Evaluating prognostic value and stage migration effects using a positive lymph node ratio in adenocarcinoma of the esophagogastric junction.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Lymph node metastasis is an important clinical issue in AEG patients. This study investigated the usefulness of a positive lymph node ratio (PLNR) to stratify prognosis and evaluate stage migration. METHODS: We retrospectively analysed 117 consecutive AEG patients (Siewert type I or II) who received a lymphadenectomy between 2000 and 2016. RESULTS: A PLNR cut-off value of 0.1 most effectively stratified patient prognosis into two groups (P < 0.001). Also, prognosis could be clearly stratified into four groups: PLNR = 0, 0 < PLNR < 0.1, 0.1 ≤ PLNR < 0.2, and 0.2 ≤ PLNR (P < 0.001, 5-year survival rates (88.6%, 61.1%, 34.3%, 10.7%)). A PLNR ≥ 0.1 significantly correlated with tumour diameter ≥ 4 cm (P < 0.001), tumour depth (P < 0.001), greater pathological N-status (P < 0.001), greater pathological Stage (P < 0.001), and oesophageal invasion length ≥ 2 cm (P = 0.002). A PLNR ≥ 0.1 was a poor independent prognostic factor (hazard ratio 6.47, P < 0.001). The PLNR could stratify prognosis if at least 11 lymph nodes were retrieved. A 0.2 PLNR cut-off value discriminated a stage migration effect in pN3 and pStage IV (P = 0.041, P = 0.015) patients; PLNR ≥ 0.2 might potentially diagnose a worse prognosis and need meticulous follow-up post-surgery. CONCLUSION: Using PLNR, we can evaluate the prognosis and detect higher malignant cases who need meticulous treatments and follow-up in the same pStage.

Log odds of positive lymph nodes show better predictive performance on the prognosis of early-onset colorectal cancer.

BACKGROUND: As the incidence of colorectal cancer tends to be younger, early-onset colorectal cancer (EOCRC) has attracted more attention in recent years. We aimed to assess the optimal lymph node staging system among EOCRC patients, and then, establish informative assessment models for prognosis prediction. METHODS: Data of EOCRC were retrieved from the Surveillance, Epidemiology, and End Results database. Survival prediction ability of three lymph node staging systems including N stage of the tumor node metastasis (TNM) staging system, lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) was assessed and compared using Akaike information criterion (AIC), Harrell's concordance index (C-index), and likelihood ratio (LR) test. Univariate and multivariate Cox regression analyses were conducted to identify the prognostic predictors for overall survival (OS) and cancer-specific survival (CSS). Effectiveness of the model was demonstrated by receiver operative curve and decision curve analysis. RESULTS: A total of 17,535 cases were finally included in this study. All three lymph node staging systems showed significant performance in survival prediction (p < 0.001). Comparatively, LODDS presented a better ability of prognosis prediction with lower AIC (OS: 70,510.99; CSS: 60,925.34), higher C-index (OS: 0.6617; CSS: 0.6799), and higher LR test score (OS: 998.65; CSS: 1103.09). Based on independent factors identified from Cox regression analysis, OS and CSS nomograms for EOCRC were established and validated. CONCLUSIONS: LODDS shows better predictive performance than N stage or LNR among patients with EOCRC. Novel validated nomograms based on LODDS could effectively provide more prognostic information than the TNM staging system.

[Impact of regional positive lymph node ratio of gallbladder carcinoma on prognosis].

