Pathologic Nodal Status Research Articles

Pan-Driver-Negatives versus Epidermal Growth Factor Receptor Mutants for C-Stage IA Lung Adenocarcinoma with Ground-Glass Opacity.

We aimed to verify the prognosis of epidermal growth factor receptor (EGFR) mutation of clinical (c)-stage IA lung adenocarcinoma with the ground-glass opacity (GGO) component. We evaluated 226 cases of surgically resected c-stage IA lung adenocarcinoma with GGO component. Endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis and the log-rank test were used to estimate the survival differences. Prognostic factors were assessed using the univariable and multivariable Cox proportional hazards model. Among the 226 cases, 177 cases harbored the EGFR-mutant adenocarcinoma with the GGO component. The mean duration of follow-up time was 54.4 ± 1.2 months. The 5-year OS and RFS did not differ significantly between the EGFR-mutant and wild-type groups (5-year OS 100% vs. 94.3%, hazard ratio [HR] 0.276, P = 0.168; 5-year RFS 94.7% vs. 95.7%, HR 0.873, P = 0.864). Multivariable Cox hazard model revealed that radiologically solid component size (P = 0.010) and pathological node-positive (P = 0.036) were significant predictors of an inferior RFS. EGFR-mutant was not a prognostic factor of OS and RFS for c-stage IA lung adenocarcinoma with the GGO component. Radiologically solid component size and pathological lymph node status were independent prognostic factors of worse RFS.

A population-based study in resected esophageal or gastroesophageal junction cancer aligned with CheckMate 577.

Background:Results of CheckMate 577 show an improved disease-free survival for patients with resected esophageal or gastroesophageal junction cancer treated with adjuvant nivolumab compared with placebo (22.4 versus 11.0 months). Population-based data can provide insights in outcomes from clinical practice. The aim of our study was to investigate disease-free and overall survival in a nationwide population aligned with the inclusion criteria of CheckMate 577.Patients and Methods:Resected patients with stage II/III esophageal or gastroesophageal junction cancer (2015–2016) treated with neoadjuvant chemoradiotherapy were selected from the Netherlands Cancer Registry. Patients with cervical esophageal cancer, irradical resection, or complete pathological response were excluded. Disease-free and overall survival were assessed from 12 weeks after resection using Kaplan-Meier methods. In addition, to adjust for differences in characteristics between CheckMate 577 and our population-based cohort, a matching-adjusted indirect comparison was performed for pathological lymph node status and pathological tumor status.Results:We identified 634 patients. Sixty percent of patients were diagnosed with recurrence or were deceased at the end of follow-up. Median disease-free survival was 19.7 months and median overall survival was 32.2 months. After the matching procedure, the median disease-free survival was 17.2 months and median overall survival was 28.2 months.Conclusions:Disease-free survival in our population-based study was considerably longer than the placebo population of CheckMate-577 (19.7 versus 11.0 months). Possible explanations are differences in characteristics, quality of esophageal cancer care, or differential strategies for evaluation of recurrence. In the Netherlands postoperative imaging is not part of the standard follow-up as opposed to the standard postoperative imaging in the CheckMate 577 trial. The difference in postoperative imaging could partially explain the longer disease-free survival observed in our study. Quality and optimization of current treatment modalities remain important aspects of esophageal cancer care.

Establishment of a Preoperative Laboratory Panel to identify Lymph Node Metastasis in Superficial Esophageal Cancer.

Background and Aims: In superficial esophageal squamous cell carcinoma (SESCC), the lymph node status is considered as one of the essential factors to determine the primary treatment strategy. Nevertheless, current noninvasive staging methods before surgical intervention have limited accuracy. This study aimed to establish a simple and noninvasive serum-testing panel that facilitates the preoperative prediction of pathological nodal status in SESCC patients.Methods: Data for preoperative hematological parameters were retrospectively collected from 256 SESCC patients who underwent esophagectomy from December 2017 to May 2020. The random forest classification and decision tree algorithms were applied to identify the optimal combination of serum parameters for accurately identifying positive nodal metastasis.Results: Twelve candidate parameters were identified for statistical significance in predicting positive nodal metastasis. A multi-analyte panel was established by using a random forest classification method, incorporating four optimal parameters: Hematocrit (HCT), Activated Partial Thromboplastin Time (APTT), Retinol-Binding Proteins (RBP), and Mean Platelet Volume (MPV). A schematic decision tree was yielded from the above panel with an 89.1% accuracy of classification capability.Conclusions: This study established a simple laboratory panel in discerning the preoperative lymph nodal status of SESCC patients. With further validation, this panel may serve as a simple tool for clinicians to choose appropriate intervention (surgery versus endoscopic resection) for SESCC patients.

