Survival analysis in pT1-3 and paracolic lymph-node invasion colorectal cancer: the prognostic role of positive paracolic lymph-node ratio for adjuvant chemotherapy.

PURPOSE: Several studies have observed that some stage III colorectal cancer (CRC) patients cannot benefit from standard adjuvant chemotherapy. However, there is no unified screening standard to date. METHODS: Consecutive patients with pathologically confirmed colon adenocarcinoma treated in 3 centers between January 2016 and December 2018 were included. Patients were divided into four groups according to different stages and positive paracolic lymph-node ratio (P-LNR) [Cohort 1: pT1-3N0M0, Cohort 2: pT1-3N + (P-LNR ≤ 0.15)M0, Cohort 3: pT4N0M0, Cohort 4: stage III patients except for pT1-3N + (P-LNR ≤ 0.15)M0], and further overall survival was compared by Kaplan-Meier method. The univariate and multivariate analyses were employed for cox proportional hazards model. RESULTS: We retrospectively reviewed 5581 consecutive CRC patients with, and 2861 eligible patients were enrolled for further analysis. The optimal cut-off value of P-LNR in our study was 0.15. There was no significant difference in OS (91.36 vs. 93.74%) and DFS (87.65 vs. 90.96%) between stage III patients with pT1-3N + (P-LNR ≤ 0.15)M0 and those with pT1-3N0M0. Further analysis demonstrated that CRC patients with pT1-3N + (P-LNR ≤ 0.15)M0 were less likely to benefit from 8 cycles of CAPOX or FOLFOX chemotherapy and suffered fewer adverse events from declining chemotherapy. Comparing with 0-4 cycles versus 8 cycles, the overall survival rates were 91.35 versus 90.19% (P = 0.79), and with a DFS of 87.50 versus 88.24% (P = 0.49), the duration of adjuvant chemotherapy was not an independent risk factor for patients with pT1-3N + (P-LNR ≤ 0.15)M0 (HR: 0.70, 95% CI 0.90-1.30, P = 0.42). CONCLUSION: The concept of P-LNR we proposed might have a high clinical application value and accurately enable clinicians to screen out specific CRC patients who decline or prefer limited chemotherapy. TRIAL REGISTRY: The clinical trial registration number: ChiCTR2300076883.

Potential of lymph-node ratio as a prognostic factor for patients with oral squamous cell carcinoma.

BACKGROUND: To analyze the influence of the lymph node ratio (LNR) in survival of patients with OSCC METHODS: Clinicopathologic data from patients with OSCC who were treated with curative surgery and neck dissection (ND) with or without adjuvant therapies from 1991 to 2015 was retrospectively assessed. The impact of LNR and other variables on overall survival (OS) and disease-free survival (DFS) was analyzed in univariate and multivariate analyses. RESULTS: One hundred nineteen patients were included. In the univariate analysis the LNR had a significant impact on OS (p = 0.01) and DFS (p = 0.01). In the multivariate analysis, the LNR was the only significantly independent factor influencing in the OS (p = 0.03). The adjuvant therapies did not influence on the OS (p = 0.42) and DFS (p = 0.10). CONCLUSIONS: The LNR is an independent prognostic factor in patients with OSCC. The LNR alone is not recommended to indicate the performance of adjuvant therapies.

Computed-tomography based scoring system predicts outcome for clinical lymph node-positive patients undergoing radical cystectomy

ABSTRACT Purpose: Contrast-enhanced CT scan is the standard staging modality for patients with bladder cancer undergoing radical cystectomy (RC). Involvement of lymph nodes (LN) determines prognosis of patients with bladder cancer. The detection of LN metastasis by CT scan is still insufficient. Therefore, we investigated various CT scan characteristics to predict lymph node ratio (LNR) and its impact on survival. Also, pre-operative CT scan characteristics might hold potential to risk stratify cN+ patients. Materials and Methods: We analyzed preoperative CT scans of patients undergoing RC in a tertiary high volume center. Retrospectively, local tumor stage and LN characteristics such as size, morphology (MLN) and number of loco-regional LN (NLN) were investigated and correlation to LNR and survival was analyzed. CT scan characteristics were used to develop a risk stratification using Kaplan-Maier and multivariate analysis. Results: 764 cN0 and 166 cN+ patients with complete follow-up and imaging data were included in the study. Accuracy to detect LN metastasis and locally advanced tumor stage in CT scan was 72% and 62%. LN larger than 15mm in diameter were significantly associated with higher LNR (p=0.002). Increased NLN correlated with decreased CSS and OS (p=0.001: p=0.002). Furthermore, CT scan based scoring system precisely differentiates low-risk and high-risk profiles to predict oncological outcome (p <0.001). Conclusion: In our study, solely LN size >15mm significantly correlated with higher LNR. Identification of increased loco-regional LN was associated with worse survival. For the first time, precise risk stratification based on computed-tomography findings was developed to predict oncological outcome for clinical lymph node-positive patients undergoing RC.