Objective: To study the impact of regional positive lymph node ratio (LNR) on prognosis of patients with gallbladder carcinoma. Methods: The clinicopathological and survival data of 53 patients with gallbladder carcinoma who underwent radical resection with regional lymph node metastasis in Ningbo University Affiliated Lihuili Hospital from May 2012 to December 2020 were collected, and receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value of LNR for predicting postoperative survival status in patients with gallbladder carcinoma. According to the critical value, the patients were divided into low LNR group and high LNR group. The clinicopathological features and prognosis of the two groups were compared. Log rank test was used for univariate analysis of prognostic factors in patients with gallbladder carcinoma, and Cox proportional hazards model was used for multivariate analysis. Results: A total of 417 regional lymph nodes were dissected in 53 patients, of which 144 lymph nodes were positive, with a positive rate of 34.5%. The optimal cut-off value of LNR for predicting postoperative survival status of patients with gallbladder carcinoma was 0.33. According to this cut-off value, patients were divided into low LNR group (LNR≤0.33, 28 cases) and high LNR group (LNR>0.33, 25 cases). The recurrence rates were 64.3% (18/28) and 88.0 % (22/25) in low LNR group and high LNR group, respectively. The median recurrence-free survival (RFS) was 8 and 7 months, respectively (P=0.032). In the low LNR group, the 1-, 3-, and 5-year survival rates were 56.2%, 38.4%, and 32.0%, respectively, and the median overall survival (OS) was 16 months. In the high LNR group, the 1-, 3-, and 5-year survival rates were 37.9%, 5.4%, and 0, respectively, and the median OS was 9 months. The postoperative survival rate of patients in the low LNR group was better than that in the high LNR group (P=0.008). Univariate analysis showed that LNR was even associated with RFS and OS in patients with gallbladder carcinoma (P<0.05). Multivariate analysis showed that LNR>0.33 was an independent risk factor for postoperative RFS (HR=1.977, 95% CI: 1.045-3.740), but not for OS (HR=1.561, 95% CI: 0.685-3.553). Conclusion: On the basis of clearing a sufficient number of regional lymph nodes, patients with gallbladder carcinoma with regional LNR>0.33 are more likely to relapse after operation, but the predictive value of LNR>0.33 OS is insufficient.

Radiotherapy is not indicated in patients with vulvar squamous cell carcinoma and only one occult intracapsular groin node metastasis.

OBJECTIVE: Most guidelines advise no adjuvant radiotherapy in vulvar squamous cell carcinoma and a single occult intracapsular lymph node metastasis. However, several recent studies have questioned the validity of this recommendation. The aim of this study was to analyze the groin recurrence rate in patients with a single intracapsular positive lymph node treated without adjuvant radiotherapy. METHODS: Patients with a single clinically occult intracapsular lymph node metastasis, treated without adjuvant radiotherapy, formed the basis for this study. Groin recurrences, and the risk of death, were analyzed in relation to the size of the metastasis in the lymph node and the lymph node ratio. Data were analyzed using SPSS, version 26.0 for Windows. RESULTS: After a median follow-up of 64 months, one of 96 patients (1%) was diagnosed with an isolated groin recurrence and another two (2.1%) were diagnosed with a combination of a local and a groin recurrence. The only isolated groin recurrence occurred in a contralateral lymph node negative groin. Size of the metastasis and lymph node ratio had no impact on the groin recurrence risk, nor on survival. The 5-year actuarial disease-specific and overall survivals were 79% and 62.5% respectively. The 5-year actuarial groin recurrence-free survival was 97%. CONCLUSION: Because of the low risk of groin recurrence and the excellent groin recurrence-free survival, we recommend that adjuvant radiotherapy to the groin in patients with vulvar squamous cell carcinoma and a single occult intracapsular lymph node metastasis can be safely omitted to prevent unnecessary toxicity and morbidity.

Predictive value of tumor-infiltrating lymphocytes for response to neoadjuvant chemotherapy and breast cancer prognosis.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are predictive for the response to neoadjuvant chemotherapy (NAC) of breast cancer. However, little is known about the predictive value of TILs for axillary lymph node involvement after NAC. METHODS: We analyzed 282 breast cancer patients who were operated following NAC and curative surgery from 2008 to 2018. TILs were assessed in core needle biopsies before NAC, and the biopsies were divided into three groups: low (0%-10% immune cells in stromal tissue within the tumor), intermediate (11%-59%), and high (≥60%). The patients were followed for an average of 63 months (range, 2-116 months). We analyzed retrospectively the predictive value of TILs for the response to NAC, including pathological complete response (pCR) and axillary lymph node involvement (positive lymph node ratio (LNR; the ratio of the number of nodes involved to the total number of nodes dissected)). The prognostic values of TILs and LNR were assessed. RESULTS: A pCR was achieved in 27 of 188 patients (14.4%) in the low-TIL group, in 14 of 57 patients (24.6%) in the intermediate-TIL group, and in 13 of 37 (35.1%) in the high-TIL group (p = .007). Among patients who underwent axillary lymph node dissection after NAC, patients with high TILs had lower LNR (p = 0021) compared with the other groups. Kaplan-Meier analysis showed that overall survival (OS; p < .001) and disease-free survival (p < .001) were significantly longer for patients with low LNR (≤0.2). TILs were positively correlated with disease-free survival (p = .028), but TILs did not correlate with OS (p = .171). Moreover, by multivariable analysis, LNR independently affected disease-free survival (p < .001). CONCLUSIONS: TILs may be predictive for pCR rate, postoperative residual lymph node involvement, and disease-free survival of breast cancer patients. High TILs may suggest favorable outcomes.

