Negative Node Status Research Articles

Elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in gastric cancer: a distinct microsatellite instability type with potential clinical impact?

We investigated the clinical impact of elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in the context of neoadjuvant chemotherapy (CTx) in gastric/gastro‐oesophageal adenocarcinomas. We analysed 583 resected tumours (272 without and 311 after CTx) and 142 tumour biopsies before CTx. If at least two or three of the five tetranucleotide repeat markers tested showed instability, the tumours were defined as EMAST (2+) or EMAST (3+), respectively. Expression of mismatch repair proteins including MSH3 was analysed using immunohistochemistry. Microsatellite instability (MSI) and Epstein–Barr virus (EBV) positivity were determined using standard assays. EMAST (2+) and (3+) were detected in 17.8 and 11.5% of the tumours, respectively. The frequency of EMAST (2+) or (3+) in MSI‐high (MSI‐H) tumours was 96.2 or 92.5%, respectively, demonstrating a high overlap with this molecular subtype, and the association of EMAST and MSI status was significant (each overall p < 0.001). EMAST (2+ or 3+) alone in MSI‐H and EBV‐negative tumours demonstrated only a statistically significant association of EMAST (2+) positivity and negative lymph node status (42.3% in EMAST (2+) and 28.8% in EMAST negative, p = 0.045). EMAST alone by neither definition was significantly associated with overall survival (OS) of the patients. The median OS for EMAST (2+) patients was 40.0 months (95% confidence interval [CI] 16.4–63.6) compared with 38.7 months (95% CI 26.3–51.1) for the EMAST‐negative group (p = 0.880). The median OS for EMAST (3+) patients was 46.7 months (95% CI 18.2–75.2) and 38.7 months (95% CI 26.2–51.2) for the negative group (p = 0.879). No statistically significant association with response to neoadjuvant CTx was observed (p = 0.992 and p = 0.433 for EMAST (2+) and (3+), respectively). In conclusion, our results demonstrate a nearly complete intersection between MSI‐H and EMAST and they indicate that EMAST alone is not a distinct instability type associated with noticeable clinico‐pathological characteristics of gastric carcinoma patients.

Intraoperative radiation therapy for early stage breast cancer

Background and objectiveWe report our experiences with Intraoperative radiation therapy (IORT) among breast cancer (BC) patients in our region.MethodsAll patients who received radical IORT from April 2014 on to March 2020 were included in the study. Patient selection criteria included: Age equal or older than 45 years old; All cases of invasive carcinomas (in cases of lobular carcinomas only with MRI and confirmation); Patients who were 45–50 years old with a tumor size of 0–2 cm, 50–55 years old with a tumor size of < 2.5 cm, and those who were ≥ 55 years old with a tumor size of < 3 cm; Invasive tumors only with a negative margin; Negative nodal status (exception in patients with micrometastasis); A positive estrogen receptor status. Primary endpoints included death and recurrence which were assessed using the Kaplan–Meier method.ResultsOverall, 252 patients entered the study. Mean (SD) age of patients was 56.43 ± 7.79 years. In total, 32.9% of patients had a family history of BC. Mean (SD) tumor size was 1.56 ± 0.55 cm. Mean (IQR) follow-up of patients was 36.3 ± 18.7 months. Overall, 8 patients (3.1%) experienced recurrence in follow-up visits (disease-free-survival of 96.1%), among which four (1.5%) were local recurrence, two (0.8%) were regional recurrence and two patients (0.8%) had metastasis. Median (IQR) time to recurrence was 46 (22, 53.7) months among the eight patient who had recurrence. Overall, one patient died due to metastasis in our series. Eleven patients (4.3%) with DCIS in our study received IORT. All these patients had free margins in histopathology examination and none experienced recurrence.ConclusionInhere we reported our experience with the use of IORT in a region where facilities for IORT are limited using our modified criteria for patient selection.

Survival of 736 Cholangiocarcinoma Patient Receiving Surgical Treatment in O. Viverrini Endemic Area, Thailand