Long term results of surgery for NSCLC and aortic invasion. A multicenter retrospective cohort study

Aortic invasion from non-small cell lung cancers (NSCLC) is a relative contraindication to surgery for oncological and technical reasons. Only a few studies have been published showing good results. Our aim was to evaluate short and long-term results of surgery for T4 NSCLC with aortic resection. This is a multicenter retrospective study including 47 patients (33 males and 14 females) who received a major lung resection with aortic surgery in our centers between January 2000 and December 2016. Adenocarcinoma was diagnosed in 31 patients (66.0%). Induction therapy was used in 14 patients. Pneumonectomy was performed in 34 patients (72.3%). A subadventitial dissection with or without endovascular stent graft was carried out in 40 patients (85.1%), a cardiopulmonary bypass was used in 3 patients and left heart bypass in 4. Intraoperatively, two patients had bleeding (4.3%) and one ventricular fibrillation (2.1%). Twenty-three patients (48.9%) experienced at least one postoperative complication. A radical resection was achieved in 39 patients (83.0%). Thirty-day and 90-day mortality were 2.1% and 4.3%. One-, 3- and 5-year overall survival were 85.1%, 57.4% and 53.2%. Overall and disease-free survivals were significantly influenced by pathological lymph node status and R status that were independent predictive factors for poorer survival at the multivariate analyses. Aortic resection during surgery for NSCLC is a challenging situation. Nevertheless, oncologic outcomes may be favorable in selected cases justifying a risky procedure that should be performed in experienced hands.

Extracellular vesicles miR-210 as a potential biomarker for diagnosis and survival prediction of oral squamous cell carcinoma patients.

BackgroundThe identification of early diagnostic and prognostic biomarkers in oral squamous cell carcinoma (OSCC) is an unmet clinical need. We hypothesized that extracellular vesicles miR‐210 expression (EV‐miR‐210) could be a potential biomarker for OSCC diagnosis and follow‐up.MethodsThe expression of EV‐miR‐210 was measured in the plasma of OSCC patients (n = 30) and compared to that of controls (n = 14).ResultsThe median EV‐miR‐210 expression was significantly higher in OSCC patients compared to controls who had often, undetectable levels (p < 0.0001). We performed receiver operating characteristic (ROC) analysis for discriminating OSCC cases from controls. EV‐miR‐210 yielded an area under the curve (AUC) of 0.9513 with sensitivity 92.3% and specificity 86.6%. Kaplan‐Meier curves indicated that high EV‐miR‐210 expression was associated with worse 3 years’ survival (p < 0.05). Cox regression hazard model indicated that high EV‐miR‐210, G2, and G3 grading and pathological nodal status (pN)>1 were independent predictors of worse survival in OSCC patients.ConclusionThese preliminary data suggest that EV‐mir‐210 may be a novel diagnostic and prognostic biomarker in OSCC.

Long-term oncologic safety of immediate reconstructive surgery in patients with invasive breast cancer: a retrospective matched-cohort study

ObjectiveImmediate reconstruction (IR) is a safe and effective surgical treatment for patients with breast cancer. We aimed to assess the prognosis, aesthetic outcomes, and patient satisfaction of IR compared with breast conservation surgery (BCS) and total mastectomy (TM).MethodsThis retrospective matched-cohort study was conducted between May 2005 and December 2014. We established two cohorts according to the tumor (T) size of breast cancer. In the T≤3cm group, cases (IR) and controls (BCS or TM) were matched for age, pathological tumor size, and pathologic nodal status in a 1:1:1 ratio. In the T>3cm group, cases (IR) and controls (TM) were matched with the same factors and ratio. The primary outcome was the 5-year disease-free survival (DFS). The secondary outcome was patient satisfaction and quality of life.ResultsA total of 12,678 breast cancer patients were assessed for eligibility, of which 587 were included (T≤3 cm group: 155 IR vs 155 BCS vs 155 TM; T>3cm group: 61 IR vs 61 TM). In the T≤3 cm cohort, patients who underwent IR had no difference compared with those who underwent BCS or TM regarding the 5-year DFS (P=0.539); however, an improved aesthetic satisfaction, psychosocial, and sexual well-being were achieved in the IR group (P<0.001). In the T>3 cm cohort, the IR group had a worse median 5-year DFS (P=0.044), especially for Her2+ or triple-negative breast carcinoma (TNBC) subtypes compared with the TM group.ConclusionsIR improves aesthetic satisfaction, psychosocial, and sexual well-being for breast cancer patients with T≤3 cm. For patients with T > 3 cm invasive breast cancer, TM is superior to IR as it predicts a better 5-year DFS.

