Presence Of Extranodal Extension Research Articles

Lymph node metastasis in cutaneous squamous cell carcinoma of the head and neck

BackgroundThe study aimed to assess the impact of parotid lymph nodes (LNs) on the prognosis of patients with cutaneous squamous cell carcinomas of the head and neck (HNcSCC), and to develop an alternative LN assessment method to enhance locoregional control (LRC) and overall survival (OS) stratification.MethodsWe retrospectively enrolled patients with surgically treated HNcSCC. Primary outcome variables were LRC and OS. The influence of parotid LNs and different LN assessment methods on prognosis was analyzed using Cox models, and comparisons were made using the C-index, Akaike Information Criterion, and Bayesian Information Criterion.ResultsA total of 126 patients were included. Both intraparotid and periparotid LN statuses significantly linked with prognosis. The presence of extranodal extension (ENE) in cervical LNs, rather than parotid LNs, was predictive of decreased LRC and OS. In the Cox analysis, only N3 of the AJCC N classification, when compared to N0, showed reduced LRC and OS. In comparison to N0P1, only N0P3/N1P1 and N2P2/N2P3 of the O’Brien staging system tended to predict poorer LRC, with no subgroup emerging as an independent predictor for OS. The proposed LN assessment method, based on the number of metastatic LNs and ENE status in cervical LNs, demonstrated superior performance in terms of C-index, Akaike Information Criterion, and Bayesian Information Criterion compared to other systems.ConclusionParotid LNs were significant determinants of prognosis in metastatic HNcSCC. The novel LN assessment method proposed (1–2 vs. 3–4 vs. 5 + or ENE) displayed similar survival stratification to the AJCC N and O’Brien staging systems.

Oncological outcomes post transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma, a single-centre retrospective Australian study

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent’s Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.

Histopathologic Predictors for Locoregional Recurrence in Patients With Oral Squamous Cell Carcinoma - A Single-Center Retrospective Study.

Oral squamous cell carcinoma (OSCC) is known for its aggressive behavior and the high potential for locoregional recurrence (LRR), contributing to poor prognostic outcomes. The aim of this study was to investigate the role of histologic parameters in predicting LRR in patients with OSCC. A retrospective analysis was performed on 58 OSCC patients treated between January 2018 and December 2022. Data were collected from medical records, focusing on demographics, clinicopathologic features, and treatment details. Different histopathologic factors such as depth of invasion, tumor stage (T), pathologic node stage (N), histologic grade of differentiation, perineural invasion, lymphovascular invasion, extranodal extension (ENE), and margin of resection were correlated with LRR. Out of 58 patients, 20 (34.4%) reported LRR within the first year of follow-up. In the recurrence group, 14 patients succumbed to death within 24 months. Among all the histopathologic parameters, our study found a statistically significant correlation between higher pathologic node stage, presence of ENE, and closest margin of resection (≤5mm) with LRR. Higher pathologic node stage, presence of ENE, and closest margin of resection (≤5mm) were the histopathologic factors associated with LRR, and can serve as deciding prognostic factors. Treatment intensification in early-stage disease with higher pathologic nodal stage, presence of ENE, and closest margin of resection (≤5mm) may improve survival outcomes.

Extranodal Extension at Pretreatment MRI and the Prognostic Value for Patients with Rectal Cancer.

Background Detection of extranodal extension (ENE) at pathology is a poor prognostic indicator for rectal cancer, but whether ENE can be identified at pretreatment MRI is, to the knowledge of the authors, unknown. Purpose To evaluate the performance of pretreatment MRI in detecting ENE using a matched pathologic reference standard and to assess its prognostic value in patients with rectal cancer. Materials and Methods This single-center study included a prospective development data set consisting of participants with rectal adenocarcinoma who underwent pretreatment MRI and radical surgery (December 2021 to January 2023). MRI characteristics were identified by their association with ENE-positive nodes (χ2 test and multivariable logistic regression) and the performance of these MRI features was assessed (area under the receiver operating characteristic curve [AUC]). Interobserver agreement was assessed by Cohen κ coefficient. The prognostic value of ENE detected with MRI for predicting 3-year disease-free survival was assessed by Cox regression analysis in a retrospective independent validation cohort of patients with locally advanced rectal cancer (December 2019 to July 2020). Results The development data set included 147 participants (mean age, 62 years ± 11 [SD]; 87 male participants). The retrospective cohort included 110 patients (mean age, 60 years ± 9; 79 male participants). Presence of vessel interruption and fusion (both P < .001), heterogeneous internal structure, and the broken-ring and tail signs (odds ratio range, 4.10-23.20; P value range, <.001 to .002) were predictors of ENE at MRI, and together achieved an AUC of 0.91 (95% CI: 0.88, 0.93) in detecting ENE. Interobserver agreement was moderate for the presence of vessel interruption and fusion (κ = 0.46 for both) and substantial for others (κ = 0.61-0.67). The presence of ENE at pretreatment MRI was independently associated with worse 3-year disease-free survival (hazard ratio, 3.00; P = .02). Conclusion ENE can be detected at pretreatment MRI, and its presence was associated with worse prognosis for patients with rectal cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Eberhardt in this issue.

