Positive Lymph Node Involvement Research Articles

The prognostic value of Dickkopf-3 (Dkk3), TGFB1 and ECM-1 in prostate cancer

Prostate cancer (PCa) is considered one of the most common cancers worldwide. Despite advances in patient diagnosis, management, and risk stratification, 10%–20% of patients progress to castration-resistant disease. Our previous report highlighted a protective role of Dickkopf-3 (DKK3) in PCa stroma. This role was proposed to be mediated through opposing extracellular matrix protein 1 (ECM-1) and TGF-β signalling activity. However, a detailed analysis of the prognostic value of DKK3, ECM-1 and members of the TGF-β signalling pathway in PCa was not thoroughly investigated. In this study, we explored the prognostic value of DKK3, ECM-1 and TGFB1 using a bioinformatical approach through analysis of large publicly available datasets from The Cancer Genome Atlas Program (TGCA) and Pan-Cancer Atlas databases. Our results showed a significant gradual loss of DKK3 expression with PCa progression (p < 0.0001) associated with increased DNA methylation in its promoter region (p < 1.63E-12). In contrast, patients with metastatic lesions showed significantly higher levels of TGFB1 expression compared to primary tumours (p < 0.00001). Our results also showed a marginal association between more advanced tumour stage presented as positive lymph node involvement and low DKK3 mRNA expression (p = 0.082). However, while ECM1 showed no association with tumour stage (p = 0.773), high TGFB1 expression showed a significant association with more advanced stage presented as advanced T3 stage compared to patients with low TGFB1 mRNA expression (p < 0.001). Interestingly, while ECM1 showed no significant association with patient outcome, patients with high DKK3 mRNA expression showed a significant association with favourable outcomes presented as prolonged disease-specific (p = 0.0266), progression-free survival (p = 0.047) and disease-free (p = 0.05). In contrast, high TGFB1 mRNA expression showed a significant association with poor patient outcomes presented as shortened progression-free (p = 0.00032) and disease-free survival (p = 0.0433). Moreover, DKK3, TGFB1 and ECM1 have acted as immune-associated genes in the PCa tumour microenvironment. In conclusion, our findings showed a distinct prognostic value for this three-gene signature in PCa. While both DKK3 and TGFB1 showed a potential role as a clinical marker for PCa stratification, ECM1 showed no significant association with the majority of clinicopathological parameters, which reduce its clinical significance as a reliable prognostic marker.

Assessing angiogenesis factors as prognostic biomarkers in breast cancer patients and their association with clinicopathological factors

Introduction Angiogenesis is fundamental for tumor growth and metastasis across many solid malignancies. Considerable interest has focused on the molecular regulation of tumor angiogenesis as a means to predict disease outcomes and guide therapeutic decisions. Methods In the present study, we investigated the prognostic value of transforming growth factor beta (TGF-β), epidermal growth factor (EGF), fibroblast growth factor (FGF), delta-like ligand 4 (DLL4), and vascular endothelial growth factor (VEGF) in the serum of 120 women diagnosed with breast cancer using ELISA as well as examined their associations with clinical parameters and the outcome of the disease. Results Our results demonstrated that the serum concentration of TGF-β and EGF were remarkably higher in patients with higher tumor size, end stages of the disease, and positive lymph node involvement compared to patients with lower tumor size, early stages of the disease, and negative lymph node involvement. In addition, we found a significant correlation between the serum concentration of VEGF and the level of EGF, FGF, and DLL4 in patients with breast cancer. Furthermore, both univariate and multivariate analyses showed that TGF-β and EGF can be used as end-stage predictors. Discussion/Conclusion Based on our findings, increasing the level of angiogenesis factors is significantly associated with higher tumor size and late stages of the disease in patients with breast cancer. Moreover, measuring the level of angiogenesis factors could lead to better prediction of disease outcomes and choosing the best treatments for patients.

Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.

Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODSAND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method. The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46years (mean, 48.1years; range, 10-80years). The tumor sizes ranged from 0.3 to 6.8cm, with a mean of 3.5cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients. Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improvediagnosis and management in this unique subtype of breast cancer.

