pN Classification Research Articles

Missed Adjuvant Therapy in Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma.

Investigate missed adjuvant therapy and associated disparities in overall survival (OS) for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). The 2010-2017 National Cancer Database was queried for patients with surgically resected HPV+ OPSCC. Indications for adjuvant radiotherapy (aRT) included pT3-4 classification, pN2-3 classification, lymphovascular invasion, pathologic extranodal extension (pENE), and/or positive surgical margins (PSM). Indication(s) for adjuvant chemoradiotherapy (aCRT) included pENE and/or PSM. Multivariable logistic and Cox regression models were implemented. Of 5297 patients satisfying inclusion criteria, 4288 had indication(s) for aRT; 775 did not receive any adjuvant therapy and were considered as missing aRT. A total of 2234 patients had indication(s) for aCRT. Of these, 1383 (61.9%) received aCRT, 555 (24.8%) patients received aRT alone and were considered as having missed aCRT, and 296 (13.2%) did not receive any adjuvant therapy. Missed aRT and missed aCRT were each associated with age, treatment facility type, pN classification, and surgical margin status (p < 0.015). Among patients with indication(s) for aRT alone, OS of those receiving no adjuvant therapy, aRT alone, and aCRT was 90.0%, 94.8%, and 93.4%, respectively (p = 0.080). Among patients with indication(s) for aCRT, those receiving aRT alone and aCRT had similar OS (89.0% vs. 86.6%, p = 0.357) which was superior to receiving no adjuvant therapy (74.9%, p < 0.001). These patterns in OS persisted on multivariable Cox regression. Among patients with HPV+ OPSCC and indication(s) for aRT, missed aRT was not associated with worse OS. For patients with indication(s) for aCRT, aRT alone was associated with similar OS as aCRT. 3 Laryngoscope, 2024.

Validation of the cutoff values for the number of metastatic lymph nodes for esophageal cancer staging: a multi-institutional analysis of 655 patients in Japan.

The number of metastatic lymph nodes (LNs) is an important prognostic factor for esophageal cancer, and N staging is important for prognostic stratification. The optimal cutoff values for clinical (cN) and pathologic N (pN) staging should be reconsidered following advances in neoadjuvant therapy. The study included 655 patients who underwent esophagectomy between January 2014 and December 2016 in four high-volume centers in Japan. Optimal cutoff values for the number of metastatic LNs in cN and pN staging were examined using X-tile, and their prognostic performance was validated using the Kaplan-Meier method. The cutoff values were 1, 2, and 3 for cN staging and 1, 3, and 7 for pN staging. Prognosis was significantly better in patients with cN0 than in those with modified (m)-cN1 (p = 0.0211). However, prognosis was not significantly different among the patients with m-cN1, m-cN2, and m-cN3 disease. Prognosis was significantly different among the patients with pN0, pN1, pN2, and pN3 disease (pN0 vs pN1, p < 0.0001; pN1 vs pN2, p < 0.0001; pN2 vs pN3, p < 0.0001). In patients who received preoperative neoadjuvant therapy, prognosis, which was not significantly different among the patients with cN0, m-cN1, m-cN2, and m-cN3 disease (cN0 vs m-cN1, p = 0.5675; m-cN1 vs m-cN2, p = 0.4425; m-cN2 vs m-cN3, p = 0.7111), was significantly different among the patients with pN0, pN1, pN2, and pN3 disease (pN0 vs pN1, p = 0.0025; pN1 vs pN2, p = 0.0046; pN2 vs pN3, p = 0.0104). cN has no prognostic impact in patients who underwent preoperative treatment followed by esophagectomy, despite the optimization of cN classification. The conventional TNM8th pN classification is useful for predicting prognosis even for patients who have undergone preoperative treatment. The conventional cutoffs for metastatic LNs in the International Union against Cancer tumor node metastasis staging system are valid and can be effectively used in clinical practice.

Can elective neck dissection for oral cancers be planned based on depth of invasion?

