Prognostic Heterogeneity Between Oral Tongue and Gingivobuccal Tumours Based on Lymph Node Ratio and Number of Positive Nodes: A Survival Analysis.

Introduction: Lymph node ratio (LNR) and number of pathological positive nodes (pN) have shown better prognostic prediction compared to laterality, size and number of nodes (single or multiple). This study evaluates the prognostic significance of LNR and the number of  pathological positive nodes in predicting the outcomes of node positive oral squamous cell carcinoma(OSCC). It attempts to assess the prognostic heterogeneity between oral tongue and gingivobuccal complex tumours based on the lymph node ratio and the number of pathological positive nodes. Materials and Methods: A retrospective chart review of 498 previously untreated OSCC patients from January 2014 to December 2017 at our tertiary cancer institute was done. Our analysis included 133 oral tongue and 79 gingivobuccal tumours with histopathologically proven lymph node metastasis. The impact of LNR and number of positive nodes on overall survival and disease free survival was studied. Results: Overall survival rate was found to vary significantly based on LNR (> 0.06) and number of positive nodes (> 2). Overall survival reduced significantly in GBC tumours when LNR was more than 0.06(63.37 vs 32.1, p 0.005) but the same trend was not seen with tongue cancers (55.61 vs 41.9, p 0.98). Both the groups shown no difference in DFS based on LNR. Overall survival reduced significantly in both the groups when >2o pathologically positive nodes were present but disease free survival did not vary significantly in both the groups. Conclusion: Lymph node ratio (> 0.06) and number of pathological positive nodes (> 2) provide a better prognostic stratification in node positive oral squamous cell carcinoma. Oral tongue and GBC tumours were found to have a differential impact on overall survival rate on the stratification based on LNR.

The Changing Face of cN0M0 Prostate Cancer Being Found With pN+ After Surgery in the Contemporary Era: Results of an International European Survey on Disease Management.

INTRODUCTION: The urological community's opinion over the management of men being found with pathologically positive nodes (pN+) following radical prostatectomy (RP) performed with curative intent after preoperative negative conventional staging (cN0M0) has never been assessed. This remains crucial, especially considering the advent of novel imaging modalities. Our aim was to investigate the current opinion on management of pN+ cN0M0 prostate cancer (PCa) in the European urological community. METHODS: Following validation, a 31-item survey, complying with the Cherries checklist, was distributed using a web link from December 2021 to April 2022 to 10 urological societies mailing list. Social media (Twitter, Facebook) were also used. RESULTS: We received 253 replies. The majority were Urologists (96.8%), younger than 60 (90.5%); 5.2% did not have access to PET-scans; 78.9% believed pN+ is a multifaceted category; 10-years CSS was marked as 71 to 95% by 17.5%. Gold standard management was stated not being ADT by 80.8% and being RT±ADT by 52.3%. Early sRT±ADT was considered an option vs. aRT±ADT by 72.4%. In case of BCR 71% would perform and decide management based on PSMA-PET whilst 3.7% would not perform PSMA-PET. pN+ management is still unclear for 77.1%. On multivariate analysis PSMA-PET availability related to a lower and higher likelihood of considering aRT±ADT as standard and of considering early salvage versus aRT respectively (P < .05). CONCLUSIONS: The Urological community has an acceptable awareness of pN+ disease and management, although it may overestimate disease aggressiveness. The majority consider pN+ PCa as a multifaceted category and rely on a risk-adapted approach. Expectant compared to immediate upfront management and new imaging modalities are increasingly considered.

Prognostic and Predictive Biomarkers in Patients with Locally Advanced Rectal Cancer (LARC) Treated with Preoperative Chemoradiotherapy.

Neoadjuvant chemoradiotherapy (CRT) is one of the standards of care in locally advanced rectal cancer (LARC). This retrospective study examines clinical, analytical, and pathological parameters collected from 77 patients with locally advanced (cT3-4 or cN+) rectal carcinoma diagnosed between 2007 and 2017 at our institution that were treated with preoperative CRT and surgery. In the prognosis analysis, lower hemoglobin levels (p = 0.008), lower lymphocyte/monocyte ratio (LMR) (p = 0.011), and higher platelet/lymphocyte ratio (PLR) (p = 0.029) in the second determination (Hb2, LMR2 and PLR2) were associated with the relapse group. The number of positive nodes after surgery (N+) showed a statistically significant association with relapse (p = 0.012). KRAS mutations were associated with a worse prognosis for 5 years progression-free and overall survival (p = 0.005 and 0.022; respectively). We propose a prognostic model based on four parameters (number of positive lymph nodes after surgery, hemoglobin levels, LMR, and PLR after neoadjuvant therapy) that can be a useful tool to estimate relapse risk. Moreover, bilirubin could be a useful parameter to predict the response to neoadjuvant CRT.

