free survival analysis based on the Kaplan-Meier Plotter database of the up-and down-regulated genes identified in spheroids, 15 up-, and 14 down-regulated genes were associated with poor prognosis of breast cancer patients.ConclusionThe media composition and spheroid culture method change in the BCSCs and EMT markers of PDBCCs, implying the importance of defining the media composition and culture method for studying PDBCCs in vitro.

A novel pathological finding, "BABA", for a prognostic factor in oral tongue carcinoma.

92 Background: Oral tongue carcinoma is one of the cancers with poor prognosis. The UICC staging classification is commonly used to predict outcomes and to select the treatments, although there are cases where cancer relapse early despite being at the same Stages, indicating a need for additional prognostic factors to predict patient outcomes accurately. Recent advances in RNA sequencing of tumor and immune cells, as well as elucidation of the tumor microenvironment, have enabled the identification of many genes associated with recurrence risk and immunosuppressive environment around the tumor, which essential for precision treatment of the patients with high risks of recurrence. However pathological findings remain the first step in selecting samples with a high risk of recurrence for further analysis of RNA sequencing or the tumor microenvironment. In this study, we identified a novel pathological feature named as “BABA” (Broadening Amoeboid Behavior of Advanced tumor cells) that appears around the invasive front of tumors. It describes the way in which cancer cells progress like amoeba between muscle fibers and affect the prognosis of oral tongue carcinoma, making it a potential factor for the future analysis of next-generation sequencing or tumor microenvironment. Methods: Patients with oral tongue squamous cell carcinoma who underwent surgery were recruited, excluding those who had received salvage treatment for recurrence, those with simultaneous occurrence of carcinoma, those who had undergone palliative therapy, postoperative therapy, or those who lacked any pathological findings. Survival analyses for existing pathological findings, such as pT (pathological primary stage), pN (pathological nodal stage), ENE (extra nodal extension) status, lymphatic invasion, venous invasion, perineural extension, margin status, WPOI (worst pattern of invasion) and BABA were conducted. Results: A total number of 211 patients were analyzed in this study. Patients with positive for BABA had a two-year overall survival rate and recurrence-free survival rate of 0.78(p=0.02) and 0.39 (p&lt;0.001), respectively, according to Kaplan-Meier analysis. In the multivariate analysis for overall survival using Cox regression model, venous invasion and pN ≥1 were significant prognostic factors, with HR (95%CI) of 3.0 (1.5-6.3) and 2.4 (1.2-4.5), respectively. In the multivariate analysis for recurrence free survival using Cox regression model, positive for lymphatic invasion, venous invasion, BABA, pN ≥1 were significant factors, with HR (95%CI) of 2.1 (1.2-3.6), 2.0 (1.1-3.4), 2.2 (1.3-3.7) and 2.0 (1.2-3.6), respectively. Conclusions: BABA is the novel risk factor for recurrence in oral tongue carcinoma. Identifying BABA could help clinicians better predict recurrence and develop more personalized treatment strategies.

Significance of Desmoplastic Histopathological Growth Pattern for Colorectal Liver Metastases Treated With Preoperative Chemotherapy.

The aim of this study was to evaluate hepatectomy cases that underwent preoperative chemotherapy to examine the relationship between the development of desmoplastic histopathological growth pattern (dHGP) and prognosis and recurrence and determine whether it is useful for evaluating preoperative chemotherapy. A total of 133 cases with hepatic metastasis for colorectal cancer that underwent surgical resection. Of the 102 cases that underwent preoperative chemotherapy, 34 (33%) were determined to be dHGP positive, which was statistically significantly higher than the 2 of 31 cases (6.5%) that had not undergone preoperative chemotherapy. Regarding the 5-year recurrence-free survival, the dHGP group had a value of 50.3%, whereas the non-dHGP group had a value of 7.1%. For the 5-year overall survival, the dHGP group had a better prognosis than the non-dHGP group (57.6% vs. 37.1%, respectively), with a statistically significant difference. Univariate analysis of recurrence-free survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and the presence or absence of dHGP were prognostic factors, whereas multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. Univariate analysis of the overall survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and presence or absence of dHGP were prognostic factors. Multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. dHGP is useful as a new evaluation method for evaluating the efficacy of preoperative chemotherapy.