e18042 Background: Elective neck dissection (END) is the standard of care for oral squamous cell carcinoma (OSCC). Literature suggests END may be avoided in primaries with depth of invasion (DOI) less than 4 mm. The present study evaluates the accuracy of DOI in predicting nodal metastases in OSCC. Methods: This retrospective study, approved by the Institutional Ethics Committee, includes all the patients with OSCC who underwent surgical excision. All tumors were classified and DOI was measured microscopically on resected specimens according to the AJCC TNM 8th ed. Statistical analysis was performed using IBM SPSS for Windows version 26. Pathological N-classification (pN) was correlated with DOI (in mm) using Spearman’s rank-order (pN1-3) and point-biserial (pN0 vs pN+) correlation statistics. Receiver operating characteristic (ROC) curve with area under the curve (AUC) were analyzed to determine the accuracy of DOI in predicting nodal metastases (pN+). Primaries were classified into three groups based on the range of DOI (≤5 mm; &gt;5 mm and ≤10 mm; &gt;10 mm) according to the AJCC TNM 8th ed. Chi-square statistic was used to measure the association between DOI groups and pN status (pN0; pN+). ANOVA with post hoc Bonferroni statistics were used to compare between three DOI groups. Results: Three hundred and thirty-seven (n=337) patients were screened for inclusion. After adjusting for missing data, 254 patients were included in the final analysis. Median age at presentation, DOI and nodal yield were 46 (24-82) years, 11 (1-40) mm, and 35 (1-121), respectively. Depth of invasion failed to demonstrate a strong positive correlation with pN classification (ρ=0.31; p&lt;0.001). DOI did not show a strong correlation with pN status (pN0 vs pN+) either (rpb=0.27; p&lt;0.001). ROC curve analysis suggested a poor accuracy of DOI in predicting nodal metastases (AUC=0.67; 95% CI 0.6-0.73). There was a statistically significant association between DOI groups and pN status (Chi-square=26.67; p&lt;0.001). ANOVA with post hoc Bonferroni showed statistical significance only for DOI &gt;10 mm group (p&lt;0.001 for DOI ≤5 mm; p=0.02 for DOI &gt;5 mm and ≤10 mm). However, the sensitivity and specificity achieved by the ROC analysis for DOI cut-off value of 10mm in the present cohort were merely 69.3% and 57.9%, respectively. Conclusions: DOI alone is a poor predictor of nodal metastases in OSCC. Though all correlations in the present study achieved statistical significance, none demonstrated a strong association or an accuracy credible enough of clinical importance. END should remain the standard-of-care for all OSCC, including early primaries with DOI &lt;4 mm.

Revolutionizing T3-4N0-2M0 gastric cancer staging with an innovative pathologic N classification system

BackgroundThe current pathologic N (pN) classification exhibits limitations in the prognostic stratification of patients with pT3-4N0-2M0 gastric cancer (GC). Therefore, this study aimed to develop and validate a new lymph nodal staging method based on the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). MethodsData from 7883 patients with pT3-4N0-2M0 GC were collected from the Surveillance, Epidemiology, and End Results (SEER) database and Zhejiang Cancer Provincial Hospital. Optimal cutoff values for ELNs and LNR were determined using X-tile software. Kaplan-Meier methods, Log-rank tests, and Cox regression analyses were employed in this study. Patients were categorized into 3 new pN stages: new pN0 (pN0 with ELNs of >16), new pN1 (pN0 with ELNs of ≤16 or pN1-2 with LNR of ≤0.15), and new pN2 (pN1-2 with LNR of >0.15). The prognostic predictive power of both current and new pN staging was evaluated using the Akaike information criterion (AIC), Bayesian information criterion, concordance index (C-index), and receiver operating characteristic curve. ResultsThe new pN classification exhibited excellent performance in Kaplan-Meier survival analysis. After adjusting for confounding factors, the new pN staging emerged as an independent prognostic indicator in patients with GC. In the SEER cohort, the new pN staging demonstrated enhanced prognostic prediction accuracy over the American Joint Committee on Cancer pN staging (AIC: 75578.85 vs 75755.06; C-index: 0.642 vs 0.630; P < .001). Similar findings were validated in the Chinese cohort. ConclusionThis study developed and validated an improved pN classification for patients with pT3-4N0-2M0 GC. Surgeons should consider ELNs and LNR when assessing postoperative prognosis in patients with GC.

Abstract PO4-25-01: Selective elimination of CD169+ macrophages in lymph nodes invaded by breast cancers