Introduction: Cholangiocarcinoma is a common cancer in Thailand, endemic area of O. Viverrini. This study aims to investigate survival outcome and prognostic factors in Cholangiocarcinoma patient receiving surgical treatment. Methods: We retrospectively reviewed 736 consecutive patients with cholangiocarcinoma who underwent surgical treatment between October 2013 to December 2018. Patients were divided into Intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) groups. Principle outcomes were long-term survival and 90-day mortality. Results: Of the 736 patients, 407 (55%) were iCCA, 240 (33%) were pCCA and 89 (12%) were dCCA. Overall resectable rate was 78.3%; 75.2% in iCCA, 83.8% in pCCA and 77.5% in dCCA. In resectable patients, overall 90-day mortality was 10.9%; 11.0% in iCCA, 11.6% in pCCA and 8.9% in dCCA. Long-term survival for resectable patients was higher in patients with CA19-9 <200 U/mL (p<0.001), intraductal growth type (p<0.001), well-differentiation (p=0.001), negative nodal status (p<0.001), R0 margin (p<0.001), absence of LVI (p=0.001), absence of PNI (p<0.001) and absence of metastasis (p<0.001). In mutivariale analysis, R0 margin (p=0.001), negative nodal status (p=0.003) and absence of metastasis (p=0.002) were significant independent prognostic factors. The median survival was better in resectable group than unresectable group (11.6 vs 3.2 months, respectively, p<0.001). Furthermore, the median survivals for R0-resection with pM0 was 19.3 months (18.2, 24.5 and 18.4 in iCCA, pCCA and dCCA, respectively). Conclusion: Negative resection margin, absence of LN and absence of distant metastasis were the important factor affecting survival in CCA patients in the endemic area of O. Viverini.

Surgery and Combined Transplant with Chemotherapy Improve Survival for Patients with Liver Limited and Locally Advanced Intrahepatic Cholangiocarcinoma: A Seer Database Analysis

Introduction: The impact of neoadjuvant chemotherapy followed by surgery for patients with intrahepatic cholangiocarcinoma (iCCA) is unclear. We sought to determine whether a multimodal treatment approach, including liver transplantation, offers survival advantage for liver-limited, locally advanced iCCA. Methods: The Surveillance, Epidemiology, and End Results (SEER) database from 2004-2014 was queried for patients with iCCA. Those with negative nodal status and no extrahepatic disease (T1-T3N0M0 AJCC 6th, T1-2N0M0 7th/8th edition) were considered. Tumor characteristics and survival outcomes were evaluated by treatment modality. Results: 1621 patients with liver limited and/or locally advanced iCCA were identified. The majority (55%) had T1 disease (AJCC 6th edition). Median survival for patients receiving surgery alone or surgery + medical therapy was 46 months, compared with 5 months for no treatment and 13 months for medical therapy. Liver transplant alone improved median survival to 19 months, with 5-year overall survival (OS) of 14%, which was similar to 27% for surgery alone and 25% for surgery + medical therapy. Liver transplant + medical therapy offered the best survival, with median survival > 60 months and 62% OS at 5 years. Patient age (>70 yo [HR=1.7, p=0.01]), tumor size >7cm [HR=1.85, p=0.04], and tumor stage (> T1 [HR=1.4, p=0.03 ], >T2 [HR=1.9, p<0.0001]) significantly increased risk of mortality. Conclusion: Liver-limited, locally advanced iCCA carries a poor prognosis. Transplant plus chemoradiation may be a viable alternative for otherwise unresectable disease. Prospective clinical trials are necessary to clearly define the role of transplant with neoadjuvant therapy in the management of iCCA.

Survival Analysis of Infiltrating Ductal Breast Cancer Patients with Cure Rate Regression Model- A Retrospective Cohort Study from a Tertiary Care Hospital in Central Kerala

Introduction: Breast cancer is a leading cause of morbidity among women all around the world. Monitoring the survival pattern and identifying the prognostic factors on survival are always great concerns in cancer researches. Cure rate regression model is a useful statistical tool to predict the cure rate of cancer diseases and to determine the factors associated with survival of patients. Aim: The current study aimed to estimate the cured proportion and to make out the factors associated with survival time of infiltrating ductal breast carcinoma patients in a tertiary care hospital of central Kerala. Materials and Methods: The retrospective cohort study was conducted in the Department of Radiotherapy of a major tertiary care hospital of central part of Kerala, India. A total of 313 female patients diagnosed with infiltrating ductal breast cancer during January 2012 to December 2015 were considered for the study. The impact of the covariates, age at diagnosis of disease, grade of cancer, stage of disease, tumour stage, status of regional lymph node, distant metastasis, and triple negative status on survival of patients were studied. The parametric mixture cure rate regression model was used for estimation and inferential procedures. The cure rate with respect to each study variable and their role on long term survival of patients were investigated. Results: Mean age of patients was 51.95±10.91 years. The minimum cure rate found out (29.8%) among the patients presented with distant metastasis. The bivariate analysis showed the factors, stage of cancer, (T-stage), status of regional lymph node and distant metastasis status influence significantly on incidence of death due to breast cancer in long run period and grade of cancer determines the survival of patients at shorter duration of time. The presence of regional lymph node and distant metastasis status were found out to be two important indicators that determine cure rate of infiltrating ductal breast cancer patients in multivariate analysis. The hazard of patients living with higher grade cancer was seen 1.48 times more than that of others (Hazard Ratio=1.48, p-value &lt;0.001). Conclusion: The cure rate of patients estimated between 29.8% and 69.6% with respect to various factors under study. The status of regional lymph node and distant metastasis status were found to be associated with cure rate of patients. The study results showed that the grade of cancer is one significant factor that determines survival of patients. The study recommends cure rate regression model as a useful tool to analyse breast cancer survival data in the presence of cured proportion.

