Node Micrometastases Research Articles

Occurrence of No.12 lymph node micrometastasis in gastric cancer and its effect on clinicopathological parameters and prognosis*

Abstract Objective This study aimed to investigate the occurrence of No.12 lymph node micrometastasis in patients with gastric cancer and its relationship with clinicopathological parameters and prognosis. Methods A cohort of 160 gastric cancer patients who underwent gastrectomy and lymph node dissection were selected as the research subjects. The immunohistochemical method was used to detect the micrometastasis of No.12 lymph node sections with negative routine pathological detection. At the same time, the clinical data of patients were collected and followed up to analyze the clinical significance of No.12 lymph node micrometastasis. Results A total of 370 No.12 lymph nodes were detected in 160 surgical specimens. Among 160 patients, 27 patients were found to be positive for No.12 lymph nodes during routine pathological examination, with a positive rate of 16.8%. A total of 308 lymph nodes from 133 patients with negative routine pathological examinations were stained by immunohistochemistry. A total of 17 lymph nodes from 10 patients were found to be positive. The results showed that 37 of the 160 patients had No.12 lymph node metastasis, and the positive rate was 23.1%, which was 6.3% higher than that of routine pathological examination. Logistic multivariate analyses showed that the depth of invasion, lymph node metastasis in other groups, and clinical stage were independent risk factors for No.12 lymph node metastasis. The average follow-up time was 79.3 months, and the overall median survival time was 47.9 months. The survival time of the No.12 lymph node-negative group was 67.3 ± 2.5 Â months, the median survival time was 73.2 months; the survival time of the No.12 lymph node-positive group was (28.4 ± 5.4) months, and the median survival time was 31.3 months. The survival time of the No.12 lymph node-negative group was significantly longer than that of the positive group (χ2 = 12.75, P = 0.000). Conclusion No.12 lymph node micrometastasis is a signal affecting the prognosis of patients with gastric cancer. Standardized dissection of No.12 lymph nodes is recommended for patients with gastric cancer who can undergo radical resection.

Micrometastasis in lymph nodes of colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Postoperative adjuvant chemotherapy is recommended for node‐positive stage III patients. A systematic meta‐analysis reported that the presence of micrometastases in regional lymph nodes (LNs) was associated with poor survival in patients with node‐negative CRC. Because most data employed in the meta‐analysis were based on retrospective studies, we conducted a prospective clinical trial and concluded that stage II is a transitional zone between stage I and stage III, where CRC tumors continuously increase the micrometastasis volume in LNs and proportionally raise the risk for tumor recurrence. The one‐step nucleic acid amplification (OSNA) assay is a simple and rapid technique to detect CK19 mRNA using the reverse‐transcription loop‐mediated isothermal amplification (RT‐LAMP) method. Using the OSNA assay, we and colleagues reported that the upstaging rates of pStages I, IIA, IIB, and IIC were 2.0%, 17.7%, 12.5%, and 25%, respectively, in 124 node‐negative patients. Survival analysis indicated that OSNA positive stage II CRC patients had a shorter 3‐y disease‐free survival rate than OSNA negative stage II CRC patients. In 2017, AJCC TNM staging (the 8th version) revised the definition of LN metastasis in colon cancer and it is stated that micrometastasis should be considered as a standard LN metastasis. To our surprise, this revision was based on a meta‐analysis to which our previous study on micrometastasis largely contributed. The remaining questions to be addressed are how to find micrometastases efficiently and whether postadjuvant chemotherapy is effective to prevent disease recurrence and to contribute to longer survival.

History and Updates of the GROINSS-V Studies.