Abstract Lymph node metastasis is a prognostically significant factor in breast cancer, though the colonization mechanism of cancer cells in this immune cell-rich organ remains elusive. This study aimed to elucidate the impact of breast cancer on the lymph node immune cell landscape. Multiscale transcriptomic analyses were performed on both metastatic and non-metastatic lymph node samples from breast cancer patients with lymph node metastasis. Twenty laser-micro-dissected sections were obtained from 17 lymph nodes across six breast cancer patients at stages II–III, with each patient contributing both types of lymph nodes for direct comparison. Comparing the transcriptomes of paired lymph nodes with and without metastasis from the same patients revealed selective downregulation of CD169+ macrophage-related genes in metastatic lymph nodes. The spatial transcriptome indicated a potential depletion of CD169+ macrophages, initiators of anticancer immunity, from their residence (sinuses) in metastatic lymph nodes, while other principal immune cell types were unaltered. Mass spectrometry imaging revealed that the numbers of CD169+ macrophages were smaller in the metastatic lymph nodes than in the non-metastatic lymph nodes, suggesting that cancer cells uprooted CD169+ macrophages from the lymph nodes. Conversely, the count of B, T, Treg, and CD11c+ cells remained comparable in both lymph node types, albeit an enrichment of Treg cells around metastasized cancer tissues was observed. Additional immunohistochemistry analysis of 315 non-metastatic lymph nodes and 159 metastatic lymph nodes from 58 patients with breast cancer showed that a reduced CD169+ macrophage population was prevalent in various breast cancer subtypes. A subset of metastatic lymph nodes (37 out of 159) displayed a complete absence of detectable CD169+ macrophages. The data also depicted a gradual decline in CD169+ macrophages correlating with the pN classification, while no correlation was identified with pathological tumor size classification (pT) or metastasized cancer volume. The data suggest precedence of CD169+ macrophage elimination over other reported immune cell abnormalities, such as cell number and metabolic irregularities. CD169+ macrophages are a unique type of resident macrophages in the lymphoid organs that present cancer-derived antigens to CD8+ cells. The antigen-presenting role of CD169+ macrophages to T cells, a pivotal step in adaptive immunity, signifies the catastrophic implications of their suppression. This study underscores CD169+ macrophage suppression as a pronounced pathological phenotype in lymph nodes with breast cancer metastasis, thereby establishing it as a critical future therapeutic target. Citation Format: Yurina Maeshima, Tatsuki R. Kataoka, Alexis Vandenbon, Masahiro Hirata, Yasuhide Takeuchi, Yutaka Suzuki, Yukiko Fukui, Yumiko Ibi, Hironori Haga, Satoshi Morita, Masakazu Toi, Shinpei Kawaoka, Kosuke Kawaguchi. Selective elimination of CD169+ macrophages in lymph nodes invaded by breast cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-01.

Extranodal extension in laryngeal squamous cell carcinoma.

Although large retrospective database studies have associated extranodal extension (ENE) with worse survival in several head and neck cancers, the prognostic significance of ENE in laryngeal squamous cell carcinoma (LSCC) remains unclear. Our study examines ENE and overall survival (OS) in LSCC. The 2006-2017 National Cancer Database was queried for patients with LSCC undergoing surgical resection and neck dissection, with or without adjuvant therapy. Kaplan-Meier and multivariable Cox regression survival analyses were implemented to identify the independent impacts of pathologic nodal (pN) classification and ENE on OS. Of 4208 patients satisfying inclusion criteria, 2343 (55.7%) were pN0/ENE-negative, 1059 (25.2%) were pN1-2/ENE-negative, and 806 (19.2%) were pN1-2/ENE-positive. The 5-year OS of pN0/ENE-negative, pN1-2/ENE-negative, and pN1-2/ENE-positive patients was 62.8%, 56.7%, and 32.9%, respectively (p < .001). Among pN1-2/ENE-positive patients undergoing no adjuvant therapy, adjuvant radiotherapy alone, and adjuvant chemoradiotherapy, 5-year OS was 24.1%, 30.7%, and 36.7%, respectively (p < .001). After adjusting for patient demographics, clinicopathologic features, and adjuvant therapy, ENE-positivity was associated with worse OS than ENE-negativity (adjusted hazard ratio [aHR] 1.76, 95% confidence interval [CI] 1.53-2.02, p < .001). pN1/ENE-positivity (aHR 1.82, 95% CI 1.31-2.54) and pN2/ENE-positivity (aHR 1.89, 95% CI 1.49-2.40) were associated with worse OS than pN1/ENE-negativity (p < .001). Microscopic (aHR 1.83, 95% CI 1.54-2.18) and macroscopic ENE-positivity (aHR 1.75, 95% 1.35-2.26) were associated with worse OS than ENE-negativity (p < .001). ENE-positivity has prognostic significance in LSCC and is associated with worse OS than ENE-negativity. pN classification did not have prognostic significance independent of ENE. ENE should be carefully considered when determining the prognosis of LSCC and selecting adjuvant therapy. 4.

Predictors of Occult Metastasis and Prognostic Factors in Patients with cN0 Oral Cancer Who Underwent Elective Neck Dissection.