Coil-assisted ethanol embolotherapy for refractory head and neck arteriovenous malformations with Onyx recrudescence: 10-Year experiences

ObjectiveThis study aimed to evaluate the outcomes of coil-assisted ethanol embolotherapy in recanalized head and neck arteriovenous malformations (HNAVMs) with dilated outflowing veins after Onyx treatment. MethodsThirty-six patients with HNAVMs (18 females and 18 males with a mean age of 26.83 years) who experienced recurrence after Onyx embolization from October 2007 to October 2017 were included in this study. All patients underwent complete clinical and angiographic examinations. Further, each patient was classified based on the Schobinger stage before undergoing staged ethanol embolization. All patients were followed up for 5 years in-person at an interval of 3 months after discharge. The Kaplan-Meier method was used to perform the recurrence-free survival analysis. ResultsSixteen patients (44.4%) had Schobinger stage II HNAVMs, and the remaining patients had Schobinger stage III or IV (20/36 patients [55.6%]) HNAVMs. A total of 116 embolization procedures were performed, coils were applied in 107 procedures (92.2%) among patients with dilated outflowing veins. The dose of absolute ethanol was 16.39 mL per procedure in patients with Schobinger II HNAVMs, and 22.45 mL per procedure in patients with Schobinger III and IV HNAVMs (P = .024, 95% confidence interval, 1.128-5.009). During the 3-month evaluation, complete response was observed in 13 of 36 patients (36.1%), and partial response was observed in 23 of 36 patients (63.9%). The 5-year recurrence-free survival rate for patients who underwent Onyx treatment had improved 58.3% after ethanol embolization (95% confidence interval, 2.853-9.595; P < .0001). ConclusionsCoil-assisted ethanol embolotherapy could treat refractory HNAVMs with Onyx recrudescence effectively.

Comparison of Prognostic Value Between Stimulated and Nonstimulated Thyroglobulins in Differentiated Thyroid Cancer: A Retrospective Study.

The growing incidence of differentiated thyroid cancer (DTC) demands dependable prognostic factors to guide follow-up and treatment plans. This study investigated the prognostic value of response to therapy (RTT) assessment using TSH stimulated-thyroglobulin (sti-Tg) and nonstimulated-thyroglobulin (nonsti-Tg) and evaluates whether RTT using nonsti-Tg (nonstiRTT) can replace RTT using sti-Tg (stiRTT) in clinical practice to improve patients' quality of life during assessment. We enrolled 419 DTC patients who underwent total thyroidectomy, radioactive iodine (RAI) therapy, and Tg assessment. Patients with structural incomplete responses were excluded. Initial RTT assessments based on the 2015 American Thyroid Association guidelines (excellent response; ER, indeterminate response, biochemical incomplete response) were performed 6-24months after RAI therapy. The second RTT assessments were performed 6-24months after the first assessment. Statistical analysis for recurrence-free survival (RFS) was done with the log-rank test for stiRTT and nonstiRTT. Although initial stiRTT and nonstiRTT were significant predictors for RFS (p < 0.0001), stiRTT provided better RFS prediction than nonstiRTT. The RFS analysis of the second RTT assessment demonstrated statistical significance only for stiRTT (p < 0.0001). In 116 patients classified as ER on initial stiRTT, there was no RFS difference between patients classified as ER on either second stiRTT or nonstiRTT. The prognostic power of stiRTT surpasses that of nonstiRTT in both the initial and second RTT assessment. Nevertheless, among patients classified as ER on initial stiRTT, a second stiRTT may not be required for those classified as ER on the second nonstiRTT. The online version contains supplementary material available at 10.1007/s13139-023-00811-8.

Tumor volume doubling time as a potential predictor of prognosis in clinical stage I lung squamous cell carcinoma.