Clinical implications of heat shock protein 70 in oral carcinogenesis and prediction of progression and recurrence in oral squamous cell carcinoma patients: a retrospective clinicopathological study

BackgroundOral cancer is a common cause of death worldwide. The search for novel biomarkers for oral cancer is an ongoing struggle. Prognostic biomarkers are of great importance in diagnosis, and prediction of the cancer outcome. There are several disagreements in oral cancer studies over the role of heat shock proteins as prognostic markers. The current study investigated HSP70 expression in diverse tissues ranging from normal oral mucosa to dysplastic oral epithelium and oral squamous cell carcinoma to determine its role in oral carcinogenesis. Moreover, HSP70 was evaluated concerning different prognostic parameters to determine its capability in predicting cancer progression. Recurrence of tumor was recorded, and patients` disease-free survival was calculated and analyzed considering HSP70 expression to determine the potential utility of HSP70 immuno-expression in predicting recurrence.MethodsA retrospective study was accomplished on 50 cases of OSCC. Biopsies from the cancerous tissue, the free surgical margin, and the normal oral mucosa were used. The grading of dysplastic epithelium and OSCCs followed the criteria of WHO classification (2017). The clinicopathological and follow-up records for each patient were retrieved. Pearson’s Chi-square test, one-way ANOVA, and post hoc tests were used to analyze the variance of HSP70 immuno-expression concerning different parameters. The Kaplan–Meier method was used to compute and visualize disease-free survival, and the log-rank test was used to analyze the data. With Cox regression, univariate and multivariate survival analyses were run. A P-value of 0.05 or less was regarded as statistically significant.ResultsA significant increased expression of HSP70 was observed as the tissue progressed from normal to dysplastic epithelium, and carcinoma (P = 0.000). HSP70 revealed a significant increased expression by progression from mild to severe dysplasia (P = 0.023), and also from well to moderately and poorly differentiated carcinoma (P = 0.000). High HSP70 immuno-expression was significantly associated with progression of OSCC; large-sized tumors (P = 0.002), advanced TNM clinical stages (P = 0.001), positive nodal involvement (P = 0.001), presence of recurrence (P = .008), and reduced DFS (P = 0.014).ConclusionHSP70 has a crucial contribution to oral carcinogenesis, and its immune-expression could potentially be used as predictor of progression and recurrence of OSCC patients.Trial registration: Retrospectively registered.

Clinical importance of serum and pleural fluid prominin-1 and hypoxia-inducible factor-1α concentration in the evaluation of lymph node involvement in patients with malignant pleural effusion.

Malignant pleural effusion (MPE) and lymph node metastasis (LNM) presence are poor prognostic factors that have importance for cancer patients. The study objective was to determine whether hypoxia-inducible factor-1α (HIF-1α) and prominin-1 (CD133) in pleural fluid (P) and serum (S) could be used as biomarkers for diagnosis of lymph node involvement in patients with MPE. Fifty-six patients with MPE and 30 healthy control subjects were included. Computerized tomography (CT) and positron emission tomography (PET) were used to diagnose pleural effusion. Patients with malignant cells in pleural fluid cytological examination were included in the MPE group. Thirty-five patients with lymph node metastases on CT were included in the LNM-positive MPE group. Serum and pleural fluid HIF-1α and CD-133 concentrations were measured manually via enzyme-linked immunosorbent assay (ELISA). Serum concentrations of HIF-1α and CD133 were higher in MPE patients. It was found that CD133/HIF-1α (S) ratio was higher in the malignant patient group with positive lymph node involvement than in the negative group, while concentrations of HIF-1α (P) were lower. Pleural fluid HIF-1α and CD133/HIF-1α (S) ratio had sufficient performance in diagnosing lymphatic metastases in patients with MPE (AUC = 0.90 and 0.83, respectively). In conclusion, serum HIF-1α and CD133 concentrations were higher in patients with MPE, consistent with our hypothesis. Concentrations of HIF-1α (P) and CD133/HIF-1α (S) ratio can be used as biomarkers in diagnosing lymph node involvement in MPE patients, according to this experiment.

Involved-field irradiation or elective-nodal irradiation in neoadjuvant chemo-radiotherapy for locally-advanced esophageal cancer: comprehensive analysis for dosimetry, treatment-related complications, impact on lymphocyte, patterns of failure and survival.