Laparoscopic gastrectomy plus D2 lymphadenectomy is as effective as open surgery in terms of long-term survival: a single-institution study on gastric cancer.

BACKGROUND: Laparoscopic surgery has been widely accepted to treat early-stage gastric cancer. However, it is still controversial to perform laparoscopic gastrectomy plus D2 lymphadenectomy for locally advanced gastric cancer. We performed the present study to compare the long-term outcomes of patients after laparoscopic or open gastrectomy plus D2 lymphadenectomy. METHODS: The clinicopathological data of 182 gastric cancer patients receiving gastrectomy plus D2 lymphadenectomy between January 2011 and December 2015 at Shenzhen Traditional Chinese Medicine Hospital were retrospectively retrieved. The overall survival (OS) and disease-free survival (DFS) of these 182 patients were compared. Then, the prognostic significance of positive lymph node ratio (LNR) was assessed. RESULTS: As a whole, OS (P = 0.789) and DFS (P = 0.672) of patients receiving laparoscopic gastrectomy plus D2 lymphadenectomy were not significantly different from those of patients receiving open surgery. For stage I patients, laparoscopic gastrectomy plus D2 lymphadenectomy was not significantly different from open surgery in terms of OS (P = 0.573) and DFS (P = 0.157). Similarly, for stage II patients, laparoscopic gastrectomy plus D2 lymphadenectomy was not significantly different from open surgery in terms of OS (P = 0.567) and DFS (P = 0.830). For stage III patients, laparoscopic gastrectomy plus D2 lymphadenectomy was not significantly different from open surgery in terms of OS (P = 0.773) and DFS (P = 0.404). Laparoscopic or open gastrectomy plus D2 lymphadenectomy was not proven by Cox regression analysis to be an independent prognostic factor for OS and DFS. High LNR was significantly associated with worse OS (P < 0.001) and DFS (P < 0.001). Surgical type did not significantly affect prognosis of patients with low LNR or survival of patients with high LNR. CONCLUSIONS: For patients with gastric cancer, laparoscopic gastrectomy plus D2 lymphadenectomy was not inferior to open surgery in terms of long-term outcomes. LNR is a useful prognostic marker for GC patients.

Consolidation chemotherapy in early-stage cervical cancer patients with lymph node metastasis after radical hysterectomy.

OBJECTIVE: Post-operative concurrent chemoradiotherapy has become the standard treatment for patients with positive lymph nodes after radical surgery. The aim of this study was to explore the efficiency and safety of consolidation chemotherapy in early-stage cervical cancer patients with lymph node metastasis after radical hysterectomy. METHOD: We reviewed the medical records of patients with early-stage cervical cancer with lymph node metastasis after radical hysterectomy from January 2010 to January 2017. All patients underwent adjuvant concurrent chemoradiotherapy (n=49) or three cycles of platinum-based consolidation chemotherapy following concurrent chemoradiotherapy (n=89). The primary end points of the study were disease-free survival and overall survival. RESULTS: The median follow-up time was 51 months (range 10-109). No significant difference was noted in disease-free survival, overall survival, or grade 3/4 gastrointestinal disorder between the consolidation chemotherapy group (78.1% vs 83.1% vs 6.7%) and the concurrent chemoradiotherapy alone group (75.4% vs 75.3% vs 4.1%), (p=0.42, 0.26, 0.80, respectively). However, the grade 3/4 myelosuppression rate in the consolidation group was higher than in the concurrent chemoradiotherapy alone group (40.4% vs 22.4%, p=0.03). For patients with >3 positive lymph nodes or patients with >2 positive lymph nodes+lymphovascular space invasion/≥1/3 stromal invasion, disease-free survival and overall survival were superior in the consolidation chemotherapy group compared with the concurrent chemoradiotherapy alone group (p<0.05). CONCLUSION: In patients with >3 positive lymph nodes or patients with >2 positive lymph nodes, lymphovascular space invasion, and greater than 1/3 stromal invasion, disease-free survival and overall survival were superior with consolidation chemotherapy. However, consolidation chemotherapy was also associated with an increased grade 3/4 myelosuppression rate.