Prognostic Significance of the Nodal Ratio and Number of Positive Nodes in Patients With Squamous Cell Carcinomas of the Head and Neck.

BACKGROUND/AIM: The lymph node status has high prognostic relevance in head and neck squamous cell carcinoma (HNSCC). This study aimed to address the hypothesis that the number of positive nodes and the nodal ratio have a prognostic impact on survival in HNSCC. PATIENTS AND METHODS: A retrospective analysis of 221 patients with HNSCC and clinical N+ status who underwent a neck dissection during primary surgery or after definitive radio(chemo)therapy was performed. The possible influence of age, sex, TNM stage, number of positive nodes and nodal ratio on survival was analyzed by univariate and multivariate Cox models and log-rank tests. RESULTS: On average, 30.1 lymph nodes were removed and 4.96 metastases were detected. The mean nodal ratio was 9.4%, the median nodal ratio was 5.3%. Multivariate analysis demonstrated a nodal ratio of ≥6-<12.5% [hazard ratio (HR)=2.33, 95% confidence interval (CI)=1.24-4.37; p=0.008] and of ≥12.5% (HR=2.86, 95% CI=1.40-5.84; p=0.004) compared to nodal ratio 0, number of positive nodes pN=1 compared to number of positive nodes=0 (HR=2.02, 95% CI=1.08-3.80. p=0.029), as well as N3 compared to N0 (HR=8.10, 95% CI=1.89-34.66; p=0.005), and Mx compared to M0 (HR of 2.76, 95% CI=1.59-4,79, p≤0.001) were of main importance for poor prognosis. Postoperative radio(chemo)therapy after surgery was associated with prolonged survival in multivariate analysis (HR=0.37, 95% CI=0.24-0.57; p≤0.001). CONCLUSION: The nodal ratio and number of positive nodes seem to have a high prognostic impact in patients with HNSCC and can be of value in identifying patients at high risk who warrant more aggressive therapy.

Clustering Molecular Subtypes in Breast Cancer, Immunohistochemical Parameters and Risk of Axillary Nodal Involvement.

(1) Background: To establish similarities in the risk of axillary lymph node metastasis between different groups of women with breast cancer according to immunohistochemical (IHC) parameters. (2) Methods: Data was collected retrospectively, from 2000 to 2013, of 1058 node-positive breast tumours. All patients were divided according to the St Gallen 2013 criteria and IHC features. The proportion of axillary involvement (pN > pN0; pN > pN1mi; pN > pN1) was calculated for each group. Similarities in axillary nodal dissemination were explored by cluster analysis and association between IHC and risk of axillary disease was studied with multivariate analysis. (3) Results: Among clinico-pathological surrogates of intrinsic subtypes, axillary involvement was more frequent in Luminal-B like HER2 negative (45.8%) and less frequent in Luminal-B HER2 positive (33.8%; p = 0.044). Axillary macroscopic involvement was more frequent in Luminal-B like HER2 negative (37.9%) and HER2 positive (37.8%) and less frequent in Luminal-B HER2 positive (25.5%) and Luminal-A like (25.6%; p = 0.002). Axillary involvement ≥pN2 was significantly less frequent in Luminal-A like (7.4%; p < 0.001). Luminal-A with Luminal-B HER2 positive, and triple-negative with Erb-B2 overexpressing tumours were clustered together regarding any axillary involvement, macroscopic disease or ≥pN2. Among the defined subgroups, axillary metastases were more frequent when Ki67 was higher. In a multivariate analysis, Ki67>14% were associated with a risk of axillary metastases (HR: 1.31; 95% CI, 1.51−6.80; p < 0.037). (4) Conclusions: there are two lymphatic drainage pathways of the breast according to the expression of hormone receptor-related genes. Positive-ER tumors are associated with lower axillary involvement and negative-ER tumors and Ki67 > 14% with higher nodal involvement.