Impact of extra-nodal extension and AJCC lymph node staging in predicting recurrence following lymphadenectomy in patients with melanoma

BackgroundRegional lymphadenectomy (RL) has traditionally been recommended in patients with melanoma found to have clinical lymphadenopathy or a positive sentinel lymph node biopsy (SLNB). Regional control of disease is still a relevant issue for patients, even after undergoing lymphadenectomy. The goal of this study was to identify the clinicopathologic characteristics that predict locoregional recurrence in patients who have undergone either therapeutic lymph node dissection (TLND) or completion lymph node dissection (CLND) following SLNB. MethodsRetrospective review of population-based cohort of patients with melanoma lymph node metastasis from the years 2005–2015. Multivariate, proportional hazards regression analysis was performed to determine factors predicting nodal recurrence. Results586 patients underwent a RL, with a median follow up of 35 months. Overall, in-basin recurrence rates in the axilla, groin, and head/neck were 7.7 ​%, 8.7 ​% and 9.2 ​%, respectively. Higher unadjusted recurrence rates occurred following CLND than TLND of the groin (12.8 ​% vs 4.5 ​%) and neck (10.0 ​% vs 4.7 ​%) but not the axilla (7.5 ​% vs 8.0 ​%). Upon multivariate analysis, ENE (HR 2.77; p=<0.0001) and the AJCC lymph node stage (N3 vs N1) (HR 2.51; p ​= ​0.025) were predictive of regional recurrence. ConclusionThe AJCC nodal stage and the presence of extranodal extension were the only variables impacting regional recurrence following regional lymphadenectomy for melanoma. When considering regional disease control, they should be factored into treatment decisions, and surveillance strategies.

Occult metastasis is no burden factor in oral squamous cell carcinoma patients when adhering to a standardized approach in neck dissection

ObjectivesManagement of the neck in patients with oral squamous cell carcinoma (OSCC) is pivotal to oncologic control and survival. However, there is controversy regarding necessity of neck dissection (ND) in patients with clinically node-negative neck. We aimed to assess risk factors for occult metastasis and to explore whether the presence of occult lymph node metastases (LNMs) has an impact on recurrence and survival.Material and methodsA retrospective cohort study was performed including patients with primary OSCC who underwent radical tumor resection and ND in a high-volume center adhering to the prevailing German guideline. The ND was performed according to a standardized approach.ResultsFour hundred twenty-one patients with primary surgically treated OSCC were included. The incidence of occult metastasis was 14.49%. A pathological T stage > 1 (multivariate analysis, odds ratio (OR) 3.958, p = 0.042) and the presence of extranodal extension in LNMs (multivariate analysis, OR 0.287, p = 0.020) were identified as independent risk factors for occult metastasis. When comparing patients with and without occult metastasis, there were no significant differences in terms of progression-free survival (log-rank, p = 0.297) and overall survival (log-rank, p = 0.320). There were no cases of ipsilateral neck recurrence. One patient developed contralateral neck metastasis; however, he initially presented with a unilateral pT1 pN0 tumor.ConclusionsOverall, our findings suggest that conducting a standardized approach in ND should be applied in terms of management of the neck in order to maintain survival rates and to prevent neck recurrence in OSCC patients.Clinical relevance.None of the risk factors for occult metastasis can be reliably assessed preoperatively. Although elective ND does not guarantee the complete prevention of neck recurrence, it increases the likelihood of either timely removal of micrometastases or strengthens the justification for adjuvant therapy. Consequently, this approach leads to improvements in clinical outcomes.

Ultrasound criteria of extra-nodal extension in papillary thyroid cancer metastases and its clinical signifcance

The purpose of the research was to identify ultrasound criteria of extranodal extension (ENE) in metastases of papillary thyroid cancer and to evaluate the clinical significance of ENE.Material and Methods. Ultrasound signs of ENE in 283 cervical lymph node metastases from papillary thyroid cancer were analyzed. Extranodal extension in 137 metastases was diagnosed by ultrasound and verified by histological examination. Micrometastases invisible on ultrasound were detected in 144 patients; metastases located inside the organ were detected in 147 patients; metastases located outside the organ were revealed in 136 patients; the size of 98 metastases was less than 1 cm; the size of 185 metastases was more than 1 cm; the age of 51 patients was under 55 years; 132 patients were older than 55 years. Diagnostic significance of ENE and its clinical significance were estimated according to χ2 Pirson criteria.Results: Two ultrasound criteria: shape change and blurred margins of metastases indicated the presence of ENE. The small number of ultrasound false-negative findings indicated the need for further research. The number of micrometastases not detected by ultrasound was 2-fold higher in patients who had metastases with ENE than in patients who had metastases without ENE. The number of patients with ENE in metastases inside the organ (T1a, T1b, T2 and T3b) was 2.7 times lower compared to patients with metastases developed outside the organ (T3a, T4a, T4b); ENE was observed in metastases of different size and did not depend on age groups.Conclusion. The ultrasound method allows intravital detection of ENE in metastases of papillary thyroid cancer. The extension is accompanied by a significantly high number of micrometastases in the neck tissue. It is detected more often in metastases located outside the organ, regardless of the size and age of the patients. The extra-nodal extension should be considered as a criterion for an unfavorable prognosis.

