Modification of N staging systems for penile cancer: a more precise prediction of prognosis.
ABSTRACT: The tumour-node-metastasis (TNM) classification is the most widely used tool for penile cancer. However, the current system is based on few studies and has been unchanged since 2009. We determined whether a modified pathological N staging system that incorporates the laterality and number of lymph node metastases (LNMs) increases the accuracy of the results in predicting survival compared with the 7th edition of the pathological N staging system of the American Joint Committee on Cancer (AJCC) for penile cancer.The clinical and histopathologic data from 111 patients with penile cancer with LNMs were analysed. Univariate and multivariate Cox proportional hazard regression analyses were used to determine the impact of the clinical and pathological factors on disease-specific survival of these patients. The predictive accuracy was further assessed using the concordance index.According to the 7th edition of the pathological N classification, the 3-year disease-specific survival (DSS) rates for patients with pN1, pN2, and pN3 disease are 89.6%, 65.9%, and 33.6%, respectively (P(N1-N2)=0.030, P(N2-N3)<0.001, P<0.001). Under the modified pathological N category criteria, the 3-year DSS rates for pN1, pN2, and pN3 patients were 90.7%, 60.5%, and 31.4%, respectively (P(N1-N2)=0.005, P(N2-N3)=0.004, P<0.001). In separate multivariate Cox regression models, only modified N stages (hazard ratio: 4.877, 10.895; P=0.018, P<0.001) exhibited independent effects on the outcome. The accuracy of the modified pathological N category was significantly increased.The modified pathological N staging system is a better reflection of the prognosis of patients with penile cancer. Our study should contribute to the improvement of prognostic stratification and systemic treatment to avoid overtreatment of patients.
Project description:In the present study, we aim to compare the rationality of proposed N classification based on the number of metastatic lymph nodes (LNs) with the current one. A total of 509 penile cancer patients at our institute were analyzed. Univariable and multivariable statistical analyses were used to assess cancer-specific survival (CSS) in 2 staging systems. Harrell's concordance index was applied to evaluate predictive accuracy of the current and proposed N classification in predicting CSS. We propose a new classification: pN1 (metastasis in 1-2 regional LNs), pN2 (metastasis in 3 regional LNs, or 3 or fewer regional lymph nodes with extranodal extension), and pN3 (metastasis in 4 or more regional LNs). According to the current and proposed N classification, the 5-year CSS of penile cancer patients with pN1, pN2 and pN3 was 85.8%, 39.0%, and 19.7%; and with pN1, pN2 and pN3 was 79.8%, 39.3% and 15.3%, which almost all showed significant difference (P < .001, P = .259) (P < .001, P < .001). Multivariable predictive accuracy of the proposed and current N staging was 76.48% and 70.92% (5.56% gain; P < .001). With a multivariable model of clinical features, both current (hazard ratio [HR], 7.761, 10.612; P < .001, P < .001) and proposed N stages (HR, 3.792, 3.971; P < .001, P < .001) exhibited independent effects on survival. The proposed N classification is superior to the current one, which is simpler and provides more accurate prognosis.
Project description:Accurate pathologic nodal staging mandates effective collaboration between surgeons and pathologists. The American College of Surgeons Oncology Group Z0030 trial (ACOSOG Z0030) tightly controlled surgical lymphadenectomy practice but not pathologic examination practice. We tested the survival impact of the thoroughness of pathologic examination (using the number of examined lymph nodes as a surrogate).We re-analyzed the mediastinal lymph node dissection arm of ACOSOG Z0030, using logistic regression and Cox proportional hazards models.Of 513 patients, 435 were pN0, 60 were pN1, and 17 were pN2. The mean number of mediastinal lymph nodes examined was 13.5, 13.1, and 17.1; station 10 lymph nodes were 2.4, 2.7, and 2.6; station 11 to 14 nodes were 4.6, 6.1, and 6.7; and total lymph nodes were 19.7, 21.3, and 25.4 respectively. The pN category and histologic evaluation were associated with increased number of examined intrapulmonary lymph nodes. Patients with pN1 had more non-hilar N1 nodes than patients with pN0, patients with N2 had more N2 nodes examined than patients with pN0 or pN1. Patients with pN0 had better survival with examination of more N1 nodes; patients with pN1 had better survival with increased mediastinal nodal examination; the likelihood of discovering N2 disease was significantly associated with increased examination of mediastinal and non-hilar N1 lymph nodes.Despite rigorously standardized surgical hilar/mediastinal lymphadenectomy, the number of lymph nodes examined was associated with the likelihood of detecting nodal metastasis and survival. This may indicate an effect of incomplete pathologic examination.