Serum HE4 is associated with clinical prognostic factors and survival outcome in female patients with primary peritoneal carcinoma.

The aim of this study was to investigate whether serum HE4 was associated with clinical risk prognostic factors and survival outcome. In this study, 72 patients with primary peritoneal carcinoma (PPC) from January 2011 to October 2019 participated. Serum HE4 and CA125 levels were detected at primary diagnosis, post-surgery, pre-recurrence and the presence of recurrence. The relations between serum HE4 levels with clinical prognostic factors were analyzed, and the hazard ratios between serum HE4 levels with overall survival and recurrence-free survival were also analyzed by univariate and multivariate survival analysis. HE4 and CA125 levels were significantly elevated in serous type, high histological grade, advanced stage and positive lymph node status and residual tumor diameter more than 1cm, respectively, compared with those in non-serous type, low histological grade, early stage, negative lymph node status and residual tumor diameter no more than 1cm, respectively. HE4 was an independent prognostic factor for recurrence-free survival and overall survival with hazard ratios of 5.36 (95% confidence interval: 2.19-13.15) and 4.48 (95% confidence interval: 1.87-10.74), respectively. HE4 is correlated with clinical risk prognostic factors in PPC and is effective in the recurrence detection and predicting outcome in PPC patients.

Sentinel Lymph Node Metastasis on Clinically Negative Patients: Preliminary Results of a Machine Learning Model Based on Histopathological Features

The reported incidence of node metastasis at sentinel lymph node biopsy is generally low, so that the majority of women underwent unnecessary invasive axilla surgery. Although the sentinel lymph node biopsy is time consuming and expensive, it is still the intra-operative exam with the highest performance, but sometimes surgery is achieved without a clear diagnosis and also with possible serious complications. In this work, we developed a machine learning model to predict the sentinel lymph nodes positivity in clinically negative patients. Breast cancer clinical and immunohistochemical features of 907 patients characterized by a clinically negative lymph node status were collected. We trained different machine learning algorithms on the retrospective collected data and selected an optimal subset of features through a sequential forward procedure. We found comparable performances for different classification algorithms: on a hold-out training set, the logistics regression classifier with seven features, i.e., tumor diameter, age, histologic type, grading, multiplicity, in situ component and Her2-neu status reached an AUC value of 71.5% and showed a better trade-off between sensitivity and specificity (69.4 and 66.9%, respectively) compared to other two classifiers. On the hold-out test set, the performance dropped by five percentage points in terms of accuracy. Overall, the histological characteristics alone did not allow us to develop a support tool suitable for actual clinical application, but it showed the maximum informative power contained in the same for the resolution of the clinical problem. The proposed study represents a starting point for future development of predictive models to obtain the probability for lymph node metastases by using histopathological features combined with other features of a different nature.

435 Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials Comparing Standard Versus Extended Lymphadenectomy Pancreatoduodenectomy For Adenocarcinoma of The Head of Pancreas

Abstract Aim To compare baseline demographics, operative, and survival outcomes of randomized controlled trials (RCTs) comparing standard versus extended lymphadenectomy in patients undergoing pancreaticoduodenectomy for pancreatic head cancer Method we performed a meta-analysis of baseline demographics, operative, and survival outcomes of RCTs comparing standard versus extended lymphadenectomy in patients undergoing pancreaticoduodenectomy for pancreatic head cancer. The uncertainties associated with varying follow-up periods among the included studies were resolved by analysis of time-to-event outcomes. Moreover, we performed trial sequential analysis (TSA) to determine whether the available evidence is conclusive and to assess the risk of type 1 or type 2 errors. Results Overall, 724 patients from 5 RCTs were included. There was no difference between standard and extended lymphadenectomy in terms of pancreatic fistula (OR0.64, P = 0.11), delayed gastric emptying (OR 0.68, P = 0.40), bile leak (OR 0.33, P = 0.06), wound infection (OR 0.53, P = 0.06), abscess (OR 0.83, P = 0.63), total complications (OR 0.73, P = 0.27), postoperative mortality (OR 1.01, P = 0.85), and overall survival (HR 1.10, P = 0.46). TSA suggested that meta-analysis was conclusive with low risk of type 2 error. Conclusions Robust evidence from randomized controlled trials (Level 1) suggests no difference in postoperative and survival outcomes between standard and extended lymphadenectomy in patients undergoing pancreaticoduodenectomy for pancreatic head cancer. The findings were consistent in patients with positive and negative lymph node status and in studies from the West or East.