Tumor volume doubling time (VDT) has been shown to predict prognosis in various non-small cell lung carcinoma with scant evidence for lung squamous cell carcinoma (SCC). The purpose of this study was to investigate the prognostic value of tumor VDT in resected lung SCCs. In this study, subjects were 51 patients who underwent lobectomy for clinical stage I SCC of the peripheral lung at our institution between January 2006 and April 2020. Univariable and multivariable analyses of overall survival (OS) and recurrence-free survival (RFS) were performed using the Cox proportional hazards model. The Kaplan-Meier method was used to create OS and RFS curves and to determine statistical significance. The cut-off value of VDT was defined by receiver operating characteristic (ROC) curve analysis on survival. Multivariable analysis found only VDT (HR, 0.990; 95% CI: 0.979-0.997) to be an independent predictor of OS. Also, only VDT (HR, 0.989; 95% CI: 0.978-0.995) was an independent predictor of RFS. The 5-year OS rates were 88.4% and 30.4% in the long (≥150 days) and short (<150 days) VDT groups, respectively (P=0.002). The 5-year RFS rates were 88.8% and 26.5% in the long (≥150 days) and short (<150 days) VDT groups, respectively (P<0.001). Tumor VDT was found to be a useful prognostic predictor in clinical stage I lung SCC in this study.

Impact of ground glass opacity in a three-dimensional analysis for pathological findings and prognosis in stage IA pure solid lung cancer.

We investigated whether a three-dimensional (3D) analysis could correct the discrepancy between conventional computed tomography findings and pathological findings and contribute to prognostic stratification in early pure solid lung cancer. A total of 370 patients with two-dimensional (2D) pure solid, clinical stage IA non-small cell lung cancer (NSCLC) who underwent complete resection at our hospital between January 2010 and March 2021 were included in the present study. We classified the patients into the 3D solid group and the 3D ground glass opacity (GGO) group according to the consolidation volume/tumor volume ratio (C/T volume ratio) measured using a Synapse Vincent 3D analysis workstation, and compared the pathological findings and prognosis between the two groups. There were 142 (38.4%) patients in the 3D GGO group. Lepidic lesions were significantly more frequent in the 3D GGO group (27.6% vs. 59.2%, P<0.001). Lymphatic invasion, vascular invasion and lymph node metastasis were significantly more frequent in the 3D solid group (52.2% vs. 27.5%, P<0.001; 67.5% vs. 43.0%, P<0.001; 22.3% vs. 11.2%, P=0.04). A Cox proportional hazards multivariate analysis for overall survival (OS) and recurrence-free survival (RFS) showed that 3D solid was an independent poor prognostic factor [hazard ratio (HR): 1.981, P=0.02; HR: 1.815, P=0.02]. Kaplan-Meier curves for 5-year OS (74.1% vs. 87.8%, P<0.001) and 5-year RFS (65.6% vs. 84.9%, P<0.001) showed significant differences between the two groups. The C/T volume ratio determined by a 3D analysis detects GGO and reflects the pathological findings, and further prognostic stratification is possible in early 2D pure solid lung cancer.

Clinical Significance of Intramural Metastasis as an Independent Prognostic Factor in Esophageal Squamous Cell Carcinoma

BackgroundAlthough intramural metastasis (IM) in esophageal cancer is considered a poor prognostic factor, there are only limited reports detailing its clinicopathologic characteristics and prognostic impact.Patients and MethodsWe retrospectively included patients with esophageal squamous cell carcinoma (ESCC) with esophagectomy at our institution between 2010 and 2016. We compared patients with intramural metastases (IMs) (IM group) versus those without IMs (non-IM group) to clarify the clinical significance of intramural metastasis in ESCC.ResultsA total of 23 (3.9%) out of all 597 patients were identified to have IM. The IMs were located on the cranial side in 13 (56.5%) and caudal side in 10 (43.5%) of the primary tumor, with two multiple cases. The IM group, compared with the non-IM group, was associated with higher percentage of cN-positive (91.3 versus 67.9%, P = 0.02), pN-positive (82.6 versus 55.9%, P = 0.04), and pM(lym)-positive (30.4 versus 12.5%, P = 0.02) cases. Five-year recurrence-free survival (RFS) was significantly worse in the IM group than the non-IM group (14.9 versus 55.0 %, P < 0.001). Multivariable analysis of recurrence-free survival identified pT (HR 1.74, 95% CI 1.36–2.23, P < 0.001), pN (HR 2.11, 95% CI 1.60–2.78, P < 0.001), histological classification (HR 1.68, 95% CI 1.21–2.35, P = 0.002), and pM(LYM) (HR 1.64, 95% CI 1.64–2.95, P < 0.001), along with presence of IM (HR 2.24, 95% CI 1.37–3.64, P < 0.001) to be independent prognostic factors. Lymphatic (65.2 versus 24.9%, P < 0.001) and hepatic (26.1 versus 6.8%, P = 0.005) recurrences were significantly more common in the IM group than in the non-IM group.ConclusionsIM was shown to be associated with dismal survival after surgery. A treatment strategy emphasizing more intensive systemic control should be considered for patients with ESCC with IM.