A prognostic nomogram for stage II/III rectal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgical resection.

BACKGROUND: The purpose of this study was to develop a large population-based nomogram incorporating the log odds of positive nodes (LODDS) for predicting the overall survival (OS) of stage II/III rectal cancer patients treated with neoadjuvant chemoradiotherapy (NCRT) followed by surgical resection. METHODS: The Surveillance, Epidemiology, and End Results database was used to collect information on patients diagnosed with stage II/III rectal cancer between 2010 and 2015 and treated with NCRT followed by surgical resection. The Cox regression analyses were performed to determine the independent prognostic factors. In this study, LODDS was employed instead of American Joint Committee on Cancer (AJCC) 7th N stage to determine lymph node status. Then a nomogram integrating independent prognostic factors was developed to predict the 24-, 36-, and 60-month overall survival. The receiver operating characteristic (ROC) curves and calibration curves were used to validate the nomogram. Furthermore, patients were stratified into three risk groups (high-, middle-, and low-risk) based on the total points obtained from the nomogram. And Kaplan-Meier curves were plotted to compare the OS of the three groups. RESULTS: A total of 3829 patients were included in the study. Race, sex, age, marital status, T stage, tumor grade, tumor size, LODDS, CEA level, and postoperative chemotherapy were identified as independent prognostic factors, based on which the prognostic nomogram was developed. The area under curve values of the nomogram for the 24-, 36-, and 60-month OS in the training cohort were 0.736, 0.720, and 0.688, respectively; and 0.691, 0.696, and 0.694 in the validation cohort, respectively. In both the validation and training cohorts, the calibration curves showed a high degree of consistency between actual and nomogram-predicted survival rates. The Kaplan-Meier curves showed that the three risk groups had significant differences in overall survival (P < 0.001). CONCLUSION: A large population-based nomogram incorporating LODDS was developed to assist in evaluating the prognosis of stage II/III rectal cancer patients treated with NCRT followed by surgical resection. The nomogram showed a satisfactorily discriminative and stable ability to predict the OS for those patients.

The Role of Simultaneous Integrated Boost in Locally Advanced Rectal Cancer Patients with Positive Lateral Pelvic Lymph Nodes.

Aims: Between 11 to 14% of patients with locally advanced rectal cancer (LARC) have positive lateral pelvic lymph nodes (LPLN) at diagnosis, related to a worse prognosis with a 5-year survival rate between 30 to 40%. The best treatment choice for this group of patients is still a challenge. The optimal radiotherapy (RT) dose for LPLN patients has been investigated. Methods: We retrospectively collected data from LARC patients with LPLN at the primary staging MRI, treated in our center from March 2003 to December 2020. Patients underwent a neoadjuvant concomitant chemo-radiotherapy (CRT) treatment on the primary tumor (T), mesorectum, and pelvic nodes, associated with a fluoride-based chemotherapy. The total reached dose was 45 Gy at 1.8 Gy/fr on the elective sites and 55 Gy at 2.2 Gy/fr on the disease and mesorectum. Patients were divided in two groups based on whether they received a simultaneous integrated RT boost on the LPLN or not. Overall Survival (OS), Disease Free Survival (DFS), Metastasis Free Survival (MFS), and Local Control (LC) were evaluated in the whole group and then compared between the two groups. Results: A total of 176 patients were evaluated: 82 were included in the RT boost group and 94 in the non-RT boost group. The median follow-up period was 57.8 months. All the clinical endpoint (OS, DFS, MFS, LC), resulted were affected by the simultaneous integrated boost on LPLN with a survival rate of 84.7%, 79.5%, 84.1%, and 92%, respectively, in the entire population. From the comparison of the two groups, there was a statistical significance towards the RT boost group with a p < 0.006, 0.030, 0.042, 0.026, respectively. Conclusions: Concomitant radiotherapy boost on positive LPLN has shown to be beneficial on the survival outcomes (OS, DFS, MFR, and LC) in patients with LARC and LPLN. This analysis demonstrates that a higher dose of radiotherapy on positive pelvic lymph nodes led not only to a higher local control but also to a better survival rate. These results, if validated by future prospective studies, can bring a valid alternative to the surgery dissection without the important side effects and permanent disabilities observed during the years.