Elective neck dissection (END) is recommended for the management of patients with oral squamous cell carcinoma (OSCC) because of the risk of occult metastasis (OM). We hypothesized that some factors predict poor prognosis regardless of a cN0 END. This study aimed to investigate the predictors of OM and prognostic factors in patients with cN0 OSCC who underwent supraomohyoid neck dissection (SOHND). A retrospective cohort study design was created and implemented. The primary predictive variables in this study were OM and risk factors for poor prognosis after SOHND. A Cox proportional hazard model was used to adjust for the effects of potential confounders on the risk factors for poor prognoses. Among 86 patients with OSCC, OMs were observed in 9 (10.5%). The neutrophil-to-lymphocyte ratio (NLR) and vascular invasion are good markers for detecting OM. A Cox multivariable analysis identified two independent predictors of overall survival: pathologic node (pN) and laterality of END. An independent predictive factor for disease-free survival, the surgical margin, was also identified in this study. According to the pN classification, pN1 patients had a worse survival rate than pN2 patients. Therefore, in the case of pN1, regardless of being cN0, additional adjuvant therapy may be necessary.

Oncologic Outcome of Patients With Pathologic T0 Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

To investigate the oncologic outcomes of patients with esophageal squamous cell carcinoma (ESCC) who have achieved a pathologic complete response (pCR) of the primary tumor (ypT0) after neoadjuvant chemoradiotherapy (NCRT). Patients with thoracic ESCC who underwent scheduled NCRT followed by surgery at our hospital between January 2010 and December 2022 were retrospectively analyzed. Only patients with ypT0 disease were enrolled in this study. A total of 118 patients were ultimately enrolled in this study. Ninety-two patients achieved pCR in the primary tumor and lymph nodes (ypT0N0), while 26 patients had residual metastatic disease in 52 lymph nodes (ypT0N+). Forty-five of the 52 lymph nodes with residual tumors were abdominal lymph nodes. Positive lymph nodes were more often observed in patients with tumors located in the lower third of the esophagus. The 1-, 3-, and 5-year overall survival (OS) rates for the entire study group were 96.5%, 79.5%, and 77.1%, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 90.5%, 76.8%, and 69.0%, respectively. According to multivariate analyses, pN classification was an independent predictor of both OS and DFS (P < 0.05), while sex and cT classification were also found to be independent prognostic factors for DFS (P < 0.05). Residual nodal metastatic disease in patients with ypT0 ESCC after NCRT was more often found in the abdominal lymph nodes. pN classification was an independent predictor of both OS and DFS for ypT0 ESCC patients after NCRT.

Prognostic Value of Metastatic Lymph Node Ratio and Identification of Factors Influencing the Lymph Node Yield in Patients Undergoing Curative Colon Cancer Resection.

Due to the impact of nodal metastasis on colon cancer prognosis, adequate regional lymph node resection and accurate pathological evaluation are required. The ratio of metastatic to examined nodes may bring an additional prognostic value to the actual staging system. This study analyzes the identification of factors influencing a high lymph node yield and its impact on survival. The lymph node ratio was determined in patients with fewer than 12 or at least 12 evaluated nodes. The study included patients after radical colon cancer resection in UICC stages II and III. For the lymph node ratio (LNR) analysis, node-positive patients were divided into four categories: i.e., LNR 1 (<0.05), LNR 2 (≥0.05; <0.2), LNR 3 (≥0.2; <0.4), and LNR 4 (≥0.4), and classified into two groups: i.e., those with <12 and ≥12 evaluated nodes. The study was conducted on 7012 patients who met the set criteria and were included in the data analysis. The mean number of examined lymph nodes was 22.08 (SD 10.64, median 20). Among the study subjects, 94.5% had 12 or more nodes evaluated. These patients were more likely to be younger, women, with a lower ASA classification, pT3 and pN2 categories. Also, they had no risk factors and frequently had a right-sided tumor. In the multivariate analysis, a younger age, ASA classification of II and III, high pT and pN categories, absence of risk factors, and right-sided location remained independent predictors for a lymph node yield ≥12. The univariate survival analysis of the entire cohort demonstrated a better five-year overall survival (OS) in patients with at least 12 lymph nodes examined (68% vs. 63%, p = 0.027). The LNR groups showed a significant association with OS, reaching from 75.5% for LNR 1 to 33.1% for LNR 4 (p < 0.001) in the ≥12 cohort, and from 74.8% for LNR2 to 49.3% for LNR4 (p = 0.007) in the <12 cohort. This influence remained significant and independent in multivariate analyses. The hazard ratios ranged from 1.016 to 2.698 for patients with less than 12 nodes, and from 1.248 to 3.615 for those with at least 12 nodes. The LNR allowed for a more precise estimation of the OS compared with the pN classification system. The metastatic lymph node ratio is an independent predictor for survival and should be included in current staging and therapeutic decision-making processes.

Lymph Node Ratio Enhances Predictive Value for Treatment Outcomes in Patients with Non-Small Cell Lung Cancer Undergoing Surgery: A Retrospective Cohort Study.