Role of lymphadenectomy in endometrial cancer with nonbulky lymph node metastasis: Comparison of comprehensive surgical staging and sentinel lymph node algorithm.

OBJECTIVES: To compare survival and progression outcomes between 2 nodal assessment approaches in patients with nonbulky stage IIIC endometrial cancer (EC). METHODS: Patients with stage IIIC EC treated at 2 institutions were retrospectively identified. At 1 institution, a historical series (2004-2008) was treated with systematic pelvic and para-aortic lymphadenectomy (LND cohort). At the other institution, more contemporary patients (2006-2013) were treated using a sentinel lymph node algorithm (SLN cohort). Outcomes (hazard ratios [HRs]) within the first 5 years after surgery were compared between cohorts using Cox models adjusted for type of adjuvant therapy. RESULTS: The study included 104 patients (48 LND, 56 SLN). The use of chemoradiotherapy was similar in the 2 cohorts (46% LND vs 50% SLN), but the use of chemotherapy alone (19% vs 36%) or radiotherapy alone (15% vs 2%) differed. Although there was evidence of higher risk of cause-specific death (HR, 2.10; 95% CI, 0.79-5.58; P = 0.14) and lower risk of para-aortic progression (HR, 0.27; 95% CI, 0.05-1.42; P = 0.12) for the LND group, the associations did not meet statistical significance. The risk of progression was not significantly different between the groups (HR, 1.27; 95% CI, 0.60-2.67; P =0 .53). In parsimonious multivariable models, high-risk tumor characteristics and nonendometrioid type were independently associated with lower cause-specific survival and progression-free survival. CONCLUSIONS: In EC patients with nonbulky positive lymph nodes, use of the SLN algorithm with limited nodal dissection does not compromise survival compared with LND. Aggressive pathologic features of the primary tumor are the strongest determinants of prognosis.

Prognostic Significance of the Lymph Node Ratio in Surgical Patients With Distal Cholangiocarcinoma.

BACKGROUND: The aim of this study was to compare the prognostic impact of the lymph node ratio (LNR) versus positive lymph node count (PLNC) in patients who had undergone resection for distal cholangiocarcinoma. METHODS: We identified 448 patients with resected distal cholangiocarcinoma from the Surveillance, Epidemiology, and End Results database. The X-Tile program was used to calculate the cutoff values for the LNR and PLNC that discriminate survival. The overall survival and cancer-specific survival rates were calculated. Relationships between clinicopathological factors and patient survival were assessed using univariate and multivariate analyses. RESULTS: The optimal cutoff values for the LNR and PLNC were 0.45 and 3, respectively. Univariate analysis revealed that tumor size, the American Joint Committee on Cancer stage, T stage, the LNR and PLNC were significantly associated with prognosis (P < 0.05). Multivariate analysis demonstrated that the LNR, T stage, and tumor size were independent prognostic factors for cancer-specific and overall survival, whereas PLNC was not. In the subgroup of patients with positive lymph nodes, patients with an LNR of greater than 0.45 had significantly worse cancer-specific survival (hazard ratio, 2.418; 95% confidence interval, 1.588 to 3.682; P < 0.001) and overall survival (hazard ratio, 2.149; 95% CI, 1.421 to 3.249; P < 0.001) than those with an LNR of 0.45 or less. CONCLUSIONS: The LNR was a better predictor of long-term prognosis than PLNC in patients with distal cholangiocarcinoma.

Prognostic impact of the number of retrieved lymph nodes in patients with gastric cancer.