Risk factors to identify the indication for regional nodal irradiation in T1-2N1M0 breast cancer: A joint analysis of 4,243 real-world cases from two institutions.

Purpose: The aim of this study is to evaluate the role of regional nodal irradiation (RNI) in patients with T1-2N1M0 breast cancer and to identify the subgroup that could benefit from RNI. Methods and materials: A total of 4,243 women with pT1-2N1M0 breast cancer treated at two institutions in China were retrospectively reviewed. Survival rates were calculated by the Kaplan-Meier method and compared by the log-rank test. The association of risk factors with survival outcomes was evaluated using multivariable proportional hazards regression. Results: A total of 932 patients (22.0%) received RNI. At a median follow-up of 5.9 years, the 5-year locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were 4.0% and 7.2% (P = 0.001), 13.2% and 10.6% (P = 0.465), 85.0% and 84.7% (P = 0.131), and 93.9% and 92.8% (P = 0.004) in the RNI and non-RNI groups, respectively. Multivariate analysis revealed that RNI was an independent prognostic factor for lower LRR (P = 0.001) and longer DFS (P = 0.013). Patients were stratified into low-, intermediate-, and high-risk groups based on the eight non-therapeutic risk factors. RNI significantly decreased the 5-year LRR (2.2% vs. 7.0%, P = 0.001) and improved the 5-year DFS (88.8% vs. 84.9%, P = 0.015) and OS (95.8% vs. 93.9%, P = 0.010) in the intermediate-risk group. However, neither the low-risk group nor the high-risk group had survival benefit from RNI. Conclusion: T1-2N1M0 breast cancer is a heterogeneous disease. We found that RNI only improved survival in the intermediate-risk group. It might be omitted in low-risk patients, and the role of RNI in high-risk patients needs further study.

The Prognostic Value of Lymph Node Involvement after Neoadjuvant Chemotherapy Is Different among Breast Cancer Subtypes.

INTRODUCTION: The three different breast cancer subtypes (Luminal, HER2-positive, and triple negative (TNBCs) display different natural history and sensitivity to treatment, but little is known about whether residual axillary disease after neoadjuvant chemotherapy (NAC) carries a different prognostic value by BC subtype. METHODS: We retrospectively evaluated the axillary involvement (0, 1 to 3 positive nodes, ≥4 positive nodes) on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between nodal involvement (ypN) binned into three classes (0; 1 to 3; 4 or more), relapse-free survival (RFS) and overall survival (OS) among the global population, and according to BC subtypes. RESULTS: 1197 patients were included in the analysis (luminal (n = 526, 43.9%), TNBCs (n = 376, 31.4%), HER2-positive BCs (n = 295, 24.6%)). After a median follow-up of 110.5 months, ypN was significantly associated with RFS, but this effect was different by BC subtype (Pinteraction = 0.004), and this effect was nonlinear. In the luminal subgroup, RFS was impaired in patients with 4 or more nodes involved (HR 2.8; 95% CI [1.93; 4.06], p < 0.001) when compared with ypN0, while it was not in patients with 1 to 3 nodes (HR = 1.24, 95% CI = [0.86; 1.79]). In patients with TNBC, both 1-3N+ and ≥4 N+ classes were associated with a decreased RFS (HR = 3.19, 95% CI = [2.05; 4.98] and HR = 4.83, 95% CI = [3.06; 7.63], respectively versus ypN0, p < 0.001). Similar decreased prognosis were observed among patients with HER2-positive BC (1-3N +: HR = 2.7, 95% CI = [1.64; 4.43] and ≥4 N +: HR = 2.69, 95% CI = [1.24; 5.8] respectively, p = 0.003). CONCLUSION: The prognostic value of residual axillary disease should be considered differently in the 3 BC subtypes to accurately stratify patients with a high risk of recurrence after NAC who should be offered second line therapies.

Radiotherapy plays an important role in improving the survival outcome in patients with T1-2N1M0 breast cancer - a joint analysis of 4262 real world cases from two institutions.

