Impact Of Micrometastases Research Articles

Prognostic impact ofmicrometastasis in patients with esophageal cancer.

Squamous cell carcinoma (SCC) oftheesophagus and adenocarcinoma oftheesophago-gastric junction (AEG) are diseases with poor prognosis. Despite radical surgery having been carried out, many patients are at risk ofcancer recurrence, especially with thepresence ofmetastases in thelymph nodes. The study involved 60 patients suffering from SCC and AEG who had lymph nodes surgically removed between 2012 and 2018. Only lymph nodes with N0 status were subjected to immunohistochemistry examination. Histopathological criteria were used for thediagnosis ofmicrometastases (MM), defined as tumor cells or cell clusters of0.2-2 mm diameter in thelymph node and tumor cell microinvolvement defined as free-floating neoplastic cells or cell clusters within thesub-capsular sinus or intramedullary sinuses ofthelymph node. Atotal of1130 lymph nodes were removed during surgery, with an average of22 lymph nodes per patient (range 8-58). Micrometastases were found in 7 (11.66%) patients: 6 (10.0%) with AEG and 1 (1.66%) with SCC, representing astatistically significant difference p = 0.017. Multivariate analysis ofthestudy group did not confirm thedependence oftheMM on theT features ( p = 0.7) or G ( p = 0.5). In aCox regression analysis, MM were not arisk factor for death, HR: 2.57 (0.95; 7.00), p = 0.064. There was no difference in overall survival for patients with MM (N (+)) and those without (N0), p = 0.055, but there was astatistically significant difference in time ofrelapse between patients with and without MM ( p = 0.049). Patients with theN (+) status are at high risk ofcancer recurrence, and therefore we believe that complementary treatment should be considered in this group.

Sentinel lymph node in cervical cancer: time to move forward.

In early-stage cervical cancer, lymph node status is of paramount importance to determine the best therapeutic strategy and is one of the most important prognostic factors of survival. According to main international guidelines, pelvic full lymphadenectomy is recommended for lymph node staging. Sentinel lymph node (SLN) biopsy is an accurate method for the assessment of lymph nodal involvement and has been suggested instead of systematic pelvic lymph node dissection (PLND). The SLN technique requires a learning-curve to be well performed. Combined detection with technetium-99 and blue dye has been widely used but the recent introduction of indocyanine green (ICG) is of growing interest since it could improve SLN detection. SLN biopsy offers a more accurate anatomical staging by finding potential metastatic nodes outside of usual lymphadenectomy areas. SLN biopsy improves the diagnostic value of lymph node staging with ultrastaging and detection of low-volume nodal metastases [isolated tumor cells (ITCs) and micrometastases]. Appropriate selection of patient and minimal training combined with some simple rules may guarantee a low false negative rate. Several studies have shown that SLN mapping in these patients is feasible, with excellent detection rates and sensitivity. Less-radical lymph node dissection decreases the associated morbidity of PLND, especially the risk of lower-limb lymphoedema, which severely affects patient quality of life. Some points are still subject to debate such as the low accuracy of intraoperative SLN status assessment by frozen section and the impact of micrometastasis on prognosis. Although international guidelines consider SLN biopsy as an alternative to PLND, SLN biopsy alone is not the gold-standard yet due to lack of prospective evidence on long-term oncological safety. The 3 ongoing prospective trials SENTIX, PHENIX and SENTICOL III will most probably give an answer to these issues.

Incidence and clinical relevance of non-small cell lung cancer lymph node micro-metastasis detected by staging endobronchial ultrasound-guided transbronchial needle aspiration.