BACKGROUND: In gastric cancer, although at least 16 lymph nodes of retrieved lymph nodes (RLNs) are recommended for nodal staging in Japanese Classification of Gastric Carcinoma and TNM classifications, we wished to clarify their appropriateness. STUDY DESIGN: A total of 1289 consecutive gastric cancer patients, who underwent gastrectomy between 1997 and 2011, were analyzed retrospectively. RESULTS: (i) The patients were divided into two groups using a cut-off RLN number of 16 (RLN < 16 or RLN ≥ 16). There were significant differences in the survival rates of patients in pStage II (P < 0.0001) and III (P = 0.0009), but not those of patients in pStage I (P = 0.0627) and IV (P = 0.1553). (ii) In 498 consecutive patients in pStage II and III, compared with patients in the RLN ≥ 16 group, those in the RLN < 16 group had a significantly higher incidence of older age (P = 0.0004) and positive lymph node ratio (PLNR) (P < 0.0001). Univariate and multivariate analyses showed that an RLN number of less than 16 was an independent poor prognostic factor (P < 0.0001, HR 2.48 [95% CI: 1.60-3.70]). (iii) A cut-off RLN number of 16 could cause the stage migration effect in pStage II or III patients. A cut-off RLN number of 25 or more could eliminate the prognostic effect. CONCLUSION: The RLN number may potentially affect the prognosis and the stage migration in pStage II or III gastric cancer patients. An RLN number of 25 or more could be sufficient for nodal staging.

Comparison of the pathological response of the mesorectal positive nodes between short-course chemoradiotherapy with delayed surgery and long-course chemoradiotherapy in patients with rectal cancer.

BACKGROUND: The aim of this study was to compare the pathological response of mesorectal positive nodes between short-course chemoradiotherapy with delayed surgery (SCRT-delay) and long-course chemoradiotherapy (LC-CRT) in patients with rectal cancer. METHOD: The resected primary tumor specimens following the two different approaches were assessed utilizing the tumor regression grade (TRG 0-4), and each positive lymph node was assessed according to the lymph node regression grade (LRG 1-3), with TRG 4 and LRG 3 indicating total regression. The lymph node sizes were measured to elucidate any correlation with LRG scores. RESULTS: Seventy-four patients with ypN-positive rectal cancer had 220 positive lymph nodes following the SCRT-delay, and 48 patients had 141 positive lymph nodes following the LC-CRT. The distribution of LRG 1/2/3 in the two groups was 123/72/25 and 60/31/50 (p < 0.001), respectively, and the distribution of TRG 0/1/2/3/4 in the two groups was 36/19/19/0 and 12/15/20/1 (p = 0.005), respectively. The requirements of total regression of positive lymph nodes were a primary tumor degenerated to TRG 3 with a size less than 6 mm in SCRT-delay (sensitivity, 60.9 %) or a primary tumor degenerated to TRG 2-4 with a size less than 5 mm at TRG 2 (sensitivity, 57.6 %) or 6 mm at TRG 3 and 4 (sensitivity, 84.2 %) in LC-CRT as indicated by the receiver operating characteristic curve analysis. CONCLUSION: The tumor regression effect of LC-CRT on the primary tumor and positive nodes was more favorable than SCRT-delay, and LC-CRT is able to predict the LRG 3 response with a high sensitivity.

Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer.

BACKGROUND: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC) patients; therefore, establishing a new predictive stage is necessary. AIM: To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC. METHODS: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed. The relationship between LNR and clinicopathological characteristics was analyzed. The survival analysis was performed using Kaplan-Meier survival curves and Cox regression model. RESULTS: Number of metastatic LNs, tumor diameter, depth of tumor invasion, Borrmann type, serum tumor biomarkers, and tumor-node-metastasis (TNM) stage were correlated with LNR stage and N stage. Univariate analysis revealed that the factors affecting survival included tumor diameter, anemia, serum tumor biomarkers, vascular or neural invasion, combined resection, LNR stage, N stage, and TNM stage (all P < 0.05). The median survival time for those with LNR0, LNR1, LNR2 and LNR3 stage were 61, 31, 23 and 17 mo, respectively, and the differences were significant (P = 0.000). Anemia, tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis (all P < 0.05). CONCLUSION: The new LNR stage is uniquely based on number of metastatic LNs, with significant prognostic value for locally advanced GRC, and could better differentiate overall survival, compared with N stage.

Implications of tumor-positive sentinel lymph nodes in single vs multiple nodal basins in melanoma.