Localized Angiosarcoma, Not One Disease: A Retrospective Single-Center Study on Prognosis Depending on the Primary Site and Etiology.

Background Angiosarcomas are rare and heterogeneous tumors with poor prognosis. The clinical subtypes are classified depending on the primary site and etiology. Methods We conducted a retrospective, monocentric study of 136 patients with localized AS between May 1985 and November 2018. Overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were estimated using the Kaplan–Meier method. To identify prognostic factors, univariate and multivariate analyses were performed based on Cox regressions. Results The median age was 67 years (19–72.8 years). Primary sites were cutaneous (27.2%), breast (38.2%), and deep soft tissue (34.6%). The majority was primary angiosarcomas (55.9%) followed by postradiation (40.4%) and chronic lymphedema angiosarcomas (2.9%). Prognosis significantly differed depending on the primary site and etiology. Shortest median OS and MFS were observed in deep soft tissue angiosarcomas, whereas cutaneous angiosarcomas, angiosarcomas of the breast, and radiation-associated angiosarcomas displayed worse median LRFS. Univariate analyses showed better OS for tumor size <10 cm (p = 0.009), negative surgical margins (p = 0.021), and negative lymph node status (p = 0.007). LRFS and MFS were longer for tumor size <10 cm (p = 0.012 and p = 0.013). In multivariate analyses, age <70 years was the only independent positive prognostic factor for OS in all subgroups. For LRFS, secondary AS of the breast was a negative prognostic factor (HR: 2.35; p = 0.035). Conclusions Different behaviors and prognoses depending on the primary site and etiology should be considered for the treatment of this heterogeneous disease. In cutaneous angiosarcomas of the head/neck and postradiation angiosarcomas of the breast, local recurrence seems to have a crucial impact on OS. Therefore, improved local therapies and local tumor staging may have to be implemented. However, in deep soft tissue angiosarcomas, distant recurrence seems to have a major influence on prognosis, which indicates a benefit of additional perioperative chemotherapy.

Ultrasound Measurement of Tumor-Free Distance from the Serosal Surface as the Alternative to Measuring the Depth of Myometrial Invasion in Predicting Lymph Node Metastases in Endometrial Cancer.

Background: Ultrasonography’s usefulness in endometrial cancer (EC) diagnosis consists in its roles in staging and prediction of metastasis. Ultrasound-measured tumor-free distance from the tumor to the uterine serosa (uTFD) is a promising marker for these diagnostic and prognostic variables. The aim of the study was to determine the usefulness of this biomarker in locoregional staging, and thus in the prediction of lymph node metastasis (LNM). Methods: We conducted a single-institutional, prospective study on 116 consecutive patients with EC who underwent 2D transvaginal ultrasound examination. The uTFD marker was compared with the depth of ultrasound-measured myometrial invasion (uMI). Univariable and multivariable logit models were evaluated to assess the predictive power of the uTFD and uMI in regard to LNM. The reference standard was a final histopathology result. Survival was assessed by the Kaplan–Meier method. Results: LNM was found in 17% of the patients (20/116). In the univariable analysis, uMI and uTFD were significant predictors of LNM. The accuracy was 70.7%, and the NPV was 92.68% (OR 4.746, 95% CI 1.710–13.174) for uMI (p = 0.002), and they were 63.8% and 89.02% (OR 0.842, 95% CI 0.736–0.963), respectively, for uTFD (p = 0.01). The cutoff value for uTFD in the prediction of LNM was 5.2 mm. The association between absence of LNM and biomarker values of uMI < 1/2 and uTFD ≥ 5.2 mm was greater than that between the presence of metastases and uMI > 1/2 and uTFD values <5.2 mm. In the multivariable analysis, the accuracy of the uMI–uTFD model was 74%, and its NPV was 90.24% (p = non-significant). Neither uMI nor uTFD were surrogates for overall and recurrence-free survivals in endometrial cancer. Conclusions: Both uMI and uTFD, either alone or in combination, were valuable tools for gaining additional preoperative information on expected lymph node status. Negative lymph nodes status was better described by ultrasound biomarkers than a positive status. It was easier to use the uTFD rather than the uMI measurement as a biomarker of EC invasion, and the former still maintained a similar predictive value for lymph node metastases to the latter at diagnosis.