Developing a Stacked Ensemble-Based Classification Scheme to Predict Second Primary Cancers in Head and Neck Cancer Survivors.

Despite a considerable expansion in the present therapeutic repertoire for other malignancy managements, mortality from head and neck cancer (HNC) has not significantly improved in recent decades. Moreover, the second primary cancer (SPC) diagnoses increased in patients with HNC, but studies providing evidence to support SPCs prediction in HNC are lacking. Several base classifiers are integrated forming an ensemble meta-classifier using a stacked ensemble method to predict SPCs and find out relevant risk features in patients with HNC. The balanced accuracy and area under the curve (AUC) are over 0.761 and 0.847, with an approximately 2% and 3% increase, respectively, compared to the best individual base classifier. Our study found the top six ensemble risk features, such as body mass index, primary site of HNC, clinical nodal (N) status, primary site surgical margins, sex, and pathologic nodal (N) status. This will help clinicians screen HNC survivors before SPCs occur.

Tumor glycolytic heterogeneity improves detection of regional nodal metastasis in patients with lung adenocarcinoma.

The diagnostic performance of 18F-FDG PET for detecting regional lymph node metastasis in resectable lung cancer is variable, and its sensitivity for adenocarcinoma is even lower. We aimed to evaluate the value of 18F-FDG PET-derived features in predicting pathological lymph node metastasis in patients with lung adenocarcinoma. We retrospectively analyzed pretreatment 18F-FDG PET-derived features of 126 lung adenocarcinoma patients who underwent curative surgery. A logistic regression model was used to analyze the association between study variables and pathological regional lymph node status obtained from the curative surgery. Furthermore, Cox regression analysis was used to test the effect of the study variables on survival outcomes, including disease-free survival (DFS) and overall survival (OS). The primary tumor entropy (OR = 1.7, p = 0.014) and visual interpretation of regional nodes via 18F-FDG PET (OR = 2.5, p = 0.026) independently predicted pathological regional lymph node metastasis. The areas under the receiver-operating-characteristic curves were 0.631, 0.671, and 0.711 for visual interpretation, primary tumor entropy, and their combination, respectively. Based on visual interpretation, a primary tumor entropy ≥ 3.0 improved the positive predictive value of positive visual interpretation from 51.2% to 63.0%, whereas an entropy < 3.0 improved the negative predictive value of negative visual interpretation from 75.3% to 82.6%. In cases with positive visual interpretation and low entropy, or negative visual interpretation and high entropy, the nodal metastasis rates were approximately 30%. In the survival analyses, the primary tumor entropy was also independently associated with DFS (HR = 2.7, p = 0.001) and OS (HR = 4.8, p = 0.001). Our preliminary results show that the primary tumor entropy may improve 18F-FDG PET visual interpretation in predicting pathological nodal metastasis in lung adenocarcinoma, and may also show a survival prognostic value. This versatile biomarker may facilitate tailored therapeutic strategies for patients with resectable lung adenocarcinoma.

The possible role of SRMS in colorectal cancer by bioinformatics analysis

BackgroundSrc-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (SRMS) is a non-receptor tyrosine kinase that has been found to be overexpressed in various tumors. However, the role of SRMS in colorectal cancer (CRC) has not been well established.MethodsWe evaluated the expression levels of SRMS in CRC using GEPIA, Oncomine, and HPA datasets. Survival information and gene expression data of CRC were obtained from The Cancer Genome Atlas (TCGA). Then, the association between SRMS and clinicopathological features was analyzed using UALCAN dataset. LinkedOmics was used to determine co-expression and functional networks associated with SRMS. Besides, we used TISIDB to assess the correlation between SRMS and immune signatures, including tumor-infiltrating immune cells and immunomodulators. Lastly, protein-protein interaction network (PPI) was established and the function enrichment analysis of the SRMS-associated immunomodulators and immune cell marker genes were performed using the STRING portal.ResultsCompared to normal colorectal tissues, SRMS was found to be overexpressed in CRC tissues, which was correlated with a poor prognosis. In colon adenocarcinoma (COAD), the expression levels of SRMS are significantly correlated with pathological stages and nodal metastasis status. Functional network analysis suggested that SRMS regulates intermediate filament-based processes, protein autophosphorylation, translational initiation, and elongation signaling through pathways involving ribosomes, proteasomes, oxidative phosphorylation, and DNA replication. In addition, SRMS expression was correlated with infiltrating levels of CD4+ T cells, CD56dim, MEM B, Neutrophils, Th2, Th17, and Act DC. The gene ontology (GO) analysis of SRMS-associated immunomodulators and immune cell marker genes showed that they were mainly enriched in the immune microenvironment molecule-related signals. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of these genes indicated that they are involved in multiple cancer-related pathways.ConclusionsSRMS is a promising prognostic biomarker and potential therapeutic target for CRC patients. In particular, SRMS regulates CRC progression by modulating cytokine-cytokine receptor interaction, chemokines, IL-17, and intestinal immune networks for IgA production signaling pathways among others. However, more studies are needed to validate these findings.