Background: Melanoma patients' prognosis is based on the primary tumor characteristics and the tumor status of the regional lymph nodes. The advent of lymphoscintigraphy with SLN biopsy (SLNB) has shown that melanoma can drain to multiple nodal basins but the significance of multiple basins (vs. one basin) with tumor-positive sentinel lymph node(s) (+SLN) of similar tumor burden has not been shown. We examined the impact of the number of nodal basins with +SLN (+basin) in melanoma patients and its significance for patients' prognosis and survival. Study design: We identified 1,915 patients with +SLN from two randomized surgical clinical trials: Multicenter Selective Lymphadenectomy Trials I and II. Patient groups were divided based on number of +SLNs and number of +basins. Disease-free survival (DFS), distant disease-free survival (DDFS) and melanoma-specific survival (MSS) were compared with the Kaplan-Meier method and log-rank tests. Univariable and multivariable analyses were performed using Cox proportional hazard regressions. Results: Among the 1,915 patients, 1,501 had only one +SLN (78%) in one basin and 414 (22%) had multiple +SLNs: 340 located in one basin and 74 in multiple basins. Among patients with multiple +SLNs, those with multiple +basins have a worse DFS, DDFS and MSS than those with a single basin (p ≤ 0.0001 for all comparisons). MSS was significantly different based on AJCC stages: AJCC IIIA and IIIB (p ≤ 0.001 and 0.0287, respectively). Conclusion: Our results suggest that the number of tumor-positive basins may be important for staging and in understanding the biology of lymph node metastases.

Patterns of regional lymph node metastasis predict postoperative overall survival and disease-free survival in locally advanced esophageal squamous cell carcinoma.

Background: Lymph nodal characteristics are highly significant in predicting the survival of patients with esophageal squamous cell carcinoma (ESCC). However, there is currently a scarcity of studies examining their role in locally advanced ESCC. In the present study, we attempted to depict the patterns of regional lymph node metastasis and investigate their predictive potential in locally advanced ESCC. Methods: Patients with locally advanced ESCC underwent esophagectomy at the Department of Thoracic Surgery, The First Affiliated Hospital of Shantou University Medical College were included. Kaplan-Meier curve was used to compare the survival differences between groups. Cox regression was constructed to screen the independent risk factors. Results: A total of 439 patients were included. We identified 10% as the optimal cutoff value for positive lymph node ratio (PLNR) with X-tile software. Statistically significant differences were found in both overall survival (OS, P<0.001) and disease-free survival (DFS, P<0.001) among different PLNR groups. PLNR [hazard ratio (HR): 1.85, P<0.001] and metastatic lymph nodes along the left gastric artery (HR: 1.63, P=0.02) were the independent prognostic factors for OS. While PLNR (HR: 1.77, P<0.001) and metastatic total main bronchus lymph nodes (HR: 2.78, P=0.047) were the independent prognostic factors for DFS. Conclusions: We discovered that higher PLNR is associated with poorer OS and DFS of locally advanced ESCC. The lymph nodes along the left gastric artery and the total main bronchus lymph nodes were independent prognosticators for OS and DFS, respectively.

Different lymph node staging systems for predicting the prognosis of colorectal neuroendocrine neoplasms.

BACKGROUND: Colorectal neuroendocrine neoplasms (NENs) are a rare malignancy that primarily arises from the diffuse distribution of neuroendocrine cells in the colon and rectum. Previous studies have pointed out that the status of lymph node may be used to predict the prognosis. AIM: To investigate the predictive values of lymph node ratio (LNR), positive lymph node (PLN), and log odds of PLNs (LODDS) staging systems on the prognosis of colorectal NENs treated surgically, and compare their predictive values. METHODS: This cohort study included 895 patients with colorectal NENs treated surgically from the Surveillance, Epidemiology, and End Results database. The endpoint was mortality of patients with colorectal NENs treated surgically. X-tile software was utilized to identify most suitable thresholds for categorizing the LNR, PLN, and LODDS. Participants were selected in a random manner to form training and testing sets. The prognosis of surgically treating colorectal NENs was examined using multivariate cox analysis to assess the associations of LNR, PLN, and LODDS with the prognosis of colorectal NENs. C-index was used for assessing the predictive effectiveness. We conducted a subgroup analysis to explore the different lymph node staging systems' predictive values. RESULTS: After adjusting all confounding factors, PLN, LNR and LODDS staging systems were linked with mortality in patients with colorectal NENs treated surgically (P < 0.05). We found that LODDS staging had a higher prognostic value for patients with colorectal NENs treated surgically than PLN and LNR staging systems. Similar results were obtained in the different G staging subgroup analyses. Furthermore, the area under the receiver operating characteristic curve values for LODDS staging system remained consistently higher than those of PLN or LNR, even at the 1-, 2-, 3-, 4-, 5- and 6-year follow-up periods. CONCLUSION: LNR, PLN, and LODDS were found to significantly predict the prognosis of patients with colorectal NENs treated surgically.