Purpose: To compare the prognostic value of lymph node ratio (LNR) and pN in patients with non-small cell lung cancer (NSCLC) undergoing surgery. Materials and methods: NSCLC patients were investigated between 2004 and 2015 from the Surveillance, Epidemiology, and End Results databases. The X-tile software was used to determine LNR cut-off values. Kaplan-Meier analysis was employed to assess cancer-specific survival (CSS) and overall survival (OS). Results: The identified cut-off values of LNR were 0.19 and 0.73. Median CSS for LNR1 (LNR < 0.19), LNR2 (0.19 ≤ LNR ≤ 0.73), and LNR3 (LNR > 0.73) were 71, 41, and 17 months. Both LNR2 (HR = 1.46, 95% CI: 1.36-1.57; P < 0.001) and LNR3 (HR = 2.85, 95% CI: 2.58-3.15; P < 0.001) demonstrated poorer median CSS compared to LNR1. Similarly, median OS for LNR1, LNR2, and LNR3 were 50, 35, and 16 months. LNR2 (HR = 1.36, 95% CI: 1.27-1.45; P < 0.001) and LNR3 (HR = 2.60, 95% CI: 2.37-2.85; P < 0.001) exhibited worse median OS compared to LNR1. A revised pN (r-pN) classification incorporating LNR and pN demonstrated superior penalized goodness-of-fit and discriminative ability in predicting CSS and OS compared to both LNR and pN. Conclusion: LNR outperformed pN in predicting CSS and OS in NSCLC patients undergoing surgery, potentially leading to more precise adjuvant treatment decisions.

Ratio of Metastatic Lymph Nodes: A Significant Prognostic Factor in Patients with Oral Squamous Cell Carcinoma

Background: One of the significant prognostic factors for survival in squamous cell carcinoma of the oral cavity is the presence or absence of cervical metastasis. Thus, management of cervical lymph nodes becomes a vital component of the overall treatment strategy for patients with cancers of the head and neck. The aim of this study was to investigate the prognostic value of the ratio of metastatic lymph nodes in patients with oral squamous cell carcinoma. Methods: A retrospective analysis of 225 biopsy-proven oral squamous cell carcinoma (OSCC) patients with T1-T4a status of the primary tumor was done. All cases had a history of surgical excision of the primary lesion and neck dissection with a follow-up period of two years. Primary tumor sites include viz buccal mucosa, tongue, alveolus, gingivo-buccal sulcus and retromolar trigone. Patients with loco-regionally advanced disease and a history of any previous surgery or radio-therapeutic treatment of the head and neck were excluded from the study. Locoregional recurrence, disease-free survival, and the associations between clinicopathological features and recurrence were analysed using univariate and multivariate analysis. p-value ≤ 0.001 was found to be significant. Survival curves were plotted using the Kaplan-Meier method for 5-year disease-free survival. Results: The patients with positive lymph nodes were divided into high- or low-risk groups using the best nodal parameter cut-off values (0.06). Our univariate analysis showed a significant correlation between locoregional recurrence and type of neck dissection, pN classification, staging, extranodal extension, perineural invasion, and ratio of metastatic lymph nodes (RML). However, on multivariate analysis, RML showed an independent prognostic predictor (p= 0.04) for locoregional recurrence. Conclusion: The findings of our study suggest that RML is a strong independent predictor of prognosis in patients with oral squamous cell carcinoma.

Extent of regional lymphadenectomy and number-based nodal classification for non-ampullary duodenal adenocarcinoma

BackgroundThis study aimed to evaluate the adequate extent of regional lymphadenectomy according to tumor location and the impact of number-based nodal classification on survival in patients with non-ampullary duodenal adenocarcinoma (NADAC). MethodsA total of 85 patients with NADAC who underwent surgery were enrolled. The frequency of metastasis was calculated for each node group in the respective tumor locations for 63 patients who underwent lymphadenectomy for pT2-pT4 tumor. ResultsThe frequency of metastasis in the pancreaticoduodenal (nos. 13 and 17) and superior mesenteric artery (no. 14) nodes was high (16.7 %–52.3 %) regardless of tumor location. Metastasis in the perigastric (nos. 3 and 4d) and right celiac artery (no. 9) nodes was not uncommon (14.3 %–22.2 %) for tumors in the first portion. The frequency of metastasis in the pyloric (nos. 5 and 6) and the other peripancreaticoduodenal (nos. 8 and 12) nodes varied depending on tumor location but could not be ignored for staging. When these nodes were classified as regional nodes, the 5-year survival in patients with pN0, pN1 (1–2 positive nodes), and pN2 (≥3 positive nodes) were 82.9 %, 51.7 %, and 19.2 %, respectively (p < 0.001). pN classification independently predicted survival (pN1, p = 0.022; pN2, p < 0.001). ConclusionsNos. 5, 6, 8, 12, 13, 14, and 17 nodes in all advanced NADAC and nos. 3, 4d, and 9 nodes in advanced NADAC in the first portion should be considered as regional nodes for accurate staging. The number-based nodal classification allows good patients’ prognostic stratification.