Simple SummarySurgical management of vulvar cancer is associated with high morbidity rates. The main aim of the GROINSS-V studies is reducing treatment-related morbidity by finding safe alternative treatment options in patients with early-stage vulvar cancer. This article reviews the history, results, and updates of the GROINSS-V studies.Surgical management of vulvar cancer is associated with high morbidity rates. The main aim of the GROINSS-V studies is reducing treatment-related morbidity by finding safe alternative treatment options in early-stage vulvar cancer patients. This article reviews the history, results, and updates of the GROINSS-V studies. The first GROINSS-V study was a multicenter observational study (from 2000 to 2006), which investigated the safety and clinical applicability of the sentinel lymph node procedure in patients with early-stage vulvar cancer. GROINSS-V-I showed that omitting inguinofemoral lymphadenectomy was safe in early-stage vulvar cancer patients with a negative sentinel lymph node, with an impressive reduction in treatment-related morbidity. GROINSS-V-II, a prospective multicenter phase II single-arm treatment trial (from 2005 to 2016) investigated whether radiotherapy could be a safe alternative for inguinofemoral lymphadenectomy in patients with a metastatic sentinel lymph node. This study showed that radiotherapy in patients with sentinel lymph node micrometastases (≤2 mm) was safe in terms of groin recurrence rate and with less treatment-related morbidity. These results, published in August 2021, should be implemented in (inter)national treatment guidelines for vulvar cancer. GROINSS-V-III recently started including patients. This study investigates the effectiveness and safety of chemoradiation in patients with a macrometastasis (>2 mm) in the sentinel lymph node.

Lymph Node Dissection During Radical Nephro-Ureterectomy for Upper Tract Urothelial Carcinoma: A Review.

Although lymphonodal dissection is well-accepted for muscle-invasive bladder cancer management, its role is still debated during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). The aim of this study was to summarize the current knowledge concerning the indication, anatomical template, prognostic, and therapeutic roles of lymph node dissection (LND) performed at the time of RNU. Quality control markers, such as the number of lymph nodes (LN) removed, lymph node density, and safety of the different surgical approaches, were assessed. We performed a narrative review using the PubMed and ClinicalTrials.gov databases. We identified and analyzed articles based on the practice and the role of lymph node dissection for non-metastatic UTUC. There are no clear guidelines regarding the indication of LND for UTUC, but aggressive tumors may beneficiate from lymphadenectomy since lymph node invasion is a clear independent poor prognostic factor, allowing for adjuvant treatments. It seems that an extended lymphadenectomy may provide therapeutic advantages as a higher number of nodes removed may be related to the removal of undetected LNs micrometastases and a subsequent improvement in recurrence rate and cancer-specific survival. Clear anatomical templates are thus needed based on the location and the laterality of the primary tumor.

Abstract P1-06-01: Insights from rapid autopsy shed light on mechanisms of cancer dissemination in metastatic breast cancer

Abstract Previously we presented our initial findings from a 9-patient rapid autopsy pilot for metastatic breast cancer (MBC). At the time of procurement, one third of subjects exhibited clinically unidentified diseased sites in organs not commonly associated with breast cancer metastases, including ovary, kidney, and pancreas. In two other instances, “resolved” bone specimens (as measured by absence of FTG uptake in PET/CT imaging) were later determined to be >30% tumor positive when assessed by a pathologist. We now expand upon these findings in a more in-depth exploration of the presence of micro-metastases in presumed tumor-negative tissues. A subset of tumor-free tissues were selected from each patient (average of 10 specimens per patient). All selected specimens were negative by clinical imaging, appeared grossly normal at procurement, and were reported to be tumor negative by H&E assessment by a clinical pathologist. We included organs both commonly and uncommonly involved in MBC, including lung, bone, spleen, pancreas, kidney, and non-tumor draining lymph nodes. Tissues were stained for one or more of the markers, pan-cytokeratin, GATA-3, HMFG, MUC1, and ER (if patient was previously ER+), depending on tissue type. Of the 87 total specimens assessed, we identified micro-metastases in 13 specimens from 4 individual patients. Across these 4 patients, micro-metastases were found in lung, bone, pancreas, spleen, and several non-tumor draining lymph nodes. While lung and bone are commonly involved in MBC and these results are not entirely surprising, pancreas and spleen involvement is extraordinarily rare. Further surprising was the identification of micro-metastases in several lymph nodes that were not located anatomically downstream from a disease-involved organ. Image patterns demonstrate tumor cell infiltration into the lymph node within the subcapsular sinus. Presence of micro-metastases in tumor-negative tissue did not correlate with tumor hormone status or cancer type (e.g. lobular vs DCIS). Combined with our previous findings, we now report unexpected and clinically undiagnosed disease involvement in 6/9, or two-thirds, of our patients. Based on these findings, we hypothesize that cancer stem cells and/or micro-metastases are present throughout the body, in all tissue types, and that their ability to grow into tumors is regulated by the local immune microenvironment. Lastly, the differing roles and mechanics of lymphatic vs hematological spread in metastatic disease has long been discussed. Our findings provide strong evidence for cancer dissemination through the lymphatics system. Further study is necessary to better understand the timing of metastatic spread, whether systemic dissemination occurs early or later in disease, and if conducive metastatic or pre-metastatic niches are already present throughout the body at the time of primary diagnosis or if these permissive environments develop slowly overtime. Citation Format: Eliza R. Bacon, Kena Ihle, Colt Egelston, Weihua Guo, Diana Simons, Dan Schmolze, Christina Wei, Lusine Tumyan, Peter P Lee, James R. Waisman. Insights from rapid autopsy shed light on mechanisms of cancer dissemination in metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-06-01.

