Postoperative Lymph Node Status Research Articles

Impact of postoperative lymph node status on the prognosis of esophageal squamous cell carcinoma after esophagectomy following neoadjuvant chemoradiotherapy: a retrospective study.

Neoadjuvant chemoradiotherapy (nCRT) and surgery are widely used treatments for locally advanced esophageal squamous cell carcinoma (ESCC). Thus, it is critically important to investigate risk factors that affect patient prognosis after preoperative chemoradiotherapy and surgery. We conducted a retrospective analysis of 77 patients with ESCC who received nCRT and underwent surgery at our center from January 2015 to December 2019. We analyzed the primary clinical data, postoperative pathological results, recurrence, and death results. Among the 77 ESCC patients who received nCRT and surgery, 19 achieved a postoperative pathologic complete response (pCR), and the overall pCR rate was 24.68%. The univariate analysis indicated that postoperative post-neoadjuvant treatment N stage (ypN) metastasis [hazards ratio (HR): 2.908; 95% confidence interval (CI): 0.874-9.676; P=0.082], a high lymph-node ratio [(LNR) >0.1] (HR: 7.149, 95% CI: 1.740-29.369; P=0.006), post-neoadjuvant treatment T3-4 (ypT3-4) (HR: 3.626, 95% CI: 0.824-15.956; P=0.088) affected disease-specific survival (DSS). The multivariate analysis indicated that a high LNR (>0.1) (HR: 6.170; 95% CI: 1.472-25.856; P=0.013) was a significant independent predictor of DSS. The univariate analysis indicated that postoperative ypN metastasis (HR: 2.283; 95% CI: 1.047-4.979; P=0.038) and a high LNR (>0.1) (HR: 4.210; 95% CI: 1.547-11.458; P=0.005) were associated with recurrence-free survival (RFS). The multivariate survival analysis showed that a high LNR (>0.1) (HR: 4.289; 95% CI: 1.538-11.965; P=0.005) was also a significant independent predictor of RFS. In this study, 57 positive lymph nodes were found in 30 of the 77 patients, including 16 left gastric lymph nodes, 9 pericardial lymph nodes, and 7 left supraclavicular lymph nodes. A high LNR (>0.1) in ESCC patients after nCRT is a risk factor of DSS and RFS. ypN metastasis is also an independent predictor of RFS. Left gastric-arterial lymph nodes, para-cardiac lymph nodes, and left supraclavicular lymph nodes are the most common sites of metastasis in ESCC after nCRT.

Preoperative chemotherapy compared with postoperative adjuvant chemotherapy for squamous cell carcinoma of the thoracic oesophagus with the detection of circulating tumour cells randomized controlled trial.

The role of preoperative chemotherapy in the treatment of patients with oesophageal squamous cell carcinoma (ESCC) remains controversial. Chemotherapy followed by surgery was compared with surgery±chemotherapy, and the detection of circulating tumour cells (CTCs) was performed on all enrolled patients. We randomly assigned patients with resectable tumours to the preoperative chemotherapy group (Pre group) or surgery group (patients who were either given or not given adjuvant chemotherapy according to their postoperative lymph node status, Post group). Blood samples were collected 1-3 days before treatment (including preoperative chemotherapy and surgery) and 7 days after surgery for CTC detection. From July 2016 to October 2018, 115 patients were enrolled in the study, of whom 57 were assigned to the Pre group and 58 to the Post group. The proportion of patients with stage III ESCC was 63.16% in the Pre group and 48.28% in the Post group. No patients died during chemotherapy. One patient exhibited a complete response to preoperative chemotherapy, and 13 patients exhibited partial responses. The 2-year progression-free survival (PFS) and overall survival (OS) rates were not significantly different between the Pre and Post groups. In the subgroup analysis, patients with CTC (+) prior to treatments receiving preoperative chemotherapy had a better 2-year PFS (71.90% vs. 38.73%, P=0.0379). In the Cox proportional hazards regression analysis, platelet count was proven to correlate significantly with disease progression (P=0.016), and no factors were proven to correlate significantly with mortality after the factors were balanced in the present analysis. Preoperative chemotherapy improved the short-term PFS when CTC detection was positive prior to any treatment for patients with stage II or III ESCC. CTC detection may be used as an index to guide individualized strategic decisions regarding preoperative chemotherapy, but more evidence is needed.

FLOT, MAGIC or CROSS for adenocarcinoma of the oesophagus and cardia?