To compare the differences between involved-field irradiation (IFI) and elective nodal irradiation (ENI) in selecting the optimal target area for neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). We retrospectively analyzed 267 patients with LA-ESCC, of whom 165 underwent ENI and 102 underwent IFI. Dosimetry, treatment-related complications, pathological responses, recurrence/metastasis patterns, and survival were compared between the two groups. The median follow-up duration was 27.9 months. The R0 resection rates in the IFI and ENI groups were 95.1% and 92.7%, respectively (p=0.441), while the pathological complete response (pCR) rates were 42.2% and 34.5%, respectively (p=0.12). The ENI group received higher radiation doses to the heart (HV30:23.9% vs. 18%, p=0.033) and lungs (LV30:7.7% vs. 4.9%, p<0.001) than the IFI group. Consequently, the ENI group showed a higher incidence of grade 2 or higher radiation pneumonitis (30.3% vs. 17.6%, p=0.004) and pericardial effusion (26.7% vs. 11.8%, p=0.021) than the IFI group. Post-operation fistulas were observed in 3 (2.9%) and 17 cases (10.3%) in the IFI and ENI groups, respectively (p=0.026). In the multivariate analysis, smoking, positive lymph node involvement (pN+), and anastomotic fistula were independent predictors of overall survival (OS). The pN+ patients exhibited a greater propensity for recurrence compared to pN- patients, especially in the first year of follow-up (6.67% vs. 0.56%, p=0.003). The ENI group had a higher incidence of radiation-induced adverse events compared to the IFI group, likely due to the higher radiation doses to normal tissues. Considering the similar disease-free survival (DFS) and OS rates in the two groups, IFI may be suitable for nCRT in patients with LA-ESCC, although further prospective studies are warranted.

Single-Fraction Pre-Operative Stereotactic Radiosurgery for Early-Stage Breast Cancer: Pathological Findings

to assess pathological results after single-fraction pre-operative stereotactic radiosurgery of early-stage breast cancer. A phase 2 clinical trial to investigate the feasibility of pre-operative radiosurgery for early-stage breast cancer was conducted. Eligible patients are women older than 50 years, with histologically proven breast invasive ductal carcinoma, hormonal receptors positive/human epidermal grow factor receptor 2 negative, any grade, tumor size < 3cm, unifocal, with no nodal involvement, and suitable for breast conservative surgery. An expert radiologist injected ultrasound-guided a fiducial marker to precisely identify tumor positioning. The Planning Target Volume (PTV) is created by adding a 3mm margin to the Gross Tumor Volume (GTV). A single fraction of 30-33 Gy is delivered to 95% of PTV. Patients had a breast MRI scan 6-12 weeks after treatment to evaluate the rate of radiological response. Surgery was performed at 9 to 16 weeks after irradiation. From January 2022 to December 2022, 33 patients underwent single-fraction radiosurgery, of whom 29 had breast conserving surgery (BCS). BCS was performed at 9-10 weeks for the first 14 patients, at 14-16 weeks for 13 patients, and at 18-19 weeks for 2 patients. The pathological response was defined as complete response (pCR) if no residual tumor cells were found, partial response (pPR), or no response. The pPR were also subdivided into 3 subgroups according to the rate of residual disease: < 10%, 10-50%, and > 50%. Two patients (7%) achieved pCR, both treated with 33 Gy and operated at 14 weeks. Twenty-five patients (86%) had pPR, of which 7 patients (24%) had residual disease < 10%, 9 patients (31%) between 10-50% and 9 patients (31%) over 50%. Two patients (7%) had no pathological response. All patients had sentinel lymph node biopsy at the time of surgery. Positive micrometastatic nodal involvement was found in 3 patients (11%), of which 2 patients (7%) had macrometastases (pN1a) and received subsequent axillary lymph node dissection. All patients had negative surgical margins. Not any acute and sub-acute surgical complications were observed. Single-fraction pre-operative stereotactic radiosurgery for early-stage breast cancer leads to a high rate of complete or partial pathological response with surgery performed at 2-4 months following irradiation.

Sociodemographic disparities associated with advanced stages and distant metastatic breast cancers at diagnosis in Indonesia: a cross-sectional study.