BACKGROUND: To compare the survival outcomes between breast-conserving surgery (BCS) and modified radical mastectomy (MRM), and to investigate the role of radiotherapy (RT) in patients with pT1-2N1M0 breast cancer. METHODS: A total of 4262 women with T1-2N1M0 breast cancer treated at two institutions were retrospectively reviewed. A total of 3858 patients underwent MRM, and 832 (21.6%) of them received postoperative RT (MRM + RT). A total of 404 patients received BCS plus postoperative RT (BCS + RT). All patients received axillary lymph node dissection, while 3.8% of them had upfront sentinel node biopsy. The association of survival outcomes with different surgical modalities (BCS vs. MRM) and the role of RT were evaluated using multivariable proportional hazards regression and confirmed by the propensity score-matching (PSM) method. RESULTS: At a median follow-up of 71 months (range of 6-230 months), the 5-year overall survival (OS) rates of the BCS and MRM groups were 96.5 and 92.7%, respectively (P = .001), and the corresponding 5-year disease-free-survival (DFS) and locoregional recurrence (LRR) rates were 92.9 and 84.0%, and 2.0 and 7.0% (P = .001), respectively (P < .001). Multivariate analysis revealed that RT was an independent prognostic factor for improved OS (P = .001) and DFS (P = .009), and decreased LRR (P < .001). However, surgery procedure was not independently associated with either OS (P = .495), DFS (P = .204), or LRR (P = .996), which was confirmed by PSM analysis. CONCLUSION: Postoperative radiotherapy rather than the surgery procedures was associated with superior survival outcomes in patients with T1-2N1M0 breast cancer.

Management of Patients with Node-positive Prostate Cancer at Radical Prostatectomy and Pelvic Lymph Node Dissection: A Systematic Review.

CONTEXT: Optimal management of prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy and pelvic lymph node dissection still remains unclear. OBJECTIVE: To assess the effectiveness of postoperative treatment strategies for pathologically node-positive PCa patients. The secondary aim was to identify the most relevant prognostic factors to guide the management of pN1 patients. EVIDENCE ACQUISITION: A systematic review was performed in January 2020 using Medline, Embase, and other databases. A total of 5063 articles were screened, and 26 studies including 12 537 men were selected for data synthesis and included in the current review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. EVIDENCE SYNTHESIS: Ten-year biochemical recurrence (BCR)-free, clinical recurrence-free, cancer-specific (CSS), and overall (OS) survival rates ranged from 28% to 56%, 70% to 92%, 72% to 98%, and 60% to 87.6%, respectively. A total of seven, five, and six studies assessed the oncological outcomes of observation, adjuvant radiotherapy (aRT), or adjuvant androgen deprivation therapy (ADT), respectively. Initial observation followed by salvage therapies at the time of recurrence represents a safe option in selected patients with a low disease burden. The use of aRT with or without ADT might improve survival in men with locally advanced disease and a higher number of positive nodes. Risk stratification according to pathological Gleason score, number of positive nodes, pathological stage, and surgical margins status is the key to risk stratification and selection of the optimal postoperative therapy. Limitations of this systematic review are the retrospective design of the studies included and the lack of data on adverse events. CONCLUSIONS: While the majority of men with pN1 disease would experience BCR after surgery, long-term disease-free survival has been reported in selected patients. Management options to improve oncological outcomes include observation versus adjuvant therapies such as aRT and/or ADT. Disease characteristics should be used to select the optimal postoperative management for pN1 PCa patients. PATIENT SUMMARY: Finding node-positive prostate cancer after a radical prostatectomy often leads to high postoperative prostate-specific antigen levels and is overall a poor prognostic factor. However, this does not necessarily translate into poor survival for all men. Management can be tailored to the severity of disease and options include observation, androgen deprivation therapy, and/or radiotherapy.

Effectiveness of the AJCC 8th edition staging system for selecting patients with T1-2N1 breast cancer for post-mastectomy radiotherapy: a joint analysis of 1986 patients from two institutions.