Diagnostic value of magnetic resonance imaging in cervical lymph node metastasis of oral squamous cell carcinoma

The objective of this study was to investigate the correlation between magnetic resonance imaging (MRI) characteristics of cervical lymph nodes and the pathologically confirmed status of cervical lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC) and to provide imaging evaluation parameters for the clinical diagnosis of cervical lymph node status in OSCC. In a retrospective analysis, 79 patients who were first pathologically diagnosed with OSCC were included. The MRI-derived imaging parameters of the cervical lymph nodes were evaluated and the pathological status of lymph nodes in neck dissection specimens was reviewed. The relationship between the imaging parameters and cervical LNM was analyzed. The MRI-derived imaging parameters of 4419 lymph nodes were evaluated, and the pathological status of 2463 lymph nodes was reviewed. The MRI-derived shortest axial diameter (SAD) and unclear boundary of the cervical lymph node were significantly related to LNM. The cutoff value of SAD that enabled identification of LNM was 3.6 mm, and it was 4.2 and 4.1 mm for the prediction of overall survival and disease-specific survival, respectively. The MRI-derived parameters SAD and unclear boundary of the cervical lymph node correlated with LNM in OSCC. MRI-derived SAD larger than 3 mm warrants simultaneous neck dissection at initial surgery.

Regional Variation in Lung Cancer Stage at an Irish Rapid Access Lung Clinic

Introduction: Regional variation in cancer outcomes is undesirable. We aim to evaluate regional variation in lung cancer in Ireland focusing on stage at presentation. Methods: A retrospective study was performed on patients who underwent surgical resection of primary lung cancer from June 2013 to March 2020. Patients included attended the St. Vincent’s University Hospital rapid access lung clinic (RALC). Patients were divided into two groups depending on regional variability with Dublin and Wicklow assigned as Group 1 and the remainder assigned to Group 2. Pathological tumour size and lymph node status were compared between the two groups. Results: Complete data was available on 152 patients. Group 1 (n=97) had significantly lower median tumour size (24.74 mm) compared to Group 2 (31.72 mm) (P = 0.026). Patients in group 1 had significantly lower stage (stage II 13.4%, stage III 9.3%) compared to Group 2 (stage II 29%, stage III 16.3%) (P = 0.013). Group 1 showed a lower incidence of squamous cell carcinoma (21.6%) compared to Group 2 (30.9%). Conclusion: Regional variation in cancer presentation is evident in this study. Larger tumors and more advance stage are associated with a more rural location. This is seen in a clinic service with equal access of both populations to diagnostic modalities and treatment, suggesting differences at presentation rather than evaluation.

Impact of preoperative chemotherapy on pathologic nodal status in muscle-invasive bladder cancer: optimal lymphadenectomy in the preoperative chemotherapy era.

To investigate the impact of preoperative chemotherapy (pCTX) on pathologic nodal (pN) status and evaluate the optimal lymphadenectomy method according to clinical nodal (cN) status in patients with muscle-invasive bladder cancer who received pCTX. We retrospectively reviewed 449 patients with muscle-invasive bladder cancer who underwent radical cystectomy. Among them, 139 (31.0%) received pCTX. We analyzed overall survival among three groups (cN-pCTX-, cN-pCTX+, and cN+pCTX+); the impact of lymphadenectomy extent according to the history of pCTX in cN- patients (n = 393); and the pN status which includes number of positive lymph nodes, and lymph node density in cN- patients who underwent extended lymphadenectomy (n = 222). Overall survival was significantly dependent on cN status, and pCTX had no survival advantage although it decreased the percentage of pN+ patients and the number of positive lymph nodes in cN- patients. Lymph node density showed a significant prognostic effect on overall survival in Cox regression analysis both in cN- and cN+ patients. In cN- patients, there was no significant survival difference according to lymphadenectomy extent regardless of receiving pCTX. pCTX can control micrometastases but not overt metastases, despite decreasing the number of positive lymph nodes in patients with muscle-invasive bladder cancer. Although extended lymphadenectomy is a reasonable diagnostic strategy in the pCTX era, standard dissection is as therapeutic as extended dissection in patients with cN- disease.