The global health burden of breast cancer is increasing with 5-year survival rates being much shorter in low-income and middle-income countries. Sociodemographic and clinical disparities in early cancer detection affect long-term outcome. The authors compared social, demographic, and pathological characteristics associated with metastatic and late stages of breast cancer diagnosis using data collected from a special registry developed by Perhimpunan Bedah Onkologi Indonesia (PERABOI) in 2015. Of 4959 patients recruited in this study, 995 women (20.1%) were diagnosed with metastatic breast cancer. Lower education status and living in rural areas were significantly associated with Stage IV at diagnosis [odds ratio (OR)=1.256, 95% CI=1.093-1.445, P=0.001; and OR=1.197, 95% CI=1.042-1.377, P=0.012; respectively). Main complaints other than lump (ulceration, breast pain, and discharge) and occupation as a housewife were also associated with the presentation of metastatic diseases (OR=2.598, 95% CI=2.538-3.448, P<0.001 and OR=1.264, 95% CI=1.056-1.567, P=0.030, respectively). Having lower education and living outside Java and Bali islands were associated with the diagnosis of late-stage breast cancers (OR=1.908, 95% CI=1.629-2.232, P<0.001 and OR=3.039, 95% CI=2.238-4.126, P<0.001; respectively). A higher proportion of breast cancer patients were relatively younger with bigger tumour size, positive axillary nodal involvement, and more frequent Human epidermal growth factor receptor 2 overexpression. The authors identified sociodemographic disparities in the metastatic and late-stage diagnosis of breast cancers among Indonesian women. The subsequent action is required to reduce disparities faced by women with lower social and educational levels for early diagnosis and better healthcare access.

Accuracy of pre-operative 18-fluoride fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting lymph node involvement in colon cancer.

Accurate staging of colon cancer is imperative in directing treatment and prognostication. Existing literature on pre-operative accuracy of FDG-PET/CT in detecting lymph node disease often combines colon and rectal cancer, examines rectal cancers alone, and rarely assesses colon cancer in isolation. Our aim was to assess pre-operative utility of FDG-PET/CT in detecting lymph node disease in colon cancer. A retrospective cohort analysis was performed at a single Australian institution between 2017 and 2022 to identify treatment naive primary colonic tumours. Primary outcome was sensitivity and specificity using formal surgical histopathology as gold standard. Secondary outcomes were patient and tumour factors predictive of FDG-PET/CT positive disease including pre-operative CEA, mismatch repair status, duration to surgery, and tumour T-stage. Three hundred and thirty-nine patients were identified. Thirty-four had pre-operative FDG-PET/CT without neoadjuvant therapy. The mean surgical lymph node harvest was 18 nodes. Twenty-five patients had moderately differentiated tumours. The median duration between FDG-PET/CT and operation was 17 days. Pre-operative FDG-PET/CT suggested positive lymph node involvement in 12 patients. Compared to final lymph node histopathology, FDG-PET/CT had a sensitivity of 53%, specificity of 82%, positive predictive value of 75%, negative predictive value of 64% and accuracy of 68%. There was no significant difference between groups for secondary outcomes. FDG-PET/CT has moderate specificity but poor sensitivity in the detection of lymph node involvement in colon cancer. Its utility should likely remain isolated to investigating equivocal lesions or follow up of known PET avid disease.

Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.

Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry. This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model. ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05). ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.

High expression of MORC2 predicts worse neoadjuvant chemotherapy efficacy in triple negative breast cancer.

Tumor infiltrating lymphocytes (TILs) are closely related to the patients' prognosis. Recently, Microrchidia 2 (MORC2) has been documented as a prognostic and predictive biomarker in triple negative breast cancer (TNBC). To compare whether MORC2 is a better predictor than TILs, as well as clinicopathological parameters, in predicting the efficacy of neoadjuvant chemotherapy (NAC) in TNBC, we detected the expression of MORC2 on neoplastic cells through immunohistochemistry and quantified the stromal TILs through Hematoxylin-eosin staining on core biopsies from 50 locally advanced TNBC patients who underwent standard NAC. Among all the 50 patients, 28 (56%) cases had residual tumors, while the other 22 (44%) achieved pathologic complete response (pCR). In these studied patients, age and T-stage showed no correlation with pCR rate, while percentage of TILs, nodal involvement and expression of MORC2 on tumor cells showed significant association with pCR rate. Positive nodal involvement was correlation with worse pathologic response at multivariate analysis (P = .0036), and high TILs levels (≥50%) was positively associated with better NAC efficacy at univariate analysis (P = .002). Whereas high expression of MORC2 was statistically associated with worse pCR rate both at univariate (P < .001) and multivariate (P = .036) analysis. Our results indicate that MORC2 expression has a better predictive role in predicting the efficacy of NAC than TILs in TNBC patients.

Lymph node metastasis in T1-2 colorectal cancer: a population-based study.