Project description:Preoperative differentiation between limited (pN1; 1-3 axillary metastases) and advanced (pN2-3; ?4 axillary metastases) nodal disease can provide relevant information regarding surgical planning and guiding adjuvant radiation therapy. The aim was to evaluate the diagnostic performance of preoperative axillary ultrasound (US) and breast MRI for differentiation between pN1 and pN2-3 in clinically node-positive breast cancer. A total of 49 patients were included with axillary metastasis confirmed by US-guided tissue sampling. All had undergone breast MRI between 2008-2014 and subsequent axillary lymph node dissection. Unenhanced T2-weighted MRI exams were reviewed by two radiologists independently. Each lymph node on the MRI exams was scored using a confidence scale (0-4) and compared with histopathology. Diagnostic performance parameters were calculated for differentiation between pN1 and pN2-3. Interobserver agreement was determined using Cohen's kappa coefficient. At final histopathology, 67.3% (33/49) and 32.7% (16/49) of patients were pN1 and pN2-3, respectively. Breast MRI was comparable to US in terms of accuracy (MRI reader 1 vs US, 71.4% vs 69.4%, p?=?0.99; MRI reader 2 vs US, 73.5% vs 69.4%, p?=?0.77). In the case of 1-3 suspicious lymph nodes, pN2-3 was observed in 30.4% on US (positive predictive value (PPV) 69.6%) and in 22.2-24.3% on MRI (PPV 75.7-77.8%). In the case of ?4 suspicious lymph nodes, pN1 was observed in 33.3% on US (negative predictive value (NPV) 66.7%) and in 38.5-41.7% on MRI (NPV 58.3-61.5%). Interobserver agreement was considered good (k?=?0.73). In clinically node-positive patients, the diagnostic performance of axillary US and breast MRI is comparable and limited for accurate differentiation between pN1 and pN2-3. Therefore, there seems no added clinical value of preoperative breast MRI regarding nodal staging in patients with positive axillary US.
Project description:To compare the prognostic value of 3 different lymph node scoring systems " log odds of positive nodes (LODDS), lymph node ratio (rN), and lymph node yield " in an effort to improve the staging of oral cancer. We identified 3958 oral cancer patients from Surveillance, Epidemiology, and End Results database from 2007 to 2013. In univariate analysis, LODDS, pN, rN, and lymph node yield were prognostic factors for 5-year disease-specific survival (DSS) and overall survival (OS). Multivariate analysis indicated that patients with LODDS 4 had worst 5-year DSS and OS. Stage migration occurred in pN1 and pN2 patients with LODDS 4. In pN1 patients, those with LODDS 4 had the worst 5-year DSS (41.2%) and OS (31.6%) than patients with pN1 and LODDS 2-3. In pN2 patients, those with LODDS4 had the worst 5-year DSS (34.5%) and OS (27.4%) than patients with pN2 and LODDS 2-3. The proposed staging system, which incorporates LODDS with AJCC pN, had better discriminability and prediction accuracy for predicting survival. We also noted that patients with LODDS 4 given adjuvant radiotherapy had better 5-year DSS and OS. The LODDS should be considered as a future candidate measurement for N category in oral cancer.