Influence of parotid lymph node metastasis on distant metastasis in parotid gland cancer.

The aim of this study was to analyze the impact of the number and extranodal extension (ENE) of positive parotid lymph nodes (LNs) on distant metastasis in parotid cancer. Patients with surgically treated parotid cancer were retrospectively enrolled. The hazard ratios (HRs) of the number and ENE of positive parotid LNs on distant metastasis-free survival (DMFS) were evaluated. In the Cox model, the groups with zero and one positive LN had comparable 10-year DMFS, but those with two positive LNs had an HR of 2.11 (95% CI: 1.36-5.29), and those with three or more positive LNs had an HR of 3.31 (95% CI: 2.05-8.43). The presence of ENE in parotid LNs did not impact the DMFS (p = 0.462; HR: 2.17; 95% CI: 0.84-6.17). Parotid LN metastasis was associated with decreased DMFS; this effect was mainly driven by the number of positive LNs rather than ENE.

Is FAST FORWARD the Way Forward in Radiotherapy for Locally Advanced Breast Cancer – Learnings From the COVID Pandemic

IntroductionLow middle-income countries (LMICs), including India, have paucity of external beam radiotherapy (RT) machines leading to prolonged wait times for RT. Delay in delivery of RT has been shown to adversely affect outcomes in locally advanced breast cancer (LABC). With the availability of results of multiple randomized controlled trials, hypofractionated RT delivered over 3 to 4 weeks became the standard of care in breast cancer RT. MethodsWe conducted a retrospective audit of 172 LABC patients treated with ultrahypofractionated adjuvant RT (radiotherapy completed in 1 week) during the COVID pandemic. Log rank and Cox-regression model used for univariate and multi-variate analyses. ResultsNo patient developed grade 3 esophagitis. Grade 2 esophagitis requiring short term narcotic analgesics was seen in 12 (6.9%) patients. Grade 2 or higher toxicity peaked between 2 and 3 weeks after RT. The estimated 2 and 3- year recurrence free survival (RFS) for the cohort is 87.1 % and 81.4 %, respectively. The estimated 2 and 3-year overall survival for the cohort is 95% and 91.3%. On multivariate analysis, presence of extra-nodal extension was found to be an independent factor associated with worse RFS (P = .028). ConclusionsFAST FORWARD protocol RT in LABC appears well tolerated.

Outcomes among oropharyngeal and oral cavity cancer patients treated with postoperative volumetric modulated arctherapy.

Presently, there are few published reports on postoperative radiation therapy for oropharyngeal and oral cavity cancers treated with IMRT/VMAT technique. This study aimed to assess the oncological outcomes of this population treated with postoperative VMAT in our institution, with a focus on loco-regional patterns of failure. Between 2011 and 2019, 167 patients were included (40% of oropharyngeal cancers, and 60% of oral cavity cancers). The median age was 60 years. There was 64.2% of stage IV cancers. All patients had both T and N surgery. 34% had a R1 margin, 42% had perineural invasion. 72% had a positive neck dissection and 42% extranodal extension (ENE). All patients were treated with VMAT with simultaneous integrated boost with three dose levels: 66Gy in case of R1 margin and/or ENE, 59.4-60Gy on the tumor bed, and 54Gy on the prophylactic areas. Concomittant cisplatin was administrated concomitantly when feasible in case of R1 and/or ENE. The 1- and 2-year loco-regional control rates were 88.6% and 85.6% respectively. Higher tumor stage (T3/T4), the presence of PNI, and time from surgery >45 days were significant predictive factors of worse loco-regional control in multivariate analysis (p=0.02, p=0.04, and p=0.02). There were 17 local recurrences: 11 (64%) were considered as infield, 4 (24%) as marginal, and 2 (12%) as outfield. There were 9 regional recurrences only, 8 (89%) were considered as infield, and 1 (11%) as outfield. The 1- and 2-year disease-free survival (DFS) rates were 78.9% and 71.8% respectively. The 1- and 2-year overall survival (OS) rates were 88.6% and 80% respectively. Higher tumor stage (T3/T4) and the presence of ENE were the two prognostic factors significantly associated with worse DFS and OS in multivariate analysis. Our outcomes for postoperative VMAT for oral cavity and oropharyngeal cancers are encouraging, with high rates of loco-regional control. However, the management of ENE still seems challenging.