We performed this study to identify predictive factors for lymph node metastasis (LNM) and analyze the impact of LNM on the prognosis of patients with T1-2 colorectal cancer (CRC), with the intention of providing guidance for the treatment. The Surveillance Epidemiology and End Result database was used to identify 20,492 patients diagnosed with T1-2 stage CRC between 2010 and 2019, who underwent surgery and lymph node evaluation and had complete prognostic information. Clinicopathological data of patients with T1-2 stage colorectal cancer treated with surgery at Peking University People's Hospital from 2017 to 2021 with complete clinical information were retrieved. We identify and confirm the risk factors for positive lymph node involvement, and the results of follow-up were analyzed. Age, preoperative carcinoembryonic antigen (CEA) level, perineural invasion, and primary tumor site were independent risk factors for LNM in T1-2 CRC based on the analysis of the SEER database, while tumor size and histology of mucinous carcinoma were also independent risk factors in T1 CRC. We then make the nomogram model for predicting LNM risk and showed an acceptable consistency and calibration capability. Survival analysis showed that LNM was an independent prognostic indicator of 5-year disease-specific survival (P = 0.013) and disease-free survival (P < 0.001) in patients with T1 and T2 CRC. Age, CEA level and primary tumor site should be taken into consideration before making the surgical decision in T1-2 CRC patients. The tumor size and histology of mucinous carcinoma also need to be thought about in T1 CRC. Conventional imaging tests do not appear to provide a precise assessment for this issue.

CORRELATION BETWEEN THE PREOPERATIVE SERUM PROSTATE SPECIFIC ANTIGEN, GLEASON SCORE AND STAGING USING MRI WITH POSTOPERATIVEHISTOPATHOLOGICAL OUTCOME FOLLOWING ROBOT ASSISTED RADICAL PROSTATECTOMY.

Introduction: Prostate cancer is second most common cancer in Indian men1. Early detection may be the cause of this increasing trend in urban areas. In our study, we have tried to study correlation between preoperative serum PSA, Gleason score and staging using MRI with postoperative histopathological outcome following robot assisted radical prostatectomy (RARP). Objectives of the study: To correlate between preoperative PSA, Gleason score, and staging with MP-MRI with pathological outcome following RARP in men with clinically localized cancer prostate and assess accuracy of preoperative Gleason score and staging with MRI with post operative histopathology. Materials and Methods:Asingle center, hospital based prospective observational study of 87 patients with age &gt; 50 years with localized prostate cancer was conducted in department of urology at tertiary care center for study period between November 2019 to November 2021. Data collected from these patients' included demographic, clinical history, physical ndings, detailed investigations, operative details, postoperative ndings and results were analyzed. Results:Atotal of 87 localized carcinoma prostate patients were enrolled into the study. It was found that in nal histopathology report post RARP, organ conned disease was seen in 52 (59.77%) patients, capsular involvement in 35(40.22%), seminal vesicle invasion seen in 14(16%) and 2 (0.25%) had positive lymph node involvement. On correlating serum PSA, biopsy Gleason score and staging with MRI with postoperative pathology, it was found that in localized carcinoma prostate on MRI with higher serum PSA, raised Gleason score and higher stage, organ conned disease decreases linearly with signicant P value of (0.005), (0.005), (0.007). Conclusion: Based on data of our study we conclude that patients with localized prostate cancer on MRI, if they have higher preoperative serum PSA, higher Gleason score, and higher stage, then they have more chances of locally advanced disease on postoperative histopathology

Radiation therapy for vulvar cancer: consensus guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 1: clinical recommendations.

The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). Given the lack of prospective data on the management of vulvar carcinoma, this document provides an up-to-date review of radiotherapy treatment in vulvar cancer and a series of consensus-based recommendations from a group of experts. A two-round, online modified Delphi study was conducted to reach consensus treatment recommendations in three clinical settings: 1) adjuvant treatment, 2) locally-advanced vulvar cancer (LAVC), and 3) recurrent disease. After the first round, we comprehensively reviewed the available medical literature from peer-reviewed journals to assess and define the evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree; strongly disagree. The main recommendations were as follows: 1) following surgical resection, adjuvant radiotherapy is recommended with the presence of adverse risk factors (primarily positive margins and lymph node involvement); 2) radiotherapy (with or without chemotherapy) should be considered in LAVC; and 3) in recurrent disease, radiotherapy should be individualised on a case-by-case basis. A high level of agreement over 80% was reached. In the absence of robust clinical data, these final recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer.