Comparison between a novel salivary marker and several clinical prognosticators in oral cavity cancer.

This study aimed to investigate the association between salivary matrix metalloproteinase-1 (MMP-1) and clinicopathological parameters of oral cavity squamous cell carcinoma (OSCC) and compare the prognostic efficacy of salivary MMP-1 and other established circulating markers for OSCC. Saliva specimens from 479 OSCC subjects were examined using an enzyme-linked immunosorbent assay. The area under the curve (AUC) values of salivary MMP-1 and other markers were calculated, and survival analyses were conducted using Kaplan-Meier and multivariate regression methods. Salivary MMP-1 showed good discrimination in predicting overall survival, with an AUC of 0.638, which was significantly higher than that of albumin (0.530, p = .021) and Charlson comorbidity index (0.568, p = .048) and comparable with neutrophil-to-lymphocyte ratio (0.620, p = .987), platelet-to-lymphocyte ratio (0.575, p = .125), and squamous cell carcinoma antigen (0.609, p = .605). Elevated levels of salivary MMP-1 were significantly associated with higher pT classification, pN classification, overall pathological stage, positive extranodal extension, tumor differentiation, positive lymphovascular invasion, positive perineural invasion, and tumor depth (p all <.05). Multivariate analyses indicated that a higher level of salivary MMP-1 (≥2060.0 pg/mL) was an independent predictive factor of poorer overall survival (adjusted hazard ratio: 1.421 [95% confidential interval: 1.014-1.989], p = .041). The study found that the salivary MMP-1 level was significantly associated with many adverse clinicopathological parameters of OSCC. In OSCC, it was found to have superior efficacy in predicting prognosis and was an independent prognostic factor of post-treatment outcome. 3.

Comparison of alternative N-staging models in patients with oral cancer. Is nodal yield or burden the most critical parameter?

BackgroundThere is increasing evidence in the literature that alternative N-classification systems offer a simpler and more precise risk stratification than the current N- classification in patients with oral squamous cell carcinoma. The purpose of this study is to compare three broadly proposed models incorporating lymph node ratio, log odds of positive lymph nodes and number of positive lymph nodes regarding disease-free and overall survival. MethodsThis is a retrospective study of patients treated in a single center between 2013 and 2019. Cox proportional hazard models, Kaplan Meier curves, the long rank test and the area under the curve were implemented to compare the risk-stratification ability of the three models. Moreover, a hazard ratio plot was calculated to investigate the association between nodal yield and disease-free survival. Results231 patients were included. All three proposed N-models were significantly correlated to the patient's prognosis in the multivariate analysis. Pairwise comparisons between the groups showed that the current pN classification offers the worst stratification and that the model incorporating the number of positive lymph nodes had a better performance for predicting both endpoints. Finally, a decrease in hazard ratio was observed with each additional lymph node removed up to the number of 39 lymph nodes. ConclusionsThe model incorporating the nodal burden offered a better predictive ability. The current N-classification cannot adequately identify patients with different prognosis. A non-linear relationship was found between nodal yield and survival, which could be the disadvantage of the lymph node ratio and log odds models.

Number of involved nodal stations: a better lymph node classification for clinical stage IA lung adenocarcinoma

BackgroundWith the popularization of lung cancer screening, more early-stage lung cancers are being detected. This study aims to compare three types of N classifications, including location-based N classification (pathologic nodal classification [pN]), the number of lymph node stations (nS)-based N classification (nS classification), and the combined approach proposed by the International Association for the Study of Lung Cancer (IASLC) which incorporates both pN and nS classification to determine if the nS classification is more appropriate for early-stage lung cancer. MethodsWe retrospectively reviewed the clinical data of lung cancer patients treated at the Cancer Hospital, Chinese Academy of Medical Sciences between 2005 and 2018. Inclusion criteria was clinical stage IA lung adenocarcinoma patients who underwent resection during this period. Sub-analyses were performed for the three types of N classifications. The optimal cutoff values for nS classification were determined with X-tile software. Kaplan‒Meier and multivariate Cox analyses were performed to assess the prognostic significance of the different N classifications. The prediction performance among the three types of N classifications was compared using the concordance index (C-index) and decision curve analysis (DCA). ResultsOf the 669 patients evaluated, 534 had pathological stage N0 disease (79.8%), 82 had N1 disease (12.3%) and 53 had N2 disease (7.9%). Multivariate Cox analysis indicated that all three types of N classifications were independent prognostic factors for prognosis (all P < 0.001). However, the prognosis overlaps between pN (N1 and N2, P = 0.052) and IASLC-proposed N classification (N1b and N2a1 [P = 0.407], N2a1 and N2a2 [P = 0.364], and N2a2 and N2b [P = 0.779]), except for nS classification subgroups (nS0 and nS1 [P < 0.001] and nS1 and nS >1 [P = 0.006]). There was no significant difference in the C-index values between the three N classifications (P = 0.370). The DCA results demonstrated that the nS classification provided greater clinical utility. ConclusionThe nS classification might be a better choice for nodal classification in clinical stage IA lung adenocarcinoma.