Sentinel lymph node mapping in breast cancer patients following neoadjuvant chemotherapy: systematic review and meta-analysis about head to head comparison of cN0 and cN + patients.

The effectiveness of sentinel lymph node (SLN) mapping and biopsy following neoadjuvant chemotherapy (NAC) in axillary lymph node staging of breast cancer (BCa) patients with initial clinical node positive status (cN +) compared to clinical node negative status (cN0) is not yet known. The aim of this meta-analysis was to compare the accuracy of SLN mapping following NAC in cN + and cN0 BCa patients. PubMed and Scopus were comprehensively reviewed to retrieve all the studies that performed SLN mapping/biopsy and standard axillary lymph node dissection on cN0 and cN + BCa patients following NAC. Pooled detection and false negative rates for N0 and N + patients including 95% confidence interval values (95% CI) were evaluated. Odds ratio (OR) and risk difference (RD) of SLN detection failure and false negative results were compared between two groups. A total of 27 articles were included for SLN detection rate evaluation and 17 for false negative assessment. The OR and RD of detection failure in N + group compared with N0 group following NAC were 2.22 (p = 0.00, 95% CI 1.4-3.4) and 4% (p = 0.00, 95% CI 2-6%), respectively. The OR and RD of false negative rate were 1.6 (p = 0.01, 95% CI 1-2.6) and 8% (p = 0.02, 95% CI 1-14%), respectively. SLN mapping in BCa patients following NAC shows high risk of detection failure and high false negative rate of SLN biopsy in cN + patients. In comparison with cN0 BCa patients, SLN mapping and biopsy after NAC was associated with almost two times higher odds of detection failure and false negative results in cN + patients; therefore, this method should not be recommended in this group of patients.

En bloc right hemicolectomy with pancreatoduodenectomy for right-sided colon cancer invading duodenum

BackgroundEn bloc right hemicolectomy with pancreatoduodenectomy (RHCPD) is the optimum treatment to achieve the adequate margin of resection (R0) for locally advanced right-sided colon cancer with duodenal invasion. Information regarding the indications and outcomes of this procedure is limited.MethodIn this retrospective study, 2269 patients with right colon cancer underwent radical right colectomy between October 2010 and May 2019, in which 19 patients underwent RHCPD for LARCC were identified. The overall survival (OS), disease-free survival (DFS), operative mortality, postsurgical complications, gene mutational analysis, and prognostic factors were evaluated. Survival was estimated using Kaplan–Meir method.ResultsOf these 19 patients who underwent LARCC, the OS was 88%, 66%, and 58% at 1, 3, and 5 years. The DFS was 72%, 56%, and 56% at 1, 3, and 5 years. The median operative time was 320 min (range: 222–410 min), and the median operative blood loss was 268 mL (range: 100–600 mL). The OS was significantly better among patients with well-differentiated tumor, N0 stage, and high microsatellite instability (MSI) and in patients who received adjuvant chemotherapy. The major postoperative complications occurred in 8 patients (42%), with pancreatic fistula (PF) being the most common. On the basis of the univariate analysis, poorly differentiated tumor, regional lymph node dissemination, MSI status, and no perioperative chemotherapy were the significant predictors of poor survival (P < 0.05).ConclusionsThis study suggests that RHCPD is feasible and can achieve complete tumor clearance with favorable outcome, particularly in patients with lymph node-negative status.

The Clinical Relevance of Target Lymph Node Biopsy after Primary Systemic Therapy in Initially Node-Positive Breast Cancer Patients.