Multi-Specialty Physician Performance in Predicting Radiographic Extranodal Extension in Nodal Metastases of Oropharyngeal Squamous Carcinoma

The presence of extranodal extension (ENE) in oropharyngeal (OPC) cancer patients is an important prognostic factor and can be used to determine the optimal course of treatment; however, currently, the gold standard method for ENE assessment is performed pathologically, which can only be done in a post-hoc fashion after surgical treatment has already been performed. Anatomic imaging features are being explored as a possible method for the pre-therapeutic determination of ENE, but there is currently no objective standard for the assessment of ENE from radiographic images. In this study we recruited expert clinicians, including surgeons, radiation oncologists, and radiologists, across multiple institutions to individually evaluate the presence of ENE from CT scans in order to assess the performance of radiographic ENE evaluation in human experts across different specialties. Pre-therapy contrast-enhanced CT scans were collected from 25 OPC patients with lymph node metastasis that were pathologically evaluated for ENE after surgical resection. 5 scans were randomly chosen to be duplicated and left/right inverted, resulting in a total of 30 scans of which 21 had pathologically-confirmed ENE. To hide the inversion, all images were cropped to only show the oropharynx region. 34 expert head and neck cancer physicians, comprised of 12 surgeons, 11 radiation oncologists, and 11 radiologists, then separately evaluated the 30 CT scans using 3D Slicer for ENE presence or absence with their prediction confidence. For each physician, discriminative performance metrics were measured by calculating the accuracy, sensitivity, specificity, area under the receiver-operating characteristic curve (AUC), and Brier score, a measure of the probabilistic prediction accuracy calculated from their confidence where a lower Brier score is better. Statistical tests were performed using the Mann Whitney U test. The median (interquartile) study results are shown in Table 1. There was no statistically significant difference among groups for accuracy or AUC, but significant differences among groups for Brier score, sensitivity, and specificity. In this study we provide evidence that expert physicians, regardless of specialty, show poor performance in assessing the presence of ENE from CT scans in OPC patients. These results agree with conclusions from previous literature, and suggest the need for further research in the automated analysis of radiographic ENE.

Diagnostic challenges and prognostic implications of extranodal extension in head and neck cancer: a state of the art review and gap analysis.

Extranodal extension (ENE) is a pattern of cancer growth from within the lymph node (LN) outward into perinodal tissues, critically defined by disruption and penetration of the tumor through the entire thickness of the LN capsule. The presence of ENE is often associated with an aggressive cancer phenotype in various malignancies including head and neck squamous cell carcinoma (HNSCC). In HNSCC, ENE is associated with increased risk of distant metastasis and lower rates of locoregional control. ENE detected on histopathology (pathologic ENE; pENE) is now incorporated as a risk-stratification factor in human papillomavirus (HPV)-negative HNSCC in the eighth edition of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) TNM classification. Although ENE was first described almost a century ago, several issues remain unresolved, including lack of consensus on definitions, terminology, and widely accepted assessment criteria and grading systems for both pENE and ENE detected on radiological imaging (imaging-detected ENE; iENE). Moreover, there is conflicting data on the prognostic significance of iENE and pENE, particularly in the context of HPV-associated HNSCC. Herein, we review the existing literature on ENE in HNSCC, highlighting areas of controversy and identifying critical gaps requiring concerted research efforts.

Imaging Characteristics Predictive of Cervical Extranodal Tumor Extension in Patients With Head and Neck Squamous Cell Carcinoma.

The aims of the study were to determine the predictive imaging findings of extranodal extension (ENE) in metastatic cervical lymph nodes of head and neck squamous cell carcinoma and to investigate the interobserver agreement among radiologists with different experience levels. Patients with cervical lymph node dissection and who had metastatic lymph nodes and preoperative imaging were included. Three radiologists evaluated nodal necrosis, irregular contour, gross invasion, and perinodal fat stranding. They also noted their overall impression regarding the presence of the ENE. Sensitivity, specificity, odds ratios based on logistic regression, and interobserver agreement of ENE status were calculated. Of 106 lymph nodes (that met inclusion criteria), 31 had radiologically determined ENE. On pathologic examination, 22 of 31 nodes were positive for ENE. The increasing number of metastatic lymph nodes was associated with the presence of the ENE ( P = 0.010). Irregular contour had the highest sensitivity (78.6%) and gross invasion had the highest specificity (96%) for the determination of the ENE. The radiologists' impression regarding the presence of the pathlogical ENE had 39.3% sensitivity and 82% specificity. Metastatic lymph nodes with a perinodal fat stranding and with the longest diameter of greater than 2 cm were found to be strong predictors of the ENE. The gross invasion demonstrated the highest κ value (0.731) among the evaluated imaging criteria. In the assessment of ENE, the gross invasion had the highest specificity among imaging features and showed the highest interobserver agreement. Perinodal fat stranding and the longest diameter of greater than 2 cm in a metastatic lymph node were the best predictors of the ENE.