T1 invasive lung adenocarcinoma: Thin-section CT solid score and histological periostin expression predict tumor recurrence.

Adenocarcinoma is the most common histological type of non-small cell lung cancer (NSCLC), and various biomarkers for predicting its prognosis after surgical resection have been suggested, particularly in early-stage lung adenocarcinoma. Periostin (also referred to as POSTN, PN or osteoblast-specific factor) is an extracellular matrix protein, the expression of which is associated with tumor invasiveness in patients with NSCLC. In the present study, the novel approach, in which the thin-section CT findings prior to surgical resection and periostin expression of resected specimens were analyzed in combination, was undertaken to assess whether the findings could be a biomarker for predicting the outcomes following resection of T1 invasive lung adenocarcinoma. A total of 73 patients who underwent surgical resection between January 2000 and December 2009 were enrolled. A total of seven parameters were assessed in the thin-section CT scans: i) Contour; ii) part-solid ground-glass nodule or solid nodule; iii) percentage of solid component (the CT solid score); iv) presence of air-bronchogram and/or bubble-like lucencies; v) number of involved vessels; vi) shape linear strands between the nodule and the visceral pleura; and vii) number of linear strands between the nodule and the visceral pleura. Two chest radiologists independently assessed the parameters. Periostin expression was evaluated on the basis of the strength and extent of staining. Univariate and multivariate analyses were subsequently performed using the Cox proportional hazards model. There was a substantial to almost perfect agreement between the two observers with regard to classification of the seven thin-section CT parameters (κ=0.64-0.85). In the univariate analysis, a CT solid score >80%, pathological lymphatic invasion, tumor and lymph node status and high periostin expression were significantly associated with recurrence (all P<0.05). Multivariate analysis demonstrated that a CT solid score >80% and high periostin expression were risk factors for recurrence (P=0.002 and P=0.011, respectively). The cumulative recurrence rates among the three groups (both negative, CT solid score >80% or high periostin expression, or both positive) were significantly different (log-rank test, P<0.001). Although the solid component is already known to be a major predictor of outcome in lung adenocarcinomas according to previous studies, the combined analysis of CT solid score and periostin expression might predict the likelihood of tumor recurrence more precisely.

MP45-19 EVALUATION OF THE UTILITY OF LYMPH-VASCULAR INVASION AS AN INDEPENDENT PROGNOSTIC PREDICTOR OF OVERALL SURVIVAL FOR PATIENTS WITH RENAL CELL CARCINOMA THAT UNDERGO NEPHRECTOMY

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging/Surveillance I (MP45)1 Sep 2021MP45-19 EVALUATION OF THE UTILITY OF LYMPH-VASCULAR INVASION AS AN INDEPENDENT PROGNOSTIC PREDICTOR OF OVERALL SURVIVAL FOR PATIENTS WITH RENAL CELL CARCINOMA THAT UNDERGO NEPHRECTOMY Nikola Rakic, Ivan Rakic, Jacob Keeley, Nicholas Corsi, Chandler Bronkema, Marcus Jamil, Akshay Sood, Giacomo Novara, Mani Menon, Craig Rogers, and Firas Abdollah Nikola RakicNikola Rakic More articles by this author , Ivan RakicIvan Rakic More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Chandler BronkemaChandler Bronkema More articles by this author , Marcus JamilMarcus Jamil More articles by this author , Akshay SoodAkshay Sood More articles by this author , Giacomo NovaraGiacomo Novara More articles by this author , Mani MenonMani Menon More articles by this author , Craig RogersCraig Rogers More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002066.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lymph-vascular invasion (LVI) is recognized as an adverse pathological feature in patients with renal cell carcinoma (RCC). However, its impact on overall survival (OS) is not clear, and scarcely addressed in literature. Our aim was to assess the prognostic ability of LVI as a predictor of OS in RCC patients using a large, North American cohort. METHODS: We included 45,036 cM0 RCC patients, diagnosed between 2010 and 2015, that underwent partial or radial nephrectomy within the National Cancer Database. Kaplan-Meier curves and long-rank test were used to depict and compare survival curves. Cox regression analysis tested the relationship between LVI and OS, after accounting for the following covariates: age, Charlson Comorbidity Index status, pathological tumor stage, number of nodes removed, number of positive nodes, pathological nodal status (LNI), and pathological LVI status. RESULTS: Median age (IQR) was 60 (52-68), and most patients had pT1 stage (70.0%). Nodal status was pN0, pN1, and pNx in 14.0%, 3.7%, and 82.3%, respectively. Overall, 7.7% of patients had LVI. Median (IQR) follow-up of the cohort was 38 months (20-59). At 5-years, OS was 59.8% in patients with LVI vs. 85.1% in patients without LVI (p-value<.0001). When patients were stratified based on nodal stage, these rates were 55.8% vs. 77.2% in pN0 patients, (p<0.0001) and 34.1% vs. 39.7% in pN1 patients (p<0.0001). LVI was an independent predictor of higher overall risk of mortality (hazard ratio [HR]: 1.53, 95% CI: 1.36–1.71, p<.001). Other covariates that had a detrimental prognostic impact included pN1 disease (HR: 2.08), Fuhrman grade 3 disease (HR: 1.30), Fuhrman grade 4 disease (HR: 2.54), a pT2 disease (HR: 1.40) and pT3/4 disease (HR: 1.92). (all p-value<0.0001) CONCLUSIONS: Our findings highlight the detrimental impact of LVI on OS in a large nationwide cohort. To the best of our knowledge, this is the first validation of the prognostic ability of LVI in RCC patients on a nationwide level, as virtually all previous studies were institutional. Besides, we observed a synergistic impact for LVI in the presence of pN1, as these patients fare worse than those who have pN1 disease without LVI. Our findings highlight an important utility that LVI can provide in deciding a patient’s prognosis after nephrectomy, and further exploration should examine exactly what its role may become. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e811-e811 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nikola Rakic More articles by this author Ivan Rakic More articles by this author Jacob Keeley More articles by this author Nicholas Corsi More articles by this author Chandler Bronkema More articles by this author Marcus Jamil More articles by this author Akshay Sood More articles by this author Giacomo Novara More articles by this author Mani Menon More articles by this author Craig Rogers More articles by this author Firas Abdollah More articles by this author Expand All Advertisement Loading ...