Efficacy and safety of MR-guided adaptive simultaneous integrated boost radiotherapy to primary lesions and positive lymph nodes in the neoadjuvant treatment of locally advanced rectal cancer: a randomized controlled phase III trial.

BACKGROUND: In locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC. METHODS: This is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60-65 Gy in 25-28 fractions to primary lesions and positive lymph nodes; 50-50.4 Gy in 25-28 fractions to the pelvis) or intensity-modulated radiotherapy (50-50.4 Gy in 25-28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life. DISCUSSION: Since dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024).

Positive lymph node ratio is an important index to predict long-term survival for advanced esophageal squamous carcinoma patients (II∼III) with R0 resection--a SEER-based analysis.

Background: Esophageal squamous carcinoma (ESCC) is one of the most malignant cancers in the world due to nodal metastasis. Therefore, a reasonable nodal staging system is extremely important for further treatment strategies. Recently the positive lymph node ratio (PLNR) is an important prognostic factor in various solid tumors. Method: In this study, we investigated the clinical significance of the PLNR in stage II∼III ESCC patients. We collected the pathological characteristics of 272 stage II∼III ESCC patients from the SEER database from 2004-2016. ROC curves were used to calculate the best cutoff value of the PLNR; Pearson's Chi-square (χ2) and Fisher's exact probability tests were used to compare the clinical baseline and characteristics of patients. For continuous variables, Student's t-test and ANOVA were performed to evaluate statistical significance. Clinical outcomes were estimated by using the Kaplan‒Meier method and log-rank test. Furthermore, univariate and multivariate Cox regression models were utilized to analyze independent prognostic factors of ESCC patients. Results: Consequently, advanced ESCC patients were effectively stratified into two groups by prognosis using a PLNR cutoff value of 0.15 (P value = 0.04). The median survival time of patients with PLNR <0.15 (n = 145) was much higher than that of patients (n = 127) in the PLNR ≥0.15 group (20.0 vs. 13.0 months, P value < 0.0001). Notably, the PLNR significantly predicted the prognosis of ESCC patients with stage N1 (P value 0.01) and stage III (P value < 0.001) disease. The multivariate Cox proportional hazard model showed that T stage (HR 1.33, 95 % CI 0.97-1.82), tumor size >45 mm (HR 1.32, 95 % CI 1.02-1.70), N stage (HR 1.41, 95 % CI 0.98-2.01) and PLNR ≥0.15 (HR 1.35, 95 % CI 0.87-1.74) were independent risk factors for prognostic prediction in ESCC patients. Meanwhile, 117 II∼III ESCC patients from Shaanxi Provincial People's Hospital shown that the overall survival with a PLNR <0.15 (n = 96) was significantly longer than that with a PLNR ≥0.15 (n = 21) . Conclusions: The PLNR is useful for accurately predicting clinical outcomes and determining postoperative strategies.

Breast cancer: emerging principles of metastasis, adjuvant and neoadjuvant treatment from cancer registry data.