Association of Core Biopsy With Extranodal Extension in Surgically Treated Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

Extranodal extension (ENE) is an adverse feature in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and is an indication for adjuvant treatment escalation. Preoperative core needle biopsy (CNB) may cause lymph node capsule disruption related to ENE development; however, evidence regarding this association in OPSCC is lacking. To assess whether preoperative nodal CNB is associated with presence of ENE in final pathology findings among patients with HPV-associated OPSCC targeted for primary surgical resection. This retrospective cohort study was conducted at a single academic tertiary care center from 2012 to 2022. All patients with OPSCC treated with transoral robotic surgery were assessed for eligibility, and primary surgical patients with HPV-associated OPSCC and node-positive disease confirmed on neck dissection were included in analyses. Data were analyzed from November 28, 2022, to May 21, 2023. Preoperative nodal CNB. The primary outcome was presence of ENE in final pathology findings. Secondary outcomes included adjuvant chemotherapy and recurrence rates. Outcomes of interest were investigated against patient demographic, clinical, and pathologic features. Of 106 patients (mean [SD] age, 60.2 [10.9] years; 99 [93.4%] men) included in analyses, 23 patients (21.7%) underwent CNB. Mean (range) preoperative node size was 3.0 (0.9-6.0) cm. Pathologic node class was pN1 in 97 patients (91.5%) and pN2 in 9 patients (8.5%). A total of 49 patients (46.2%) had ENE identified in final pathology analysis. Of 94 patients who received adjuvant therapy, 58 (61.7%) underwent radiation therapy and 36 (38.3%) underwent chemoradiation therapy. There were 9 recurrences (8.5%). In univariate analysis, CNB was associated with ENE (odds ratio [OR], 2.70; 95% CI, 1.03-7.08), but there was no association in a multivariable model including pN class and preoperative node size (OR, 2.56; 95% CI, 0.97-7.27). Compared with pN1 class, pN2 class was associated with ENE (OR, 10.93; 95% CI, 1.32-90.80). There were no associations of ENE with preoperative node size, presence of cystic or necrotic nodes, fine needle aspiration, tobacco or alcohol exposure, pathologic T class, prior radiation, or age. Furthermore, use of CNB was not associated with macroscopic ENE, adjuvant chemotherapy, or recurrence. This cohort study of patients with HPV-associated OPSCC found that preoperative nodal CNB was strongly associated with ENE in final pathology, supporting the possibility of an artifactual ENE component in this population.

Prognostic significance of extranodal extension in patients with pathologic N1 non-small cell lung cancer undergoing complete resection.

The prognostic significance of extranodal extension (ENE) remains unclear in patients with pathologic N1 (pN1) non-small-cell lung cancer (NSCLC) undergoing surgery. We evaluated the prognostic impact of ENE in patients with pN1 NSCLC. From 2004 to 2018, we retrospectively analyzed the data of 862 patients with pN1 NSCLC who underwent lobectomy and more (lobectomy, bilobectomy, pneumonectomy, sleeve lobectomy). According to their resection status and the presence of ENE, patients were classified into R0 without ENE (pure R0) (n=645), R0 with ENE (R0-ENE) (n=130), and incomplete resection (R1/R2) groups (n=87). The primary and secondary endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS), respectively. The prognosis of the R0-ENE group was significantly worse than the pure R0 group for both OS (5-year rate: 51.6% vs. 65.4%, P=0.008) and RFS (44.4% vs. 53.0%, P=0.04). According to the recurrence pattern, a difference of RFS was found only for distant metastasis (55.2% vs. 65.0%, P=0.02). The multivariable Cox analysis revealed that the presence of ENE was a negative prognostic factor in patients who did not undergo adjuvant chemotherapy [hazard ratio (HR) =1.58; 95% confidence interval (CI): 1.06-2.36; P=0.03], but it was not in those with adjuvant chemotherapy (HR =1.20; 95% CI: 0.80-1.81; P=0.38). For patients with pN1 NSCLC, the presence of ENE was a negative prognostic factor for both OS and RFS, regardless of resection status. The negative prognostic effect of ENE was significantly associated with an increase in distant metastasis and was not observed in patients who underwent adjuvant chemotherapy.

Abstract 1327: Mechanism of tumor microenvironment remodeling and progression based on FAM20C-mediated extracellular kinome network in oral squamous cell carcinoma