BACKGROUND: The role of post-mastectomy radiotherapy (PMRT) in the treatment of patients with T1-2N1 breast cancer is controversial. This study's purpose was to evaluate the risk of recurrence of T1-2N1 breast cancer and the efficacy of PMRT in low-, medium- and high-risk groups of patients. METHODS: Post-mastectomy patients with T1-2N1 breast cancer were restaged according to the American Joint Committee on Cancer Staging Manual, 8th edition (AJCC 8th ed.) staging system. Recurrence scores were generated using prognostic factors identified for loco-regional recurrence and distant metastasis in patients without PMRT, and three risk groups were identified. Rates of loco-regional recurrence and distant metastasis were calculated with a competing risk model and compared using Gray's test. Disease-free survival and overall survival were calculated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards regression model was used for the multivariate analysis. RESULTS: Data from 1986 patients (1521without PMRT; 465 with PMRT) were analyzed. Patients without PMRT were stratified into low-, intermediate- and high-risk groups by age, tumor location, AJCC 8th ed. stage, number of positive nodes and lympho-vascular invasion. The 5-year loco-regional recurrence rate and distant metastasis rates for the three risk groups were significant at 2.5, 5.4 and 16.2% (p <  0.001) respectively, and 4.9, 8.4 and 18.6% (p <  0.001) respectively. In the high-risk group, loco-regional recurrence (p <  0.001), and distant metastasis (p = 0.044) were significantly reduced, and disease free survival (p = 0.004), and overall survival (p = 0.029) were significantly improved after PMRT. In the low- and intermediate-risk groups, PMRT had no significant effect on loco-regional recurrence (p = 0.268), distant metastasis (p = 0.252), disease free survival (p = 0.608) or overall survival (p = 0.986). CONCLUSION: Our results showed no benefits of PMRT in the low-risk group, and thus, omitting PMRT radiotherapy in this population could be considered.

Development and external validation of a nomogram to predict four or more positive nodes in breast cancer patients with one to three positive sentinel lymph nodes.

OBJECTIVE: To develop a nomogram for predicting the possibility of four or more positive nodes in breast cancer patients with 1-3 positive sentinel lymph nodes (SLN). MATERIALS AND METHODS: Retrospective analysis of data of patients from two institutions was conducted. The inclusion criteria were: invasive breast cancer; clinically node negative; received lumpectomy or mastectomy plus SLN biopsy followed by axillary lymph node dissection (ALND); and pathologically confirmed T1-2 tumor, with 1-3 positive SLNs. Patients from one institution formed the training group and patients from the other the validation group. Univariate and multivariate analyses were performed to identify the predictors of four or more positive nodes. These predictors were used to build the nomogram. The area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of the model. RESULTS: Of the 1480 patients (966 patients in the training group, 514 in the validation group), 306 (20.7%) had four or more positive nodes. Multivariate stepwise logistic regression showed number of positive (p < .001) and negative SLN (p < .001), extracapsular extension (p < .001), pT stage (p = .016), and tumor location in outer upper quadrant (p = .031) to be independent predictors of four or more positive nodes. The nomogram was built using these five factors. The AUC was 0.845 in the training group and 0.804 in the validation group. CONCLUSION: The proposed nomogram appears to accurately estimate the likelihood of four or more positive nodes and could help radiation oncologists to decide on use of regional nodal irradiation (RNI) for breast cancer patients with 1-3 positive nodes but no ALND.

The 8th TNM classification for oral squamous cell carcinoma: What is gained, what is lost, and what is missing.

OBJECTIVES: The 8th TNM edition remarkably changed the classification of T and N categories for oral squamous cell carcinoma (OSCC). The present study aims at evaluating the improvement in prognostic power compared to the 7th edition, pros and cons of the modifications, and parameters deserving consideration for further implementations. MATERIALS AND METHODS: All OSCCs treated with upfront surgery at our institution between 2002 and 2017 were included. Demographics, clinical-pathological and treatment variables were retrieved. All tumors were classified according to both the 7th and 8th TNM edition, and patients were grouped according to the shift in T category and stage. Survivals were calculated with the Kaplan-Meier method. Univariate and multivariate analysis were carried out. Receiver Operating Characteristics (ROC) curve analyses were performed to find the best cut-off of DOI (in patients with DOI > 10 mm) and number of involved nodes (in positive neck patients). RESULTS: 244 patients were included. T, N categories, and stage changed in 59.2%, 20.5%, and 49.1% patients, respectively; 41.5% of patients were upstaged. The new T classification well depicted prognosis according to OS. Five-year overall (OS), disease-specific, recurrence-free (RFS) survivals were 60.5%, 70.9%, 59.8%, respectively. According to ROC curves, DOI > 20 mm and 4 positive nodes were the best cutoffs for OS and RFS. CONCLUSION: The novelties introduced in 8th TNM edition were positive. DOI > 20 mm for T4 definition and number of positive nodes (0, <4, 4 or more) for N classification emerged as the most urgent factors to be implemented.