Specific diagnosis of lymph node micrometastasis in breast cancer by targeting activatable near-infrared fluorescence imaging

Axillary lymph node metastasis has always been defined as the most important prognostic factor in the treatment of early breast cancer. Ultrasound and MRI can detect only 10% of lymph node micrometastases in early breast cancer. Therefore, it is crucial to detect early breast cancer with lymph node metastasis, however, there is no current examination method for accurate diagnosis. When breast cancer presents a malignant tendency, colony stimulating factor-1 and chemokine CCL-2 absorb mononuclear cells from the surrounding environment and differentiate into M2 Tumor associated macrophages (TAM), which increase the invasion of tumor cells and further promote the development of tumors. Mannose, as a simple natural ligand, can selectively bind to TAM surface CD206 (macrophage mannose receptor, MMR). In this study, mannose was connected with near infrared dye (NIR) IR780 via disulfide bond to obtain Mannose-IR780 conjugate (MR780), which was further self-assembled into near infrared nanoprobe (MR780 NPs) with quenched fluorescence. When selectively targeting CD206 highly expressed on the surface of TAM, disulfide bond was cleaved by the glutathione enriched in the microenvironment, resulting in fluorescence recovery, thus achieving NIR fluorescence molecular imaging of TAM and diagnosis of tumor lymph node metastasis in mouse models. Our findings suggest that targeted imaging of TAM enable noninvasive and sensitive detection of metastatic lymph nodes in vivo, which is instructive for tumor therapy.

Impact of Lymph Node Micrometastases and Isolated Tumour Cells in Canine Mammary Cancer Prognosis

Impact of Lymph Node Micrometastases and Isolated Tumour Cells in Canine Mammary Cancer Prognosis

Retrospective analysis of para-aortic lymph node recurrence in locally advanced cervix cancers treated with “pelvic-only field” radiotherapy