Adjunctive treatment with perioperative chemotherapy or neoadjuvant chemoradiotherapy in addition to surgery improves long term survival for patients with operable gastroesophageal adenocarcinoma. Although epirubicin, cisplatin and fluoropyrimidine based chemotherapy was previously a standard of care based on the MAGIC trial, following presentation of the results of the FLOT4/AIO study anthracycline containing regimens have been superseded by taxane based FLOT chemotherapy (docetaxel, oxaliplatin and 5-fluorouracil). Neoadjuvant chemoradiotherapy with carboplatin and paclitaxel as used in the CROSS regimen results in comparable survival to perioperative chemotherapy, however no large randomised trials have directly compared perioperative chemotherapy vs. neoadjuvant chemoradiotherapy in terms of overall survival. This question is being addressed in several ongoing international randomised studies. Currently both perioperative chemotherapy and neoadjuvant chemoradiotherapy are recommended by international guidelines. Whether there are specific groups of patients who may benefit more or less from either treatment has yet to be determined, as is the optimal partner for addition of targeted or immunotherapies. There is still significant room for improvement in treating patients with operable gastroesophageal adenocarcinoma, as regardless of the treatment paradigm, more than half of patients who undergo potentially curative surgery will relapse and die from their disease. Emerging data suggests that risk stratification using easily identifiable biomarkers such as postoperative lymph node status, R0 resection, and the presence or absence of mismatch repair deficiency might allow for a more personalised approach, both in the pre- and postoperative setting. The aim of this presentation is to review the available data on treatment for oesophageal and proximal gastric adenocarcinomas with a view to determining the best treatment for individual patients.

Prostate-specific antigen density as a parameter for the prediction of positive lymph nodes at radical prostatectomy.

Objective:The aim was to determine the prognostic ability of Partin's tables for a patient collective undergoing radical prostatectomy (RP) and to evaluate the association of prostate-specific antigen (PSA) density (PSAD) and postoperative lymph node status.Methods:From 1999 to 2006, 393 consecutive patients underwent RP at our Urology department. Patients with Gleason scores < 6, clinical stages >T2c or neoadjuvant hormonal therapy were excluded. Preoperative PSA, biopsy results, digital rectal examination, and prostate size at transrectal ultrasound were recorded. Risk stratification according to the Partin scoring system was performed. Postoperative results were compared with preoperative risk estimation. Univariate and multivariate statistical analysis about prediction of postoperative lymph node status was performed.Results:Lymph node invasion (LNI) was found in 36 patients (9.16%). Kendall's rank correlation analysis revealed a significant association between the number of removed LN and LNI (P = 0.016). Patients with LNI had a significantly higher preoperative PSA and PSAD. Preoperative Gleason score was a significant predictor of LNI. The Partin tables' prediction of organ confined stages, extraprostatic extension, and seminal vesicle invasion was in line with the pathological findings in our collective. PSAD was a significant predictor of LNI in univariate and multivariate analysis.Conclusion:The most widely used nomogram is of high value in therapy decision-making, although it remains an auxiliary means. Considering the performance of lymph node dissection, surgeons should be aware of the specifics of the applied nomogram. PSAD appears as a useful adjunctive parameter for preoperative prostate risk estimation and warrants further evaluation.

Clinical results and prognostic factors of patients with locally advanced cervical carcinoma treated with neoadjuvant therapy followed by radical hysterectomy : a retrospective study of 182 patients

Objective To analyze the clinical outcome and prognostic factors of concurrent radiochemotherapy (CRCT) or radiotherapy (RT) alone followed by radical hysterectomy in cervical cancer.Methods Between April 2006 and June 2011,182 patients with FIGO ⅠB2-ⅢB cervical carcinoma were treated with preoperative CRCT ( 123 patients) or RT alone ( 59 patients) followed by radical surgery.Weekly cisplatin (40 mg/m2) were administered during radiotherapy for patients treated with CRCT.Preoperative RT doses were 40-50 Gy in 20-25 fractions.Total hysterosalpingo-oophorectomy and pelvic lymph node dissection was performed 2-3 weeks after neoadjuvant therapy.The prognostic factors were analyzed by Cox-regression method.Results Sixty-nine patients were followed up for 3 years.For patients with tumor ≥4.5 cm,there were no significant differences in the 3-year progression-free survival (PFS) and overall survival (OS) rates between CRCT and RT alone ( x2 =1.84 and 1.56,P =0.176 and 0.221 ).For patients with tumor ＜ 4.5 cm,CRCT group had higher PFS and OS rates than RT alone ( x2 =5.22 and 4.81,P=0.022 and 0.018).The 3-year PFS and OS rates were 92.0％ and 93.8％.By multivariate analysis,tumor diameter ( ≥6 cm vs.＜ 6 cm) was significant prognostic factor for PFS and OS (x2 =2.56,P =0.011 ;x2 =4.06,P =0.007 ),age ( ＜ 48 vs.≥ 48 years) was significant prognostic factor for OS (x2=4.86,P =0.046),and postoperative lymph node status (positive vs.negative) was significant prognostic factor for PFS ( x2 =1.04,P =0.010).Conclusions Treatment with CRCT or RT followed by radical surgery has achieved good OS and PFS for patients with FIGO ⅠB2-ⅢB cervical cancer.Tumor diameter,age and postoperative lymph node status are important prognostic factors for survival. Key words: Cervical neoplasms/surgery; Cervical neoplasms/radiotherapy; Cervical neoplasms/chemotherapy; Prognosis