PD19-12 EXAMINING THE PREDICTIVE ROLE OF LYMPH-VASCULAR INVASION IN PATIENTS WITH VERY HIGH-RISK PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy II (PD19)1 Sep 2021PD19-12 EXAMINING THE PREDICTIVE ROLE OF LYMPH-VASCULAR INVASION IN PATIENTS WITH VERY HIGH-RISK PROSTATE CANCER Nikola Rakic, Ivan Rakic, Jacob Keeley, Christian Meyer, Markus Graefen, Randi Pose, Perre Tennstedt, Nicholas Corsi, Chandler Bronkema, Akshay Sood, Sohrab Arora, Craig Rogers, Mani Menon, and Firas Abdollah Nikola RakicNikola Rakic More articles by this author , Ivan RakicIvan Rakic More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Christian MeyerChristian Meyer More articles by this author , Markus GraefenMarkus Graefen More articles by this author , Randi PoseRandi Pose More articles by this author , Perre TennstedtPerre Tennstedt More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Chandler BronkemaChandler Bronkema More articles by this author , Akshay SoodAkshay Sood More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Craig RogersCraig Rogers More articles by this author , Mani MenonMani Menon More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002008.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lymph-vascular invasion (LVI) at radical prostatectomy (RP) is recognized as an adverse pathological feature in patients with prostate cancer (PCa). Recent literature showed a detrimental impact of LVI on overall survival in all patients with PCa, regardless of risk stratification. That said, the predictive performance of LVI in patients with very have high-risk disease, where it could serve as a guide for the necessity of multimodal treatment has not been elucidated. We tested the hypothesis that LVI is an independent predictor of cancer-specific mortality (CSM) in patients with very high-risk PCa. METHODS: We included 2,058 PCa cM0 patients who underwent RP with lymph node dissection, between 2001 and 2019, in two tertiary care centers. Included patients were considered high-risk due to harboring ≥2 of the following adverse disease features: ≥pT3b stage, pathological Gleason 8-10, and/or positive nodal involvement (pN1). Cumulative incidence curves were used to estimate CSM, after accounting for other cause mortality. Regression analysis tested the relationship between LVI and CSM after accounting for the following covariates: PSA, pathological tumor stage, Gleason grade, pathological nodal status, and surgical margin status. RESULTS: Within our cohort, most patients had a pT3b disease (86.2%), pN1 status (75.4%), positive margins (PSM) (73.9%), LVI (59.0%) and pathological Gleason 9 disease (69.1%). Median (IQR) follow-up of the cohort was 36 months (13-61). At 5-year, CSM rate was 11.2% in patients with LVI vs 7.2% in patients without LVI (p=.03). However, on multivariable analysis, LVI was not an independent predictor of less favorable CSM rate (hazard ratio [HR]:1.071, 95% CI:0.718–1.599, p=0.7366). Covariates that were found to be independent predictors of CSM included Gleason score ≥ 8 (HR: 5.668, 95% CI: 2.704-11.830, p<.0001), PSM (HR: 1.774, 95% CI: 1.080-2.915, p=.02), pN1 (HR: 2.147, 95% CI: 1.278-3.607, p=.003), and stage ≥ pT3b (HR: 3.113, 95% CI: 1.334-7.265, p=.008). CONCLUSIONS: In patients with very high-risk PCa, where the stakes are the highest, and multimodal treatment is frequently discussed after radical prostatectomy, LVI fails to provide further guidance when compared to routinely available and utilized clinical and pathological features. In a quest to continuously optimize outcomes for our patients, our findings highlight an important shortcoming for LVI in very high-risk patients and further show the prognostic value of widely accepted adverse disease characteristics. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e366-e366 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nikola Rakic More articles by this author Ivan Rakic More articles by this author Jacob Keeley More articles by this author Christian Meyer More articles by this author Markus Graefen More articles by this author Randi Pose More articles by this author Perre Tennstedt More articles by this author Nicholas Corsi More articles by this author Chandler Bronkema More articles by this author Akshay Sood More articles by this author Sohrab Arora More articles by this author Craig Rogers More articles by this author Mani Menon More articles by this author Firas Abdollah More articles by this author Expand All Advertisement Loading ...