INTRODUCTION: Previous studies suggested that treating para-aortic lymph node micro-metastases with extended-field radiotherapy could result in higher rate of tumor control in high-risk locally advanced cervical cancers. Our study aimed to assess the patterns of recurrences following pelvic-only irradiation, with an emphasis on recurrence in para-aortic lymph node. MATERIALS AND METHODS: We retrospectively evaluated patterns of recurrences in patients with cervical cancers who were treated with definitive pelvic radiotherapy at our institution from 2013 to 2016. Univariate and multivariate analyses were performed to identify risk factors associated with para-aortic lymph node recurrence. RESULTS: We enrolled 463 patients in the study. The median of follow-up was 63.5 months. Five-years overall survival, recurrence-free survival, and para-aortic lymph node recurrence rates were respectively 78.9%, 76.2% and 6.5%. During follow-up, 23.33% experienced recurrences. Most often tumors recurred locally (42.60%). Para-aortic recurrences were found in 26 patients. Patients’ age (≤57 years) (HR=4.9, p=0.002), histological subtype (adenocarcinoma) (HR=2.7, p=0.035), presence of pelvic lymph node metastasis (HR=0.3, p=0.037) and absence of brachytherapy (HR=6.5, p<0.0001) were significantly associated with para-aortic lymph node (PALN) recurrence in multivariate analysis. CONCLUSION: Recurrences following pelvic-only irradiation were frequently observed in the pelvis. Clinical characteristics associated with a high risk of PALN recurrence were young age, absence of brachytherapy, presence of pelvic lymph node metastases, and the adenocarcinoma subtype. However, further studies with a greater number of patients need to be undertaken.

Lymph node micrometastasis of poorly differentiated node-negative gastric cancer risks a worse-than-expected survival outcome under standard management algorithm

BackgroundInvestigation of lymph node micrometastasis (mN) of gastric cancer has been focused on either T1 disease or T1-4N0 disease. Yet, it is unclear whether standard management algorithm toward poorly differentiated gastric cancer (PDGC) is more vulnerable to existence of mN, given its inherently biological aggressiveness, as compared with other histological types. Patients and methodsA surgical series (n = 3456) of gastric cancer categorized by histological differentiation was enrolled to analyze survival stratification. Of them, a cohort of T1-T4 N0 PDGC (n = 100) were subjected to cytokeratin immunohistochemistry, a surrogate of mN. ResultsCancer-specific survival by AJCC8 staging system could be nicely differentiated in both well-/moderately differentiated and signet ring cell types, while those between stage IA versus IB (p = 0.105), and stage IB versus IIA (p = 0.141) in PDGC could not. Thirteen (13%) out of 100 node-negative PDGC cases exhibited mN, with 5, 2, 5 and 1 cases occurring in T1, T2, T3, and T4 stage, respectively, without identifiable contributing factors. Prognostic performance of AJCC8 working upon PDGC became more discriminative by incorporating mN, as hazard ratio of stage IIIC referenced to stage IA increased from 43 to 78. ConclusionDefective discriminative survival of PDGC by standard staging algorithm prompted us to survey mN occurring in T1-T4N0 PDGC. The prognostic performance of AJCC8 working upon PDGC was enhanced by incorporating mN. As so, we recommend documentation of mN exclusively on node-negative PDGC that helps unveil stage migration phenomenon and switch to appropriate adjuvant therapy in need.

Impact of Post-Mastectomy Radiation Therapy for Sentinel Lymph Node Micrometastases in Early-Stage Breast Cancer Patients.

BackgroundThe association of radiotherapy with breast cancer survival in patients who underwent a mastectomy and had micrometastases in the sentinel lymph node is unclear.Material/MethodsThe survival benefit of radiotherapy was examined in patients with T0/1-T2N1mi breast cancer undergoing mastectomy plus sentinel lymph node biopsy (SLNB). Kaplan-Meier curves were employed for survival analysis and competing risk analysis, and a propensity score matching (PSM) cohort was enrolled to investigate whether such patients benefit from radiotherapy.ResultsWe identified 2864 patients in the SEER database from 2004 to 2015. All eligible patients were divided into the radiotherapy and the no-radiotherapy cohorts. With the median follow-up of 53 months, 5-year breast cancer-specific survival (BCSS) was 94.4% vs 95.2% (P=0.135), and 5-year overall survival (OS) was 91.2% vs 90.1% (P=0.466) in the radiotherapy cohorts and no-radiotherapy cohorts, respectively. The results of the competing risk analysis showed a comparable 5-year cumulative incidence of breast cancer-specific death (BCSD) in the radiotherapy and no-radiotherapy groups (5.5% vs 4.7%, P=0.107) but a higher 5-year cumulative incidence of other causes of death (OCD) in the no-radiotherapy cohort (3.3% vs 5.3%, P=0.011). No significant difference was observed for BCSS or OS in the PSM cohort.ConclusionsRadiotherapy has no benefit for patients with T0/1-T2 breast cancer undergoing mastectomy with N1mi disease on SLNB. This analysis provides evidence that radiotherapy may safely be omitted in this group of patients.