Computed-tomography based scoring system predicts outcome for clinical lymph node-positive patients undergoing radical cystectomy.

PURPOSE: Contrast-enhanced CT scan is the standard staging modality for patients with bladder cancer undergoing radical cystectomy (RC). Involvement of lymph nodes (LN) determines prognosis of patients with bladder cancer. The detection of LN metastasis by CT scan is still insufficient. Therefore, we investigated various CT scan characteristics to predict lymph node ratio (LNR) and its impact on survival. Also, pre-operative CT scan characteristics might hold potential to risk stratify cN+ patients. MATERIALS AND METHODS: We analyzed preoperative CT scans of patients undergoing RC in a tertiary high volume center. Retrospectively, local tumor stage and LN characteristics such as size, morphology (MLN) and number of loco-regional LN (NLN) were investigated and correlation to LNR and survival was analyzed. CT scan characteristics were used to develop a risk stratification using Kaplan-Maier and multivariate analysis. RESULTS: 764 cN0 and 166 cN+ patients with complete follow-up and imaging data were included in the study. Accuracy to detect LN metastasis and locally advanced tumor stage in CT scan was 72% and 62%. LN larger than 15mm in diameter were significantly associated with higher LNR (p=0.002). Increased NLN correlated with decreased CSS and OS (p=0.001: p=0.002). Furthermore, CT scan based scoring system precisely differentiates low-risk and high-risk profiles to predict oncological outcome (p < 0.001). CONCLUSION: In our study, solely LN size >15mm significantly correlated with higher LNR. Identification of increased loco-regional LN was associated with worse survival. For the first time, precise risk stratification based on computed-tomography findings was developed to predict oncological outcome for clinical lymph node-positive patients undergoing RC.

Prognostic analysis of lymph node ratio of patients with disease recurrence previously submitted to cervical dissection surgery for head and neck cancer / Análise prognóstica da densidade linfonodal de pacientes recidivados previamente submetidos à cirurgia de esvaziamento cervical por neoplasia de cabeça e pescoço

ABSTRACT Introduction: the variable lymph node ratio has recently been studied as a possible influencer in the survival of patients diagnosed with head and neck cancer. Objective: to analyze the correlation between lymph node density and survival of recurred disease patients previously submitted to cervical dissection surgery due to head and neck squamous cell carcinoma. Method: we retrospectively analyzed 71 medical records of patients treated at the Head and Neck Surgery Service of the Pontifícia Universidade Católica de Campinas who had undergone cervical dissection surgery and presented tumor recurrence between 2006 and 2019. Patient and tumor data such as age, gender, skin color, smoking, alcohol consumption, location of the primary tumor, anatomopathological characteristics and lymph node status were correlated with the survival time. Results: we found a predominance of males and the mean age was 59.5 years. The most frequent primary site was the oral cavity followed by the larynx and oropharynx. The mortality rate was 53.52% and the mean lymph node ratio 0.28. We found influence on survival with statistical significance for the parameters: lymph node ratio, number of dissected and affected lymph nodes, T and N staging, type of treatment proposed (palliative or surgical), presence of compromited margins in the primary tumor and lymph node extravasation. Conclusion: the calculation of lymph node density in patients with recurred disease after cervical dissection surgery by head and neck squamous cell carcinoma should be taken into account during therapeutic planning and prognostic evaluation due to its direct influence on the survival.

RESUMO Introdução: recentemente tem-se estudado a variável densidade linfonodal como possível influenciador na sobrevida de pacientes com diagnóstico de câncer de cabeça e pescoço. Objetivo: analisar a relação entre a densidade linfonodal e a sobrevida de pacientes recidivados previamente submetidos a cirurgia de esvaziamento cervical por carcinoma espinocelular de cabeça e pescoço. Método: foram analisados retrospectivamente 71 prontuários pacientes atendidos no Serviço de Cirurgia de Cabeça e Pescoço da Pontifícia Universidade Católica de Campinas que tinham sido submetidos a cirurgia de esvaziamento cervical e apresentaram recidiva tumoral entre os anos de 2006 e 2019. Dados relativos ao paciente e ao tumor tais como: idade, sexo, cor da pele, tabagismo, etilismo, localização do tumor primário, características anatomopatológicas e status linfonodal foram correlacionados ao tempo de sobrevida dos indivíduos. Resultados: encontramos predominância do sexo masculino e a média de idade foi de 59,5 anos. O sítio primário mais frequente foi a cavidade oral seguido da laringe e orofaringe. A taxa de mortalidade foi de 53,52% e a densidade linfonodal média 0,28. Encontramos influência na sobrevida com significância estatística para os parâmetros: densidade linfonodal, número de linfonodos dissecados e acometidos, estadiamento T e N, tipo de tratamento proposto (paliativo ou cirúrgico), presença de margens comprometidas no tumor primário e extravasamento linfonodal. Conclusão: o cálculo da densidade linfonodal em pacientes recidivados após cirurgia de esvaziamento cervical por carcinoma espinocelular de cabeça e pescoço deve ser levado em consideração durante o planejamento terapêutico e na avaliação prognóstica devido à sua direta influencia na sobrevida dos indivíduos.