Abstract Tumorigenesis and tumor growth are accomplished through the crosstalk between intra- and extracellular molecules, which is often mediated by phosphorylation, and research on intracellular signal transduction has made great progress. Despite the significance of the tumor microenvironment (TME) for tumor progression, relatively few kinome studies have been conducted on phosphorylation cascade in the TME of oral squamous cell carcinoma (OSCC). OSCC is an aggressive cancer with a high recurrence rate of 40-60%, but there are uncertain molecular classification and no identifiable driver mutation genes to be a druggable target. As the presence of extranodal extension (ENE) is currently the most significant risk factor for locoregional recurrence or distant metastasis, differences in molecular profiles between patients with and without ENE may provide insight into regulatory mechanisms that are critical for the recurrence and progression of OSCC. Using LC-MS-based secretome analysis, we examined total and phosphoproteins from ten patients' plasma with or without ENE. Global proteome analysis revealed that the ENE group had higher levels of protein phosphorylation, the ERK 1/2 cascade, signal transduction, phagocytosis, and the integrin-mediated signaling pathway than the without ENE group. Furthermore, 319 phosphosites originating from 165 proteins were discovered, with the majority of phosphorylated proteins having lipid binding, complement system, extracellular matrix, and calcium binding. Interestingly, we discovered 82 proteins with Ser-x-Glu/pSer sites among the phosphorylated proteins, indicating that they could be substrates of the unique extracellular secreted serine kinase, family with sequence similarity 20C (FAM20C). Proteins associated to tumor metastasis, such as insulin-like growth factor-binding proteins (IGFBPs), osteopontin (OPN), and serine protease inhibitors (Serpins), are known as substrates for the FAM20C. In accordance with the proteome results in plasma, gene ontology (GO) term analysis using the NanoString oncology panel revealed that extracellular structure organization-related genes were up-regulated and enzyme inhibitor, kinase regulator, and protein tyrosine kinase activity-related genes were down-regulated in human OSCC cell line, Cal-27, with knockout of FAM20C. Furthermore, we functionally demonstrated that FAM20C depletion inhibited invasion by lowering protein production of Vimentin, TGF-β, and ERK phosphorylation. Collectively, we discovered that the secreted kinase FAM20C controls metastasis by cross-talking with proteins in the TME and propose that this may be the evidence for OSCC prognosis. (This research was supported by National Cancer Center, Korea (No. 2210980) and National Research Foundation of Korea grant funded by the Korea government (No. 2020M3A9A5036362)). Citation Format: Mi Rim Lee, Yu-Sun Lee, Sumin Kang, Hye Won Shon, Jeong Eun Gong, Hye Joo Park, Jung-Ah Hwang, Kyung-Hee Kim, Sung Weon Choi, Yun-Hee Kim. Mechanism of tumor microenvironment remodeling and progression based on FAM20C-mediated extracellular kinome network in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1327.

MP33-02 PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION FOR METASTATIC NONSEMINOMATOUS GERM CELL TUMOR: REVIEW OF ONCOLOGIC OUTCOMES AND THE ROLE OF ADJUVANT CHEMOTHERAPY

You have accessJournal of UrologyCME1 Apr 2023MP33-02 PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION FOR METASTATIC NONSEMINOMATOUS GERM CELL TUMOR: REVIEW OF ONCOLOGIC OUTCOMES AND THE ROLE OF ADJUVANT CHEMOTHERAPY Ahmad Mousa, Lynn Anson-Cartwright, Eshetu Atenafu, Michael Jewett, Philippe Bedard, Di Maria Jiang, Rachel Glicksman, Peter Chung, Padraig Warde, Martin O'Malley, Susan Prendeville, and Robert Hamilton Ahmad MousaAhmad Mousa More articles by this author , Lynn Anson-CartwrightLynn Anson-Cartwright More articles by this author , Eshetu AtenafuEshetu Atenafu More articles by this author , Michael JewettMichael Jewett More articles by this author , Philippe BedardPhilippe Bedard More articles by this author , Di Maria JiangDi Maria Jiang More articles by this author , Rachel GlicksmanRachel Glicksman More articles by this author , Peter ChungPeter Chung More articles by this author , Padraig WardePadraig Warde More articles by this author , Martin O'MalleyMartin O'Malley More articles by this author , Susan PrendevilleSusan Prendeville More articles by this author , and Robert HamiltonRobert Hamilton More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003266.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is renewed controversy regarding the role of adjuvant chemotherapy post primary retroperitoneal lymph node dissection (pRPLND) in the management of pathologic stage II (pN1-3) nonseminomatous germ cell tumours (NSGCT). We compared the outcomes and treatment burden of pRPLND alone versus pRPLND + adjuvant chemotherapy (AC) in this setting. METHODS: Retrospective review of the Princess Margaret Cancer Center eTestes cancer database identified men with pathologic stage II NSGCT after pRPLND between 1995-2020. The primary outcome was relapse-free survival (RFS). Secondary outcomes included disease specific survival (DSS) and burden of relapse treatment. Uni- and multivariable analyses were conducted to identify factors associated with relapse. RESULTS: A total of 109 pathologic stage II patients were included in the study. There were 96 patients treated with pRPLND alone and 13 treated with pRLND + AC (majority 2 cycles of Bleomycin, Etoposide, Cisplatin). Median follow up was 58 months. Of the 109 patients, 20 (18%) had pN1 and 89 (82%) had pN2/3 disease. The 5-year RFS was 72% for the pRPLND only group vs. 92% for the pRPLND + AC group (p=0.11). Within the pRPLND only group 5-year RFS differed by pN stage (pN1 = 94% vs. pN2/N3 = 67%, p=0.03). The presence of extra-nodal extension in the RPLND specimen was associated with relapse (HR 3.97, 95%CI 1.68-9.36, p=0.002). Despite a higher relapse rate within the pRPLND only group, DSS was similar at 5 years (98% pRPLND only vs. 100% pRPLND + AC, p=0.48). Only 24 (25%) of patients in the pRPLND only group required any chemotherapy. Extrapolating our outcomes to compare a hypothetical group of 100 patients treated with pRPLND alone to 100 with pRPLND + AC, the overall burden of chemotherapy was substantially higher in the pRPLND + AC arm (246 vs. 79 cycles). CONCLUSIONS: The majority of men with pathologic stage II NSGCT treated with pRPLND alone do not experience a recurrence or require systemic therapy. Despite a trend towards lower relapse risk when adjuvant chemotherapy is given, no difference in survival was seen but higher chemotherapy burden was entertained. Thus, AC for patients with pathologic stage II NSGCT may constitute overtreatment. Source of Funding: The Dell’Elce Family Testis Cancer Research Fund © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e450 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmad Mousa More articles by this author Lynn Anson-Cartwright More articles by this author Eshetu Atenafu More articles by this author Michael Jewett More articles by this author Philippe Bedard More articles by this author Di Maria Jiang More articles by this author Rachel Glicksman More articles by this author Peter Chung More articles by this author Padraig Warde More articles by this author Martin O'Malley More articles by this author Susan Prendeville More articles by this author Robert Hamilton More articles by this author Expand All Advertisement PDF downloadLoading ...