Approximately twenty percent of lymph node (LN) negative non-small cell lung cancer (NSCLC) patients who undergo curative intent surgery have pan-cytokeratin immunohistochemistry (IHC)-detectable occult micro-metastases (MMs) in resected LNs. The presence of the MMs in NSCLC is associated worsened outcomes. As a substantial proportion of NSCLC LN staging is conducted using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), we sought to determine the frequency of detection of occult MMs in EBUS-TBNA specimens and to evaluate the impact of MMs on progression-free and overall survival. We performed retrospective IHC staining for pan-cytokeratin of EBUS-TBNA specimens previously deemed negative by a cytopathologist based on conventional hematoxylin and eosin staining. The results were correlated with clinical variables, including survival outcomes. Of 887 patients screened, 44 patients were identified meeting inclusion criteria with sufficient additional tissue for testing. With respect to the time of the EBUS-TBNA procedure, 52% of patients were clinical stage I, 34% clinical stage II, and clinical 14% stage IIIa NSCLC. Three patients (6.8%) were found to have cytokeratin positive MMs. All 3 MMs detected were at N2 LN stations. The presence of MMs was associated with significantly decreased progression-free (median 210 vs. 1,293 days, P=0.0093) and overall survival (median 239 vs. 1,120 days, P=0.0357). Occult LN MMs can be detected in EBUS-TBNA specimens obtained during staging examinations and are associated with poor clinical outcomes. If prospectively confirmed, these results have significant implications for EBUS-TBNA specimen analyses and possibly for the NSCLC staging paradigm.

Post San Antonio Breast Cancer Symposium 2018

This short review summarizes the most important facts presented at the San Antonio Breast Cancer Symposium 2018 concerning local therapy of breast cancer, including breast and lymph node surgery as well as radiotherapy. Despite the increasing use of neoadjuvant chemotherapy (nCHT) and consequently higher response and pathologic complete response (pCR) rates in the past years, breast-conserving surgery (BCS) has not increased. This is not only due to positive genetic testing, but it is mostly based on patients’ preference. On the other hand, quality of life seems to be better in young patients undergoing BCS regarding satisfaction with breasts and sexual and psychosocial well-being. Thus, surgical decision-making is crucial in young women with breast cancer and long-term quality of life aspects have to be taken into account. The safe performance of sentinel lymph node biopsy in N+ patients with or without neoadjuvant therapy is the current focus of several large randomized controlled trials. In San Antonio, new data about the impact of micro-metastases or extracapsular extension were presented. The 10-year follow-up data from the AMAROS study demonstrated similar axillary recurrence rates in patients with positive sentinel nodes undergoing complete axillary dissection or radiotherapy only. The RAPID study showed that in patients with unifocal small DCIS (Ductal carcinoma in situ) or invasive cancer <3 cm, accelerated partial breast irradiation with three-dimensional conformal radiotherapy was not inferior compared to whole breast irradiation regarding ipsilateral recurrence rate, but the regimen has to be adapted to achieve similar cosmetic results.

Impact of micrometastasis and isolated tumor cells found on sentinel lymph nodes in early breast cancer

Impact of micrometastasis and isolated tumor cells found on sentinel lymph nodes in early breast cancer

Abstract P1-01-28: What is the actual impact of micrometastases in sentinel lymph nodes in regards to global survival and disease free survival

Abstract OBJECTIVE: Assess the clinical relevance of micro metastasis in sentinel lymph nodes in the overall survival and disease free survival of 1,211 patients undergoing sentinel lymph node biopsy. METHODS: Retrospective cohort study including 1,211 patients undergoing consecutive SLB from 1998 to 2010. SLB were performed in patients with invasive carcinoma of the breast with clinically negative axilla. Age, tumor size, and histologic grades, estrogen and progesterone receptors expression, HER-2, lymphovascular invasion and size of metastases in lymph nodes were assessed. Tumor sizes were divided according to pathologic staging into pT1(&amp;lt; 2,0mm) and pT2(&amp;gt;2,0mm). Lymph nodes were classified as negative (pN0), positive with micro metastases with diameter ranging from 0,21mm to 2,0mm(pN1mi) and positive with macro metastases with diameter greater than 2,0mm(pN1). Statistical analyses were performed by the Likelihood ratio test or Chi-square test for insufficient samples between macro metastases and micro metastases in SLB. Time was considered in months and the overall follow-up time was 125 months and mean time was 65 months. Local regional and distant recurrences were considered as events for disease free survival and Kaplan-Meier survival functions were constructed, testing time between metastases sizes in SLB using the Log-rank test, with a significance level of 5%. RESULTS: Of the studied variables, lymphovascular invasion(p = 0,068) and local regional and distant metastases(p = 0,002) had a statistically significant association with overall survival. Tumor size(p = 0,016); lymph vascular invasion(p = 0,002) and metastases types in sentinel lymph node(p &amp;lt; 0,001) were associated to disease free survival. In the association tests with types of metastases in sentinel lymph node, the following were statistically significant: age(p = 0,004), tumor size(p &amp;lt; 0,001), lymph vascular invasion(p &amp;lt; 0,001) and local regional and distant recurrences. In the interim and final Cox regression analysis, macro metastases were the only statistically relevant factor for disease free survival(p &amp;lt; 0,001). CONCLUSION: The presence of micro metastases(pN1mi) in sentinel lymph node is associated to a prognosis similar to that of negative axilla patients(pN0), indicating that other risk factors for local regional and systemic recurrences should be taken into account. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-28.