Triple-Negative Breast Cancer: Assessing the Role of Immunohistochemical Biomarkers on Neoadjuvant Treatment.

OBJECTIVE: This study aimed to investigate the influence of immunohistochemical (IHC) biomarkers in the response to neoadjuvant chemotherapy (NACT) and survival outcomes in the subset of locally advanced triple-negative breast cancer (TNBC). MATERIALS AND METHODS: The epidermal growth factor receptor (EGFR), androgen receptor (AR), cytokeratins (CK5/6, CK14 and CK17), Ki67 and p53 immunohistochemistry were evaluated on 171 cases of TNBC submitted to NACT and subsequently to surgery. Intensity and percentage of the expression of these biomarkers were combined to formulate a specific score, that was correlated with prognostic features and assessed for survival outcomes. RESULTS: Most patients had advanced clinical-stage tumors (stage III: 83.6%; cT3/T4: 85.9%; cN1-3: 71.3%). The predominant histological subtype was high-grade (67.3%) and invasive ductal carcinoma (93.6%). The residual cancer burden (RCB) 0-1 corresponded to 28.7% of cases and low-risk lymph node ratio (LNR) represented 77.2%. High Ki67 expression only showed a significant correlation with grade 3 tumors (p = 0.0157). CK5/6 was observed in 16% (27/169), CK14 was positive in 10.1% (17/169), CK17 in 91.1% (153/168), p53 in 52.6% (70/133), EGFR in 92.9% (157/169 cases), AR in 13% (22/169) and Ki67 index was scored ≥40% in 57.9% (95/165). No IHC biomarker significantly impacted response or survival. Regarding the analysis of the outcomes of event-free survival (EFS) and overall survival (OS), clinical stage (p = 0.014 and p = 0.042, respectively), RCB (p < 0.0001 and p <0.0001, respectively) and LNR (p <0.0001 and p <0.0001, respectively) showed significant association. CONCLUSION: No IHC biomarker evaluated showed a significant association with a response or survival outcomes in TNBC patients. Clinical stage, LNR and RCB stood out for strongly influencing survival.

Prognostic Factors of Long-term Survival Following Radical Resection for Ampullary Carcinoma.

BACKGROUND: The incidence of adenocarcinoma of the ampulla of Vater has been increasing over the past years. Nevertheless, it is still a rare disease and the prognostic factors predicting long-term survival are not sufficiently clarified. This study aims to evaluate the association between histopathological characteristics and long-term survival of patients with ampullary cancer after curative resection, as well as the efficiency of immunohistochemical expression of CK7, CK20, and CDX2 to distinguish the histopathological (intestinal or pancreaticobiliary) patterns. METHODS: Demographic, histopathological data, pTNM stage, and immunohistochemical expression patterns were collected from 65 patients with adenocarcinoma of the ampulla of Vater. Five and 10-year overall and disease-free survival rates after curative resection were determined. RESULTS: Of the 65 patients with ampullary carcinoma, 47 (72%) underwent radical resection. The 5- and 10-year overall survival rate was 46% and 37%, respectively. Our results demonstrate that the main prognostic factors were the presence and number of lymph node metastases, lymph node ratio (LNR), differentiation grade, and lymphovascular invasion. After multivariate analysis, only lymph node ratio ≥ 20% remained an independent prognostic factor of survival (HR: 2.63 95% CI: 1.05-6.61; p = 0.039). CONCLUSION: Here, we demonstrated more evidence that the lymph node metastases are associated with poor prognosis in ampullary carcinoma. Particularly, the relation between the number of metastatic lymph nodes and the number of harvested lymph node (LNR) should be considered a major prognostic factor.

Impact of Number of Positive Lymph Nodes and Lymph Node Ratio on Survival of Women with Node-Positive Breast Cancer.