MP33-05 NEOADJUVANT PLATINUM-BASED CHEMOTHERAPY FOR CLINICALLY NODE-POSITIVE PENILE SQUAMOUS CELL CARCINOMA: AN INTERNATIONAL, MULTICENTER, REAL-WORLD STUDY

You have accessJournal of UrologyCME1 Apr 2023MP33-05 NEOADJUVANT PLATINUM-BASED CHEMOTHERAPY FOR CLINICALLY NODE-POSITIVE PENILE SQUAMOUS CELL CARCINOMA: AN INTERNATIONAL, MULTICENTER, REAL-WORLD STUDY Kyle Rose, Darren Sanchez, Arfa Mustasam, Kathryn Marchetti, Reagan Sandstrom, Lance Pagliaro, Niki Millward, Constantine Alifrangis, Kelvin Moses, Maarten Albersen, Eduard Roussel, Viraj Master, Bahzel Nazha, Tony Zhuang, Jeffrey Montgomery, Chris Protzel, Marcos Tobias-Machado, Philippe Spiess, Curtis Pettaway, and Jad Chahoud Kyle RoseKyle Rose More articles by this author , Darren SanchezDarren Sanchez More articles by this author , Arfa MustasamArfa Mustasam More articles by this author , Kathryn MarchettiKathryn Marchetti More articles by this author , Reagan SandstromReagan Sandstrom More articles by this author , Lance PagliaroLance Pagliaro More articles by this author , Niki MillwardNiki Millward More articles by this author , Constantine AlifrangisConstantine Alifrangis More articles by this author , Kelvin MosesKelvin Moses More articles by this author , Maarten AlbersenMaarten Albersen More articles by this author , Eduard RousselEduard Roussel More articles by this author , Viraj MasterViraj Master More articles by this author , Bahzel NazhaBahzel Nazha More articles by this author , Tony ZhuangTony Zhuang More articles by this author , Jeffrey MontgomeryJeffrey Montgomery More articles by this author , Chris ProtzelChris Protzel More articles by this author , Marcos Tobias-MachadoMarcos Tobias-Machado More articles by this author , Philippe SpiessPhilippe Spiess More articles by this author , Curtis PettawayCurtis Pettaway More articles by this author , and Jad ChahoudJad Chahoud More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003266.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The efficacy of neoadjuvant platinum-based chemotherapy (NAPC) in locally advanced Penile Squamous Cell Carcinoma (PSCC) has been demonstrated in prior small studies, leaving clinicians with scant evidence-based guidance. Thus, we aimed to provide evidence on real-world outcomes of patients with PSCC who received NAPC prior to surgical resection. METHODS: Patients who had undergone NAPC prior to surgical resection for PSCC were included from ten centers. Patients had locally advanced (cTany, cN+), non-metastatic (M0) disease. Clinicopathologic data, chemotherapeutic agents utilized including TIP (Paclitaxel - Ifosfamide - Cisplatin), surgical modalities, and clinicopathologic outcomes were assessed. The primary outcome was overall survival (OS), analyzed using Kaplan-Meier Method and compared using Cox Proportional Hazard Modelling. The secondary outcome was progression-free survival (PFS). Response was determined via best overall response measured with RECIST 1.1 criteria following completion of NAPC. RESULTS: 167 patients with PSCC treated with NAPC were included, 137 (84%) of whom received TIP. 92 (55%) patients died during follow up, and the median follow up for survivors was 57 months. The median OS was 42.0 months, while the median PFS was 17.0 months. After NAC, 22% had progressive disease (PD), 20% had stable disease, 47% had partial response, and 11% had complete response, with median OS of 16 months, 51 months, 56 months, and 119 months, respectively (p<0.01). Predictors for OS and RFS included lymphovascular invasion, positive number of lymph nodes, extranodal extension, downstaging after chemotherapy, best overall response, and ypN status. Figure 1 demonstrates OS outcomes by RECIST best response after chemotherapy, presence of downstaging after NAPC, ypN stage, and presence of extranodal extension. CONCLUSIONS: NAPC is effective in patients with lymph node metastases from PSCC. This study represents the largest conglomeration of multi-institutional penile carcinoma patients treated with upfront cisplatin based therapy, and provides further supportive data for multimodal therapy for advanced penile cancer patients while prospective clinical trials complete accrual . Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e451 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kyle Rose More articles by this author Darren Sanchez More articles by this author Arfa Mustasam More articles by this author Kathryn Marchetti More articles by this author Reagan Sandstrom More articles by this author Lance Pagliaro More articles by this author Niki Millward More articles by this author Constantine Alifrangis More articles by this author Kelvin Moses More articles by this author Maarten Albersen More articles by this author Eduard Roussel More articles by this author Viraj Master More articles by this author Bahzel Nazha More articles by this author Tony Zhuang More articles by this author Jeffrey Montgomery More articles by this author Chris Protzel More articles by this author Marcos Tobias-Machado More articles by this author Philippe Spiess More articles by this author Curtis Pettaway More articles by this author Jad Chahoud More articles by this author Expand All Advertisement PDF downloadLoading ...