Identification of nodal micrometastasis in colorectal cancer using deep learning on annotation-free whole-slide images

Detection of nodal micrometastasis (tumor size: 0.2–2.0 mm) is challenging for pathologists due to the small size of metastatic foci. Since lymph nodes with micrometastasis are counted as positive nodes, detecting micrometastasis is crucial for accurate pathologic staging of colorectal cancer. Previously, deep learning algorithms developed with manually annotated images performed well in identifying micrometastasis of breast cancer in sentinel lymph nodes. However, the process of manual annotation is labor intensive and time consuming. Multiple instance learning was later used to identify metastatic breast cancer without manual annotation, but its performance appears worse in detecting micrometastasis. Here, we developed a deep learning model using whole-slide images of regional lymph nodes of colorectal cancer with only a slide-level label (either a positive or negative slide). The training, validation, and testing sets included 1963, 219, and 1000 slides, respectively. A supercomputer TAIWANIA 2 was used to train a deep learning model to identify metastasis. At slide level, our algorithm performed well in identifying both macrometastasis (tumor size > 2.0 mm) and micrometastasis with an area under the receiver operating characteristics curve (AUC) of 0.9993 and 0.9956, respectively. Since most of our slides had more than one lymph node, we then tested the performance of our algorithm on 538 single-lymph node images randomly cropped from the testing set. At single-lymph node level, our algorithm maintained good performance in identifying macrometastasis and micrometastasis with an AUC of 0.9944 and 0.9476, respectively. Visualization using class activation mapping confirmed that our model identified nodal metastasis based on areas of tumor cells. Our results demonstrate for the first time that micrometastasis could be detected by deep learning on whole-slide images without manual annotation.

305 RISK OF GENERALIZATON IN PATIENTS WITH HIGH-RISK EARLY ESOPHAGEAL CANCER: RETROSPECTIVE ANALYSIS OF PROSPECTIVELY COLLECTED DATA INCLUDING LYMPH-NODE MICROMETASTASES ASSESSMENT

Abstract Esophagectomy is a standard of care for patients with "high-risk" early esophageal cancer (HRC) despite a growing evidence that endoscopic treatment may be a safe alternative. Our aims were 1. to prospectively evaluate the long-term results of endoscopic and surgical treatments in consecutive patients with HRC and 2. to determine the risk of lymph node (LN) metastases and micrometastases in patients with HRC. Methods HRC was defined as any cancer with submucosal (sm) invasion or mucosal cancer with at least one of the following: poor differentiation, invasion to blood or lymphatic vessels and high tumor cell dissociation (TCD3). All patients (n = 69) underwent endoscopic resection (ER or ESD) and after the histopathological diagnosis of HRC, patients without contraindications were referred to surgery (n = 30). The remaining patients (n = 39) continued in endoscopic treatment, if necessary. All resected LNs were stained for hematoxylin–eosin to evaluate metastases and immunohistochemistry was used for the detection of micrometastases or isolated tumor cells. Results Eighteen patients (26%) had T1a and 51 (74%) had T1b cancer; 51 had adenocarcinoma (AC) and 18 had squamous cell carcinoma (SCC). The median follow-up was 32 months (3–120). No patient with mucosal invasion (15 AC, 3 SCC) experienced LN involvement. Among 17 patients with sm1 invasion, only 2 (12%, both AC)experienced generalization or LN involvement. The further rates of LN involvement were 0% (0/5) in sm2 AC, 50% (3/6) in sm2 SCC, 25% (4/16) in sm3 AC and 29% (2/7) in sm3 SCC. 60% (18/30) of surgically treated patients would have been completely cured by endoscopy (Table 1). Conclusion The risk of LN metastases/micrometastases was lower than expected. No patients with high-risk mucosal cancer or low-risk sm1 cancer experienced lymph node involvement. Endoscopic treatment provided long-term remission (or cure) in considerable number of patients and it may represent a valid alternative to surgery in patients with high-risk early esophageal cancer.