Combined associations of a healthy lifestyle and body mass index on colorectal cancer recurrence and survival: A cohort study.

3609 Background: Colorectal cancer (CRC) risk is associated with modifiable lifestyle factors including smoking, physical inactivity, Western diet, and excess body weight. The impact of lifestyle factors on survival is less known. A cohort study was conducted to investigate the combined effects of a pre-diagnostic healthy lifestyle and body mass index (BMI) on prognosis following CRC diagnosis. Methods: Treatment and follow-up data were collected from the patient files of 1098 participants from the Swedish Colorectal cancer low-risk study cohort including stage I-III CRC patients. A healthy lifestyle and BMI (HL) score was computed using self-reported data on smoking status, physical activity, adherence to a Mediterranean diet pattern, and BMI five years before diagnosis, and divided into four categories ranging from least to most healthy. Survival analyses were performed to assess recurrence-free survival and overall survival across categories of exposure, using the Kaplan-Meier method and Cox proportional hazards model, the latter adjusted for age, sex, and educational level. Results: Among 1098 participants with stage I-III CRC, 233 (21.2%) had an HL score of 0-1 (least healthy), 354 (32.2%) HL score of 2, 357 (32.5%) HL score of 3 and 154 (14.0) HL score of 4 (most healthy). Participants missing follow-up data (n = 29) or relapsing ≤ 6 months (n = 29) were excluded from the recurrence-free survival analysis. 221 events of cancer recurrence were observed among 1040 participants during a median follow-up time of 4.3 years, and 542 deaths among 1098 participants during a median follow-up time of 6.3 years. Patients with the healthiest lifestyle had an improved recurrence-free survival (HL 4 vs HL0-1, HRadj 0.51 (95% CI 0.31-0.83) and overall survival (HL 4 vs HL 0-1, HRadj 0.52 (95% CI 0.38-0.70)). Stratifying these results for cancer stage (I-III) and tumor site (colon/rectum) did not alter estimated HR:s or 95% CI:s. Avoidance of smoking and being physically active were independently associated with improved recurrence-free survival and overall survival: non-smoking vs smoking HRadj 0.62 (95% CI 0.43-0.90), high vs low levels of physical activity HRadj 0.71 (95% CI 0.54-0-94)). Conclusions: Our study indicates that pre-diagnostic adherence to a healthy lifestyle may increase the recurrence-free and overall survival of patients with stage I-III CRC. Avoidance of smoking and being physically active were the strongest risk-reducing factors for these outcomes. [Table: see text]

Pathological Nodal and Vascular Involvement Significantly Impacts the Recurrence Risk in Different Time Frames in Patients With Resectable and Borderline Resectable Pancreatic Cancer: Long-term Conditional Recurrence-free Survival Analysis in the Setting of a Neoadjuvant Treatment Strategy.

To investigate the long-term dynamics of recurrence risk and the significance of prognostic variables using conditional recurrence-free survival (C-RFS) analysis in neoadjuvant treatment (NAT) for resectable (R) and borderline resectable (BR) pancreatic cancer (PC). C-RFS analysis assesses the probability of achieving additional RFS according to the RFS already accrued. Patients with NAT and subsequent resection for R/BRPC were enrolled. In the C-RFS analysis, the actual 5-year RFS (5yRFS) rate was calculated separately in the subgroup that had already gained a given amount of RFS. The significance levels of prognostic variables associated with 5yRFS were assessed regarding their time-dependent dynamics in a conditional fashion. Among the total 397 patients, 160 survived for more than 5 years without recurrence after surgery (actual 5yRFS rate: 45%). The probability of 5yRFS incrementally increased based on the RFS already accrued. Pathological nodal and vascular involvement were significant influencers of 5yRFS. The patients with nodal involvement consistently remained at significantly higher risk of recurrence than those without, even after 5yRFS, whereas positivity of vascular involvement was significantly associated with the risk of recurrence only during the early postoperative period and lost its significance after 3yRFS accrued. In NAT for R/BRPC, the probability of gaining additional RFS increases as a function of RFS already accrued, and the significance of prognostic variables time-dependently evolves in their own patterns during the long-term postoperative period.