Reconsidering N component of cancer staging for T1-2N0-2M0 small-cell lung cancer: a retrospective study based on multicenter cohort

BackgroundThe current nodal (pN) classification still has limitations in stratifying the prognosis of small cell lung cancer (SCLC) patients with pathological classifications T1-2N0-2M0. Thus. This study aimed to develop and validate a modified nodal classification based on a multicenter cohort.Materials and methodsWe collected 1156 SCLC patients with pathological classifications T1-2N0-2M0 from the Surveillance, Epidemiology, and End Results database and a multicenter database in China. The X-tile software was conducted to determine the optimal cutoff points of the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). The Kaplan-Meier method, the Log-rank test, and the Cox regression method were used in this study. We classified patients into three pathological N modification categories, new pN#1 (pN0-#ELNs > 3), new pN#2 (pN0-#ELNs ≤ 3 or pN1-2-#LNR ≤ 0.14), and new pN#3 (N1-2-#LNR > 0.14). The Akaike information criterion (AIC), Bayesian Information Criterion, and Concordance index (C-index) were used to compare the prognostic, predictive ability between the current pN classification and the new pN component.ResultsThe new pN classification had a satisfactory effect on survival curves (Log-rank P < 0.001). After adjusting for other confounders, the new pN classification could be an independent prognostic indicator. Besides, the new pN component had a much more accurate predictive ability in the prognostic assessment for SCLC patients of pathological classifications T1-2N0-2M0 compared with the current pN classification in the SEER database (AIC: 4705.544 vs. 4731.775; C-index: 0.654 vs. 0.617, P < 0.001). Those results were validated in the MCDB from China.ConclusionsThe multicenter cohort developed and validated a modified nodal classification for SCLC patients with pathological category T1-2N0-2M0 after surgery. Besides, we propose that an adequate lymph node dissection is essential; surgeons should perform and consider the situation of ELNs and LNR when they evaluate postoperative prognoses of SCLC patients.

Log odds of positive lymph nodes as a novel prognostic predictor for gastric cancer: a systematic review and meta-analysis

BackgroundWe conducted a systematic review and meta-analysis to summarize the predictive and prognostic ability of the log odds of positive lymph nodes (LODDS) staging system and compare it with pathological N (pN) classification and the ratio-based lymph node system (rN) for the overall survival (OS) of gastric cancer (GC).MethodsThrough a systematic review till March 7, 2022, we identified population-based studies that reported the prognostic effects of LODDS in patients with GC. We compare the predictive effectiveness of the LODDS staging system with that of the rN and pN classification systems for the OS of GC.ResultsTwelve studies comprising 20,312 patients were included in this systematic review and meta-analysis. The results showed that LODDS1, LODDS2, LODDS3, and LODDS4 in GC patients were correlated with poor OS compared with LODDS0 (LODDS1 vs. LODDS0: HR = 1.62, 95% CI (1.42, 1.85); LODDS2 vs. LODDS0: HR = 2.47, 95% CI (2.02, 3.03); LODDS3 vs. LODDS0: HR = 3.15, 95% CI (2.50, 3.97); LODDS4 vs. LODDS0: HR = 4.55, 95% CI (3.29, 6.29)). Additionally, significant differences in survival were observed among patients with different LODDS classifications (all P-values were < 0.001) with the same rN and pN classifications. Meanwhile, for patients with different pN or rN classifications with the same LODDS classification, prognosis was highly similar.ConclusionThe findings show that LODDS is correlated with the prognosis of GC patients and is superior to the pN and rN classifications for prognostic assessment.

Oncological outcomes and prognostic factors of squamous cell carcinoma of the upper gingiva and hard palate: a retrospective study.