Abstract 3440: Effect of neoadjuvant therapy for the number of lymph node micrometastasis in esophageal squamous cell carcinoma

Abstract [Introduction] Esophageal squamous cell carcinoma (ESCC) often develops lymph node metastasis. Several study demonstrated that micrometastasis (MM) in lymph nodes was an independent prognostic factor for ESCC. Recently effect of neoadjuvant therapy including chemotherapy and chemoradiontherapy has been reported. The aim of this study was to investigate the affect of on MM in lymph nodes for ESCC. [Materials and methods] We retrospectively reviewed clinical data of consecutive162 patients with ESCC who underwent esophagectomy accompanied with systemic lymphadectomy in our institution from 2000 to 2010. Firstly, we analyzed the relapse free survival of 90 patients who underwent surgical resection without neoadjuvant therapy and assessed the impact of MM in lymph nodes on prognosis of ESCC by immunohistochemistry using anti-cytokeratin antibody. Next we examined MM in lymph nodes of 72 patients who underwent surgical resection with neoadjuvant therapy and evaluate the effect of neoadjuvant therapy on MM in lymph nodes. [Results] Of 5414 lymph nodes from 90 patients with cStage II/III (surgery group), we detected 311(5.1%) of overt metastasis detected by H&amp;E staining and 124(2.3%) of MM in lymph nodes. The clinicopathological factors related to the postoperative relapse included pTNM Stage and number of lymph node metastasis with MM. Otherwise, in neoadjuvant Group, Of 3466 lymph nodes from 72 patients, we detected 154(4.4%) of overt metastasis and 19(0.4%) of MM. In neoadjuvant group, the rate of MM was decreased from 2.3% to 0.4% as compared to that of surgery group. Importantly, the rate of MM in upper mediastinal region was decreased by neoadjuvant therapy. [Conclusion] We demonstrated the significance of micrometastasis in lymph nodes for prognosis of esophageal cancer. Our findings suggested that neoadjuvant therapy may reduce the number of micrometastasis. Neoadjuvant therapy should be estimated as the standard therapy against esophageal squamous cell carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3440. doi:1538-7445.AM2012-3440

Sentinel lymph node in colorectal cancer — 5 years follow up

AbstractTo assess the impact of micrometastases in sentinel and non-sentinel lymph nodes on long-term survival rates of patients treated for colorectal cancer (CRC). Data of 57 patients diagnosed with CRC and treated in the Department of Surgical Oncology in Gdansk in the years 2002–2006 were retrospectively analyzed. Clinico-histopathological data were analyzed using chi-square tests. The effect on long-time survival rates was analyzed using Kaplan-Meier survival probability estimates. Identification of the SLN was performed using the blue dye staining method. All regional lymph nodes were subject to standard histopathological examination. Additionally in 32(56.14%) patients whose nodes were found negative for metastases on standard staining further immunohistochemical analyses were performed. In the analyzed group SLNB was performed in 42(73.7%) patients with colon cancer and in 15(26.3%) with rectal cancer. Identification of the SLN was possible in 45(78.9%) patients. The sensitivity of SLNB was 33%. False negatives were found in 66%. SLNB is a feasible method in CRC patients. We presume that lack of micrometastases in the SLN and non-SLN cannot be regarded as a prognostic factor.