ASSOCIATION BETWEEN TWENTY SERUM MIRNAS AND CLINICOPATHOLOGICAL VARIABLES IN PATIENTS WITH BREAST CANCER

Determining that miRNAs play a role in breast cancer pathogenesis suggests that it may be useful in the diagnosis and treatment of breast cancer. In this study, 39 patients with invasive breast cancer were diagnosed with serum levels of 20 miRNAs(miR-105, miR-21, miR-141, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-375, miR-34a, miR-133a, miR-155, miR-139-5p, miR-143, miR-145, miR-365, miR-299-5p, miR-411, miR-452, miR-17) were analyzed during diagnosis and after treatment. In the analysis results, it is detected that serum levels of miR-200c(p=0.030), miR-375(p=0.045), miR-34a(p=0.042) were significantly higher in the local advanced/metastatic group. Serum level of miR-141(p=0.062) was lower in patients with positive lymph node involvement, whereas miR-133a(p=0.037) levels were higher in the same patient group. MiR-105(p=0.015), miR-203(p=0.015), miR-375(p=0.033), miR-145(p=0.025) serum levels were significantly higher in the progesterone receptor negative group, likewise miR-105(p=0.053) levels were high in the estrogen receptor negative patient group. The high levels of miR-375 and miR-133a were noticeable in human epidermal growth factor receptor-2 positive patients(p=0.037 and p=0.014, respectively). MiR-143(p=0.009) and miR-145(p=0.017) levels were observed to be higher in the patient group with a ki-67 index&gt;20%. It was found that 2 miRNAs(miR-133a(p=0.018) and miR-139-5p(p=0.004)) were significantly higher in patients in the luminal B group, which were separated by molecular subgroups. Nine of miRNAs that evaluated(miR-105(p=0.0001), miR-21(p=0.001), miR-141(p=0.041), miR-200a(p=0.003), miR-200b(p=0.0001), miR-200c(p=0.0001), miR-203(p=0.0001), miR-34a(p=0.0001), miR-452(p=0.018)) significantly increased after treatment and 5 of the miRNAs(miR-155(p=0.0001), miR-143(p=0.0001), miR-145(p=0.0001), miR-365(p=0.0001), miR-299-5p(p=0.0001)) were significantly reduced after treatment. We think that miRNAs may help in evaluating the follow-up and prognosis of invasive breast cancer.

Abstract P3-06-09: Real-world toxicity of pembrolizumab-based neoadjuvant regimen in patients with early triple negative breast cancer