Assessment of Occult Nodal Micrometastases to the Clinically Negative Contralateral Neck in Locally Advanced Supraglottic Squamous Cell Carcinoma.

The aim of this study is to study the incidence of occult nodal micrometastases (ONM) in the contralateral neck and compare it to the laterality of the primary tumor. Retrospective analysis of the medical records of patients with locally advanced supraglottic squamous cell carcinoma andClinically negative contralateral neck (cN0-CLN) - who had concurrent total laryngectomy and bilateral neck dissection as their primary treatment at the Otolaryngology Department, Al Kas Al Ainy School of Medicine-Cairo University between 2015 and 2020- was conducted. Patients were divided into 3 groups according to the extent of the primary tumor. 28 patients met the inclusion criteria. Patients with well-lateralized tumors were 14 (Group A), tumors abutting the midline were 4 (Group B) and tumors significantly involving the contralateral side were 14 (Group C). There was no statistically significant difference in age of patients among the three groups. Eleven patients had cervical lymphadenopathy in the final pathology reports. Seven patients had ONM, all of whom were among group C patients (7/14; 50%). The degree of tumor differentiation was not associated with the presence of ONM. Treatment of the cN0-CLN is justified in locally advance supraglottic carcinoma significantly crossing the midline. The total number of patients with ONM in the cN0-CLN exceeds the threshold for observation, however the authors could not recommend or refute the practice of routine prophylactic treatment of the cN0-CLN as none of the patients-in this study-with well-lateralized tumors or tumors just abutting the midline showed ONM.

Outcomes of Stage I and II Breast Cancer with Nodal Micrometastases Treated with Mastectomy without Axillary Therapy.

Studies that report equivalent oncologic outcomes of sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) for T1-2N1mi breast cancers are heavily weighted with patients who received breast-conserving surgery (BCS). The impact of omitting ALND in N1mi patients treated with mastectomy is not well studied. It is also unknown if these patients would benefit from post-mastectomy radiotherapy (PMRT). This study reports the outcomes of patients with T1-2N1mi breast cancer treated by mastectomy without axillary therapy. Patients who had T1-2N1mi breast cancer and underwent mastectomy from January 1998 to December 2018 were identified from our multi-institutional prospective database. Axillary recurrence rate (ARR), disease-free survival (DFS), and overall survival (OS) are reported. 260 patients with pT1-2N1mi breast cancer who had mastectomy were identified. They had either SLNB (35.4%) or ALND (64.6%). Majority of these patients received adjuvant systemic therapy (93.8%). 77 (29.6%) patients received radiotherapy, 31 after SLNB and 46 after ALND. At median follow-up of 61months, ARR was 1.1% (n = 1) in the SLNB only group, vs. 0.6% (n = 1) in the ALND group (p = 0.752). DFS and OS were not significantly different between patients with SLNB alone versus ALND (p = 0.40 and p = 0.27, respectively). Among 92 patients who had SLNB only, no DFS or OS difference was observed with the use of PMRT. In T1-2N1mi patients with mastectomy and SLNB, axillary recurrences were rare. No statistically significant differences were noted between patients with SLNB, ALND, or PMRT. Our findings suggest that these patients may be safely treated without axillary therapy.

Clinical Significance of Metastasis or Micrometastasis to the Lymph Node Along the Superior Mesenteric Vein in Gastric Carcinoma: A Retrospective Analysis.