Despite sharing the same staging system as oral cavity cancers, upper gingiva and hard palate (UGHP) squamous cell carcinoma (SCC) have several features that make them a different entity. We aimed to analyze oncological outcomes and adverse prognostic factors of UGHP SCC, and assess an alternate T classification specific to UGHP SCC. Retrospective bicentric study including all patients treated by surgery for a UGHP SCC between 2006 and 2021. We included 123 patients with a median age of 75years. After a median follow-up of 45months, the 5-year overall survival (OS), disease-free survival (DFS) and local control (LC) were 57.3%, 52.7% and 74.7%, respectively. Perineural invasion, tumor size, bone invasion, pT classification and pN classification were statistically associated with poorer OS, DFS and LC on univariate analysis. On multivariable analysis, the following variable were statistically associated with a poorer OS: past history of HN radiotherapy (p = 0.018), age > 70years (p = 0.005), perineural invasions (p = 0.019) and bone invasion (p = 0.030). Median survivals after isolated local recurrence were 17.7 and 3months in case of surgical and non-surgical treatment, respectively (p = 0.066). The alternate classification allowed better patient distribution among T-categories, however without improving prognostication. There is a broad variety of clinical and pathological factors influencing prognosis of SCC of the UGHP. A comprehensive knowledge of their prognostic factors may pave the way towards a specific and more appropriate classification for these tumors.

The stratification of positive lymph nodes into pN1 and pN2 for upper urinary tract carcinoma is not prognostically significant

The 3rd-7th edition of the American Joint Committee on Cancer had 3 categories for positive lymph nodes (pN1-3) in upper urinary tract carcinoma. The 8th edition removed pN3, defining pN1 as one lymph node with tumor deposit ≤ 2 cm and pN2 as a node with tumor deposit > 2 cm or metastases in multiple nodes. The aim of this study was to assess if the current pN categories impact survival in renal pelvic and ureteral carcinoma. Nephroureterectomies performed at our institution for primary upper urinary tract carcinoma between 2010-2019 were reviewed. Lymphadenectomy was performed in 73.3% of cases (151/206, median 9 nodes). Eighty-one (53.6%) patients were deceased at last review [pN0, 53 (44.5%); pN1-2, 28 (87.5%)]. There was no difference in overall or recurrence free survival between pN1 and pN2 with 5-year overall survival (95% confidence interval) of pN0, 60.7% (52.0-70.8%); pN1, 15.4% (4.3-35.2%); and pN2, 21.1% (8.8-40.3%). The metastatic deposit size threshold of 2 cm, number of positive lymph nodes, as well as extranodal extension did not correlate with overall or recurrence free survival. As such, pN1 and pN2 were grouped together with a 5-year overall survival of 18.8% (9.12-28.6%). The current stratification of upper urinary tract carcinoma into pN1 and pN2 does not provide prognostic information, and both yield a stage IV classification, regardless of pT or pM category. Therefore, we recommend further simplification of pN classification into one category for regional lymph node metastasis, irrespective of lymph node deposit size or number of positive lymph nodes.

Rational Extent of Regional Lymphadenectomy and the Prognostic Impact of the Number of Positive Lymph Nodes for Perihilar Cholangiocarcinoma.

The definition and classification of regional nodes are not standardized for perihilar cholangiocarcinoma. This study aimed to clarify the rational extent of regional lymphadenectomy and to elucidate the impact of number-based regionalnodal classification on survival of patients with this disease. Data of 136 patients with perihilar cholangiocarcinoma who underwent surgery were reviewed. The incidence of metastasis and the survival of patients with metastasis were calculated for each node group. The incidence of metastasis for the node groups in the hepatoduodenal ligament (denoted as no. 12) ranged from 3.7% to 25.4%, with 5-year disease-specific survival of 12.9% to 33.3% for patients with metastasis. The incidences of metastasis in the common hepatic artery (no. 8) and posterior superior pancreaticoduodenal (no. 13a) node groups were 14.4% and 11.2%,respectively, with 5-year disease-specific survival rates of 16.7% and 20.0% for the patients with metastasis. When these node groups were defined as regional nodes, the 5-year disease-specific survival rates for the patients with pN0 (n = 80), pN1 (1-3 positive nodes, n = 38), and pN2 (≥4 positive nodes, n = 18) were 61.4%, 22.9%, and 17.6%, respectively (p < 0.001). The pN classification was independently associated with disease-specificsurvival (p < 0.001). When only the no. 12 node groups were regarded as regional nodes, pN classification failed to stratify the patients prognostically. No. 8 and no. 13a node groupsshould be considered regional nodes in addition to no. 12 node groupsand should be dissected. The number-based regionalnodal classification allows patients with this disease to be stratified prognostically.