LB759 Post-operative radiation therapy to prevent local recurrence of low-risk Merkel cell carcinomas of the head and neck versus other sites

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a recurrence risk of ∼40%; however, prognosis for low-risk, stage I disease is excellent with primary surgical management and wide local excision. The role of post-operative radiation therapy (PORT) is controversial. Here, we assess the efficacy of PORT on local recurrence (LR) rates in a cohort of patients with low-risk, pathological stage I MCC with primary tumors on the head/neck (HN) vs. non-head and neck (Non-HN) sites. One hundred forty-seven MCC patients treated from 2006-2020 were identified from an IRB-approved prospective registry who had ‘low risk’ disease: pathological T1 primary tumor resected with negative microscopic margins, negative pathologic node status, and no immunosuppression or prior systemic therapy.

High mitochondrial content is associated with breast cancer aggressiveness.

Mitochondria are relevant for cancer initiation and progression. Antibodies against mitochondrially encoded cytochrome c oxidase II (MTCO2), targeting a mitochondria specific epitope, can be used to quantitate the mitochondria content of tumor cells. The present study evaluated the impact of the cellular mitochondrial content on the prognosis of patients with breast cancer using immunohistochemical analysis on 2,197 arrayed breast cancer specimens. Results were compared with histological tumor parameters, patient overall survival, tumor cell proliferation using Ki67 labeling index (Ki67LI) and various other molecular features. Tumor cells exhibited stronger MTCO2 expression than normal breast epithelial cells. MTCO2 immunostaining was largely absent in normal breast epithelium, but was observed in 71.9% of 1,797 analyzable cancer specimens, including 34.6% tumors with weak expression, 22.3% with moderate expression and 15.0% with strong expression. High MTCO2 expression was significantly associated with advanced tumor stage, high Bloom-Richardson-Elston/Nottingham (BRE) grade, nodal metastasis and shorter overall survival (P<0.0001 each). In multivariate analysis, MTCO2 expression did not provide prognostic information independent of BRE grade, pathological tumor and pathological lymph node status. Additionally, significant associations were observed for high MTCO2 expression and various molecular features, including high Ki67LI, amplifications of HER2, MYC, CCND1 and MDM2, deletions of PTEN, 8p21 and 9p, low estrogen receptor expression (P<0.0001 each) and progesterone receptor expression (P<0.0001). The present study demonstrated that high MTCO2 expression was strongly associated with a poor prognosis and unfavorable phenotypical and molecular tumor features in patients with breast cancer. This suggests that the mitochondrial content may have a pivotal role in breast cancer progression.

Extracapsular extension, pathologic node status, and adjuvant treatment in primary surgery patients with human papillomavirus-mediated oropharyngeal cancer: National hospital-based retrospective cohort analysis.