Project description:PURPOSE:To determine the postoperative effects of radiotherapy (PORT) on the local recurrence-free survival (LRFS) and overall survival (OS) of stage III-N2 non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS:183 patients with resected stage III-pN2 NSCLC from Hunan Cancer Hospital between 2013 and 2016 were divided into two groups for postoperative chemotherapy (POCT) (n = 105) or combination chemotherapy and radiotherapy (POCRT) (n = 78). The LRFS and OS were compared and the factors affecting local recurrence were illustrated in these two groups. The sites of failure based on the lobe of the primary tumor in two groups were described. RESULTS:PORT leads to a strikingly lower risk for local recurrence and brought superior OS benefit. For different pN2 Subclassification, Patients with multiple-station pN2 ± pN1 disease had the worst LRFS (11 months) and single-station pN2 + multiple station pN1 disease had a relatively short LRFS (24 months) in group POCT. Short LRFS is correlated with multiple-station pN2, older age (Y > 55), patients with a high positive LN ratio > 1/3 and a poor tumor histological differentiation degree. In group POCT, the most frequent failure site occurs at the ipsilateral hilum (21.0%), the bronchial stump (20.0%), followed by LNs4R (19.0%), LNs4L (18.1%), LNs7 (15.2%), most of left-sided tumors more frequently involved the contralateral mediastinum, whereas the ipsilateral recurrences dominated for right-sided tumors, especially for LNs4R. In group POCRT, the highest failure site was the bronchial stump (11.5%), followed by LNs4L (8.97%), LNs1 (7.69%), the ipsilateral hilum (6.41%) and LNs4R (6.41%). CONCLUSION:PORT remarkably reduced local recurrence and improved OS in stage III-pN2 NSCLC, especially in the multiple-station pN2 group.
Project description:Background:In the TNM system only the anatomic location is used to define nodal status. In this study we aim to evaluate the effectiveness of combining the location and ratio of metastatic lymph node (pN-NR) for the prognosis of non-small cell lung cancer (NSCLC). Methods:Patients with pN1/pN2 NSCLC were retrieved from the SEER database. The optimal cut point of NR was determined with the maximal selecting test. All patients were divided into 4 categories with combination of pN (pN1 or pN2) and NR (low or high). The pN-NR was investigated as a predictor of overall survival (OS) and cause-specific survival (CSS) using Cox regression models. Survival curves were plotted using the Kaplan-Meier method and the difference was compared with log-rank test. Results:A total of 12,170 patients were enrolled. The optimal cut point of NR was 0.3. Patients were divided into 4 groups: pN1-NR <0.3, pN1-NR ?0.3, pN2-NR <0.3 and pN2-NR ?0.3. The pN-NR was an independent prognostic factor for survival. Compared with pN1-NR <0.3, the hazard ratio of OS was 1.405 (95% CI: 1.295-1.524), 1.183 (95% CI: 1.113-1257) and 1.717 (95% CI: 1.607-1.835) times higher for pN1-NR ?0.3, pN2-NR <0.3 and pN2-NR ?0.3 group, respectively. The survival curves of OS separated well between the 4 pN-NR groups, with 5-year OS 47.1% for pN1-NR <0.3, 43.0% for pN2-NR <0.3, 35.0% for pN1-NR ?0.3 and 28.5% for pN2-NR ?0.3, and the P value between neighboring curves was statistically significantly. The same trend was observed for CSS. Subgroup analysis revealed similar results except the pneumonectomy group. Conclusions:pN-NR could be a good predictor for the prognosis of NSCLC.
Project description:State of the art variable composition structure prediction based on density functional theory demonstrates that two new stoichiometries of PN, PN3 and PN2, become viable at high pressure. PN3 has a skutterudite-like Immm structure and is metastable with positive phonon frequencies at pressures between 10 and 100 GPa. PN3 is metallic and is the first reported nitrogen-based skutterudite. Its metallicity arises from nitrogen p-states which delocalise across N4 rings characteristic of skutterudites, and it becomes a good electron-phonon superconductor at 10 GPa, with a Tc of around 18 K. The superconductivity arises from strongly enhanced electron-phonon coupling at lower pressures, originating primarily from soft collective P-N phonon modes. The PN2 phase is an insulator with P2/m symmetry and is stable at pressures in excess of 200 GPa.