Neoadjuvant platinum-based chemotherapy for clinically node-positive penile squamous cell carcinoma: An international, multicenter, real-world study.

9 Background: The efficacy of neoadjuvant platinum-based chemotherapy (NAPC) in penile squamous cell carcinoma (PSCC) was provided by small clinical trials, leaving clinicians with scant evidence-based guidance. Thus, we aimed to analyze real-world outcomes of patients with PSCC who received NAPC prior to surgical resection. Methods: Patients from 9 tertiary care centers who had undergone NAPC prior surgical resection for PSCC were included with locally advanced (cTany, cN+), non-metastatic (M0) disease. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), Response was determined via best overall response measured with RECIST 1.1 criteria. Results: 167 patients were included, 137 (84%), of which received TIP prior to surgical resection. Ninety-two (55%) patients died during follow up, and the mean follow up for survivors was 57 months. The median OS was 42 months, while the median PFS was 17 months. The table details the response rates to NAPC, the associated survival, and Cox Proportional Hazards Modelling of OS and PFS. Predictors for OS and RFS included lymphovascular invasion, positive number of lymph nodes, extranodal extension, downstaging, best overall response, and ypN status. Figure 1 demonstrates OS outcomes by RECIST best response after chemotherapy, presence of downstaging after NAPC, ypN stage, and presence of extranodal extension. Conclusions: Upfront NAPC is effective in patients with lymph node metastases from penile carcinoma. Unsurprisingly, patients who demonstrated a robust response to therapy had improved survival outcomes compared to those who had not—as measured by RECIST criteria, tumor downstaging, pN staging, and presence of extranodal extension. This study represents the largest conglomeration of multi-institutional penile carcinoma patients treated with NAPC, and provides further supportive data for multimodal therapy for advanced penile cancer patients while prospective clinical trials complete accrual. [Table: see text]

Relationship Between Worst Pattern of Invasion and Extranodal Extension in Oral Tongue Squamous Cell Carcinomas.

Oral tongue squamous cell carcinoma (OTSCC) is a common malignancy of the oral cavity with poor survival rates. The aim of this project is to investigate the relationship between certain histopathological factors such as Worst Pattern of Invasion (WPOI) and Extranodal Extension (ENE) in patients with oral tongue squamous cell carcinoma (OTSCC) who underwent surgical resection at Loyola University Medical Center. This was a retrospective cohort study at a tertiary care academic medical center. All patients that underwent primary surgical resection of OTSCC between 1/1/2015 and 1/1/2022 were reviewed. Patients were identified using the Cerner CoPath Laboratory Information System. A total of 82 patients met inclusion criteria and were included in the study. Higher grades of WPOI (WPOI 5) were not significantly associated with the presence of ENE in our study (P = 0.82), regardless of the presence of major or minor ENE. WPOI 5 was associated with a higher incidence of local recurrence (P = 0.011). Higher grades of WPOI were not found to correlate with the presence of ENE, a common histopathological factor that is used as an important prognostic indicator in OTSCC. It is important for clinicians to consider these factors separately when determining whether a patient is high-risk and would benefit from aggressive multimodal treatment.