Abstract 3294: The impact of occult nodal metastasis on the recurrence of esophageal squamous cell carcinoma

Abstract Esophageal cancer (ESC) is an aggressive disease with a poor overall prognosis. Survival rate of patients with cStage II/III ESC who underwerrt surgical resection have been improved, whereas half of these patients frequently caused recurrences. It has been thought that the lymph node metastasis was deeply related to the relapse of ESC. However, clinical signification of micrometastases in lymph nodes remain unclear because of complexity in the procedure to detect micrometastasis. Here we report that the impact of micrometastasis in lymph nodes on the recurrence of ESC. The aim of this study was to confirm the relation between noccult nodal metastasis and recurrence of in resected cStage II/III ESC. A total of 98 patients with ESC resected at Osaka City University hospital between January 2000 and January 2007 were targeted. Micrometastasis was investigated with one-level cytokeratin immunohistochemistry(IHC)and routine histological assessment by hematoxylin-eosin sections. Judgment of micrometastasis was done with discovery of cluster cells. Uni-and multivariate analyses of the independent recurrect facters were performed using the Cox proportional hazards regression model. A total of 6,172 lymph nodes(average 63) were examined from 98 patient, also 140 lymph nodes of micrometastasis(average 1.4) were detected. The micrometastasis was not possible to detect with routine histological assessment by hematoxylin-eosin sections. A clear difference of detected micrometastasis between relapse patients(45 patients,83%) and no relapse patient(15patients,34%) was admitted. In univariate analyses, curability(p=0.000),v facter(p=0.046),pN facter(p=0.026),pM facter(p=0.016),pStage(p=0.002),total metastatic lymph node count(p=0.000),total metastatic lymph node count added micrometastasis(p=0.000) were recurrence facters. In multivariate analyses, total metastatic lymph node count added micrometastasis were independent recurrence facters(Hazard ration 13.059,p=0.000) finally. Therefore, the number of total metastatic lymph nodes with micrometastasis have pivotal impact on the recurrence of ESC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3294.

Impact of Micrometastases in the Sentinel Node of Patients With Invasive Breast Cancer

Impact of Micrometastases in the Sentinel Node of Patients With Invasive Breast Cancer

Impact of Micrometastases in the Sentinel Node of Patients With Invasive Breast Cancer

Impact of Micrometastases in the Sentinel Node of Patients With Invasive Breast Cancer

Non-Sentinel Lymph Node Status of Patients with T1/T2 Breast Cancer and Micrometastasis in the Sentinel Lymph Node.

Abstract Background: Micrometastatic disease in the sentinel lymph node is still an indication for complete axillary lymph node dissection. To further reduce morbidity in breast cancer patients the omission of complete axillary lymph node dissection in patients with micrometastasis in the sentinel lymph node would be desirable.Methods: We retrieved our data-base and looked for the non-sentinel lymph node status in patients with micrometastasis in the sentinel lymph node.Patients with primary T1/T2 breast cancer and sentinel lymph node biopsy were examined for their sentinel lymph node status. Patients with a micrometastasis in the sentinel lymph node, who received a complete axillary lymph node dissection were eligible for evaluation. Patients with a micrometastisis in the sentinel lymph node, who did not receive complete axillary lymph node dissection and patients after primary systemic therapy were excluded.Results: 103 patients were eligible for evaluation. All patients had micrometastases (0,2 to 2,0mm) in the sentinel lymph nodes. In total 15/103 patients (14.6%) had a further metastasis in one or two non-sentinel lymph nodes. 8/103 patients (7.8%) had one macrometastasis in a non-sentinel lymph node with sizes from 2.1mm to 5.0mm. 3/103 patients (2.9%) had a micrometastasis in two non-sentinel lymph nodes and 4/103 patients (3.9%) had one micrometastasis in one non-sentinel lymph node.Mean age of the patients was 57 years, 34 (33%) being premenopausal and 69 (67%) being postmenopausal. 22 patients (21.4%) received immediate axillary dissection after sentinel lymph node biopsy, but 81 patients (78.6%) had a secondary axillary lymph node dissection after the final pathological report. In 19 patients (18.4%) the micrometastasis in the sentinel lymph node could be detected by frozen sections, in 77 patients (74.8%) by serial sections at 250µm in the paraffin embedded sentinel lymph node and in 22 patients (21.4%) by immunohistochemistry only.Discussion: As long as we are lacking reliable methods for predicting the non-sentinel lymph node status for patients with micrometastases in the sentinel lymph node, and as long as the impact of micrometastases in the axilla are subject of debate, axillary lymph node dissection should be performed after sentinel lymph node biopsy with micrometastases in the sentinel lymph node. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1034.