Development of a deep pathomics score for predicting hepatocellular carcinoma recurrence after liver transplantation

Background and purposeTumor recurrence after liver transplantation (LT) impedes the curative chance for hepatocellular carcinoma (HCC) patients. This study aimed to develop a deep pathomics score (DPS) for predicting tumor recurrence after liver transplantation using deep learning.Patients and methodsTwo datasets of 380 HCC patients who underwent LT were enrolled. Residual convolutional neural networks were used to identify six histological structures of HCC. The individual risk score of each structure and DPS were derived by a modified DeepSurv network. Cox regression analysis and Concordance index were used to evaluate the prognostic significance. The cellular exploration of prognostic immune biomarkers was performed by quantitative and spatial proximity analysis according to three panels of 7-color immunofluorescence.ResultsThe overall classification accuracy of HCC tissue was 97%. At the structural level, immune cells were the most significant tissue category for predicting post-LT recurrence (HR 1.907, 95% CI 1.490–2.440). The C-indices of DPS achieved 0.827 and 0.794 in the training and validation cohorts, respectively. Multivariate analysis for recurrence-free survival (RFS) showed that DPS (HR 4.795, 95% CI 3.017–7.619) was an independent risk factor. Patients in the high-risk subgroup had a shorter RFS, larger tumor diameter and a lower proportion of clear tumor borders. At the cellular level, a higher infiltration of intratumoral NK cells was negatively correlated with recurrence risk.ConclusionsThis study established an effective DPS. Immune cells were the most significant histological structure related to HCC recurrence. DPS performed well in post-LT recurrence prediction and the identification of clinicopathological features.

The Role of Surgery in Primary Chest Wall Tumors: Over 20 Years' Experience in Resection and Reconstruction.

Primary chest wall tumors comprise a heterogeneous group of neoplasms arising from soft tissues and bones. While surgical excision is the standard of care for benign tumors, the management of malignant tumors requires multimodal treatment. We conducted a predictive analysis of outcome, recurrence-free and overall survival. We retrospectively reviewed the clinical and pathological records of all patients treated in our center between 1998 and 2020. 53 patients (15-85 years) were treated in our department. The average tumor diameter was 65 ± 35 mm (10-160 mm). Negative margins were obtained in 48 patients (90.6%), whereas in the remaining 5, R1 resection was accomplished. Median overall survival was 63,03 months (1-282 months). Overall survival was 90% at 1 year, 78% at 2 years, and 61% at 5 years. Our analysis identified tumor diameter, postoperative complications, and high grade of malignancy as factors that can influence prognosis. The treatment of primary chest wall tumors remains a very challenging process. Different histological types preclude definition of an unequivocal approach. Complete resection with healthy margins remains a definitive cornerstone in the treatment of these cancers as part of a more comprehensive approach.

Abstract P3-05-32: Positive sentinel lymph node does not affect prognosis in T1 breast cancer patients who undergo breast conserving surgery with sentinel lymph node biopsy