Prognostic significance of cancer within 1 mm of the circumferential resection margin in oesophageal cancer patients following neo-adjuvant chemotherapy†‡

The prognostic significance of the circumferential resection margin (CRM) status in oesophageal cancer patients treated with neo-adjuvant chemotherapy and radical resection is controversial. Furthermore, it is currently unclear whether patients with cancer located at the CRM have a prognosis different from that of those with cancer within 1 mm of the CRM. This is the first study aiming to establish the optimal tumour-free distance from the CRM of an oesophagectomy in patients who have undergone neo-adjuvant chemotherapy. The clinicopathological data of 232 oesophageal cancer patients from two UK centres were analysed. The CRM status was classified as Group A (cancer at the CRM), Group B (cancer within 1 mm but not at the CRM) and Group C (no cancer within 1 mm from the CRM). The relationship between the CRM status and patient survival was investigated. Thirty-eight specimens were classified as Group A, 89 as Group B and 105 as Group C. CRM status was related to the depth of tumour invasion (P < 0.001) and lymph node status (P < 0.001). The prognoses of the Group A and the Group B patients were similar. Both were poorer than that of the Group C patients (P = 0.008). Lymph node status was the only independent prognostic marker in multivariate analysis. Oesophageal cancer patients treated with preoperative chemotherapy with cancer cells at the CRM or within 1 mm of the CRM of the resected specimen have a significantly worse survival than patients with no cancer cells within 1 mm of the margin. However, this study suggests that the overall prognostic significance of the CRM status is limited in this cohort and the postoperative lymph node status is the most important prognostic factor in oesophageal cancer patients treated with neo-adjuvant chemotherapy and surgery.

P2-08-04: Computer-Derived Breast MRI Features Have Complementary Value for Preoperative Selection of Systemic Drug Therapy in Node-Negative Stage-I/II Breast Cancer Patients.

Abstract Background: Typical guidelines for adjuvant systemic drug therapy require assessment of lymph node status, tumor extent and grade. Increasing interest exists, however, for preoperative therapy (neoadjuvant drug therapy and preoperative partial breast irradiation). Here, representative excision specimens are not available to assess eligibility for systemic therapy. Moreover, tumor grade may be difficult to assess in core biopsies resulting in underestimation rates up to 40%. Contrast-enhanced MRI has been shown to correlate with underlying tumor biology, but it is unknown whether it can complement eligibility criteria for systemic drug therapy. Purpose: To assess the complementary value of MRI to determine eligibility for systemic drug therapy prior to breast-conserving surgery in node-negative stage-I/II breast cancer patients. Materials and methods: Patients with preoperative node-negative invasive breast cancer ≥1.0 cm and eligible for breast-conserving therapy after conventional breast imaging and MRI were consecutively included between February 2000 and March 2007. Informed consent was obtained from all patients. Eligibility to systemic therapy was determined on the basis of national guidelines using age, size, tumor grade, as well as axillary lymph node status at final pathology. Twenty temporal and morphological features of contrast uptake at MRI were automatically analyzed by a previously build CAD workstation1,2. Preoperative lymph node status was derived from ultrasound-guided fine-needle aspiration. Multivariate logistic regression and receiver-operating characteristics (ROC) analysis was used to assess associations between preoperative features (age, ER status, computer-extracted MRI features) and eligibility to systemic therapy based on post-operative features (tumor size, grade, lymph node status). Results: Three-hundred-and-eighty-six patients were included. The mean patient age was 58 years. The mean tumor size at pathology was 1.6 cm. Tumor grade was I, II and III in 128 (33%), 163 (42%), and 94 (24%) of tumors, respectively. Post-operative lymph node status was positive in 115/386 (30%) patients. In total, 262/386 (68%) patients were eligible for systemic drug therapy based on post-operative pathology. Multivariate analysis of preoperatively available features yielded ER status, and principle components 1, 6, 8 and 15 of the computer-extracted features. These components describe tumor volume and shape, heterogeneity of contrast uptake, late-enhancement kinetics, and probability of malignancy. The resulting model correlated with the Adjuvant! program (R=0.55, p&amp;lt;0.0001). The area under the ROC curve was 0.82 (p&amp;lt;0.0001). Without the model, agreement between preoperative and postoperative assessment of eligibility to drug therapy was 232/386 (60%) at 15/124 (12%) overestimation rate. With the MRI model, it increased to 258/386 (67%) (p=0.004) without increasing overestimation rate. Conclusion: Computer-analysis of contrast-enhanced MRI has potential to complement preoperative selection of stage I/II node-negative breast-cancer patients for systemic drug therapy. Ref: 1. Gilhuijs et al., Radiology 2002; 225: 907–916 2. Deurloo et al., Radiology 2005; 234: 693–701 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-04.