Simple SummaryCurrently, the optimal axillary surgical approach for breast cancer patients with initial node-positive disease and conversion to clinically node-negative status after primary systemic therapy is unclear. The aim of our study was to evaluate the clinical impact of removing the initially most suspicious, labeled axillary lymph node in addition to the sentinel lymph node. Metastatic target lymph nodes were found in five out of 63 patients (7.9%), while the sentinel lymph node was either tumor-free or not detected. The removal of the target lymph node influenced the adjuvant systemic therapy in only one case (1.6%). However, complete axillary dissection was indicated in all five cases. Furthermore, with fewer than three sentinel lymph nodes removed, the target lymph node reduced the false-negative rate to less than 10%. We therefore conclude that although the target lymph node has a minor impact on adjuvant systemic therapy, it is relevant for surgical axillary management.Purpose: To assess the impact of the removal of the target lymph node (TLN) on therapy after the completion of primary systemic therapy (PST) in initially node-positive breast cancer patients. Methods: Pooled data analysis of participants of the prospective CLIP- and TATTOO-study at the University of Rostock was performed. Results: A total of 75 patients were included; 63 of them (84.0%) converted to clinically node-negative after PST. Both TLN and sentinel lymph node (SLN) were identified in 41 patients (51.2%). In five out of 63 patients (7.9%), the TLN was metastatic after PST and the SLN was either tumor-free or not detected. Axillary lymph node dissection (ALND) was conducted in all five patients. In one patient, systemic therapy recommendation was influenced by the TLN; adjuvant radiotherapy was influenced by the TLN in zero patients. For patients with fewer than three removed SLNs, the FNR was 28.6% for the SLN biopsy alone and 7.1% for targeted axillary dissection (TAD). Conclusions: Removal of the TLN in addition to the SLN after PST has only minimal impact on the type of adjuvant systemic therapy and radiotherapy. However, the extent of axillary surgery was relevantly affected and FNR was improved by TAD.

Assessment of axillary node status by ultrasound after neoadjuvant chemotherapy in patients with clinically node-positive breast cancer according to breast cancer subtype

The use of sentinel node biopsy (SNB) following neoadjuvant chemotherapy (NAC) for patients with cN1 breast cancer is controversial. Improvements of negative predictive value (NPV) by axillary ultrasound (AUS), which corresponds to the accurate prediction rate of node-negative status after NAC, would lead to decreased FNR of SNB following NAC. In this study, we retrospectively investigated the accurate prediction rate of NPV by AUS after NAC in patients with cytologically node-positive breast cancer treated between January 2012 and December 2016. Of 279 eligible patients, the NPV was 49.2% in all patients, but varied significantly by tumor subtype (p < 0.001) and tumor response determined by magnetic resonance imaging (MRI) (p = 0.0003). Of the 23 patients with clinically node negative (ycN0) by AUS and clinical complete response in primary lesion by MRI, the NPV was 100% in patients with HR±/HER2+ or HR−/HER2− breast cancer. In conclusion, regarding FNR reduction post-NAC, it will be of clinical value to take tumor subtype and primary tumor response using MRI into account to identify patients for SNB after NAC.

A multiparameter model for prediction of pathological nodal status in clinically early stage oral cancer using machine learning.

e18025 Background: The current approach to neck treatment in clinical T1-2 oral cancers is to offer elective nodal dissection to all patients, despite the fact that the majority of patients are pathologically node negative. This is due to the poor predictive ability of clinico-radiological assessment and subsequently poorer survival in those in whom neck dissection is omitted based on this. A robust prediction model for pathological nodal status may allow individualized decisions for neck dissection. Our aim was to develop a multiparameter prediction model to identify pathological node-negative status using machine learning. Methods: We identified 497 patients with cT1-2 oral cancer from a single institutional database from 2011-2018 who underwent primary resection and neck dissection. We compared the sensitivity, positive predictive value and accuracy of prediction of pathologically negative neck from clinico-radiological staging alone vs. a model created from multiple parameters including clinical features (clinico-radiological nodal status, ages, sex, subsite of primary lesion) and pathological features of the resected primary tumor (maximum dimension, depth of invasion, lymphovascular invasion, perineural invasion, grade and margins of resection). The multiparameter model was built from a training dataset of the first 400 patients using an ensemble of logistic regression, random forests and support vector machines. A cohort of 97 patients was used for independent validation. Results: In this cohort 232 (47%) were clinico-radiologically node negative, while 307(62%) were pathologically node negative. The sensitivity, positive predictive value and accuracy of the clinico-radiologically assigned nodal status was 56%, 74% and 61%, while that of the multiparameter machine learning model was 87%, 89% and 89% respectively. The area under curve (AUC) of the clinico-radiological prediction was 0.62 whereas that of the multiparameter predictive model was 0.91. In the validation dataset, 58/62 pathologically node negative patients were predicted correctly by the model. The accuracy of the model on the external validation dataset was 82%. Conclusions: The performance of the multiparameter predictive model was considerably superior to clinico-radiological neck staging for prediction of pathological node negative neck. This could be validated on an independent dataset. This could be considered for prospective clinical evaluation of individualized neck dissection.