Project description:Background: This study aimed to develop a predictive model based on the risk of locoregional recurrence (LRR) in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma after complete resection. Methods: A total of 11,020 patients with lung surgery were screened to determine completely resected EGFR-mutant stage III-pN2 lung adenocarcinoma. Patients were excluded if they received preoperative therapy or postoperative radiation therapy (PORT). The time from surgery to LRR was recorded. Clinicopathological variables with statistical significance predicting LRR in the multivariate Cox regression were incorporated into the competing risk nomogram. Patients were then sub-grouped based on different recurrence risk as a result of the nomogram. Results: Two hundred and eighty-eight patients were enrolled, including 191 (66.3%) with unforeseen N2 (IIIA1-2), 75 (26.0%) with minimal/single station N2 (IIIA3), and 22 (7.6%) with bulky and/or multilevel N2 (IIIA4). The 2-year overall cumulative incidence of LRR was 27.2% (confidence interval [CI], 16.3%-38.0%). IIIA4 disease (hazard ratio, 2.65; CI, 1.15-6.07; P=0.022) and extranodal extension (hazard ratio, 3.33; CI, 1.76-6.30; P<0.001) were independent risk factors for LRR and were incorporated into the nomogram. Based on the nomogram, patients who did not have any risk factor (low-risk) had a significantly lower predicted 2-year incidence of LRR than those with any of the risk factors (high-risk; 4.6% vs 21.9%, P<0.001). Conclusions: Pre-treatment bulky/multilevel N2 and pathological extranodal extension are risk factors for locoregional recurrence in EGFR-mutant stage III-pN2 lung adenocarcinoma. Intensive adjuvant therapies and active follow-up should be considered in patients with any of the risk factors.
Project description:<h4>Purpose</h4>Pathologic downstaging following chemotherapy for stage III-N2 NSCLC is a well-known positive prognostic indicator. However, the predictive factors for locoregional recurrence (LRR) in these patients are largely unknown.<h4>Methods</h4>Between 1998 and 2008, 153 patients with clinically or pathologically staged III-N2 NSCLC from two cancer centers in the United States were treated with induction chemotherapy and surgery. All had pathologic N0-1 disease, and none received postoperative radiotherapy. LRR were defined as recurrence at the surgical site, lymph nodes (levels 1-14 including supraclavicular), or both.<h4>Results</h4>Median follow-up was 39.3 months. Pretreatment N2 status was confirmed pathologically (18.2 %) or by PET/CT (81.8 %). Overall, the 5-year LRR rate was 30.8 % (n = 38), with LRR being the first site of failure in 51 % (22/+99877943). Five-year overall survival for patients with LRR compared with those without was 21 versus 60.1 % (p < 0.001). Using multivariate analysis, significant predictors for LRR were pN1 disease at time of surgery (p < 0.001, HR 3.43, 95 % CI 1.80-6.56) and a trend for squamous histology (p = 0.072, HR 1.93, 95 % CI 0.94-3.98). Five-year LRR rate for pN1 versus pN0 disease was 62 versus 20 %. Neither single versus multistation N2 disease (p = 0.291) nor initial staging technique (p = 0.306) were predictors for LRR. N1 status also was predictive for higher distant recurrence (p = 0.021, HR 1.91, 95 % CI 1.1-3.3) but only trended for poorer survival (p = 0.123, HR 1.48, 95 % CI 0.9-2.44).<h4>Conclusions</h4>LRR remains high in resected stage III-N2 NSCLC patients after induction chemotherapy and nodal downstaging, particularly in patients with persistent N1 disease.
Project description:INTRODUCTION: Lymph node ratio (LNR, i.e. the ratio of the number of positive nodes to the total number of nodes excised) is reported to be superior to the absolute number of nodes involved (pN stage) in classifying patients at high versus low risk of death following breast cancer. The added prognostic value of LNR over pN in addition to other prognostic factors has never been assessed. METHODS: All patients diagnosed with lymph node positive, non-metastatic invasive breast cancer at the National University Hospital (Singapore) and University of Malaya Medical Center (Kuala Lumpur) between 1990-2007 were included (n = 1589). Overall survival of the patients was estimated by the Kaplan Meier method for LNR [categorized as low (>0 and <0.2), intermediate (0.2-0.65) and high (>0.65-1)] and pN staging [pN1, pN2 and pN3]. Adjusted overall relative mortality risks associated with LNR and pN were calculated by Cox regression. The added prognostic value of LNR over pN was evaluated by comparing the discriminating capacity (as indicated by the c statistic) of two multivariate models, one including pN and one including LNR. RESULTS: LNR was superior to pN in categorizing mortality risks for women ?60 years, those with ER negative or grade 3 tumors. In combination with other factors (i.e. age, treatment, grade, tumor size and receptor status), substituting pN by LNR did not result in better discrimination of women at high versus low risk of death, neither for the entire cohort (c statistic 0.72 [0.70-0.75] and 0.73 [0.71-0.76] respectively for pN versus LNR), nor for the subgroups mentioned above. CONCLUSION: In combination with other prognosticators, substitution of pN by LNR did not provide any added prognostic value for South East Asian breast cancer patients.