Significance of Histopathological Tumor Regression After Neoadjuvant Chemotherapy in Gastric Adenocarcinomas

An increasing number of patients with locally advanced gastric carcinomas (GC) are being treated with preoperative chemotherapy before surgery. Histopathological tumor regression may have an important prognostic impact in addition to the UICC-TNM classification system. We evaluated the histopathological tumor regression in 480 surgical resection specimens of GC after neoadjuvant cisplatin-based chemotherapy, using an established system encompassing three tumor regression grades based on the estimation of the percentage of residual tumor tissue at the primary tumor site in relation to the macroscopically identifiable former tumor bed. Tumor regression was correlated to clinicopathological characteristics and patient survival. Of the patients in this study, 102 (21.2%) had complete or subtotal tumor regression (<10% residual tumor), 121 (25.2%) had partial tumor regression (10-50% residual tumor), and 257 (53.5%) had minimal or no regression (>50% residual tumor). Tumor regression was significantly associated with posttreatment tumor category (pT), lymph node status (pN), lymphatic invasion status (pL), and resection status (P < 0.001). Major histopathological regression was less frequent in tumors of the distal stomach and tumors of nonintestinal type (P = 0.003). Tumor regression (P = 0.009) and postoperative Lymph node status (P < 0.001) were independent prognostic factors for survival in a multivariate analysis of tumor regression, ypT/N/L category, resection status, grading and Lauren´s classification. Assessment of histological tumor regression after preoperative chemotherapy in GC provides objective and highly valuable prognostic information in addition to posttherapeutic lymph node status. A standardized tumor regression grading system should be implemented in pathological reports of these tumors.

The recurrence pattern of esophageal carcinoma after transhiatal resection

Background: There is much controversy about the optimal resection for carcinoma of the esophagus. Little is known about the pattern of recurrence after transhiatal resection for esophageal carcinoma. Study Design: We retrospectively reviewed the charts of 149 patients who underwent transhiatal esophagectomy for carcinoma of the mid or distal esophagus or gastroesophageal junction between June 1993 and June 1997. Recurrence was classified as locoregional or distant recurrence. Nine patients with macroscopically evident tumor left after resection and three patients (2.0%) who died in the hospital were excluded from the analysis. This left 137 patients; 105 men and 32 women with a median age 65 years (range 37 to 84 years). Results: There were 95 adenocarcinomas (69.3%) and 42 squamous cell carcinomas (30.7%). Overall the median followup was 24.0 months (range 1.4 to 69.2 months). For patients alive at the end of followup without recurrence, the median followup was 36.5 months (range 23.6 to 69.2 months). Seven patients died of other causes. The median interval between operation and recurrence was 11 months (range 1.4 to 62.5 months) for patients who had recurrence, with no significant difference in interval between locoregional and systemic recurrence. Seventy-two of the 137 patients (52.6%) developed recurrent disease. Thirty-two patients (23.4%) developed locoregional recurrence only, 21 patients (15.3%) developed systemic recurrence only, and 19 patients (13.9%) had a combination of both. In only 8.0% of all patients was there recurrence in the cervical lymph nodes. The most frequent sites of distant recurrence were liver (37.5%), bone (25.0%), and lung (17.5%). Recurrence was related to postoperative lymph node status (p < 0.001) and the radicality of the operation (p < 0.001) in multivariate analysis. Recurrence was not associated with localization or histologic type of the tumor. Conclusions: Recurrence after transhiatal resection is an early event. Almost 40% of patients developed locoregional recurrent disease. For this patient group a more extended procedure may be of benefit, especially in the patients (23.4%) with locoregional recurrence in whom this is the only site of recurrent disease. But the potential benefit of a more extended procedure has to be balanced against a possible increase in perioperative morbidity and mortality.