BackgroundThe validity of lymphadenectomy of the lymph node along the superior mesenteric vein (LN14v) in gastric cancer remains controversial. The study investigated the characteristics and prognosis of gastric cancer with metastasis or micrometastasis to LN14v.MethodsA retrospective study of 626 patients undergoing radical gastrectomy in our center from January 2003 to December 2015 was analyzed. In total, 303 patients had lymphadenectomy of LN14v, and lymph node micrometastasis was evaluated by immunohistochemical staining for cytokeratin nodes CK8/18. A logistic regression model was applied to confirm the predictive factors of micrometastasis. Survival analysis was performed to evaluate the effect of micrometastasis or metastasis on prognosis.ResultsThe metastatic rate of the LN14v lymph node was 15.8%, and the micrometastatic rate was 3.3%. Multivariate analysis showed site, Borrmann classification, postoperative lymph node metastasis (pN), and metastasis in LN6 and LN9 were predictive factors for LN14v micrometastasis or metastasis (P < 0.05). The 5-year survival rate in the positive group (LN14v micrometastasis or metastasis) was 12.4%. The prognosis of patients without LN14v lymph node micrometastasis was better than that of the positive group, whereas the difference between group of LN14v micrometastasis and LN14v metastasis was not obvious. In matched analysis, patients with stage III gastric cancer L/M area, pN2-3, and LN6(+) who underwent lymphadenectomy of LN14v had better survival than those without lymphadenectomy of LN14v.ConclusionLymph node micrometastasis may provide accurate prognostic information for patients with gastric cancer. Moreover, lymphadenectomy of LN14v might improve the survival of patients with stage III gastric cancer of L/M area, pN2-3, and LN6(+).

Pathologic Lymph Node Staging of Gastric Cancer.

The TNM classification is the main tool for lymph node (LN) staging in gastric cancer (GC). However, alternative LN staging systems have been proposed, and the role of features other than the number of metastatic LNs is being investigated. Our aim is to discuss the main challenges of LN assessment in GC. Comprehensive review of the literature on alternative LN staging systems, examined LNs, sentinel LN (SLN) biopsy, LN micrometastases (LNMIs), extracapsular extension (ECE), and tumor deposits (TDs) in GC. Many controversies exist regarding LN assessment in GC. The TNM classification shows excellent prognostic performance, but alternative prognostic methods such as the LN ratio or log odds of positive LNs have demonstrated to be better than the TNM system in terms of prognostic accuracy. The value of SLN biopsy and LNMIs in GC is still unclear, and several challenges concerning their clinical impact and pathologic analysis must be overcome before their introduction in clinical practice. Most authors have identified ECE and TDs as independent prognostic factors for survival in GC. Further studies should be performed to evaluate the impact of these features on the TNM classification and patient outcomes, as well as to standardize alternative LN staging systems.

Recurrence of Lymph Node Micrometastases After Radiotherapy for Head and Neck Carcinoma: A Propensity Score-matched Study.

The standard irradiation dose to the elective lymph node area (ELNA) in locally patients with advanced head and neck squamous cell carcinoma (LA-HNSCC) to control lymph node micrometastases (LN-MM) has not changed since it was empirically determined in the 1950s. We investigated the optimal irradiation dose for controlling LN-MM in ELNAs. The pattern of recurrence of LA-HNSCC was retrospectively evaluated in patients who underwent concurrent chemoradiotherapy with cisplatin or radiation therapy alone. In total, 162 patients were enrolled. The median observation period was 34 months. No recurrence was found in ELNAs. After propensity score matching, a cisplatin dose of ≥200 mg/m 2 yielded a significantly higher overall survival rate (p≤0.001) and locoregional control rate (p=0.034) than did a dose of <100 mg/m 2 . CCRT with a cisplatin dose of ≥200 mg/m 2 can reduce the irradiation dose to 40-44 Gy at 2 Gy per fraction to control LN-MM.

Machine Learning for the Prediction of Lymph Nodes Micrometastasis in Patients with Non-Small Cell Lung Cancer: A Comparative Analysis of Two Practical Prediction Models for Gross Target Volume Delineation.