Abstract Background Pembrolizumab (pembro, anti-PD-1 antibody) combined to chemotherapy (CT) in neoadjuvant/adjuvant setting has demonstrated its efficacy for early triple negative breast cancer (eTNBC). Pembro obtained FDA marketing authorization on July 26, 2021 and is available in France through the French Early Access Program. Methods We built an ambispective cohort that aimed to evaluate the efficacy and safety of the pembro-CT combination in the real world setting in patients with eTNBC. This study included patients treated from September 2021 to May 2022, at Institut Curie, France. Patients provided written authorization to report their clinical data. We report here the safety results. Results Between September 2021 and May 2022, 51 patients were included. Median age was 49 years [29; 68]. Germline mutations were recorded in 8 patients (22.2% of 36 tested patients). All pts were ECOG PS 0 or 1. Baseline clinical TNM stage were T1 (8 pts, 15.7%), T2 (30 pts, 58.9%), T3 (7 pts, 13.7%) and T4 (6 pts, 11.7%). Out of 37 pts (72.5%) with radiological axillary lymph node involvement, 19 pts (51.4%) had positive node involvement confirmed by guided fine needle aspiration. SBR grade 2 and 3 were observed in 9 (17.6%) and 42 (82.4%) pts, respectively. HER2 score was 0 or 1+/2+(FISH neg) for 31 (60.8 %) and 20 pts (39.2 %), respectively. A CPS score ≥ 10 was observed in 19 pts (50% of 38 tested patients). The CT backbone was a combination of carboplatin (Cb) plus weekly paclitaxel (wP) 4 courses (with Cb regimen AUC 5 q3W (81.1%), AUC4 q3w (5.4%) and AUC1,5 q1w (13.5%), and wP 80 mg/m²), followed by standard AC60/600 q3w for 4 courses. Out of the 37 pts (72.5%) who completed the Cb + wP 4 courses, all experienced adverse events (AEs), including 21 pts (56.8%) with at least 1 grade ≥ 3 AE (anemia 5.4%, thrombopenia 5.4%, neutropenia 51.5%, neuropathy 2.7%). Transfusion support was needed for 8 pts (21.6%). Grade ≥ 2 neuropathy occurred in 3 pts (8.1 %). Dose reduction and drug discontinuation were performed in 9 (24.3%) and 5 pts (13.5%), respectively. On the entire cohort, 15 pts (29.4%) had IrAE all grades: dysthyroidism (6 pts, 11.7%), skin toxicity (2 pts, 3.9%), adrenal insufficiency (1 pt, 2%), hypophysitis (1 pt, 2%), immune-allergic nephropathy (1 pt, 2%), suspicion of myocarditis (1 pt, 2%), hepatitis (1 pt, 2%) and ophthalmologic AE (1 pt, 2%). Consequently, after a median follow up of 5 months, pembro postponement and permanent discontinuation were performed in 7 (13,7%) and 5 pts (9,8%), respectively. At abstract submission 6 pts had breast surgery (pCR in 5 pts = 83.3%). Conclusions Our real-world data are consistent with the results of the KEYNOTE-522 trial in terms of patients characteristics. We observed a very high rate of hematological and immune related adverse events, frequently leading to dose reduction or discontinuation, underlying the need for a very close clinical management of those patients. Updated data including toxicity during the whole neoadjuvant sequence and pCR rate will be presented at the meeting. Citation Format: Delphine Loirat, Emilie ARNAUD, Khaoula ALAOUI, Pauline VAFLARD, Sinen KORBI, Dalila MEZIANI, Lucie THIBAULT, Romain-Pacome DESMARIS, Jean-Guillaume FERON, Jean-Yves Pierga, Francois-Clement Bidard, Paul COTTU. Real-world toxicity of pembrolizumab-based neoadjuvant regimen in patients with early triple negative breast cancer [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 P3-06-09.

Prognostic Impact of Margin Status in Distal Cholangiocarcinoma.

A positive ductal margin is strongly associated with poor survival in patients with distal cholangiocarcinoma. However, the significance of the radial margin status and its effect on survival are not fully clarified. All patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy between January 2000 and December 2018 at Tokai University Hospital were retrospectively analyzed. Positive margins were divided into positive ductal margin and positive radial margin. One hundred and eight consecutive patients with distal cholangiocarcinoma underwent pancreatoduodenectomy. Margin-negative R0 resection was performed in 85 patients (79%). Twenty-three patients (21%) had a positive resection margin (R1 resection). The 5-year survival rate and median overall survival for patients with R0 resection and those with R1 resection was 64%, 98months and 25%, 26months, respectively. There was a significant difference in survival between patients with R0 resection and those with R1 resection (p < 0.001). Patients with positive radial margin (n = 10) had a significantly worse outcome than those with positive ductal margin (n = 13) (p = 0.016). Univariate analysis showed that R1 resection, lymph node metastasis, tumor depth, portal vein invasion, pancreatic invasion, lymphatic invasion, and venous invasion were significant prognostic factors. Multivariate analysis confirmed that R1 resection and nodal involvement were significant independent prognostic indicators after surgical resection for distal cholangiocarcinoma. Positive surgical margin and nodal involvement were the strongest predictors of poor survival in patients with distal cholangiocarcinoma. Patients with a positive radial margin had a significantly worse outcome than those with a positive ductal margin.

Management of Radiographically Positive Pelvic and/or Para-aortic Lymph Nodes During Primary Chemoradiation Therapy for Cervix Cancer