PURPOSE: Growing primary breast cancers (PT) can initiate local recurrences (LR), regional lymph nodes (pLN) and distant metastases (MET). Components of these progressions are initiation, frequency, growth duration, and survival. These characteristics describe principles which proposed molecular concepts and hypotheses must align with. METHODS: In a population-based retrospective modeling approach using data from the Munich Cancer Registry key steps and factors associated with metastasis were identified and quantified. Analysis of 66.800 patient datasets over four time periods since 1978, reliable evidence is obtained even in small subgroups. Together with results of clinical trials on prevention and adjuvant treatment (AT) principles for the MET process and AT are derived. RESULTS: The median growth periods for PT/MET/LR/pLN comes to 12.5/8.8/5/3.5 years, respectively. Even if 30% of METs only appear after 10 years, a pre-diagnosis MET initiation principle not a delayed one should be true. The growth times of PTs and METs vary by a factor of 10 or more but their ratio is robust at about 1.4. Principles of AT are 50% PT eradication, the selective and partial eradication of bone and lung METs. This cannot be improved by extending the duration of the previously known ATs. CONCLUSION: A paradigm of ten principles for the MET process and ATs is derived from real world data and clinical trials indicates that there is no rationale for the long-term application of endocrine ATs, risk of PTs by hormone replacement therapies, or cascading initiation of METs. The principles show limits and opportunities for innovation also through alternative interpretations of well-known studies. The outlined MET process should be generalizable to all solid tumors.

Role of Radiotherapy and Hormone Therapy in Patients with Node-Positive Locally Advanced Prostate Cancer.

BACKGROUND: New-generation imaging techniques and the increasing use of surgery in high-risk prostate cancer (PCa) allow us to detect many cases of nodal disease at initial diagnosis or after resection. The treatment of PCa with pathologic regional nodes has evolved from the exclusive use of systemic therapy to its combination with locoregional treatment. It can also represent a benefit in the overall survival. However, the evidence from randomised studies is limited. Thus, we review the most relevant results in this scenario. MATERIALS AND METHODS: A literature search was conducted in MEDLINE, PubMed, EMBASE, Clinical-Trials.gov and Web of Science on January 2023 to review node-positive PCa by considering the relevant literature on this topic published with no restrictions on date and language. The search keywords used were "Prostatic Neoplasms" (MeSh) and "Node-positive" (Text Word) and "Radiotherapy" (MeSh) and ("Androgen Antagonists" (MeSh) or "Antineoplastic Agents, Hormonal" (MeSh)), which are indexed within the Medical Subject Headings database. RESULTS: The management of node-positive PCa has no clear definitive consensus at the initial disease diagnosis or after surgery. However, in this review, we summarise the existing literature for the management of these patients in both scenarios, considering imaging tests, radiotherapy, hormone therapy and second-generation hormonal treatments. CONCLUSIONS: The combination of radiotherapy and androgen-deprivation therapy is the treatment of choice. The addition of second-generation hormone therapy, plus the intensification of radiotherapy schedules, will likely change the treatment paradigm for these patients.

Patients with Lower Positive Lymph Nodes Ratio May Benefit from Preoperative Radiotherapy in Stage III Non-Small Cell Lung Cancer.

BACKGROUND: Although preoperative radiotherapy (PORT) is a promising therapeutic option for stage III non-small cell lung cancer (NSCLC), the efficacy of this treatment remains controversial. The positive lymph node ratio (PLNR) is recognized as an independent prognostic factor for survival. However, no previous studies have focused on the association between PLNR and PORT in stage III NSCLC. METHODS: Data were collected from the Surveillance, Epidemiology and End Results (SEER) database, and all patients enrolled in this analysis were diagnosed during 2010-2015. The primary endpoint was overall survival (OS). Univariate and multivariate Cox regression analysis was used to identify factors associated with survival before and after case-control matching. PLNR was defined as the ratio of the number of positive lymph nodes to the total number of retrieved or examined lymph nodes. A cutoff value for PLNR was calculated using an X-tile model. RESULTS: Overall, 391 patients with PORT and 2814 patients without PORT were enrolled in this study. The cohort after 1:1 case-control matching included 322 patients who received PORT and 322 patients without PORT. PORT was not associated with a significant effect on OS (HR = 1.14; 95% CI: 0.91-1.43; P = 0.825). Multivariate Cox regression analysis showed that PLNR (P < 0.001) was independently associated with OS in patients with stage III NSCLC. An X-tile model was used to identify a cutoff value for PLNR: the risk of death was significantly lower in patients with PLNR ≤0.41 who received PORT than in those with PLNR >0.41 who received PORT (HR = 0.59; 95% CI: 0.38-0.91; P = 0.015). CONCLUSION: PLNR may be a prognostic factor for survival in patients with stage III NSCLC who undergo PORT. Lower PLNR is a predictor of better OS and thus warrants further study.