Is pre-operative axillary ultrasound alone sufficient to determine need for axillary dissection in early breast cancer patients?

Pre-operative status of axillary lymph node (ALN) in early breast cancer is usually initially assessed by pre-operative ultrasound, followed by ultrasound-guided needle biopsy (UNB) confirmation. Patients with positive nodal status will undergo axillary lymph node dissection (ALND), while those with negative nodal status will have sentinel lymph node biopsy. ALND is associated with higher morbidity than Sentinel lymph node biopsy. The objective of this study is to determine if axillary ultrasound alone without UNB is predictive enough to assign patients to ALND and to identify ultrasound features that are significantly associated with pathologically positive ALN.383 newly diagnosed primary breast cancer patients between 2012 and 2014, and who had undergone pre-operative axillary ultrasound in University Malaya Medical Centre with a complete histopathology report of the axillary surgery were retrospectively reviewed. ALN was considered positive if it had any of these features: cortical thickening > 3 mm, loss of fatty hilum, hypoechoic solid node, mass-like appearance, round shape and lymph node size > 5 mm. Post-operative histopathological reports were then analyzed for nodal involvement.The overall sensitivity, specificity, and accuracy of pre-operative axillary ultrasound in detecting diseased nodes were 45.5%, 80.7%, and 60.3% respectively. The positive (PPV) and negative predictive values were 76.5% and 51.8%. Round shape, loss of fatty hilum and mass-like appearance had the highest PPVs of 87%, 83% and 81.6% respectively and significant odds ratios (ORs) of 5.22 (95% confidence interval [CI]: 1.52 - 17.86), ORs of 4.77 (95% CI: 2.62 - 8.70) and ORs of 4.26 (95% CI: 2.37 - 7.67) respectively (P-value < .05). Cortical thickness of > 3 mm was identified to have low PPV at 69.1%, ORs of 1.71 (95% CI: 0.86 - 3.41, P = .126).There are features on axillary ultrasound that confer high PPV for axillary involvement i.e. round shape, loss of fatty hilum, and mass-like appearance. In a low resource setting, these features may benefit from ALND without further pre-operative biopsies. However, pre-operative UNB for features with low PPV that is, cortical thickness > 3 mm should be considered to obviate the unnecessary morbidity associated with ALND.

Cytoplasmic DDX3 as prognosticator in male breast cancer

Male breast cancer (MBC) is a rare disease. Due to its rarity, treatment is still directed by data mainly extrapolated from female breast cancer (FBC) treatment, despite the fact that it has recently become clear that MBC has its own molecular characteristics. DDX3 is a RNA helicase with tumor suppressor and oncogenic potential that was described as a prognosticator in FBC and can be targeted by small molecule inhibitors of DDX3. The aim of this study was to evaluate if DDX3 is a useful prognosticator for MBC patients. Nuclear as well as cytoplasmic DDX3 expression was studied by immunohistochemistry in a Dutch retrospective cohort of 106 MBC patients. Differences in 10-year survival by DDX3 expression were analyzed using log-rank test. The association between clinicopathologic variables, DDX3 expression, and survival was tested in uni- and multivariate Cox-regression analysis. High cytoplasmic DDX3 was associated with high androgen receptor (AR) expression while low nuclear DDX3 was associated with negative lymph node status. Nuclear and cytoplasmic DDX3 were not associated with each other. In a univariate analysis, high cytoplasmic DDX3 (p = 0.045) was significantly associated with better 10-year overall survival. In multivariate analyses, cytoplasmic DDX3 had independent prognostic value (p = 0.017). In conclusion, cytoplasmic DDX3 expression seems to be a useful prognosticator in MBC, as high cytoplasmic DDX3 indicated better 10-year survival.

Carbon nanoparticle-guided intraoperative lymph node biopsy predicts the status of lymph nodes posterior to right recurrent laryngeal nerve in cN0 papillary thyroid carcinoma.