OBJECTIVE: This study aimed to evaluate the association of axillary lymph node ratio (LNR) and number of positive lymph nodes (pN) with the risk of breast cancer recurrence and death. MATERIALS AND METHODS: A retrospective cohort study of node-positive stage II and III breast cancer patients diagnosed and treated between 2008 and 2009 at the Brazilian National Cancer Institute (INCA), Brazil. Overall and disease-free survival curves for number of positive lymph nodes (pN) and lymph node ratio (LNR) risk groups were constructed using the Kaplan-Meier method and compared by the log-rank test. Multivariate analysis was performed using stepwise forward Cox regression models. RESULTS: In total, 628 women with node-positive breast cancer were included. Most patients (69.5%) had advanced clinical stage tumors (≥IIB). The median follow-up was 58 months (range: 3-92 months). The adjusted recurrence hazard of pN2 and pN3 patients was 2.47 (95% Confidence Interval [CI] 1.72-3.56) and 2.42 (1.62-3.60), respectively, compared to pN1 patients (p<0.001), while the hazard of intermediate (0.21-0.65) and high-risk (>0.65) LNR was 2.11 (1.49-3.00) and 3.19 (2.12-4.80), respectively, compared to low-risk LNR (≤0.20) patients (p<0.001). On the other hand, the hazard of death of pN2 and pN3 patients was 2.17 (1.42-3.30) and 2.41 (1.53-3.78), respectively (p<0.001), and the hazard of intermediate (0.21-0.65) and high-risk (>0.65) LNR patients was 1.70 (1.13-2.56) and 2.74 (1.75-4.28), respectively (p≤0.001). CONCLUSION: Higher pN and LNR were associated with shorter disease-free survival and overall survival times.

Comparison of 3 Ways of Dissecting the Pancreatoduodenectomy Specimen and Their Impact in the Lymph Node Count and the Lymph Node Metastatic Ratio.

BACKGROUND: Lymph node metastasis (LNM) is a strong prognostic factor in the cancer of the pancreatobiliary tree, but it is influenced by the number of lymph nodes (LNs). The lymph node ratio (LNR) is considered a more reliable factor than the number of LNM. The aim was to examine the LN retrieval and the LNR of 3 pathologic work-up strategies. METHODS: Pancreaticoduodenectomies (n = 165) were analyzed comparing 3 pathological dissection techniques, classified as "control," "Verbeke method," and "Adsay method" groups. RESULTS: The mean of the dissected LNs and the number of cases with >20 LNs were superior in the Adsay method group, compared with the other groups ( P < .001). The LNR was different between the Adsay and Verbeke groups (0.144 vs 0.069, P = .032). The median of the 3 positive LNs was associated with decreased survival compared with an absence of LNM (3-year specific survival of 48% vs 22%, P = .011). In the multivariate analysis, LNM (hazard ratio = 6.148, 95% confidence interval = 2.02-8.1, P = .042) and the evaluation of >15 LNs (hazard ratio = 12.52, 95% confidence interval = 5.51-21.01, P = .001) were independent predictors of survival. CONCLUSION: The Adsay technique for LN retrieval was associated with a better LN count, more cases with LNM, and an LNR >0.1.

Prognostic importance of lymph node ratio after resection of ampullary carcinomas.

BACKGROUND: The prognosis of the lymph node ratio (LNR) in Vater's ampulla carcinomas (VACs) is recently studied. However, there are not enough data in several populations like Latin American people. Our aim is to demonstrate the prognosis significance of the LNR in this setting. METHODS: Pancreaticoduodenectomies for VACs were identified (n=128) from 1980 through 2015. Based on a ROC curve, a cut-off point of 0.1 was assigned for the LNR and the population was divided into two groups for comparison. RESULTS: The LNR ≥0.1 group was statistically significant associated with recurrence (38.5% vs. 19.5%), pT3-T4 tumors (69.2% vs. 29.3%), poorly differentiated tumors (46.2% vs. 17.5%), lymphovascular invasion (61.5 vs. 17.1%), perineural invasion (38.5% vs. 19.5%), and positive margins (15.4% vs. 2.4%). In the multivariate analysis, LNR (HR 2.891; CI: 1.987-3.458, P=0.02), LNM (HR 2.945; CI: 2.478-3.245, P=0.002), perineural invasion (HR 3.327; CI: 3.172-4.156, P=0.003), and recurrence (HR 3.490; CI: 2.896-4.122, P=0.001) were associated with lower survival. CONCLUSIONS: The LNR is a good predictor of survival and worse oncological outcomes for VACs after resection.