The significance of extracapsular extension (ECE) and adjuvant treatment paradigm in patients with surgically managed human papillomavirus-positive (HPV+) oropharyngeal cancer (OPC) is debated. National, hospital-based, retrospective cohort study of 2663 patients pN+ HPV+ OPC who underwent primary surgery. Patients with ECE had a 1.74-times risk of death (95% confidence interval [CI]: 1.26-2.40, p=0.001) compared to patients without ECE. Among patients with pN1, ECE-positive disease, risk of overall mortality was similar across treatment paradigms (surgery alone: ref; adjuvant radiation therapy [RT]: aHR: 0.81; 95% CI: 0.36-1.85; p=0.62; adjuvant CRT: aHR: 0.66; 95% CI: 0.34-1.32; p=0.24). Patients with pN2 ECE-positive disease treated with adjuvant RT alone exhibited similar risk of all-cause mortality (hazard ratio: 1.04, 95% CI: 0.24-4.47, p=0.96) compared to adjuvant chemoradiation (CRT). In patients with advanced, ECE-positive disease (e.g., pT3-T4pN2), adjuvant CRT did not reduce the risk of overall mortality relative to adjuvant RT. Although pathologic ECE negatively predicts for survival in patients with HPV+ OPC, our analyses support expansion of postoperative de-intensification clinical trial eligibility criteria in patients with ECE-positive disease.

Should we distinguish between intra and extrapericardial pulmonary artery involvement in NSCLC? A multicenter retrospective case-control study

T4 tumours comprise a heterogeneous group of locally invasive non-small cell lung cancers (NSCLC). Intrapericardial and extrapericardial involvement of the pulmonary artery (PA) may have a different prognosis. We compared the short and long-term surgery outcomes for NSCLC of the PA with intrapericardial or extrapericardial involvement. This is a multicenter retrospective study that included 129 patients who received an anatomical resection with PA resection and reconstruction in our centres between January 2000 and December 2018. Extrapericardial group included 70 patients, while the intrapericardial included 59. Differences in outcomes were found in terms of left side surgery (more common in extrapericardial, p=0.010), type of lung resection (p<0.001), Clavien-Dindo score (p=0.012) and 90-day mortality (1.4 vs 16.9%, p=0.002). Overall survival (OS, 91.11±63.78 vs 63.78±58.241 months, p=0.008) and tumour-free survival (TFS, 68.17±71.57 vs 45.44±61.32 months, p=0.007) were statistically different. OS stratification for performed pneumonectomy, pathological lymph node status and pattern of recurrence were statistically different (p=0.017, 0.040, <0.001). Differences were found in terms of recurrence months stratified for recurrence pattern (p<0.001). According to our results, the difference between PA involvement is significant in terms of survival and complications. A T4 subset or a shift to T3 for extrapericardial involvement of the PA may lead to a change in staging and surgical approach for these patients.

Abstract 476: Clinical characteristics and outcome of pathologic N0 NSCLC patients with false positive on FDG PET-CT

Abstract Background Preoperative Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET-CT) is a non-invasive and useful diagnostic tool to evaluate mediastinal lymph node metastasis in lung cancer. However, there are often false-positive lymph node cases in FDG PET-CT. We enrolled patients diagnosed with clinical N1-3 on FDG PET-CT, but pathologic N0 after mediastinal lymph node dissection. We aimed to explore clinical characteristics and outcome of pathologic N0 non-small cell lung cancer patients with false positive mediastinal lymph nodes on FDG PET-CT. Methods We enrolled total 147 patients who took pre-operative PET-CT scan and mediastinal lymph node dissection. Among them, 40 patients were diagnosed with clinical N1-3 by PET-CT. These patients were re-evaluated by post-operative pathologic nodal metastasis and divided into false-positive group and others. We retrospectively analyzed clinicopathologic features and recurrence free survival among patients diagnosed with same pathologic stage. Results Among 40 patients diagnosed with clinical N1-3 on FDG PET-CT, 19 (47.5%) patients were pathologic N0, which means false positive lymph node by PET-CT. Preoperative absolute platelet count (279.79 x 109/L versus 218.67 x 109/L; P = 0.012) and Platelet-Lymphocyte Ratio (PLR, 16.93 versus 11.53; P = 0.012) were significantly higher in the patients with pathologic N0. Among patients with pathologic N0, the presence of lymphatic invasion was significantly lower than other group (31.6% versus 85.7%; P = 0.001). Recurrence free survival was significantly shorter in pathologic N0 patients than those with same pathologic stage (P = 0.037). In addition, cox regression analysis showed smoking status (P = 0.045) and lymphatic invasion (P = 0.047) were independent factors for recurrence, significantly. Conclusions In conclusion, higher absolute platelet count, PLR and lower proportion of lymphatic invasion were associated with false positive mediastinal lymph node on preoperative FDG PET-CT. Furthermore, recurrence free survival was significantly shorter in these patients than those with same pathologic stage. In the future, preoperative biomarkers to predict pathologic nodal status need to be investigated. Citation Format: Changdong Yeo, Hye Seon Kang, Sang Haak Lee. Clinical characteristics and outcome of pathologic N0 NSCLC patients with false positive on FDG PET-CT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 476.