The lymph nodes in the right central compartment can be divided into 2 parts by the right recurrent laryngeal nerve (RLN), and there is a lack of an accurate and convenient method for assessing metastases in the lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) in cN0 thyroid papillary carcinoma patients. Patients diagnosed with cN0 thyroid papillary carcinoma and underwent intraoperative carbon nanoparticle-guided lymph node biopsy from January 2017 to November 2020 at the Center for Thyroid and Breast Surgery of Xuanwu Hospital were retrospectively analyzed. The intraoperative frozen section examination and postoperative LN-prRLN status should have been comprehensively recorded. The participants were divided into the LN-prRLN positive group and LN-prRLN negative group according to their recorded LN-prRLN status. In total, 189 cases (LN-prRLN positive group, n=30; LN-prRLN negative group, n=159) were included in the analysis. The univariate and multivariate regression analyses revealed that the number of metastatic lymph nodes during intraoperative lymph node biopsy was the potential predictor for LN-prRLN metastasis [odds ratio (OR): 1.320, 95% confidence interval (CI): 1.057 to 1.649, P=0.014]. The receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) reached 0.7 upon a combined analysis of multiple lymph node statuses located at pre-laryngeal (Delphian), pre-tracheal, and para-tracheal lymph nodes ipsilateral to the tumor in predicting the metastasis of LN-prRLN, and the cut-off value was 0.5. Number of metastatic lymph nodes in intraoperative biopsy was an indicator of LN-prRLN metastasis in cN0 thyroid carcinoma patients. Patients staging in cN0 with negative intraoperative lymph node status might be considered not to require LN-prRLN dissection during central lymph nodes dissection.

Targeted Axillary Dissection in Node-Positive Breast Cancer: A Retrospective Study and Cost Analysis.

IntroductionTargeted axillary dissection (TAD) is a novel technique in the field of surgical oncology. During TAD, patients with node-positive breast cancer who clinically responded to neoadjuvant chemotherapy undergo resection of a previously proven metastatic node together with sentinel lymph node dissection (SLND). We aimed to assess the success rates of seed insertion and seed retrieval in the Canadian setting, as well as hospital costs of the procedure.MethodsPatients converted to clinically node-negative status post-neoadjuvant chemotherapy underwent TAD. Before surgery, an iodine-125 radioactive seed was inserted in the previously proven metastatic node. The seed node was resected together with an SLND. Axillary lymph node dissection (ALND) was performed in all patients with residual metastases.ResultsRadioactive seeds were successfully inserted in 34/35 patients. In 34 patients, the targeted node was successfully resected with the radioactive probe during TAD. In one patient, the seed was retrieved inferiorly in the axilla during surgery. There was no adverse event. In total, 50% (17/34) of patients had no residual metastases and were able to avoid ALND. Eight out of 17 patients who underwent ALND did not have any residual disease in their specimen. The mean cost of TAD was 25% superior to the mean cost of ALND (p = 0.02). However, the mean total cost of the hospital stay for TAD was 20% superior to the mean cost of ALND (p = 0.11). The mean cost of TAD was 4,322 Can$ (Canadian dollars), similar to the mean cost of both ALND and SLND performed during the same procedure (4,479 Can$).ConclusionsTAD was successful in 97% of patients. Despite increased procedural costs, with a lesser impact on total hospital stay costs, TAD was beneficial in 50% of patients. These patients avoided the unnecessary morbidity associated with ALND.

Strong impact of pathological node-negative on long-term overall survival of patients with triple-negative breast cancer receiving neoadjuvant chemotherapy.

Triple-negative breast cancer (TNBC) has a high pathological complete response (pCR) rate; however patients without a high pCR are reported to have a poor prognosis. The current study investigated the long-term overall survival of patients with TNBC who received neoadjuvant chemotherapy (NAC) and analyzed various prognostic factors including basal marker and claudin expressions. Between November 2005 and March 2012, the current study retrospectively reviewed the records of 323 patients with breast cancer who received anthracycline followed by taxane as NAC at the Jikei University Hospital Basal marker and claudin expression was determined via immunohistochemistry. The median age of the patients was 53.0 years. Of the 323 patients, 26 (8%) achieved a pCR, including 13 patients (19.7%) with TNBC and 13 (5.1%) with non-TNBC (P<0.001). Of the 66 patients with TNBC, 13 (19.7%) demonstrated recurrence and 8 (12.1%) died after a median follow-up time of 111.5 months [10-year disease-free survival (DFS), 80.3%; 95% confidence interval (CI), 0.68-0.88; 10-year overall survival (OS), 84.8%; 95% CI, 0.72-0.92]. Of the 257 patients with non-TNBC, 45 (17.5%) patients demonstrated recurrence and 26 (10.1%) died (10-year DFS, 82.1%; 95% CI, 0.76-0.87; 10-year OS, 88.6%; 95% CI, 0.83-0.92). There was no statistical difference between the patients with and without TNBC. In the TNBC group, patients with pathological node-negative status survived without distant recurrence. Additionally, negative lymphovascular infiltration was another favorable prognostic factor. Patients with TNBC who received NAC demonstrated comparably high prognoses to non-TNBC patients. Overall, pathological node status after NAC had a strong impact on the prognosis of patients with TNBC.