Utility of regional nodal irradiation in Japanese patients with breast cancer with 1-3 positive nodes after breast-conserving surgery and axillary lymph-node dissection.

The utility of regional nodal irradiation (RNI) is being considered in cases of 1-3 axillary node metastases after breast-conserving surgery (BCS) with axillary lymph-node dissection (ALND). Therefore, we examined the necessity of RNI by examining the sites of recurrences in cases at our institution. We retrospectively analyzed 5,164 cases of primary breast cancer between January 2000 and December 2014 at the Aichi Cancer Centre, identifying local and distant recurrences in 152 patients with primary breast cancer treated with BCS and ALND and who had 1-3 positive axillary nodes. All patients received whole-breast irradiation (WBI) and adjuvant systemic therapy with either chemotherapy or anti-endocrine therapy with or without anti-human epidermal growth factor receptor 2 therapy. The present study excluded patients with ipsilateral breast tumor recurrence, contralateral breast cancer, neoadjuvant chemotherapy, T4 tumors or N2-3 nodes and distant metastasis. From the database of our institution, we identified 152 cases that met the defined criteria. The median follow-up period was 71 months (1-176). Isolated locoregional recurrences were found in three patients (2.0%) and were recurrent only in the breast. Only one patient had local lymph node recurrence with distant recurrence. The 10-year rates of isolated regional disease-free survival (DFS), DFS, and overall survival were 95.41, 89.50 and 96.75%, respectively, which was better compared with previous studies. We conclude that the addition of RNI to WBI is not necessary for Japanese patients who have 1-3 positive axillary nodes and ALND.

Number of positive nodes - Current relevance in determining prognosis of oral cavity cancer after the recent AJCC staging update.

INTRODUCTION: Lymph node involvement and the number of positive nodes is a significant prognosticator in oral cavity cancers and current staging system does not incorporate it as an integral part. MATERIAL AND METHODS: This was a retrospective study of oral cavity cancer patients who were operated during the time period of 2009-2017. The data was collected and analysed to assess the impact of increase in the number of positive nodes on survival and its comparison of survival statistics to current AJCC staging. RESULTS: A total of 1431 patients were included in this study and 32.5% of these patients had a node positive disease. Nodal positivity was a significant prognosticator on multivariate analysis. Number of positive nodes was modelled with restricted cubic spline function and it showed progressive worsening of survival functions with increase in number. On Kaplan Meier analysis there was a better separation of curves when number of positive nodes was used and Akaike information criterion (AIC) showed that it was a better prognosticator than existing AJCC staging. CONCLUSION: Number of positive nodes is a significant prognosticator of prognosis and hence should be considered in the AJCC staging system.

Selective Neck Dissection and Survival in Pathologically Node-Positive Oral Squamous Cell Carcinoma.

The most important prognostic factor in oral squamous cell carcinoma (OSCC) is neck metastasis, which is treated by neck dissection. Although selective neck dissection (SND) is a useful tool for clinically node-negative OSCC, its efficacy for neck node-positive OSCC has not been established. Sixty-eight OSCC patients with pN1⁻3 disease who were treated with curative surgery using SND and/or modified-radical/radical neck dissection (MRND/RND) were retrospectively reviewed. The neck control rate was 94% for pN1⁻3 patients who underwent SND. The five-year overall survival (OS) and disease-specific survival (DSS) in pN1-3 OSCC patients were 62% and 71%, respectively. The multivariate analysis of clinical and pathological variables identified the number of positive nodes as an independent predictor of SND outcome (OS, hazard ratio (HR) = 4.98, 95% confidence interval (CI): 1.48⁻16.72, p < 0.01; DSS, HR = 6.44, 95% CI: 1.76⁻23.50, p < 0.01). The results of this retrospective study showed that only SND for neck node-positive OSCC was appropriate for those with up to 2 lymph nodes that had a largest diameter ≤3 cm without extranodal extension (ENE) of the neck and adjuvant radiotherapy. However, the availability of postoperative therapeutic options for high-risk OSCC, including ENE and/or multiple positive lymph nodes, needs to be further investigated.