Advanced imaging in the initial workup of cervix cancer has become standard of care and has led to the need for complex decision making regarding optimal management of locoregional nodal metastases. 1 National Comprehensive Cancer Network. Cervical cancer. National Comprehensive Cancer Network guidelines. 2021;1:1-90. Google Scholar When treating a patient with cervix cancer using primary radiation therapy (RT) or chemoradiation therapy (CRT), radiation oncologists must decide on the total radiation therapy dose and fractionation for radiographically positive pelvic and/or para-aortic lymph nodes. It is evident that nodal involvement negatively affects disease-free survival and risk of developing distant metastases; thus, the updated International Federation of Gynecology and Obstetrics (FIGO) 2018 cervix cancer staging system includes lymph node status. 2 MacDonald KO Chen J Dodson M et al. Prognostic significance of histology and positive lymph node involvement following radical hysterectomy in carcinoma of the cervix. Am J Clin Oncol. 2009; 32: 411-416 Crossref PubMed Scopus (77) Google Scholar , 3 Kidd EA Siegel BA Dehdashti F et al. Lymph node staging by positron emission tomography in cervical cancer: Relationship to prognosis. J Clin Oncol. 2010; 28: 2108-2113 Crossref PubMed Scopus (241) Google Scholar , 4 Bhatla N Berek JS Fredes MC et al. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol Obstet. 2019; 145: 129-135 Crossref PubMed Scopus (413) Google Scholar This article will first summarize the available data regarding RT dose for positive nodes and then discuss the treatment typically used at our institutions.

Treatment and Outcomes of Proximal Esophageal Squamous Cell Carcinoma.

This study evaluated the treatment of proximal (cervical or upper thoracic) esophageal squamous cell carcinoma (SCC), for which chemoradiation is the recommended therapy. Treatment and outcomes of patients with cT1-3N0-1M0 proximal esophageal SCC in the National Cancer Database between 2004 and 2016 was evaluated using logistic regression, Kaplan-Meier analysis, and propensity-score matching. Therapy of 2159 patients was chemoradiation (n=1500, 69.5%), no treatment (n=205, 9.5%), surgery (n=203, 9.4%), radiation alone (n=190, 8.8%), and chemotherapy alone (n=61, 2.8%). Factors associated with definitive therapy with either chemoradiation or surgery were younger age, non-Black race, being insured, cervical tumor location, clinical T2 and T3 stage, clinical nodal involvement, and treatment at a research/academic program. Five-year survival was significantly better in patients treated with definitive therapy than patients not treated definitively (34.0% vs. 13.3%, p<0.001). In multivariable survival analysis, receiving definitive therapy (hazard ratio [HR] 0.39, p=0.017) was associated with improved survival, while increasing age, male sex, clinical T3 stage, positive clinical nodal involvement, and increasing Charlson Comorbidity Index were associated with worse survival. Esophagectomy was not associated with improved survival in multivariable analysis of the definitive therapy cohort (HR 0.84, p=0.08) or propensity matched analysis. However, the pathologic complete response was only 33.3% (40/120) for patients who did have an esophagectomy after chemoradiation. This national analysis supports definitive chemoradiation for not only cervical but also proximal thoracic esophageal SCC. Routine surgery does not appear to be necessary but may have a role in patients with residual disease after chemoradiation.

Impact of margin width on local recurrence after breast conservative surgery following neoadjuvant chemotherapy

Background: The main goal of BCS after NAC is complete excision of the tumor with clear margin, however, no clear definition of what constitutes a clear margin has been proposed. An additional challenge for surgeons is the extent of resection especially in good responders to NAC. The aim of this study was to determine the impact of margin width on local recurrence after breast conservative surgery for patients who responded to neoadjuvant chemotherapy. Patients and Methods: This study is a prospective observational cohort study conducted at the National Cancer Institute, Cairo university, Egypt. The study included 75 Egyptian female breast cancer patients who responded to NAC and then assigned to BCS in the period from October 2019 till October 2020. Patients were assessed with regular appointments at the outpatient clinics up to 2 years follow up after surgery.Results: The mean age was 43.8±9.5 years and 65.3 % of patients were in the premenopausal status. All patients (75 cases) had either cT2 or cT3 disease. Clinical nodal disease (cN1-3) was found in 68 patients (90.7%). Radiologic complete response was seen in 31 patients (41.3%). Most patients (85.3%) had a least circumferential margin of more than 2 mm. Positive nodal involvement was confirmed in 22 patients (29.3%). Over 70% of patients had ypT stage 1c or 2 and over 60 % of patients had ypN stage 0. By the end of follow up, four patients developed local recurrence. The unadjusted local recurrence rate was 5.3% and cumulative local recurrence free survival of the whole studied group at 36 months was 94.6%. The least circumferential resection margin (2mm) had no impact on local recurrence free survival.Conclusion: Margin after NAC and BCS is safe according to ‘‘no ink on tumor’’ guideline and we emphasize the resection of the clipped area in cases of cCR and/or rCR, however, further studies with larger sample size and longer duration of follow up are required to mitigate the local recurrence after BCS following NAC.