PurposeThe lymph node gross target volume (GTV) delineation in patients with non-small cell lung cancer (NSCLC) is crucial for prognosis. This study aimed to develop a predictive model that can be used to differentiate between lymph nodes micrometastasis (LNM) and non-lymph nodes micrometastasis (non-LNM).Patients and MethodsA retrospective study involving 1524 patients diagnosed with NSCLC was collected in the First Hospital of Wuhan between January 1, 2017, and April 1, 2020. Duplicated and useless variables were excluded, and 16 candidate variables were selected for further analysis. The random forest (RF) algorithm and generalized linear (GL) algorithm were used to screen out the variables that greatly affected the LNM prediction, respectively. The area under the curve (AUC) was compared between the RF model and GL model.ResultsThe RF model revealed that the variables, including pathology, degree of differentiation, maximum short diameter of lymph node, tumor diameter, pulmonary membrane invasion, clustered lymph nodes, and T stage, were more significant for LNM prediction. Multifactorial logistic regression analysis for the GL model indicated that vascular invasion, tumor diameter, degree of differentiation, pulmonary membrane invasion, and maximum standard uptake value (SUVmax) were positively associated with LNM. The AUC for the RF model and GL model was 0.83 (95% CI: 0.75 to 0.90) and 0.64 (95% CI: 0.60 to 0.70), respectively.ConclusionWe successfully established an accurate and optimized RF model that could be used to predict LNM in patients with NSCLC. This model can be used to evaluate the risk of an individual patient experiencing LNM and therefore facilitate the choice of treatment.

Prognostic impact of lymph node micrometastasis in patients with gastric cancer.

The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of LNMM in patients with GC. A total of 624 patients with pathologically lymph node metastasis-negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. Patients with lymph node tumors < 1500μm in diameter (LNMM) had a significantly better prognosis than those with tumors ≥ 1500μm in diameter (p = 0.012; log-rank test). Cox's proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for the overall survival of patients with pN1 GC. There was no significant difference in the overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). LNMM is associated with a favorable prognosis and maybe an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered a factor preventing adjuvant chemotherapy.

Omitting completion axillary lymph node dissection after detection of sentinel node micrometastases in breast cancer: first results from the prospective SENOMIC trial.

Completion axillary lymph node dissection has been abandoned widely among patients with breast cancer and sentinel lymph node micrometastases, based on evidence from prospective RCTs. Inclusion in these trials has been subject to selection bias, with patients undergoing mastectomy being under-represented. The aim of the SENOMIC (omission of axillary lymph node dissection in SENtinel NOde MICrometases) trial was to confirm the safety of omission of axillary lymph node dissection in patients with breast cancer and sentinel lymph node micrometastases, and including patients undergoing mastectomy. The prospective SENOMIC multicentre cohort trial enrolled patients with breast cancer and sentinel lymph node micrometastases who had breast-conserving surgery or mastectomy at one of 23 Swedish hospitals between October 2013 and March 2017. No completion axillary lymph node dissection was performed. The primary endpoint was event-free survival, with a trial accrual target of 452 patients. Survival proportions were based on Kaplan-Meier survival estimates. The trial included 566 patients. Median follow-up was 38 (range 7-67) months. The 3-year event-free survival rate was 96.2 per cent, based on 26 reported breast cancer recurrences, including five isolated axillary recurrences. The unadjusted 3-year event-free survival rate was higher than anticipated, but differed between patients who had mastectomy and those who underwent breast-conserving surgery (93.8 versus 97.8 per cent respectively; P = 0.011). Patients who underwent mastectomy had significantly worse tumour characteristics. On univariable Cox proportional hazards regression analysis, patients who had mastectomy without adjuvant radiotherapy had a significantly higher risk of recurrence than those who underwent breast-conserving surgery (hazard ratio 2.91, 95 per cent c.i. 1.25 to 6.75). After 3 years, event-free survival was excellent in patients with breast cancer and sentinel node micrometastases despite omission of axillary lymph node dissection. Long-term follow-up and continued enrolment of patients having mastectomy, especially those not receiving adjuvant radiotherapy, are of utmost importance.