High metastatic node number, not extranodal extension, as a node-related prognosticator in surgically treated patients with nodal metastatic salivary gland carcinoma.

BACKGROUND: The prognostic relevance of extranodal extension (ENE) for salivary gland carcinoma (SGC) remains unclear. The present study is undertaken to investigate the predictive significance of pathological nodal parameters in surgically treated patients with nodal metastatic SGC. METHODS: This multicenter cohort included 114 patients with pathologically proven node-positive SGC between 2000 and 2014. Possible correlations of clinicopathological parameters and outcomes were examined. RESULTS: The median follow-up was 69 months (range, 11-173 months). The multivariate analysis identified metastatic node number (1-2 vs 3-6; 1-2 vs ≥7) as an independent predictor for regional control (P = 0.005; P = 0.02), locoregional control (P = 0.008; P = 0.04), distant metastasis-free survival (P = 0.17; P = 0.006), disease-free survival (P = 0.05; P = 0.002), and overall survival (P = 0.18; P = 0.009), whereas ENE was not associated with survival outcomes. CONCLUSIONS: Metastatic node number, not ENE, is an independent node-related prognosticator for SGC. Integration of ENE into the American Joint Committee on Cancer 8th edition staging criteria may not improve prognostic performance.

Chest wall recurrence in pT1-2N0-1 breast cancer patients after mastectomy without radiotherapy.

PURPOSE: In correlation with the nodal status in the era of modern radiotherapy, the chest wall recurrence (CWR) rate was investigated in pT1-2N0-1 breast cancer patients after a mastectomy without post-mastectomy radiotherapy (PMRT). METHODS: The data from the patients participating in two South Korean multi-institutional studies (KROG 14-22; N = 1842 and KROG 14-23; N = 1382) were analyzed. In total, 3224 pT1-2N0-1 breast cancer patients who underwent mastectomy without PMRT were analyzed. RESULTS: The median follow-up time was 72.2 months (range 0.8-125.2 months). The overall CWRs during the follow-up period were 1.68% in N0 patients and 2.82% in N1 patients. There was no statistically significant difference in 5-year and 10-year CWR-free survival (CWRFS) between the N0 and N1 patients. Of the 70 patients with CWR, 33 (1% of all the patients) had isolated CWR, and the 10-year overall survival rate in this group was 96.9%. After the propensity score matching of the N0 and N1 groups, there was still no difference in CWRFS by nodal status. CONCLUSIONS: The incidence of CWR in pT1-2N0-1 breast cancer patients is very low, especially with isolated recurrence. Also, the obtained data showed that the nodal status had no impact on CWRFS.

Post-operative radiotherapy is beneficial for T1/T2 triple negative breast cancer patients with four or more positive lymph nodes.

The efficacy of adjuvant radiotherapy for the treatment of triple negative breast cancer patients with varying numbers of positive lymph nodes is not clear. We assessed the association between adjuvant radiotherapy and survival in 943 T1/T2 triple negative breast cancer patients treated at our institute between 2008 and 2012. We determined that post-operative radiotherapy improved overall survival (OS), disease-free survival (DFS), and local recurrence-free survival (LRFS) in patients with ≥ 4 positive nodes (p = 0.037, p = 0.035, and p = 0.012, respectively). Although Cox regression analysis demonstrated that radiotherapy was a significant prognostic factor in triple negative breast cancer with ≥ 4 positive nodes, post-operative radiotherapy had no clear effect on OS, DFS, or LRFS in patients with 1-3 positive nodes (p = 0.849, p = 0.860, and p = 0.162, respectively). The prognosis (i.e., OS, DFS, and LRFS) of triple negative breast cancer patients without lymph node metastasis who underwent breast-conserving surgery and post-operative radiotherapy was similar to that of patients who underwent mastectomy alone (p = 0.336, p = 0.537, and p = 0.978, respectively). Our findings demonstrate that post-operative radiotherapy is beneficial for T1/T2 triple negative breast cancer patients with ≥ 4 positive lymph nodes.