Abstract Backgrounds: The ACOSOG Z0011 trial revealed oncologic outcomes in patients who underwent breast conserving surgery (BCS) and sentinel lymph node biopsy only versus completion axillary dissection to be equivalent. It was also reported that axillary recurrence rate to be not different between axillary dissection group and SLNB only group, despite the positive rate of over 20% in non-sentinel lymph nodes. It led to suspicion that the role of SLNB in local control to be less significant than previously recognized. Currently trials such as SOUND trial and NAUTILUS trial are being conducted in cT1N0 breast cancer undergoing BCS to compare the outcomes between the current standard surgery and no axillary surgery. Purposes: This study aimed to investigate the factors associated with positive SLN in patients with T1 breast cancer, including T substages. We also evaluated the oncologic outcomes according to SLN positivity. Method: We retrospectively reviewed medical records of patients with pT1 breast cancer who underwent BCS including SLNB at Seoul National University Bundang Hospital from 2010 to 2015 (n=986). SLN positive was defined as one or more micro- to macro-metastasis in axillary lymph node specimen. Overall, regional, and systemic recurrence-free survival (RFS, RRFS, SRFS) and overall survival (OS) were estimated by the Kaplan-Meier analysis. Result: Of 986 patients, positive SLN was observed in 116 patients (11.8%). Regarding T substages, T1mic, T1a, and T1b gouprs showed SLN positive rate of 0%, 3.4%, and 8.5% respectively whereas T1c showed 15.3%. Multivariable logistic regression analyses revealed clinical T stage (OR 1.791, 95% CI 1.061-3.023, P=0.029), &amp;gt;C2 finding in preoperative axillary ultrasonograpy (OR 3.021, 95% CI 1.740-5.248, P&amp;lt; 0.001), usual histologic type including invasive ductal carcinoma, invasive lobular carcinoma, and metaplastic carcinoma confirmed in preoperative biopsy (OR 4.406, 95% CI 1.357-14.305, P=0.014) to be independent predictive factors for SLN positivity. The median follow-up period was 103.03 months. The 5 year RFS, RRFS, SRFS, and OS showed no statistical difference between SLN positive group and negative group. In multivariable Cox regression analysis, serum CEA level higher than 5ng/ml at diagnosis (HR 7.534, 95% CI 3.336-17.019, P=0.002) and Ki-67 level higher than 20% (HR 7.534, 95% CI 3.336-17.019, P&amp;lt; 0.001) were shown to be the independent prognostic factors for RFS. Conclusion: Our data implicates that patients with T1c breast cancer should undergo SLNB at all times presently, considering substantially higher SLN positive rate compared to other T1 substages (16.8% vs. 6.1%, P&amp;lt; 0.001) although no survival difference was observed between SLN positive group and negative group. Kaplan-Meier curve of recurrence-free survival and overall survival Kaplan-Meier curve of recurrence-free survival and overall survival Kaplan-Meier analyses revealed no difference of recurrence-free survival, overall survival between SLN-positive and SLN-negative group. Univariable and multivariable model for recurrence-free survival Higher Ki-67 expression, ER negativity, PR negativity, HER2 positivity were shown to be independent risk factors associated with shorter RFS. Multivariable analysis showed higher Ki-67 expression as the sole independent risk factor for shorter RFS. Citation Format: Hyoung Won Koh, Hee-Chul Shin, Eun-Kyu Kim, Eunyoung Kang. Positive sentinel lymph node does not affect prognosis in T1 breast cancer patients who undergo breast conserving surgery with sentinel lymph node biopsy. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-32.

A genomic enhancer signature associates with hepatocellular carcinoma prognosis

Background & AimsLifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours and the matched adjacent normal tissues to understand the aberrant epigenetic events associated with HCC. MethodsWe identified tumour differential enhancers and the associated genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) and Hi-C/HiChIP data from the resected tumour samples of 30 patients with early-stage HCC. This epigenome dataset was analysed with previously reported genome and transcriptome data of the overlapping group of patients from the same cohort. We performed patient-specific differential expression testing using multiregion sequencing data to identify genes that undergo both enhancer and gene expression changes. Based on the genes selected, we identified two patient groups and performed a recurrence-free survival analysis. ResultsWe observed large-scale changes in the enhancer distribution between HCC tumours and the adjacent normal samples. Many of the gain-in-tumour enhancers showed corresponding upregulation of the associated genes and vice versa, but much of the enhancer and gene expression changes were patient-specific. A subset of the upregulated genes was activated in a subgroup of patients’ tumours. Recurrence-free survival analysis revealed that the patients with a more robust upregulation of those genes showed a worse prognosis. ConclusionsWe report the genomic enhancer signature associated with differential prognosis in HCC. Findings that cohere with oncofoetal reprogramming in HCC were underpinned by genome-wide enhancer rewiring. Our results present the epigenetic changes in HCC that offer the rational selection of epigenetic-driven gene targets for therapeutic intervention or disease prognostication in HCC. Impact and ImplicationsLifestyle and environmental-related exposures are the important risk factors of hepatocellular carcinoma (HCC), suggesting that tumour-associated epigenetic dysregulations may significantly underpin HCC. We profiled tumour tissues and their matched normal from 30 patients with early-stage HCC to study the dysregulated epigenetic changes associated with HCC. By also analysing the patients’ RNA-seq and clinical data, we found the signature genes – with epigenetic and transcriptomic dysregulation – associated with worse prognosis. Our findings suggest that systemic approaches are needed to consider the surrounding cellular environmental and epigenetic changes in HCC tumours.