Prognostic impact of micrometastases in colon cancer

Prognostic impact of micrometastases in colon cancer

Breast Cancer Outcomes and Micrometastatic Disease

In Response: We appreciate the letter to the Editor by Drs. Harissis and Fatouros and agree in large part with their sentiment that new prognostic biomarkers both individually and in combination are likely the future of prognostication. Indeed, our own institution has pursued a variety of approaches including examining circulating tumor cells, circulating tumor DNA integrity, and proteomics. Currently, however, with the increased use of sentinel node biopsy, the diagnosis of micrometastasis is increasing. With so many conflicting reports as to the significance of these micrometastases, we have attempted to add some information that we hope will be helpful to clinicians in counseling patients as to their likely breast cancer outcomes. Because of the limitations of using the Surveillance Epidemiology and End Results (SEER) registry to determine the nonsurgical treatment of patients and the techniques of nodal evaluation, we have been careful to not assume that our findings indicate that micrometastatic disease requires more aggressive therapy. Rather, we merely reported outcomes. We encourage those designing trials to consider including these patients but stratifying them into pre-planned analyses, or to consider direct comparisons to determine the best treatment of this subgroup. While the challenge in showing superiority or equivalence for small absolute differences is difficult, this is a challenge that is common in breast cancer studies. A number of trials for early breast cancer have expected absolute improvements in survival at the single-digit level for their tested interventions, and treatment decisions are made every day based on such small changes in absolute survival. We would hope that these efforts to further elucidate the impact of micrometastases would complement rather than replace biomarker research, as one could easily envision how such complementary concepts could be unified into analyses done on a single large accrued patient population.

Prognostic Impact of Micrometastases in Colon Cancer

The 25% rate of recurrence after complete resection of stage II colon cancer (CC) suggests the presence of occult nodal metastases not identified by hematoxylin and eosin staining (H&E). Interim data from our ongoing prospective multicenter trial of sentinel node (SN) biopsy indicate a 29.6% rate of micrometastases (MM) identified by immunohistochemical staining (IHC) of H&E-negative SNs in CC. We hypothesized that these MM have prognostic importance. Between March 2001 and August 2006, 152 patients with resectable colorectal cancer were enrolled in the trial. IHC and quantitative RT-PCR (qRT) assay were performed on H&E-negative SNs. Results were correlated with disease-free survival. The sensitivity of lymphatic mapping was significantly better in CC (75%) than rectal cancer (36%), P<0.05. Of 92 node-negative CC patients 7 (8%) were upstaged to N1 and 18 (22%) had IHC MM. Four patients negative by H&E and IHC were positive by qRT. At a mean follow-up of 25 months, 15 patients had died from noncancer-related causes, 12 had developed recurrence, 5 had died of CC (2 with macrometastases, 3 with MM), and 7 were alive with disease. The 12 recurrences included 4 patients with SN macrometastases and 6 with SN MM (2 by IHC, 4 by qRT). One of the 2 SN-negative recurrences had other positive lymph nodes by H&E. All patients with CC recurrences had a positive SN by either H&E/IHC or qRT. No CC patient with a negative SN by H&E and qRT has recurred (P=0.002). This is the first prospective evaluation of the prognostic impact of MM in colorectal cancer. These results indicate that the detection of MM may be clinically relevant in CC and may improve the selection of patients for adjuvant systemic chemotherapy. Patients with CC who are node negative by cumulative detection methods (H&E/IHC and qRT) are likely to be cured by surgery alone.

Sentinel lymph node biopsy for breast cancer.

Sentinel lymph node biopsy (SLNB) is an emerging surgical technique to improve lymph node staging for breast cancer. Despite the rapid development of this technique, there remain aspects of SLNB that need to be further defined to provide a standardized approach. Variables, including patient selection, technical details for the performance of SLNB, extent of pathologic evaluation of the sentinel lymph node, and the impact of micrometastases, are areas of controversy. This paper reviews the controversies and discusses available data as well as personal experience and opinion.